AU2008203478A1 - Human analogs of murine deubiquitinating protease genes - Google Patents

Description

P001 Section 29 Regulation 3.2(2) 00 00 0 0

AUSTRALIA

Patents Act 1990 COMPLETE SPECIFICATION STANDARD PATENT Application Number: Lodged: Invention Title: Human analogs of murine deubiquitinating protease genes The following statement is a full description of this invention, including the best method of performing it known to us: P111AHAU/1107 O IPAD Cop 00 Human Analogs of Murine Deubiquitinating Protease Genes Background of the Invention 00 The role of ubiquitin in protein degradation was discovered and the main enzymatic S reactions of this system elucidated in biochemical studies in a cell-free system from S reticulocytes. In this system, proteins are targeted for degradation by covalent ligation to 00 ubiquitin, a 76-amino-acid-residue protein. Briefly, ubiquitin-protein ligation requires the 0 sequential action of three enzymes. The C-terminal Gly residue of ubiquitin is activated in an N ATP-requiring step by a specific activating enzyme, El (Step This step consists of an intermediate formation of ubiquitin adenylate, with the release of PPi, followed by the binding of ubiquitin to a Cys residue of El in a thiolester linkage, with the release of AMP. Activated ubiquitin is next transferred to an active site Cys residue of a ubiquitin-carrier protein, E2 (Step In the third step catalyzed by a ubiquitin-protein ligase or E3 enzyme, ubiquitin is linked by its C-terminus in an amide isopeptide linkage to an -amino group of the substrate protein's Lys residues (Step 3).

Proteins ligated to polyubiquitin chains are usually degraded by the 26S proteasome complex that requires ATP hydrolysis for its action. The 26S proteasome is formed by an ATP-dependent assembly of a 20S proteasome, a complex that contains the protease catalytic sites, with 19S "cap" or regulatory complexes. The 19S complexes contain several ATPase subunits and other subunits that are presumably involved in the specific action of the 26S proteasome on ubiquitinylated proteins. The roles of ATP in the assembly of the 26S proteasome complex and in its proteolytic action are not understood. The action of the 26S proteasome presumably generates several types of products: free peptides, short peptides still linked to ubiquitin via their Lys residues, and polyubiquitin chains (Step The latter two products are converted to free and reusable ubiquitin by the action of ubiquitin-C-terminal hydrolases or isopeptidases (Steps 5 and Some isopeptidases may also disassemble certain ubiquitin-protein conjugates (Step 7) and thus prevent their proteolysis by the 26S proteasome.

The latter type of isopeptidase action may have a correction function to salvage incorrectly ubiquitinylated proteins or may have a regulatory role. Short peptides formed by the above processes can be further degraded to free amino acids by cytosolic peptidases (Step 8).

00 -2jUbiquitin-mediated degradation of protein is involved in various biological processes.

The selective and programmed degradation of cell-cycle regulatory proteins, such as cyclins, inhibitors of cyclin-dependent kinases, and anaphase inhibitors are essential events in cellcycle progression. Cell growth and proliferation are further controlled by ubiquitin-mediated 00 5 degradation of tumor suppressors, protooncogenes, and components of signal transduction Ssystems. The rapid degradation of numerous transcriptional regulators is involved in a variety Sof signal transduction processes and responses to environmental cues. The ubiquitin system is 00 clearly involved in endocytosis and down-regulation of receptors and transporters, as well as 0 in the degradation of resident or abnormal proteins in the endoplasmic reticulum. There are strong indications for roles of the ubiquitin system in development and apoptosis, although the target proteins involved in these cases have not been identified. Dysfunction in several ubiquitin-mediated processes causes pathological conditions, including malignant transformation.

Our knowledge of different signals in proteins that mark them for ubiquitinylation is also limited. Recent reports indicate that manyproteins are targeted for degradation by phosphorylation. It was observed previously that many rapidly degraded proteins contain PEST elements, regions enriched in Pro, Glu, Ser, and Thr residues. More recently, it was pointed out that PEST elements are rich in S/TP sequences, which are minimum consensus phosphorylation sites for Cdks and some other protein kinases. Indeed, it now appears that in several (though certainly not all) instances, PEST elements contain phosphorylation sites necessary for degradation. Thus multiple phosphorylations within PEST elements are required for the ubiquitinylation and degradation of the yeast G1 cyclins Cln3 and Cln2, as well as the Gcn4 transcriptional activator. Other proteins, such as the mammalian G regulators cyclin E and cyclin D1, are targeted for ubiquitinylation by phosphorylation at specific, single sites. In the case of the IkBa inhibitor of the NF-kB transcriptional regulator, phosphorylation at two specific sites, Ser-32 and Ser-36, is required for ubiquitin ligation. p-cateinin, which is targeted for ubiquitin-mediated degradation by phosphorylation, has a sequence motif similar to that of IkBa around these phosphorylation sites. However, the homology in phosphorylation patterns of these two proteins is not complete, because phosphorylation of other sites of B-catenin is also required for its degradation. Other proteins targeted for degradation by phosphorylation include the Cdk inhibitor Siclp and the STAT1 transcription factor. Though different patterns of phosphorylation target different proteins for degradation, a 00 C1 common feature appears to be that the initial regulatory event is carried out by a protein kinase, while the role of a ubiquitin ligase would be to recognize the phosphorylated form of the protein substrate. It further appears that different ubiquitin ligases recognize different 0 phosphorylation patterns as well as additional motifs in the various protein substrates.

However, the identity of such E3s is unknown, except for some PULC-type ubiquitin ligases 00 that act on some phosphorylated cell-cycle regulators in the budding yeast. The multiplicity of signals that target proteins for ubiquitin-mediated degradation (and of ligases that have to S recognize such signals) is underscored by observations that the phosphorylation of some 00 S proteins actually prevents their degradation. Thus the phosphorylation of the c-Mos CI protooncogene on Ser3 and the multiple phosphorylations of c-Fos and c-Jun protooncogenes at multiple sites by MAP kinases suppress their ubiquitinylation and degradation.

In addition to the families of enzymes involved in conjugation of ubiquitin, a very large family of deubiquitinating enzymes has recently been identified from various organisms.

S These enzymes have several possible functions. First, they may have peptidase activity and cleave the products of ubiquitin genes. Ubiquitin is encoded by two distinct classes of genes.

One is a polyubiquitin gene, which encodes a linear polymer of ubiquitins linked through peptide bonds between the C-terminal Gly and N-terminal Met of contiguous ubiquitin molecules. Each copy of ubiquitin must be released by precise cleavage of the peptide bond 0 between Gly-76-Met-1 of successive ubiquitin moieties. The other class of ubiquitin genes encodes ubiquitin C-terminal extension proteins, which are peptide bond fusions between the C-terminal Gly of ubiquitin and N-terminal Met of the extension protein. To date, the extensions described are ribosomal proteins consisting of 52 or 76-80 amino acids. These ubiquitin fusion proteins are processed to yield ubiquitin and the corresponding C-terminal extension proteins. Second, deubiquitinating enzymes may have isopeptidase activities. When a target protein is degraded, deubiquitinating enzymes can cleave the polyubiquitin chain from the target protein or its remnants. The polyubiquitin chain must also be disassembled by deubiquitinating enzymes during or after proteolysis by the 26 S proteasome, regenerating free monomeric ubiquitin. In this way, deubiquitinating enzymes can facilitate the ability of the 26 S proteasome to degrade ubiquitinated proteins. Third, deubiquitinating enzymes may hydrolyze ester, thiolester, and amide linkages to the carboxyl group of Gly-76 of ubiquitin.

Such nonfunctional linkages may arise from reactions between small intracellular compounds such as glutathione and the El-, E2-, or E3-ubiquitin thiolester intermediates. Fourth, 00 t deubiquitinating enzymes may compete with the conjugating system by removing ubiquitin S from protein substrates, thereby rescuing them from degradation or any other function S mediated by ubiquitination. Thus generation of ubiquitin by deubiquitinating enzymes from the linear polyubiquitin and ubiquitin fusion proteins and from the branched polyubiquitin 00 ligated to proteins should be essential for maintaining a sufficient pool of free ubiquitin. Many S deubiquitinating enzymes exist, suggesting that these deubiquitinating enzymes recognize 0 distinct substrates and are therefore involved in specific cellular processes. Although there is 00 recent evidence to support such specificity of these deubiquitinating enzymes, the structurefunction relationships of these enzymes remain poorly studied.

Deubiquitinating enzymes can be divided broadly on the basis of sequence homology into two classes, the ubiquitin-specific processing protease (UBP or USP, also known as type 2 ubiquitin C-terminal hydrolase (type 2 UCH)) and the UCH, also known as type 1 UCH).

UCH (type 1 UCH) enzymes hydrolyze primarily C-terminal esters and amides of ubiquitin but may also cleave ubiquitin gene products and disassemble polyubiquitin chains. They have in common a 210-amino acid catalytic domain, with four highly conserved blocks of sequences that identify these enzymes. They contain two very conserved motifs, the CYS and HIS boxes. Mutagenesis studies revealed that the two boxes play important roles in catalysis.

Some UCH enzymes have significant C-terminal extensions. The functions of the C-terminal extensions are still unknown but appear to be involved in proper localization of the enzyme.

The active site of these UCH enzymes contains a catalytic triad consisting of cysteine, histidine, and aspartate and utilizes a chemical mechanism similar to that of papain. The crystal structure of one of these, UCH-L3, has been solved at 1.8 A resolution. The enzyme comprises a central antiparallel B-sheet flanked on both sides by helices. The B-sheet and one of the helices are similar to those observed in the thiol protease cathepsin B. The similarity includes the three amino acid residues that comprise the active site, Cys 95 His 169 and Asp1 84 The active site appears to fit the binding of ubiquitin that may anchor also at an additional site.

The catalytic site in the free enzyme is masked by two different segments of the molecule that limit nonspecific hydrolysis and must undergo conformational rearrangement after substrate binding.

UBP (type 2 UCH) enzymes are capable of cleaving the ubiquitin gene products and disassembling polyubiquitin chains after hydrolysis. It appears that there is a core region of 00

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N about 450 amino acids delimited by CYS and HIS boxes. Many of these isoforms have Nterminal extensions and a few have C-terminal extensions. In addition, there are variable sequences in the core region of many of the isoforms. The functions of these divergent S sequences remain poorly characterized. Another interesting function of specific UBPs is the regulation of cell proliferation. It was observed that cytokines induced in T-cells specific de- 00 S ubiquitinating enzymes (DUBs), termed DUB-I and DUB-2. DUB-1 is induced by stimulation cr of the cytokine receptors for IL-3, IL-5, and GM-CSF, suggesting a role in its induction for the N B-common (betac) subunit of the interleukin receptors. Overexpression of a dominant negative 00 0 mutant of JAK2 inhibits cytokine induction of DUB-1, suggesting that the regulation of the C enzyme is part of the cell response to the JAK/STAT signal transduction pathway. Continued expression of DUB-I arrests cells at G1; therefore, the enzyme appears to regulate cellular growth via control of the Go-GI transition. The catalytic conserved Cys residue of the enzyme is required for its activity. DUB-2 is induced by IL-2 as an immediate early (IE) gene that is down-regulated shortly after the initiation of stimulation. The function of this enzyme is also obscure. It may stimulate or inhibit the degradation of a critical cell-cycle regulator.

Cytokines, such as interleukin-2 activate intracellular signaling pathways via rapid tyrosine phosphorylation of their receptors, resulting in the activation of many genes involved in cell growth and survival. The deubiquitinating enzyme DUB-2 is induced in response to IL-2 and is expressed in human T-cell lymphotropic virus-I (HTLV-1)transformed T cells that exhibit constitutive activation of the IL-2 JAK/STAT (signal transducers and activators of transcription) pathway, and when expressed in Ba/F3 cells DUB- 2 markedly prolonged IL-2-induced STATS phosphorylation. Although DUB-2 does not enhance IL-2-mediated proliferation, when withdrawn from growth factor, cells expressing DUB-2 had sustained STATS phosphorylation and enhanced expression of IL-2-induced genes cis and c-myc. DUB-2 expression markedly inhibited apoptosis induced by cytokine withdrawal allowing cells to survive. Therefore, DUB-2 has a role in enhancing signaling through the JAK/STAT pathway, prolonging lymphocyte survival, and, when constitutively expressed, may contribute to the activation of the JAK/STAT pathway observed in some transformed cells. (Migone, et al., Blood. 2001;98:1935-1941).

Protein ubiquitination is an important regulator of cytokine-activated signal transduction pathways and hematopoietic cell growth. Protein ubiquitination is controlled by 00 -6-

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b the coordinate action of ubiquitin-conjugating enzymes and deubiquitinating enzymes.

Recently a novel family of genes encoding growth-regulatory deubiquitinating enzymes (DUB-1 and DUB-2) has been identified. DUBs are immediate-early genes and are induced rapidly and transiently in response to cytokine stimuli. By means of polymerase chain reaction 0 amplification with degenerate primers for the DUB-2 complementary DNA, 3 murine bacterial rartificial chromosome (BAC) clones that contain DUB gene sequences were isolated. One BAC contained a novel DUB gene (DUB-2A) with extensive homology to DUB-2. Like DUB- 1 and DUB-2, the DUB-2A gene consists of 2 exons. The predicted DUB-2A protein is highly related to other DUBs throughout the primary amino acid sequence, with a hypervariable 0 region at its C-terminus. In vitro, DUB-2A had functional deubiquitinating activity; mutation of its conserved amino acid residues abolished this activity. The 5' flanking sequence of the DUB-2A gene has a hematopoietic-specific functional enhancer sequence. It is proposed that there are at least 3 members of the DUB subfamily (DUB-i, DUB-2, and DUB-2A) and that different hematopoietic cytokines induce specific DUB genes, thereby initiating a cytokinespecific growth response. (Baek et al, Blood. 2001;98:636-642).

Protein ubiquitination also serves regulatory functions in the cell that do not involve proteasome-mediated degradation. For example, Hicke and Riezman have recently demonstrated ligand-inducible ubiquitination of the Ste2 receptor in yeast. Ubiquitination of the Ste2 receptor triggers receptor endocytosis and receptor targeting to vacuoles, not proteasomes. Also, Chen et al. have demonstrated that activation of the IB kinase requires a rapid, inducible ubiquitination event. This ubiquitination event is a prerequisite for the specific phosphorylation of IB and does not result in subsequent proteolysis of the kinase complex. The ubiquitination of Ste2 and IB kinase appears reversible, perhaps resulting from the action of a specific deubiquitinating enzyme.

A large superfamily of genes encoding deubiquitinating enzymes, or UBPs, has recently been identified. UBPs are ubiquitin-specific thiol-proteases that cleave either linear ubiquitin precursor proteins or post-translationally modified proteins containing isopeptide ubiquitin conjugates. The large number of UBPs suggests that protein ubiquitination, like protein phosphorylation, is a highly reversible process that is regulated in the cell.

00 C1 Interestingly, UBPs vary greatly in length and structural complexity, suggesting functional diversity. While there is little amino acid sequence similarity throughout their coding region, sequence comparison reveals two conserved domains. The Cys domain contains 0 a cysteine residue that serves as the active enzymatic nucleophile. The His domain contains a histidine residue that contributes to the enzyme's active site. More recent evidence 00 Sdemonstrates six homology domains contained by all members of the ubp superfamily.

SMutagenesis of conserved residues in the Cys and His domains has identified several residues C that are essential for UBP activity.

00 1Recently, a growth regulatory deubiquitinating enzyme, DUB-I, that is rapidly induced in response to cytokine receptor stimulation was identified. DUB-1 is specifically induced by the receptors for IL-3, granulocyte macrophage-colony-stimulating factor, and suggesting a specific role for the c subunit shared by these receptors. In the process of cloning theDUB-1 gene, a family of related, cross-hybridizing DUB genes was identified. From this, other DUB genes might be induced by different growth factors. Using this approach, an IL-2inducible DUB enzyme, DUB-2 and closely related DUB-2a were identified. DUB-1 and DUB-2 are more related to each other than to other members of the ubp superfamily and thereby define a novel subfamily of deubiquitinating enzymes.

Hematopoietic-specific, cytokine induced DUBs in murine system have shown to prolong cytokine receptor, see Migone, T. et al. (2001). The deubiquitinating enzyme DUB-2 prolongs cytokine-induced signal transducers and activators of transcription activation and suppresses apoptosis following cytokine withdrawal, Blood 98, 1935-41; Zhu, et al., (1997). DUB-2 is a member of a novel family of cytokine-inducible deubiquitinating enzymes, J Biol Chem 272, 51-7 and Zhu, et al., (1996). The murine DUB-1 gene is specifically induced by the betac subunit of interleukin-3 receptor, Mol Cell Biol 16, 4808- These effects are likely due to the deubiquitination of receptors or other signaling intermediates by DUB-1 or DUB-2, murine analogs of hDUBs. Inhibition of hDUBs may achieve downregulation of specific cytokine receptor signaling, thus modulating specific immune responses.

Cytokines regulate cell growth by inducing the expression of specific target genes. A recently identified a cytokine-inducible, immediate-early gene, DUB-i, encodes a 00 S deubiquitinating enzyme with growth regulatory activity. In addition, a highly related gene, DUB-2, that is induced by interleukin-2 was identified. The DUB-2 mRNA was induced in T cells as an immediate-early gene and was rapidly down-regulated. Like DUB-I, the DUB-2 S protein had deubiquitinating activity in vitro. When a conserved cysteine residue of DUB-2, 0 required for ubiquitin-specific thiol protease activity, was mutated to serine deubiquitinating activity was abolished. DUB-1 and DUB-2 proteins are highly related S throughout their primary amino acid sequence except for a hypervariable region at their 00 COOH terminus. Moreover, the DUB genes co-localize to a region of mouse chromosome 7, suggesting that they arose by a tandem duplication of an ancestral DUB gene. Additional

DUB

genes co-localize to this region, suggesting a larger family ofcytokine-inducible

DUB

enzymes. We propose that different cytokines induce specific DUB genes. Each induced DUB enzyme thereby regulates the degradation or the ubiquitination state of an unknown growth regulatory factor, resulting in a cytokine-specific growth response.

On the basis of these structural criteria, additional members of the DUB subfamily can be identified in the GenBankTM. The highest degree of homology is in the Cys and His domains.

Additionally, this putative human DUB protein contains a Lys domain (amino acids 400-410) and a hypervariable region (amino acids 413-442).

Murine DUB (mDUB) subfamily members differ from other UBPs by functional 0 criteria as well. mDUB subfamily members are cytokine-inducible, immediate-early genes and may therefore play regulatory roles in cellular growth or differentiation. Also, DUB proteins are unstable and are rapidly degraded by ubiquitin-mediated proteolysis shortly after their induction.

mDUB reports demonstrate that specific cytokines, such as IL-2 and IL-3, induce specific deubiquitinating enzymes (DUBs). TheDUB proteins may modify the ubiquitinproteolytic pathway and thereby mediate specific cell growth or differentiation signals. These modifications are temporally regulated. The DUB-2 protein, for instance, is rapidly but transiently induced by IL-2. Interference of DUB enzymes with specific isopeptidase inhibitors may block specific cytokine signaling events.

Defensins constitute a major family of antimicrobial peptides in mammals. Depending on the distribution of the cysteines and the linkages of the disulfide bonds, human defensins 00 can be divided into two categories: a-defensins, which can be found in granulocytes and in epithelial cells of the small intestine, and P-defensins, which are expressed by epithelial cells and leukocytes including macrophages. Some defensins are expressed constitutive manner in granulocytes and epithelial cells where as others are induces by either exposure to microbial pathogens or pro-inflammatory cytokines such as IL-13, TNF-a and interferon-y. The genes r> coding for human defensins are clustered within 1 Mb segment on chromosome 8P23, and it g has been suggested that p-defensins may predate the a-defensin family during recent gene 00 amplification since a-defensin cannot be detected even in many mammalians including cow.

0 Cow has at least 13 p-defensins but no a-defensin. p-defensins contribute to early host defense against several bacterial and fungal pathogens, as an important mechanism of innate immune response. Beside this antimicrobial activity, a chemoattractant activity on both immature dentritic cells and memory T cells, as well as monocytes, has been recently described, demonstrating that p-defensins may promote both innate and adaptive immune response.

Summary of the Invention The present invention is directed to analogs of murine DUBs, hematopoietic-specific, cytokine-inducible deubiquitinating proteases found as a cluster of genes on chromosomes 4 and 8 and respective regulatory regions. Eleven novel human DUBs and four potential genes 0 that express truncated form of DUBs not previously reported in public databases were identified by searching human genome database using murine DUB-1 and DUB-2 sequences.

These genes share open reading frames (ORFs) that are 88 to 99% amino acid identity to each other, when gaps caused by deletion and N-terminal and/or C-terminal extension was not counted as mismatch, and exhibit approximately 50% identity to murine DUBs. Eight of eleven ORFs generate a protein of 530 amino acids. Two ORFs (hDUB8.3 and hDUB8.1 1) have internal in-frame deletions such that the genes are capable of generating 497 and 417 amino acid long polypeptides, respectively. One ORF (hDUB4.5) exhibits extension at both and 3' end of the ORF so that the gene is capable of expressing 574 amino acid long polypeptide. Surprisingly, this 5' extension results in specific pro-polypeptide sequence that can direct polypeptide targeting to the mitochondria. Furthermore, the respective regulatory regions, putative promoters, of these genes also share close to 90% identity each other suggesting that their expression is coordinated. In addition, we found that two of these genes 00 -lt-

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can be expressed under the control of separate promoters that can be controlled independently S and expressing potentially distinctive protein products.

O Manipulation of these gene products by small molecular compounds can reduce 00 5 inflammation by regulating proinflammatory cytokine signaling, modulate autoimmune Sdiseases by regulating cytokine receptor signaling that are critical for lymphocytes 0 proliferation, and immune over-reaction during infection using above mechanisms.

00 Two of cluster genes (hDUB4.1 and hDUB4.2) possesses two distinctive promoter domains in front of their ORFs such that they can be regulated independently in their transcription potential. The longer transcripts of these ORFs (called hDUB4.1a and hDUB4.2a) has 12 and 4 exons respectively and capable of generating 1016 and 1021 amino acid long polypeptides, respectively. These polypeptides share C-terminal 530 amino acids with their shorter form that can be expressed separately from independent promoters (called hDUB4.1b and hDUB4.2b, respectively). In addition, two other ORFs are capable of generating longer than 530 amino acid polypeptides (hDUB4.10 and hDUB4.11).

Remarkably, these two deduced polypeptides shares significant homology within portion of N-terminal portions (I added alignment file of these at the end of sequence file). Three of the ORFs (hDUB4.5, 4.8, and 8.2) has N-terminal insertion that is typical for mitochondria targeting sequence. An alignment of these sequences is provide in the Tables. The promoter sequences defined as upstream of initiation ATG of the ORF exhibit remarkable level of homology each other except that of hDUB4.1a. The sequence identity among all promoter sequences except that of hDUB4.1a is approximately 90% in 2000 base pair span upstream of initiation ATG. Two of the promoter sequences (hDUB8.3 and 8.11) have 334 nucleotides insertion at approximately 1000 base pair upstream of initiation ATG. Interestingly, hDUB8.3 and hDUB8.11 are the only ones with shorter ORFs due to the internal deletions. In addition to these ORFs, there are 5 ORFs that are capable of expressing polypeptides (hDUB4.4, hDUB4.9, hDUB8.2, hDUB8.9, and hDUB8.10) that share initiation codon with other 530 amino acid long polypeptides but terminate prematurely due to the in frame termination sequences. These also shares significant homology upstream of ATG initiation codon suggesting they may expressed as truncated proteins, potential regulatory functions. All 11 hDUB8 genes are clustered with the defensin clusters within 2 Mb region in 8P23, implying that both acquisition and amplification are relatively recent event, perhaps during mammalian 00

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S evolution. It is of interest that hDUB4 gene cluster is.also in highly amplified cluster region of ;Z chromosome 4P16 that is yet to be assigned in chromosome location. These data suggest that hDUB4s and hDUB8s are within very dynamic region of the human chromosomes (both 4pl 6 S and 8p23) that are undergoing volatile amplifications. The data also suggest that expression of hDUB8 may also be coordinated in conjunction with defensins that are critical components of 00 innate immune response and inflammation.

C Search methods for identifying human analogs of mDUBs: 00 S In order to identify human analogs of mDUBI, -2A, mDUBI (U41636), mDUB2 (NM_010089), and mDUB2A (AF393637) DNA sequences were used to search against Ensembl entire "golden path" (as contigs) using Ensembl blast search engine (http://www.ensembl.org/perl/blastview). All three mDUBs have significant alignments with contig AC083981, AF252831, AF228730, AF252830, AC068974 on chromosome 8 with the high score above 2000 and the probability less than e-87. In order to find all the homolog genes in the genome, exhaust search was performed using genomic aligned sequence to search against the "golden path" contigs. Two more contigs were found to have significant alignment that has probability less than e-100: one is AC074340 on chromosome 8 and the other is AC022770 on chromosome 4.

DNA sequences for contig AC083981, AF252831, AF228730, AF252830, AC068974, AC074340 and AC022770 were downloaded from Ensembl and gene annotation for each contig was performed using GenScan gene annotation program. Genes having homolog with mDUBs were named in sequence based on their locations on chromosomes.

For example, hDUB8.1 was derived from AF228730, 8.2, 8.3 were derived from AF252830, were derived from AC074340, 8.6 were derived from AF252831, 8.7, 8.8 and 8.9 were derived from AC083981, and 8.10 and 8.11 were derived from AC068974. hDUB4.1, 4.2, 4.3, 4.4, 4.5 were derived from AC022770 on chromosome 4.

Using these hDUB4s and hDUB8s, both Ensemble and NCBI blast search was performed.

Further contig NT_028165 that covers chromosome 4 was identified. From this and already assembled chromosome 4pl6.1 region, further annotation was performed using GenScan gene annotation program. From this we identified hDUB4.6, 4.7, 4.8, 4.9, 4.10, and 4.11.

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Analysis of the hDUB gene clusters in chromosome 4 reveals that at least five ORFs in San unmapped cOntig (AC022770) were identified by nucleotide homology search with murine DUB1 and 2. At least four out of five ORFs share core 530 amino acid sequences. Two 00 5 ORFs (hDUB4.1 and hDUB4.2) are multi-exon ORFs that extend N-terminal part of Spolypeptides that shares minimal sequence identity. However, there is a conserved putative Spromoter sequences that encompass over 2,000 bases in the intron region proximal to the last 0O exon that is conserved among all 5 genes. Three of the ORFs (hDUB4.5, 4.8, and 8.2) has N- O terminal insertion that is typical for mitochondria targeting sequence. The hDUB genes 0 cluster in 4P16 of the human chromosome, which is an unmapped part of the human chromosome.

Analysis of the hDUB gene clusters in chromosome 8 reveals that at least eleven ORFs in six different contigs (AC068974, AC074340, AC083981, AF228730, AF252830, and AF252831) were identified by nucleotide homology search with murine DUBI and 2. At least seven out of eleven ORFs share significant identities with similar length. There are conserved putative promoter sequences that encompass over 2,000 bases in all 11 genes. The hDUB genes cluster in 8P23.1 of the human chromosome and clustered with defensin molecules (at lease 9 defensins are clustered with hDUB8s) and the whole domain belongs the olfactory GPCR cluster.

Analysis of the' deduced amino acid sequences of the hDUBs reveals polypeptides consistent with mDUBs, which contain highly conserved Cys and His domains that are likely to form the enzyme's active site. The putative active site nucleophile of mDUB-2 is. a cysteine residue (Cys- 60 in the Cys domain. Both mDUB-1 and mDUB-2 have a lysinerich region (Lys domain; amino acids 374-384 of mDUB-2) and a short hypervariable region (amino acids 385- 451 of mDUB-2), in which the mDUB-1 and mDUB-2 sequences diverge considerably. The hypervariable(HV) region of mDUB-2 contains a duplication of the eight-amino acid sequence: PQEQNHQK.

TaqMan real time PCR analysis of expression of hDUB4s and hDUB8s in human immunocytes upon various stimulation -13- 00 N Protocol of reverse transcription (RT) from total cellular RNA using random hexamer as t primer (using TaqMan Reverse Transcription Reagents Cat# N808-0234) 1 ug of total RNA preparation in 100 ul of IxTaqMan RT Buffer Mix, 5.5mM MgC 2 mM dNTPs, 2.5 uM Random Hexamers, 40 U RNAse inhibitor, 125U Multiscribe Reverse 00 Transcriptase. Mix by pipeting up and down. Incubate 25 0 C for 10 minutes (annealing step), S48 0 C for 30 minutes (reverse transcription), and 95 0 C for 5 minutes (heat killing of the enzyme). The samples can be left at the machine at 4 0 C, or alternatively, can be stored at 0 C. Yield of cDNA synthesis can be measured by incorporation of small portion of S0 radioactive dATP (or dCTP). Average efficiency for this protocol is between 60-80% of conversion of RNA to cDNA.

Protocol of TaqMan real-time quantitative PCR 1 ul of TaqMan RT product in 12.5 ul of lx master Mix (Applied Biosystems Cat# 4304437)containing all necessary reaction components except primers and probes, 0.9 uM forward primer, 0.9 uM reverse primer, 0.2 uM probe. Mix by pipetting up and down.

Samples containing GADPH primer pair and probe were also prepared as control. Thermal cycling and detection of the real-time amplification were performed using the ABI PRISM 7900HT Sequuence Detection System. The quantity of target gene is given relative to the GADPH control based on C, values determined during the exponential phase of PCR.

Primer-probe sets used and their specificities: Primer 4.1 is unique for hDUB 4.1 Primer 4.2 covers hDUB 4.2, 4.3, 4.5 and 8.1 Primer 8.3 covers hDUB 8.3 and 8.11 Primer 8.5 is unique for hDUB Primer 8.6 covers hDUB 8.6, 8.7 and 8.8 Table 1. Expression of hDUBs in PBMC stimulated with LPS (100 ng/ml) and PHA (5 ug/ml) for 7 hours.

Donor 1 Primer Fold-Upregulation Relative upon stimulation expression 4.1 2.2 1 4.2 2.0 21000 8.3 1.8 5560 2.1 80 8.6 2.6 19200 Donor 2 Fold-Upregulation Relative upon stimulation expression 3.8 1 2.0 16400 1.8 5500 3.1 310 3.0 23000 Table 2. Expression ofhDUBs in PBMC stimulated with LPS (100 ng/ml) for 1.5, 7and 24 hours (Donor 3) Table 3. Expression of DUBs in PBMC stimulated with LPS (100 ng/ml) and/or PHA ug/ml) for 1.5, 7, 24 hours (donor 4) hours Primer Fold- Relative Upregulation expression upon stimulation 4.2 0.4 39 8.3 0.5 5 0.9 1 8.6 0.6 26 4.2 3.5 367 8.3 1.5 13 1.9 2 8.6 2.3 103 4.2 1.2 129 8.3 1.0 9 8.5 1.0 1 8.6 1.3 56 7 hours 24 hours Fold- Relative Fold- Relative Upregulation expression Upregulation expression upon upon stimulation stimulation 2.5 54 1.6 48 1.6 6 1.1 7 1.5 1.7 1.4 2 1.7 57 1.0 21 4.4 94 0.9 26 1.7 6 0.7 0.9 1 0.7 1 2.5 23 0.8 17 3.4 73 0.8 23 2.2 8 0.7 0.9 1.3 0.9 1.2 2.5 33 0.8 18

PHA

LPS

PA

PHA

There is no increase of expression in T lymphocytes (donor 5) and B lymphocytes (donor 6) when stimulated with anti-CD4/CD28 and anti-CD40/IL-4, respectively.

00 Table 4. Expression of hDU B 4.2, 4.3, 4.5 and 8.1 examined by primer 4.2 in different human organ panel by TaqMan analysis.

Tissue Type Mean B 2 H~ Ct Expression 00 Mean r- Adrenal Gland 29.72 20.00 10.08 0.92 Bone marrow 34.02 20.49 13.89 0.07 S Brain 26.92 22.73 4.54 42.84 ri Colon 32.03 19.97 12.42 0.18 00 Fetal Brain 27.59 24.23 3.71 76.15 0 Fetal Liver 33.22 .22.58 10.99 0.49 N7 Heart 33.09 21.60 11.85 0.27 Kidney 29.93 21.97 8.32 3.13 Lung 32.10 19.31 13.15 0.11 Mammary Gland 30.00 21.74 8.61 2.56 Pancreas 34.83 24.07 11.11 0.45 Placenta 36.60 23.77 13.19 0.00 Prostate 29.14 20.93 8.55 2.66 Salivary Gland 32.11 21.39 11.07 0.46 Skeletal Muscle .28.27 20.44 8.18 3.45 Small Intestine 34.33 21.00 13.69 0.08 Spinal Cord 27.04 21.91 5.47 22.48 Spleen 32.45 19.02 13.78 0.07 Stomach 32.15 21.66 10.84 0.55.

Testis 28.57 23.07 5.87 17.16 Thymnus 31.01 20.68 10.69 0.61 Thyroid 28.84 20.80 8.39 2.97 Trachea 31.39 19.63 12.11 0.23 Uterus 30.37 21.09 9.64 1.25 PBMCfControl 33.98 18.82 15.52 0.02 PBMC/PMA 33.62 18.81 15.17 0.03 PBMC/PHA 34.20 18.77 15.78 0.02 PBMC/HDM 34.23 17.81 16.77 0.01 A549 Cells 31.98 21.57 10.77 0.57 THP- 1 35.48 20.75 15.09 0.00 Ovary 31.84 21.55 10.65 0.62 Positive Control 29.61 21.86 8.11 3.62 Table 5. Expression of hDUB 4.2, 4.3, 4.5 and 8.1 examined by primer 4.2 in human immunocytes panel: Cell Type and stimulation Mean B 2 8a Ct Expression condition Mean Granulocyte resting 34.18 17.22 17.50 0.005 Granulocyte TNF-1 4/24 hr 32.39 17.16 15.76 0.018 CDI19 (tonsillar CD4OL) 28.7 19.92 9.32 1.565 00

;Z

00 CID19 (tonsillar LPS)

FLS-REST

FLS-ILl 4/24 hr FLS-TNF-P 4/24 hr Monocyte resting (pool 1.5, 7, 24 hr) Monocyte LPS (pool 1.5, 7, 24 hi) Monocyte IiNF-g (pool 1.5, 7, 24 hi) Monocyte LPS EFN-q (pool 7, 24 hi) DCs progenitors (CD14+) DCs immature DCs mature THO resting THO activated Th I resting Thi CD28/CD3 Th.2 resting Th2 CD28/CD3

BSMC

BSMC IL-4 TNF-f 24 hr BSMC IL-13 +TNF-P 24 hr BSMC IL-4 IL-13 NHBE dO NHIBE IL-4 +TNF-P dO NI-BE IL- 13 +TNF- fdO NI{BE resting d7 d 14 NI{BE IL-4 TNF- d7V d 14 NI{BE IL-13 +TNF- V7+ d14 CD8 T cell 0 hour CD8 T cell a-CD3/CD28 4 hour CD8 T cell a-CD3/CD28 24 hour 1-MvVEC resting HMVEC TNF- I+ IL-4 24hr I-MVEC TNT-I 24hr HIMvVEC TNF- I+ IL- 13 24hr Normnal synovium pool RA synovium pool Normal colon Colitis Colon Crohns colon pooled Normal Lung COPID Lung.

Positive control Cloning of h DUB4,8s by PCR 31.14 34.67 34.26 34.91 33.63 20.67 20.43 20.41 20.15 18.29 11.00 14.78 14.38 15.31 15.89 0.488 0.036 0.047 0.025 0.017 34.55 18.03 17.06 0.007 34.62 17.27 17.88 0.004 34.87 17.38 18.03 0.004 35.87 35.48 37.46 31.11 31.29 33.88 32.15 33.94 33.27 35.33 36.44 35.94 36.28 36.63 35.72 36.35 .34.89 38.59 37.62 30.15 32.08 30.94 35.09 35.91 35.57 36.38 34.92 33.65 32.5 33.17 32.91 31.01 35.09 28.4.

19.73 18.18 17.92 17.63 18.23 18.27 19.31 18.07 18.78 21.64 21.52 21.41 22.09 22.24 21.42 21.37 22.41 22.02 21.93 19.52 19.6 18.64 20.25 20.86 21.06 20.61 21.16 20.88 21.68 21.32 22.06 20.5 22.14 22.29 16.67 17.84 20.07 14.02 13.60 16.15 13.38 16.40 15.02 14.22 15.45 15.07 14.73 14.92 14.83 15.52 13.01 17.11 16.23 11.16 13.01 12.84 15.38 15.59 15.05 16.31 14.3 13.3 11.36 12.39 11.39 11.05 13.49 6.64 0.000 0.000 0.000 0.060 0.081 0.014 0.094 0.012 0.030 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.12 1 0.000 0.000 0.43 7 0.121 0.137 0.000 0.000 0.000 0.000 0.050 0.099 0.38 1 0.187 0.374 0.472 0.000 9.992 00

O

Following promer set was used to clone 530 amino acid open reading frame portion of single exon hDUB4s and 8s from human genomic DNA: N-terminal primer: 5'-atggaggacgactcactct-3' (19 mer) C-terminal primer: 5'-ctggcacacaagcaga-3' (19 mer) 00 r- S Underlined triplet nucleotides in each primer represent translational initiation and termination O codon. This primer set can amplify most of hDUB4s and hDUB8s as well as potentially yet to 0 0 be identified hDUBs that are similar enough to hDUB4s and hDUB8s due to the high homology in nucleotide sequences in this part of the ORF. 1593 base pair fragment was successfully amplified from genomic DNA from two healthy human subjects and cloned into pCR2.1 vector and transformed into TOP10 strain of E coli. Over 300 independent clones with appropriate size insert were obtained and sequences are obtained by ABI automated DNA sequencers.

Deubiquitination Assay Confirmation that the DUB is a deubiquitinating enzyme may be shown using previously identified deubiquitination assay of ubiquitin--galactosidase fusion proteins, as described previously in the literature. Briefly, a fragment of the DUB, of approximately 1,500 nucleotides, based on the wild-type DUB cDNA (corresponding to amino acids 1 to about 500) and a cDNA containing a missense mutation are generated by PCR and inserted, in frame, into pGEX (Pharmacia), downstream of the glutathione S-transferase (GST) coding element. Ub-Met--gal is expressed from a pACYC184-based plasmid. Plasmids are cotransformed as indicated into MC1061 Escherichia coli. Plasmid-bearing E. coli MC1061 cells are lysed and analyzed by immunoblotting with a rabbit anti--gal antiserum (Cappel), a rabbit anti-GST antiserum (Santa Cruz), and the ECL system (Amersham Corp.). in vitro deubiquitinating enzyme activity may be shown from purified hDUB fusion protein using commercial polyubiquitinated protein as substrate.

HDUB4s and hDUB8s are potential inflamatory cytokins specific Immediate-early Genes mDUB-1 was originally cloned as an IL-3-inducible immediate-early gene. Similarly, mDUB-2 was cloned as an IL-2-inducible immediate-early gene. We examined inducibility as 00 -18-

O

well as cell-type specific expression of these genes using multiple TaqMan analysis from human organ RNA samples and human immunocytes RNA samples. Our data suggest that expression of hDUBs are not apparent in lymphocytes and granulocytes but high in fresh human PBMC from several donor. This strongly suggest that expression may be limited to the 00 5 monocytes/macrophages and potentially NK cells. hDUB4s and hDUB8s are upregulated in PBMC stimulated with stimuli (LPS and/or PHA) that is known to upregulate various inflammatory cytokines such as TNF-alpha, IL-1 beta etc. This increase of expression is S almost completely disappeared 20 to 24 hours after stimulation suggesting this is an early C gene. The fact that there is only weak expression upregulation at 1.5 hours after stimulation o suggests that stimuli by themselves may not upregulate hDUB4s and hDUB8s, but cytokines that are upregulated within couple of hours after stimulation may be responsible for upregulation of the hDUB4s and hDUB8s.

The DUB Subfamily of the ubp Superfamily From these data we propose that hDUB4s and hDUB8s are members of a discrete subfamily of deubiquitinating enzymes that shows the strongest similarity to mDUB subfamily including mDUB1, mDUB2, and mDUB2A, called the DUB subfamily. DUB subfamily members contain distinct structural features that distinguish them from other ubps.

!0 First, DUB subfamily members are comparatively small enzymes of approximately 500-550 amino acids. Second, DUB subfamily members share amino acid similarity not only in the Cys and His domains but also throughout their primary amino acid sequence. For instance, DUB proteins contain a lysine-rich region (Lys domain) and a HV domain near their carboxyl terminus.

The regulatory regions, or promoter regions, of each of the DUBs was analyzed for putative transcription factor binding motifs using TRANSFACFind, a dynamic programming method, see Heinemeyer, et al., "Expanding the TRANSFAC database towards an expert system of regulatory molecular mechanisms" Nucleic Acids Res. 27, 318-322, (1999). The Transfac database provides eukaryotic cis- and trans-acting regulatory elements.

Table 6, putative transcription factor binding motifs within the DUB regulatory or promoter, region of hDUB 4.1a. The position is indicated by nucleotides.

00

;Z

00 7 1 Description Tvrnncfi~ki I Pndtinn(~nrp'~ Name M00271 729..724(100) AML- Ia runt-factor AML-1I MOO0148 296..302(100) SRY sex-determining region Y gene product 1016..1010(96) 958..964(94) 47.4..480(94) 1982..1988(92) 129..123(90) 857..863(90) 776..782(90) 1919..1913(90) 122 123 3(90_ 276..282(90 174 1..1735(90) 193.. 199(90) 105 111(90)__ M00240 1600..1606(100) Nkx-2.5 homneo domain factor tinman homolog 700..694(100) M00083 92.9(0)MZFI IMZF1 M00101 161..156(100) 100O8..1002( 100) 421..429(100) t153..147(99) 359..353(98) 1388..I134(9 1644.. 1650(97) 1702..1696(97).

250..256(97) 231. .237(97) 617. .6 11(94) 509..503(93) 432..426(92) 3-07..313(92) 153 1-59(92-) 1832..1838(92) 1366.. 1372(92) 494..500(92)- 1450..1456(91) 1456.. 1450(9 1) 722..716(90) 991..985 986..992(90) 1646..1640(90) CdxA UCdxA M00253 1142..1149(97) 1344..1351(96) 639..632(95) cap signal for transcription initiation 00 00 00 M00099 9 1 M0O0285 M00347 M00135 M00075 M00278 MOO0157 M00127 MOO -109 MOO0190 MOO0137 M00302 313..1320(94) 872..1879(93) 69..262(92) 57..250(91) 103..1110(91) 752(91) 589..1596(90)_ p78. .993(96) 637..1652(94) ?95..980(93) 62..156(96) 008..1002(96) ~23..429(96) [774..1768(96) 115..421(92) 860..854(91) 1026..1020(91) 494..500(91) 94:,100(91) 725..713(95) 98')..970(92) 531..522(95) 1642..1660(95) 217..226(94) 530.. 522(94) S8 S8 CdxA CdxA TCF1 I TCF1 1/KCR-FI/Nrfl homodimers GATA-1 GATA-binding factor I Oct- I ocanrfactor 1 GATA-1 GjATA-binding factor I Lmo2 complex of Lmo2 bound to TaI-1, E2A ____rotei ns, and GATA-1, half-site 2 900..908(90)-_ 990. .97 8(94) 533..520(93 1933.. 1920(93) 1656..1643(93, 1193..1205(93) 248..260(90) 1652.. 1640(90) 1501.. 1512(92) RORalpha2 GATA-1 C/EBPbeta

C/EBP

Oct- I

NF-AT

RAR-r elated orphan receptor alpha2

I

GATA-binding factor 1 CCAAT/enhancer binding protein beta CAAT/enhancer binding factor octarner factor I Nuclear factor of activated T-cells GATA-binding factor 3 M00077 M00126 900..908(91) 530..522(90) 533..520(91)2 GATA-3 L GATA-1 GATA-binding factor I CCAAT/enhancer binding protein IvL1-11, 121Q(1 M00074 1280.. 1292(91) c-Ets- I(p5 c-Ets- l(p5 4 M00042 192..201(91) Sox-5 M00241 1650..1643(91) Nkx-2.5 homco domain factor tinman homolog r MOO] 16 138..125(91) CIEBPalpha CCAAT/enhancer binding protein alpha M0-0138 -1640.. 1662(91) Oct- I octamer factor]1 M00128 532..520(90)' GATA-1 GATA-binding factor I' M00248 i7.rn()V)Q 1AAr, 1ASOUGO) ()ct er tactor I 1{FH-3 HNF-3/Fkh Homolog 3 Freac-6) 101(0 HFH-- 00 00 Table 7, putative transcription factor binding motifs within the DUB regulatory or promoter, region of hDUB 4.1lb. The position is indicated by nucleotides.

Transfac IPosition(Score) Name Description M00254 1831.. 1820(99) CCAAT -e-llular and viral CGAAT box MOOIOl 832..826(98) CdxA CdxA 727..721(92) .64(92) 570. .564(92) 523..529(92) 425..431(92) 1682..1688(91) 1409.. 1415(91) 1415..1409(91) 1682(9 1) M00054 470..461(97) -NF-kappaB NF-kappaB 634(95) MOO0148 946..940(96) SRY sex-determitinig region Y gene product 1564.. 1570(92) 1528..1534(92) 1092.. 1098(92) 1048..1054(90) 708..714(90) 655..661(90) 1360..1354(90) 1824..1818(90) 396..390(90) 749..743(90) 1016..1010(90) M00053 470..461(95) c-Rel c-Rel.

634(94) M00285 1734..1 746(95) TCFI 1 TCF1 1/KCR-F1/Nrfl hornodimers 1111..1123(91) 17. M00052 470..461(95) NF-kappaB NF-kappaB .634(94) M00077 1933..1941(95) 1 GATA-3 IGATA-binding factor 3 M00253 485..492(95) 1893..1886(95) 749..756(94) 834..841(93) 1484.. 1477(92) 511..504(92) 1194..1201(91) 163..170(91) cap signal for transcription initiaion 00

;Z

00 MQQ9 6 M00194 M00209 M00O1 16 M203 M241 M00033 M00127 M00158 M00075 M00286 MO0278 M00076 M0O0208 -MOO i8 M00302 M0034 MO134 M0022E, _M0003 M00271 M0071 M0028~ M00l 9 M0003' M0014' 321..328(91) 340..347(91) 1815..1808(90) 563..570(90) 652..660(95) 472..459(95) j 1818..1831(9.4) 1238..1225(94)_ 1699..1689(94) 1227..1217(90) 535. .542(94) 759..746(94) 333..320(90) 1703.1690(93) 323..3 IL(93) 1889..1898(93) 14F2..113 3 1736..17745(90) 963..976(93) 1933 194 1(93) 1932..1941(93 983 992(92) ,471..460(93) 1829..1819(92) 232..243(92)_ 98.. 107(92) 308..326(92) 48..540(92) 1046..1039(22)_ I1955..1960(2) S231..243(91) _252..264(91L_ 385..397(91) 2 254..263(91I) Pbx-I .4-kaaB

NF-Y

Y/EBPalpha

GATA-X

p 3 00 GATA-1

COIJP-TF

GATA-1

GKLF

L no2 GATA-2 NF-kappaB

NF-Y

NF-AT

GATA-2 H-NF-4 STATx

CREB.

AML- 1 a c-Ets-1 (p 54 Pbx-l NF-ka paB NF-Ysbinding site CCAAT/enhaflcer binding protein alpha GATA binding site GATA-binding factor I COUJPJJNF-4 heterodimer GATA-binding factor I gut-enriched Krueppel-like factor complex of Lmo2 bound to Tal-1, E2A proteins, and GATA- 1, half-site 2 GATA-binding factor 2 NF-kappaB binding site nuclear factor Y (Y-box. binding factor) Nuclear factor of activated T-cells GATA-binding factor 2 epicnuclear factor 4 signal transducers and activators of transcription cAMIP-responsive element binding protein runt-factor AML- I )c-Ets-1I(p54) HNF-3/Fkh Homolog 3( Freac-6) AP-1 binding site ~)lc-Ets-1 (p54) HFH-3

AP-I

v54 7 77M9fl V 4 HSF2 heat shock factor 2 782 77391)CdSA ~irAA1(~A hIAl 1AQVQ1' fld~ A NfQ9.4.

2 650. .659(90) Sox-5 _MoQoi83 1026..1035(90) c-Myb c-Myb M00O240 963..957(90) Nkx-2.5 homeo domain factor Nkx-2.5/Csx, tinman 1272.. M00190 1238..1225(90) C/EBP CCA-AT/enhancer binding factor _M00083 49..42(90) MZFI

MZFI

MOO0184 275..284(90 MyoD myoblast deteriin aco -23- 00 M00087 980..991(90) Lk-2 Ikaros 2 M00221 1860.. 1850(90)_ SRBP-1I sterol regulatory element-binding protein I M00137 1388..1376(90) Oct- I octamer factor I Table 8, putative transcription factor binding motifs within the DUB regulatory or promoter, region of hDUB 4.2a. The position is indicated by nucleotides.

00 Transfac Position(Score Name Description: M00148 992..986(100) SRY sex-determining region Y gene product 00 942..948(100) 0 919..913(96) 1544..1550(92) 1505..1511(92) 815..809(90) 1068.. 1074(90) 1196..1190(90) 1337..1331(90) 680..686(90) 1697..1691(90) 1802..1796(90) 368..362(90) 721..715(90) 274. .280(90) MOOIOO 1077..1071(10 CdxA CdxA 0) M00271 1933..1938(10 AML-lIa runt-factor AML-1 0) 12204. .2209(92) M00101 1077..1071(99) CdxA CdxA 805..799(98) 699. .693(92) 1384..1390(92) 936..942(92) 495..501(92 1660.. 1666(91) M00076 716..707(98) GATA-2 GATA-binding factor 2 1910..1919(95) 959..968(92 ___1679..1670(91) M00285 1712.. 1724(96) TCFI 1 TCFI l/KCR-F1/Nrfl homodimers 1099(91) M _00272 1242..1251(96)1 p53 tumor suppressor p53 M002 53 13 5..142(96) 457..464(95) 187 1..1864(95) cap signal for transcription initiation 00

;Z

00 MOO0106 _MO O 116 M00254 M00249 MUOOO54 MOO 147 _MOO 104 _M00 1 34 M00052 M00053 M00033 MOO0158 721..728(94) 1461..1454(92) 312..319(92 1989..1996(92) 1855..1848(91) 770..777(90) 1793..1786(90) 295..302(90) 1274..1281(9O) 627..636(95) 634..625(93L_ 1215 1202(95) 1809..1798(25) 1117..1105(95) 442..433(95) 2182..2173(94) 2173..2182(92) 754..745(91) 141..132(90) 634..625(94)_ 2..11 (92) 280..298(94) 442..433(94) 442..433(94) 785..794(90) 731..718(94) 295..282(93)

CDP

C/EBPalpha

CCAAT

CHOP-

C/EBPalpha- N'F-kappaB HSF2

CDP

_NF4 NF-kappaB .c-Rel p 3 0 0

COUP-TF

cut-like homeodomain protein CCAAT/enhancer binding protein alpha cellular and viral CCAAT box heterodimers of C-P and C/EBPal~pha NE-kappaB heat shock factor 2 cut-like homeodomain protein hepatic nuclear factor 4 NF-kappaB c-Rel p 3 0 COUJP/NF-4 heterodimner MO0032j 225.216(93) 226..235(93) c-Ets-1(p54) Ic-Ets-1(p54) MO)OI72 tAP-Il aitor protein I signal transducers and activators oftrnsctio.

1 SZ51 1861(92)

AF

S2O~.S12(92~ STATx M00075 I1679.. 1670(92) 1867..1876(91) 716..707(91) ciATA-binclrng tactor i GATA-1 ATA-binding tactor I M001 84 1463..1472(91) MyoD myoblast determining factor 1472..1463(91) 247..256(90) 2057..2048(90)______ _Ij?.2= 9 357..369(91) LiFI--3 H-NF-3/Fkh Homnolog 3 Freac-6) M00109 1202..1215(91) CIEBPbeta CCAAT/enhancer binding protein beta ___2036..2023(90)_ M00268 937,.950(91) XFD-2 Xenopus fork head domain factor 2 _M=00208 443..432(90) NF-kappaB NIF-kappaB binding site _UQ 17 3 1851..1861(90) AP-1 activator protein I M00183 1002-1l011i 90) c-Myb c-Myb 2020-.20190) 00

;Z

00 M00240 217..21 1(90) Nkx-2.5 homeo domain factor Nkx-2.5ICsx, tinman homolog _M00188 1851..186)(90) A.P-lI activator protein 1 M00099 1086..1101(90) S8 S8 M00302 .813..802(90) Nf-AT Nuclear factor of activated T-cells M00083 21..14(90) MZF I MZFI M00190 1215..1202(9 0) C/EBP CCAAT/enhancer binding factor M00221 1838..1828(90)' SREBP-1 sterol regulatory element-binding protein I M00294 949..937(90) HFH-8 HNTF-3/Fkh Homolog-8 M00137 1365..1353(90) Oct- .I octarner factor 1 M00077 1911..1919(90) GATA-3 GATA-binding factor 3 M0O0194 444..431(90) NIF-kappaB NF-kappaB.

Table 9, putative traniscription factor binding motifs within the DUB regulatory or promoter, region of h.DUB 4.2b. The position is indicated by nucleotides.

Transfac f Psition(Score) Name MOQIQO 1102..1096(100) CdxA Description CdxA sex-determining region Y gene product M00148 M00253 1017..1011(100) 967..973( 00) 944..938(96) 1566..1572(92) 1530..1536 92 840.. 834(90) 1093..1099(90 705..711(90) 1362.1356(90) 1719..1713(90) 1824..1818(90) 393..387(90) 746..740(90) 299..305(90) 1120..1 127(99) 160..167(96) 482..489(95) 1893..1886(95) 746..753(94) 1486..1479 92_ 337..344(92) 1877..1870(91) 795..802(?90 l815.18q00 320..327(90) 1299.. 1306(90) SRY I cap tcap signal for transcription initiation MOO 10 1

-I

1409.. 1415(92) CdxA CdxA 00

;Z

00 792..1892)9 520..526(9a2 1682..16882D91 1688..1682(91).

_M0072 71672 96) M00106I4 65.6195 111..112(9) M001 16 1240..1227(95) M00254 _M0249 M0O0054 M00104 _MOO 134 M00052_ M0O0053 M00033 M00158 M00075 Mj001 60 M00032 1831..1820( 9 5) 1-42.1130(95) 467..458(95) 659..650(94) 27. .36(92) 305..323(94) 467..458(94) 467..458(94) 756..743(94) 320..307(93) 1889..1898(93) 1701..169ZL 92 741..732(91) 341..32Z(9) 641..632(90) 965.'.76(93) 250..241(93) 251..260(93) p530

COJP-T

GATA-alp c-Res I (p 54 GATA-binding factor 2 TCFL 1/KCR-FI/Nrfl homodimers tumor suppressor p 5 3 cut-like home odomain protein CCAAT/enhancer binding protein alpha cellular and viral CCAAT box heterodimers of Cl-OP and C/EBPalpha NF-kappaB cut-like horneodomain ro7tein hepatic nuclear factor 4 NF-kappaB (p 6 5 GATA-binding factor 1 sex-determining region Y gene product c-Ets-1 (p54) activator protein I signal transducers and activators of transcription M0LO017 2 1873..1883(92) 0,T AL Tv IVIIIIJLLJ I _M00271 1955..1960(92) AML-la runt- factor AML-lI MO184 1488.. 1497(91) MyoD myoblast determining factor 1497..1488 91 M00O289 382..394(91) HFH-3 HNF-3fFkh Homolog 3 Frac-6) Mj0 0 109 1227..1240(91) C/EBPbeta CCAAT/enhancer binding protein beta M00147 779..770(91) HSF2 heat shock factor 2 M00208 1468..457(90) NF-kappaB NF-kappaB binding site M0Q0183 1027..1036(90) c-Myb Ic-Myb 00

;Z

00 MOO] 73 1873..1883(90) AP-l activator protein 1 M00240 242.. 236(90) Nkx-2.5 homeo domain factor Nkx-2.5ICsx, tinman _______homolog MOO]188 1873..1883(90) AP- I activator protein 1 M00302 838..827(90) NP-AT Nuclear factor of activated T-cells M00083 46..39(90) MZFI MZFI M00190 1240..1227(90) C/EBP CCAAT/enhancer binding~factor M00096 .1115..1123(90) Pbx-l Pbx- 1 M00221 1860..1850(90) SREBP-1 sterol regulatory element-binding protein I M00194 469..456(90) NF-kappaB NE-kappaB M0 ,71933..1941(90) GATA-3 GATA-binding factor 3 Table 10, putative transcription factor binding motifs within the DUB regulatory or promoter, region of hDUB 4.3. The position is indicated by nucleotides.

Transfac Position(Score) Na me Description M00148 1015..1009(100) SRY sex-determining region Y gene product 965..971(10O 942. .936(96)' 1566..1572(92) 1528..1534(92) 838..832(90) .109l.. 1097(90) 1219.. 12 13(90) 703..709(90) .1360..1354(90) .1719..1713(90) 1824..1818(90) 391..385(90) .744.. 73 8(90) 297..303(90) MOQIQO 1100..1094(100) CdxA CdxA MOOIOI 1100..1094(99) CdxA CdxA 828.. 822(98) 1407..1413(92) 722..716(92) 959..965(92) 518..524(92) 1682.. 1688(91) 1688..1682(91) M00076 739..730(98) GATA-2 GATA-binding factor 2 1932..1941(95) 982..991(92) 170 1..1692(91) M00285 1734..1746(96) TCFlI TCF1I/KCR-F1/Nrfl homodimers 1110..1122(91) M00272 1265.. 1274(96) tumor suppressor p53 00

;Z

00 M00253 158..165(96) 480..487(95) 1893 1886(95) 744..751(94) 1484..1477(92) 335..342(92) 1871..1870(91) 793..800(90) 318..325(90) cap signal for transcription initiation MOO0106 650..659(95) CDP cut-like homeodomain protein __657..648(93)__ MOO 116 1238..1225(95) CIEBPalph CCAAT/enhancer binding protein alpha a M00254 1831.. 1820(95 CCAAT cellular and viral CCAAT box M00249 1140.. 1128(95) CHOP- heterodimers of CHOP and C/EBPalpha C/EBPalph a M00054 465..456(95) NE-kappaB.NF-kappaB MOO0104 657..648(94) CDP Icut-like homeodomain protein MOO0134 303..321(94) HI4F-4 hepatic nuclear factor 4 M00052 465..456(94) NF-kappaB NF-kappaB M00053 465..456(94) c-Rel c -e M00033 754..741(94) p300 p300 M00158 318..305(93) COUP-TF COUP/HNF-4 heterodimer M00075 1889..1898(93) GATA-1 GATA-binding factor 1 1701 1692(92)_ 739..730(91) 339..330(90) MOO0160 963..974(93) SRY sex-determining region Y gene product M00032 248..239(93) c-Ets- c-Ets-1(p54) '(P5 4 M00172 1873..1883(92) AP-1 activator protein 1 M00223 543..535(92) STATx signal transducers and activators of transcription M00271 1955..1960(92) AML-la runt-factor AML- 1 M00173 1873..1883(91) AP- I activator protein 1 M00184 1486.. 1495(91) MyoD myoblast determining factor 1495.. 1486(9 1) 270..279(90) _M0O0289 380..392(91) HFH-3 HNF-3/Fkh Homolog 3 Freac-6) _M00O109 1225..1238(91) C/EBPbeta CCAAT/enhancer binding protein beta MOO0147 777..768(91) HSF2 heat shock factor 2 MK00208 466. .455(90) NF-kappaBINF-kappaB binding site- _M00O18 3 1025..1034(n_ c-Myb ic-Myb,.

M00240 240..234(90) Nkx&2.5 orneo domain -factor Nldc-2.5/Csx, tiunman 00

;Z

00 M00099 1109..1124(90) S8 S8 M00302 836..825(90) NF-AT Nuclear factor of activated T-cells M00083 44..37(90) MZFI MZFl M00190 1238..1225(90) C/EBP CCAAT/enhancer binding factor M00221 1860..1850(90) SREBP-1I sterol regulatory element-binding protein 1 M00174 1873..1883(90) AP-1I activator protein I M00077 1933.. 1941(90) .GATA-3 GATA-binding factor 3 MOO0194 1467..454(90) INF-kappaBINF-kappaB Table 11, putative transcription factor binding motifs within the DUB regulatory or promoter, region of WDUB 4.4. The position is indicated by nucleotides.

Transfac IPosition(Score) Name' Description MOOIOO 1101..1095(100) CdxA CdxA M00148 1016.. 1010(100) SRY sex-determining region Y genie product 966..972(100) 944..938(96) 1566.. 1572(92) 1529..1535(92) 840.. 834(90) 1092..1098(90) 705..711(90) 136 1..1355(90) 1719.. 1713(90) 1824..1818(90) 393..387(90) 746. .740(90) MOOIOI 1101..1095(99) CdxA CdxA 830..824(98) 1230..1224(98) 1408.. 1414(92) 724..718(92) 520..526(92) 1682..1688(91) 1688..1682(91) M00076 741..732(98) GATA-2 GATA-binding factor 2 1932..1941(95) 983..992(92) _M00350 876.. 867(96) GATA-3 GATA-binding factor 3 M00285 .1734.. 1746(96) TCFI I TCFI IKCR-FI/Nrfl homodimers M00272 1266.. 1275(96) p 53 itumor suppressor p53 M00253 160..167(96) 482..489(95) cap signal for transcription initiation 00 1893..1886(95) 746..753(94) 148S..41478(92) 337..344(92) 1877..1870(91 795..802(90., 1815..1808(90) 320..327(90) 1298..1305(90) M00106 652..661(95) CDP cut-like homeodomain protein 659..650(93) M001 16 1239.. 1226(95) C/EBPalpha CCAAT/enhancer binding protein alpha M00254 1831.. 1820(95) CCAAT cellular and viral CCAAT box M00249 1141 1 129(95) CHOP- heterodimers of CHOP and C/EBPalpha M00349 876.. 867(9D) GATA-2 GATA-binding factor 2 M00054 467..458(95) NF-kappaB NF-kappaB M00104 659..650(94) CDP cut-like homeodomain protein M00134 305..323(94) HNF-4 hepatic nuclear factor 4 M00052 467..458(94) 14F-kappaB hTF-kappaB M00053 467. .458(94) c-Rel c-Rel M00033 756. .743(94) p 30 0 p 3 00 MOO'348 876.. 867(93) GATA-2 GATA-binding factor 2 M001 58 320..307(93) COUP-TF COUP/HNF-4 heterodimer M00075 1889..1898(93) GATA-1 GATA-binding factor 1 1701.. 1692(92) 741..732(91) MOO0160 964..975(93) SRY sex-determnining region Y gene product M00347 876..867(93) GATA-I GATA-binding factor 1 M00032 250..241(93) c-Ets-l(p54) c-Ets-l(p54) 251..260(93) MOO0172 1873..1883(92) API1 activator protein I1 M00223 545..537(92) STATx signal transducers and activators of transcription M00271 1955..1960(92) AML-la runt-factor AML-1 M00184 1487..1496(91) MyoD. myoblast determining factor 1496.. 1487(91) ___272..281(90) M00289 382..394(91) HFH-3 HNF-3/Fkh Homolog 3 Freac-6) M00109 1226..1239(91) C/EBPbeta CCAAT/enhancer binding protein beta M0L28 468..457(90) NF-kappaB NF-kappaB binding site M00183 1026..1035(90) c-Myb c-Myb M00173 1873..1883(90) AP- I activator protein I M00240 242..236(90) Nkx-2.5 homeo, domain factor Nkx-2.5/Csx, tinman M400188 1 873..1 883(90) AY- I activator protein .1 00

;Z

00 M00302 838..827(90) NF-AT Nuclear factor of activated T-cells M00083 46..39(90) MZFlI MZF I M00190 1239.. 1226(90) C/EBP CCAAT/enhancer binding facto r M00147 166..157(90) HSF2 heat shock factor 2 M00080 874..864(96) Evi-1 ecto c yiral integration site I encoded factor M00082 874..864(90) Evi-I ectopic viral integration site I encoded factor M00221 1860..1850(90) SREBP-1 sterol regulatory element-binding protein 1.

M00194 1469..456(90) 1NF-kappaB INF--kappaB FM00077 1933..1941(90) 1GATA-3 IGATA-binding factor 3 Table 12, putative transcription factor binding motifs within the DUB regulatory or promoter, region of hDUB 4.5. The position is indicated by nucleotides.

r Tr~nd'~u' I Pg~dfmnnKpnrp~ Name Description Trancrac I Position(Scorel ame M00148 I 963. .969(100) 1013..1007(100) 940. .934(96) 1526..1532(92) 1089..1095(90) 836..830(90) 701..707(90) 1358..1352(90) 1720..1714(90) 1825 18 19(90) 389..383(90) 742.-.736(90) SRY sex-determining region Y gene procduct MOOl100 1098..1092(100) CdxA CdxA MOOI 1098..1092(99) CdxA CdxA 826..820(98) 1405..1411(92) 720..714(92) 957..963(92) 516..522(92) 1683 1689(9 1) M00076 737..728(98) GATA-2 GATA-binding fatr2 980. .989(92) 1702..1693(91) 1308(90) _M00285 1735..1747(96) TCFI 1 TGF1I/KCR-F/Nrfl homodimers LM00272 1263..1272(96) p5 tumor suppressor p53 M00253 156..163(96) 478..485(95) 742..749(94) 1482..1475(92) cap signal for transcniption initiation 00 00 00 L0106 M00116 333..340(92) 791 798(90) 1816..1809(90) 316..323(90) 648..657(95)

.CDP

L T cut-like homeodomnain protein.

CCA/nacerbidn prtn b 655 646(93) 1236..12-23(95) C/EBPal ha rc~A~A I CCAAT/enhan" "'5ra' na CCAAT, ce lular and viral CCAA I Dox qel lu lan vira M00254 1832 1821(95 M00249 M00054 M00183 1138..1126(95)

CHOP-

C/EBPalpha heterodimers of CHOP and C/EBPalpha I 4t;3 4S4(9S~ NF-kappa IN-kappaB .63 454(95) 1493..1484(94) 1023..1032(90) c-Myb c-Myb rnnl flA 1 1 rmp Ii-i it.1~1c~ hAm ~cidomain nrotein IVIUUIV'4 t _UOO 104 655.. )94 CDP cut-like homeodomain protein 23..32(92) M00134 301..319(94) 463 .454(94) INF-4! NF-kappaB hepatic nuclear factor 4 NE-kappaB M00052 M00053 463..454(94) 806..815(90) c-Re] ce-Ret M00033 M00032 752..739(94) p 30 0

COUP-TF

CP /H 3 0 0 etrdie t I 1 246..237(93) c-Ets- I(p 5 4 c-Ets- l(p54) Mi00278 1300..1308(92) Lmo2 complex of Lmno2 bound to Tal-1, E2A proteins, and half-site 2 M00223 54L..533 (92) STATx signal transducers and activators of transcription M00075 1702.. 1693(92) GATA-1 GATA-binding factor I 737..728(91) MI00077 1300.. 1308(91) GATA-3 GATA-binding factor 3 M00289 378..390(91) 1-FH-3 HNF-3/Fkh Homolog 3 Freac-6) _M00 109 1223..1236(91) C/EBPbeta CCAAT/enhancer binding protein beta M0026 958..971(91) XFD-2 Xenopus fork head domain factor 2 _M001 47 775..766(91) HSF2 heat shock factor 2 162..153(90) _00208 464. .453(90) NF-kappaB NF-kappaB binding site _M00240 238. .232(90) Nkx-15 honieo domain factor Nkx-2.5/Csx, tininan homolog MI00099 1107..1122(90) S8 S8 _M00302 834.. 823(90) 1'.F-AT Nuclear factor of activated T-cells _M090083 42..35(90) MZFl MZFl.

MOOQ184 268..277(90) MyoD) myoblast determining factor M00190 1236..1223(90) C/EBP CCAAT/enhancer binding factor M00221 1861..1851(90) SREBP-1, sterol regulatory element-binding protein I M294 970. .958(90) }FH-8 HNF-3/Fkh Homolog-8 M00137 1386..1374(90) Oct- I octamner factor 1 1M00194 1465..452(90) INF-kappaBINF-kappaB Table 13, putative transcription factor binding motifs within the DUB regulatory or promoter, region of hDUB S. 1. The position is indicated by nucleotides.

Transfac Position(Score) Name Description' M00148 1015..1009(100) SRY sex-determining region Y gene product 965. .97 1(100) 942. .936(96) 1544..1550(92) 838..832(90) 702..708(90) 1719.. 1713(90) 1824.. 1818(90) 390. .384(90) 1384.. 1390(90) 1356..1350(90) 296. .302(90) MOO100 1100..1094(100) CdxA CdxA 724..730(96) 1547.. 1541(91) _M00349 93.. 102(100) GATA-2 GATA-binding factor 2 _M00350 93.. 102(100) GATA-3 GATA-binding factor 3 M00241 1800.. 1807(100) Nkx-2.5 homeo domain factor Nkx-2.5/Csx, tinman homolog _M00348 93.. 102(100) GATA-2 GATA-binding factor 2 MOOIOl 1100..1094(99) CdxA CdxA 828..822(98) 1229.. 1223(98) 1203..1209(94) 72 1..7 15(92) 959..965(92) 65..59(92) 517..523(92) 419..425(92) 1682..1688(91) 1688..1682(91) M00203 95 105(98) GATA-X GATA binding site M00347 93.. 102(97) GATA- 1 GATA-binding factor I M00075 1838..1847(97) GATA-1I GATA-binding factor I 1701..1692(95) 137..128(92) 1483..1492(92) 1889..1898(91) _______1736..1745(90) M00158 317..304(96) COU.P- COUP/HNF-4 heterodimer

TF

00 r M00253 15 8..165(96) 1794..1801(95) 479..486(95) 1297.. 1304(93) 337..344(93) 48..55(93) 1484.. 14.77(92) 1324..1317(91) 557..564(91) 1893 1886(91) 1877..1870(91) 793 800(90) 1356..1363(90) 1815..1808(90) '1 7 23'A(QOfl cap cap signal for transcription initiation M00285 1734..1746(95) TCF11I TCF1 1/KCR-FI/NrflI homodimers 1110..1122(91) 13 1(90) MOO0134 302..320(95) HNF-4 hepatic nuclear factor 4 M00077 1933..1941(95) GATA-3 GATA-binding factor 3 M00096 1827..1819(95) Pbx-1 Pbx-1 M00141 451..459(94) Lyf-1 LyF-1 M00199 1797..1789(94) AP-1 A-P-1 binding site 17..1797 91) MOO0174 1788-..1798(94) A-P-1, activator protein .1 M00076 1483.. 1492(93) GATA-2 GATA-binding factor 2 1932..1941(93) 1701..1692(92) MO0278 1933..1941(93) Lmo2 complex of Lmo2 bound to Tal-1, E2A proteins, and half-site 2 MJ 00099 1813..1798(92) S8 S8 1109..1124(90)1 M00294 155 1..1539(92) HIFH-8 IiNF-3/Fkh Homolog-8 M00223 1542..534(92) STATx signal transducers and activators of transcription M00073 136..46(92) deltaEFlI deltaEFl M00271 1955..1960(92) AML-la runt- factor AM L- 1 127(92) M00137 .335..323(91) Oct-1 Ioctanier factor 1 M00042 644..653(91) Sox-5 1820(90) M00289 379..391(91) HiFH-3 HN-3/Fkh Homolog 3 (=Freac-6) MUOO 18 3 1025.. 1034(90) c-Myb c-Myb M00O240 239..233(90) Nkx-2.5 horneo domain factor Nkx-2.5/Csx, tinmnan homnolog _MOO18 8 1788..1798(90) AP-1I activator protein I MOO3O2 836. .825(90) NF-AT Nuclear factor of activated TPeells IMOO0128 192.. 104(90) GATA-1 IGATA-binding factor 1 IM001 84 1269. .278(90) MyoD Imyoblast determiniing factor 00 M00147 M00087 M001 72 SM00221 1- 164.155(90~ IHSF2 heat shock factor 2 164..155(90)~ nV7(n nona(O 11-arns I [1788..1798(9 1860..1850(90) 1API activator protein I sterol regulatory element-binding protein I SRiEBP-

I

Table 14, putative transcription factor binding motifs within the DUB regulatory or promoter, region of hDUTB 8.2. The position is indicated by nucleotides.

Transfac PosiinSoe M00241 1804..1811(100)~ M00240 556..562(100) 1354..1360(90) M00096 1342..1350(100) M00271 702..707(100) 1955..1960(92) M00050 104..111(100) M00148 1271..1277(100) 1572..1578(92) 1345 135 1(90) 1719..1713(90) 1828..1822(90) 1634..1628(90) M00272 472..463(97) 463..472(97) M00075 1842..1851(97) 1893..1902(93) 1380.. 1371(92) 1740.. 1749(90) M00253 1072..1065(96) 1798..1805(95) 1897..1890(95) 769. .776(92) 1701..17018(92) 1881..1874(91_ 497..504(90) 1819..1812 21..28(90) M00285 1738..1750(95) 366..378(93) M000Q 77 1933..1941(95) M00147 148..139(94) 139..148(92) Name N'kx-2.5 Nkx-2.5 Description: omain factor Nkx-2.5/Csx, timnan homolog omain factor Nk-x-2.5/Csx, tirnan homolog

I~

Pbx- I Pbx- I AML-la jrunt-factor AML-1 E2F

SRY

E2F sex-determining region Y gene product p53 ~tumor suppressor p53 GATA-l IGATA-binding factor 1 cap tcap signal for transcription initiation TCFI I GATA-3 HSF2 TCFI I/KCR-FIfNrfl homodimers GATA-binding factor 3 heat shock factor 2 00

;Z

00 M00199 1801..1793(94) AP-1I AP-l binding site 1037..1029(94) 1793..1801(91) 1029.. 1037(90) MOO0174 1792..1802(94) A-P-I activator protein 1 1038..1028(92) M00074 1247..1259(93) c-Ets7 c-Ets-1(p54) I I(p5 4 M00211I 702..710(93) Poly, Retroviral Poly A downstream element M00124 1339..1353(93) Pbxlb homeo domain factor Pbx-1I M00278 1933..1941(93) Lmo2 complex of Lmo2 bound to TAl-1, E2A proteins, and, half-site 2 M00052 1261..1252(93) NF- NF-kappaB I_ kappaB M00076 1932..1941(93) GATA-2 GATA-binding factor 2 837..828(90) M00099 1817..1802(92) S8 S8 MOOlOl 987..981(92) CdxA CdxA M00042 1635..1626(92) ISox-5 -M00254 1835..1824(91) CCAAT cellular and viral CCAAT box M00008 252..243(91) Spi stimulating protein I S1323.. 13 14(91) M00227 933..941(90) v-Myb v-Myb -M00141 1328..1320(90) Lyf- L LyF- I _M00183 1033..1042(90) Ic-Myb c-Myb M00001 654..665(90) MyoD myoblast determination gene product M001 88 1792..1802(90) AP- I activator protein 1 M001 84 23.. 14(90) MyoD myoblast determining factor _M00172 1792.. 1802(90) AP-lI activator protein I M0022 1 1864.. 1854(90) SREBP-1 sterol regulatory element-binding protein I _M00037 871..861(90) NP-E2 NF-E2 -M00053 1261-.1252(90) c-Rel c-Rel M00249 823..835(90) CHOP- beterodimers of CHOP and C/EBPalpha.

C/EBPalph a M0002 1248.. 1259(90) 1NE-AT INuclear factor of activated T-cells 00

;Z

00 Table 1 5, putative transcription factor binding motifs within the DUJB regulatory or promoter, region of hDUJB 8.3. The position is indicated by nucleotides.

Transfac _Position(Score) Name Description M00348 71 80(100) GATA-2 GATA-binding factor 2 M00349 71..80(100) GATA-2 GATA-binding factor 2 MOO 148 990..'984(100) SRY sex-determnining region Y gene product 1654..1648(100) 813..807(96) 917..911(96) 1848..1854(92) 1840..1846(92) 1826..1832(92) 1504..1498(92) 1391..1397(90) 680..686(90) 2094..2088(90) 368..362(90) 721..715(90) 1002..996(90) 1900..1894(90) 274..280(90) M00350 71..80(100) GATA-3 GATA-binding factor 3 MOOIOO 595..589(100) CdxA CdxA 1394(100) MOOlOl 595..589(99) CdxA. CdxA 1400..1394(99) 803..797(98) 1527..1521(98) 1705.. 1711(92) 699. .693 (92) 43..37(92) 495 501(92) M00141 1274..1266(98) Lyf-1I LyF-1I, M0-0347 71 80(97)- GATA-1I GATA-binding factor 1 M00272 1563..1572(96) p53 tumor suppressor p53 M002 53 1128..1135(96) 136..143(96) 2064..2071(95) 457. .464(95) 2163..2156(95) 721 7289 94 660..653(94) 1782..1775(92) 312. .3 19(92) cap signal tor transcription initiation 00

;Z

00 M00285 M00254 M00130 M00054 M00077 M00052 M00203 M00199 MOO 174 M00075 M -0-005 3 M00241.

M00076 1622..1615(91) 53S..542(91) 2085..2078(91) 2147..2140 91 1350..1357 91 768..775(90), 295. .302(90) 2004..2016(9S) 1410..1422(91) 2101..2090(95) 1647..1658(95) 442. .433(95) 2203..221 1(95) 442. .433(94) 73..83(94) 2067..2059(94) 2059..2067(91) 1984..1992(90) 2058..2068(94) 895..886(94) 2159..2168 9 1082..1073(93) 197 1..1962(92) 2006..2015(90) 442..433(94) 2070. .2077(94) 716..707(94) 1599..1608(92) 957..966(92) 895..886(91) TCFI I

CGAAT

TCF1 I1./KCR-FI/Nrfl hornodimners cellular and viral CCAAT box HFH-2 N-F-kappaB_ GATA-3 NF-kappaB

GATA-X

AP-1 AP-1I GATA-1 c-Re] HNF-3/Fkh Homolog 2 NF-kappaB GATA-binding factor 3 NE-kappaB (p 6 5 GATA binding site AP-I binding site' activator protein 1 GATA-binding factor I c-Rel Nkx-2.5 borneo domain factor Nkx-235/Csx, tinrnan

I

GATA-2 GATA-binding factor 2 MOO0106 627..636(94) CDP cut-like horneodomain protein M00033 731..718(94) p300 p.

3 0 0 M00227 2139..2131(94) v-Myb v-Myb M00158 295..282(93) COUP-TF COUP/HNF-4 heterodimer MROO0 162 2070..2083(93) Oct-I octamer-binding factor I MOO0134 280..298(93) HNF-4 _hepatic nuclear factor .4 M00032 226..235(93) c-Ets-1(p54) c-Ets-1t~p54)..

MOO 117 1080..1O67(92) C/EBPbeta CCAAT/enhancer binding protein beta M00223 520..5 12(92) STATx signal transducers and activators of transcription M00042 1901..1892(92) Sox-5 622..631(91) MO0313..23(92) deltaEFl deltaEFl1 M00099 2083..2068(91) S8 S8 2066..2081(90) 1409.. 1424(9) 00

;Z

00 MAfl9RQ h 4716S9(Q1'i HFH-3 HNF-3/Fkh Hornolog 3 Freac-6) 357..369(91) M00147 752..743(91)- *HSF2 beat shock factor 2 M00208 443..432(90) NF-kappaB NF-kappaB binding site M00217 1 15..108(90) USF USF binding site M00183 1325..1334(90) c-Myb c-Myb M00240 217..211(90) Nkx-2.5 homeo domain factor'Nkx-2-.5/Csx, tinmian MOO] 88 205 8..2068(90) AP- I activator protein 1 MOO0184 1955..1964(90) MyoD myoblast determining factor 247..256(90) M00087 954..965(90) Lk-2 Ikaros 2 M00128 70..82(90) GATA-1 GATA-binding factor I MOO] 72 205 8..2068(90) NP-I activator protein 1 MOO 145 1339..1354(90) Brn-2 POU factor Bm-2 M00062 1217.. 1205(90) IRF-1I interferon regulatory'factor I MOO0194 444..431(90) 1NF-kappaB INF-kappaB Table 16, putative transcription factor binding-motifs within the DUB regulatory or promoter, region of hDUB-8.4. The position is indicated by nucleotides.

Transfac Position(Score) Name Description MOQIQO 1105..1099(100) CdxA CdxA M00241 1800..1807(100) Nkx-2.5 homeo domain factor Nkx-2.5/Csx, tinman MOO0148 1020..1014(100) SRY sex-deteriiining region Y gene product 970..976(100) 947..941(96) 1550.. 1556(92) 843..837(90) 707..713(90) 1362..1356(90) 1719..1713(90) 1824..1818(90), 395..389(90) 748. .742(90) 300..306(90) M-OO 1-0l 1105..1099(99) CdxA CdxA 833..827(98) 1385..1379(98) 1409..1415(92) 964..970(92) 726..720(92).

.430(92) M0O0075 1838..1847(97) 1889..1898(93) GATA-l- GATA-binding factor I 00 925..916(93)_ 1736..1745(9)) tumor supeso M00272 M002 53 1267..1276(96 161..168(96) 1794..180.1(95) 484..491(951_ 1893..1986(95) 1452..1459(94)..

798..805(94) 748..755(94) 957..964(94) 1486..1479 2 338..345(92) 1697..1704(92) 562..569(91) 1877..1870(91) 1815 1808(90) 321..328(90) 1326..1319(90) 1299..1306(90) p 53 cap cap signal for transcription initiation 'KAo()()QA L 4- Pbx- 1 Pbx- I 1 1819(96) 1 M00285 1734.. 1746(95) TCF1 1 TCFI 1/KCR-FL/Nrfl homodimners M00077 1933.:*1941(95) GATA-3 GATA-binding factor 3 M00054 469..460(95) NF-kappaB, NF-kappaB M00141 456..464(94.) Lyf--i LyF-I M00134 306..324(94) HNF-4 .hepatic nuclear factor 4 M00052 469..460(94) NF-kappaB NF-kappaB M001.99 1797..1789(94) AP-1 AP-1I binding site 1789..1797(91) M-W001 74 1788..1798(94) AP-1 activator protein 1 M00053 469..460(94) c-Rel c-ReI M00033 758..745(94) p300 p 3 0 0 .795(92) M00158 321..308(93) COIJP-TF COUPIHTNF-4 heterodimer.

M00278 1933..1941 (93) Lmo2 complex of Lmo2 bound to Tal-1, E2A and GATA-1, half-site 2 M00076 1932..1941(93) GATA-2 GATA-binding factor 2 1303..1312(92) 743..734(92) 987. .996(92) 925..916(90)__ M00-O099 1813..1798(92) S8 S8 1114..1129(90) M00104 28..37(92) CDP cut-like homeodomain protein M00223 547..539(92) STATx signal transducers and activators of ___transcription M00271 1955..1960(92) 1AML-la Irunt-factor AML-1 00

;Z

00 M00254 1831..1820(91) CCAAT cellular and viral CCAAT box M00042 649..658(91) Sox-5 M00289 384..396(91) HFH-3 HNF-3/Fkh Homolog 3 Freac-6) M00302 1384..1395(91) NF-AT Nuclear factor of activated T-cells 830(90) M00155 367..382(91) ARP- 1 apolipoprotein Al regulatory-protein 1 M00208 470..459(90) NF-kappaB NF-kappaB binding site M00183 1030..1039(90) c-Myb c-Myb M00240 243..237(90) Nkx-2.5 borneo domain factor Nkx-2.5ICsx, tinman 1448(90) M00188 1788..1798(90) AP-1I activator protein 1 M00083 47..40(90) MZF1 MZFI M00184 273..282(90) MyoD) myoblast determining factor MOO0147 167..158(90) HSF2 heat shock factor2 M00087 984..995(90) Ik-2 ikaros 2 M00172 1788..1798(90) N-P-i activator protein I M00221 1860..1 850(90) SREBP-1 sterol regulatory element-binding protein 1 MOO0194 471..458(90) NF-kappaB INF-kappaB Table 17, putative transcription factor binding motifs within the DUB regulatory or promoter, region of hDUB 8.5. The position is indicated by nucleotides.

Transfac Position(Score) Name Description MOO1OO 1105..1099(100) CdxA CdxA M00241 1800..1807(100) Nkx-2.5 homeo domain factor Nkx-2.5/Csx, tinman M00271 27..32(100) AML- Ia runt-factor AML- 1 1955.. 1960(92) M00148 1020.. 1014(100) SRY sex-determining region Y gene product 970. .976( 100) 947..941(96) 1553..1559(92) 100.. 106(92) 141.. 135(90) 843..837(90) 1365..1359(90) 1719..1713(90) 1818(90) AOO 101 1105..1099(99) 833..827(98) 1234.1228(98) 1388..1382(98) 1300.. 1294(93) 1412.. 1418(92) 964. .970(92) 1682 1688(91) CdxA ICdxA 00 00 00 M 00278 M00075 M00054 FM002 53 1688..1682(91) 618. .6 10(98) 1933.. 1941(93) 1838..1847(97) 619..610(97) 1701 1692(95) 1889.. 1898(93) 903..894(91) 1736..1745(90) 442..451(96) 451..442(91) 175..168(96) 1794..1801(95) 1893..1886(95) 1455.. 1462(94) 798..805(94) 629..636(94) 1489.. 1482(92) 433..426(92) 1329..1322(91) 1877.. 1870(9 1) 921..928(91) 957..964(90) 1815..1808(90) Lmno2 complex of Lmo2 bound to Tal-1, E2A proteins, and GATA- 1, half-site 2 GATA-1 jGATA-binding factor.1

NF-

kappaB NE-kappaB cap cap signal for transcription: initiation 130 1309(90) M00272 1270.. 1279(96) p53 tumor suppressor p53 M 00096 1827..1819(96) Pbx-1 Pbx-1 M00285 1734..1746(95) TCFl I TGFI1/K.CR-F1/Nrfl homodimers 1115..1127(91) 1490.. 1478(91) M00076 619..610(95) GATA-2 GATA-binding factor 2 1932..1941(93) 170 1..1692(92) 1306..1315(92) M0O0077 1933..1941(95) GATA-3 GATA-binding factor 3 M 00199 1797..1789(94) AP-1I AP-1I binding site 1789..1797(91) _M0174 1788..1798(94) A.P-1 activator protein I _M00083 566..559(93) MZFI MZFI M099 1813..1798(92) S8 S8 M00208 441..452(92) NF- NE-kappaB binding site kappaB M0033 808..795(92) p 3 00 -43- 00 00 00 M00227 1677..1669(91) v -Myb- v-Myb M00254 183 1..1820(91) CCA.AT cellular and viral CCAAT box M00183 166..157(91) c-Myb c-Myb M00267 102..89(91) XFD-1 Xenopus fork head domain factor I M00240 1457..1451(90) Nkx-2.5 homeo domain factor Nkx-2.5/Cs)(, tinman ________homolog 296. .302(90) MOO] 88 1 788..1 798(902 AP-1 activator protein I M00302 841..830(90) NF-AT -Nuclear factor of activated T-cells M00087 984. .995(90) Ik-2 Ikaros 2 M00172 1788..1798(92L AP-1I activator protein 1 M00003 965..956(90) v-Myb v-Myb M00221 1860.. 1850(90) SRLEBP-1 sterol regulatory element-binding protein 1 M00053 1441 450(90) c-Rel c-Rel Table 18 putatiye transcription factor binding mi~fs. within the DUB regulatory or promoter, region of h.DUB 8.6. The position is indicated by nucleotides.

Transfac IPosition(Score) Name ~.Description

MOOIOO

M00241 M00148 MKOO -10 1 M00075 FM00272 1105..1099(100) 1800..1807(100) 1020..1014(100) 970..976(100) 947..941(96) 1550..1556(92'! 843. .837(90) 707..713(90) 1362..1356(90) 1719..1713(90) 1824..1818(90) 395 389 748 742(90) 300. .306(90) 1105..1099(99) 833..827(98) 1385-1379(98) 1409..1415(92) 964..970(92) 726. .720(92) 424..430(92) 1838..1847(97) 1889.. 1898(93) 925..916(93) 1736..1745(90) CdxA Nlcx-2 .5

SRY

CdxA homeo domain factor Nkx-2.5/Csx, tinman homolog.

sex-determining region Y gene product CdxA ICdxA GATA-1 IGATA-binding factor I I 1267..1276(96) tuinor suppressor p53 1267..1276(96'~ tumor suppressor p5 3 00 M00253 161..168(96) 1794..1801.(95) 484..49](95) 1893..1886(95) 1452.. 1459(94) 798. .805(94) 748..755(94) 957. .964(94) 1486..1479(92) 338..345(92).

1697..1704(92) 562..569(91) 1877..1870(91) 18-15 1808(90) 321..328(90) 1326.. 13 19(90) 1299..1306(90) cap signal for transcription initiation M00096 1827..1819(96) Pbx-1 Pbx-I M00285 1734..1746(95) TCF I I ,TCFI IIKCR-FI/Nrfl homodimers 1115..1127(91) M00077 1933.. 1941,(95) GATA-3 GATA-binding factor 3 M00054 469. .460(95) NF-kappaB NF-kappaB M00141 456..464(94) Lyf- I LyF-1 M00134 306..324(94) HNF-4 hepatic nuclear factor 4 M00052 469. .460(94) NF-kappaB NF-kappaB MOO0199 1797..1789(94) AP-1I AP-1I binding site 1789..1797(91) M00174 1788..1798(94) AP- 1 activator protein 1 M00053 469. .460(94) c-Rel c-Rel M0003 3 758..745(94) p300 p300 808.. M001 58 321 308(93) COUP-TF COUP/JTNF-4 heterodimer M00278 1933..1941(93) Lmo2 complex of Lmo2 bound to Tal-l, E2A and GATA-1, half-site 2 M00076 1932..1941(93) GATA-2 GATA-binding factor 2 1303..1312(92) 743-.734(92) 987. .996(92) 925..916(90) M00099 1813..1798(92) S8 S8 1114..1129(90) MOO 104 28..37(92) CDP cut-like homeodomain protein M00223 547..539(92) STATx signal transducers and activators of __________transcription M00271 1955..1960(92) AML-l a runt-factor AML-1I M00254 1831l..1820(91) CCAAT cellular and viral CCAAT box M00042 649..658(91) Sox-5 M00289 384..396(91) -IFH-3 IINF-3/Fkh Homolog 3 Freac-6).

00

;Z

00 M00302 1384.. 1395(91) N F-AT Nuclear factor of activated T-cells 841..830(90) M00155 367..382(91) AR.P-1I apolipoprotein Al regulatory protein I M00208 470..459(90),. NF-kappa]B NF-kappaB bindii~g site M00183 1030..1039(90)' c-Myb c-Myb M00240 243..237(90) Nkx-2.5- homneo domain factor Nkx-2.5ICsx, tinnian 1448(90) M00188 1788..1798(90) AP-1I activator protein 1 M00083 47..40(90) ZI MF MOO 184 273..282(90) MyoD myoblast determining factor M00147 167..158(90) HSF2 heat shock factor *2 M00087 984. .995(90) Ik-2 Ikaros 2'.

M00172 1788..1798(90) AP-1I activator protein I M00221 1860..1850(90)' SREBP-1 steroliregulatory elemfent-binding protein I M00194 471..458(90) NF-kappaB NF-kappaB Table 19, putative transcription factor binding motifs within the DUB regulatory or promoter, region of hDUJB 8.7. The position is indicated by nucleotides.

Transfac Position(Score) Name Description M00349_ 94..103(100) GATA-2 GATA-binding factor 2- M00348. 94..103(100) GATA-2 GATA-binding factor;2 M00241. 1800.. 1807(100) Nkx-2.5 homeo domain factor Nkx-2.5/Csx, tinman I homolog MOO]I00 1102..1096(100) CdxA CdxA M00148 1017-.1011(100' SRY sex-determining region Y gene product 967..973(100) 704..710(100) 944. .938(96) 1550.. 1556(92) 840..834(90) 1362.. 1356(90) 1719..1713(90) 1824.. 18 18(90) 392..386(90) 745 739(90) 1298 304(90) M00350 194.. 103(100) 1GATA-3 GATA-binding factor 3 MO0l01 1102.. 1096(99) 830..824(98) 1231..1225(98) 1385.. 1379(98) 1297.. 1291(93) -409..1415(92) 723'..717(92) 961..967(92) CdxA CdxA 00

;Z

00 M00203 66..60(92) 42l..427(92) 1682.. 1688 9 1688.. 1682(91) 96..106(98) I

I

GATA-X

GATA binding site, I (~ATA..1 I flATA-hindin~ factor .1 jVjUU.4i t..I i~ .tor-1, M00075 1838..1847(97) GATA- I GATA-binding factor I 1701 1692(95) IMAM.89 93 900..891(91) 138..129(90)_ M00158 319..306(96) COUP-TF COUP/ITNF-4 heterodimer M00272 1267..1276(96) p53 tumor suppressor p53 MOO] 34 304..322(96) HNF-4. hepatc nuclear factor 4 M00096 1821..1819(96) Pbx-1 Pbx-1I M00285 1734..1746(95) TCFl I TCFIL/KCR-FlfNrfl homnodimers 1487..147(211_ 13.. 1(90) M00077 1933..1941(95) GATA-3 GATA-binding factor 3 M00253 1794..1801( 95) cap cap signal for transcription initiation 481..488(95) 1893 1886(95) 1452..1459(94) 795 802(94) 656..649(93) 1486.. 1479(92) 1326..1319(91) 559..566( 91) 1877..1870(91) 745..752(91) 918..925(91) 954..961(90) 1815..1808(90) 1299..1306(90) _M00054 466..457(95) NF-kappaB NF-kappaB _M00146 165..156(94) HSF1 heat shock factor 1 M00147 165..156(94) HSF2 heat shock factor 2 156.. 165(94)._ M00O141 453..461(94) Lyf- I LyF-1 Mh0052 466..457(94) NF-kappaB NE-kappaB M199 1797..1789(94) A.P-1I AP-1I binding site 1789..1797(91) MN00174 1788..1798(94) AP- I activator protein 1 M0I0053 466. .457(94) c-Re] c-Rel N400278 1933..1941(93) Lmo2 complex of Lmo2 bound -to Tal-1', E2A proteins, I I and GATA-1, half-site 2 00

;Z

00 M00076 193 2..1941 (93) GATA-2' GATA-binding factor 2 1701.. 1692(92) 1303..1312(92) .993(92) M00099 1813..1798(92) S8 S8 M001 84 271 280(92) MyoD myoblast determining factor* M00223 544..536(92) STATx signal transducers and activators of transcription M00073 36..46(92) deltaEF1 deltaEFI M00033 805..792(92) p300' p300 M00271 1955.. 1960(92) AML-la runt-factor AML-1I M00254 1831..1820(91) CCAAT cellular and viral CCAAT box M00277 281..270(91) Lmo2 complex of Lmo2 bound to Tal-1, E2A proteins, and GATA-1, half-site 1 M00289 381 393(91) HFH-3 HNF-3/Fkh Homolog 3 (=Freac-6) M00208 467..456(90) NE-kappaB NE-kappaB binding site M00183 1027..1036(90) c-Myb c-Myb M00240 241 235(90) Nkcx-2.5 homeo domain factor Nkx-2.5/Csx, tinman M001 88 1788..1798(90) AP- I activator protein I M00302 838..827(90) NE-AT Nuclear factor of activated T-cells M00128 93.. 105(90) GATA-1 GATA-binding factor I M00087 981..992(90) Lk-2 Ikaros 2 M00172 1788..1798(90) AP-1 activator protein 1 M00042 69.. 78(90) Sox-5 M00003 962..953(90) v-Myb v-Myb M00221 1860..1850(90) SREBP- I sterol regulatory element-binding protein I MOO] 94 468..455(90) NF-kappaB INF-kappaB Table 20, putative transcription factor binding motifs within the DUB regulatory or promoter, region of hDUB 8.8. The position is indicated by nucleotides.' Tr-nfe escription Pncifinn(Score) Name M00148I 1020..1014(100) 970..976(100) 947..941(96) 1550..1556(92) 843..837(90) 707..713(90) 1362.. 1356(90) 1719..1713(90) 1824..1818(90) 395..389(90) 748..742(90) SRY sex-determining region r -gene proui.

30. 3(9) I I ~A~~FVA 1 iQAA 1k't71rAA Nkx-2.5 Thomeo domain factor Nkx-2.5/Csx, tinman I 00

;Z

00 homolog MOOQ100 1105..1099(100) CdxA CdxA MOQOI0 1105..1099(99) CdxA CdxA MOOIOO833..827(98) 1385.. 1379(98) 1409..1415(92) 964. .970(92) 726..720(92) 424. .430(92) M00075 1838..1847(97 GATA-1 GATA-binding factor 1 1889.. 1898(93) 925..916(93) M00272 1267.. 1276(96) p 5 3 tumor suppressor p53 M00253 161...168(96) cap cap signal for transcription initiation 1794..1801(95) 484..491(95) 1893..1886(95) 1452.. 1459(94) 798..805(94) 748..755(94) 957..964(94) 1486.. 1479(92) 338..345( 92) 1697..1704(92) 562..569(91) 1877..1870(91) 1815 1808(90) 321.'.28(90) 1326..1319(90) M00096 1827..1819(96) Pbx-1' Pbx-1> M00285 1734..1746(95) TCFI 1 TCF1I/KCR-F1/Nrfl homodimers.

1115..1127(91) M00077 1933..1941(95) GATA-3 GATA-binding factor 3 M00054 469.'~460(95) NF-kappaB NF-kappaB -M00141 456..464(94) Lyf-l LyF-1 MOO0134 306..324(94) I-HF-4 hepatic nuclear factor 4, M00052 469. .460(94) NE-kappaB NF-kappaB M001 99 1797..1789(941 AP-1I AP-1 binding site MOO0174 1788..1798(94) AP-1I activator protein I M00053 469. .460(94) c-Rel c-Rel M00033 758..745(94) p 30 0 p 3 0 0 -M00158 321..308(93) COI.P-TF COUP/J{NF-4 heterodimer M00278 1933..1941(93) Lmo2 complex of Lmo2 bound to Tal-1, E2A proteins, ___and GATA-l, half-site 2 00

;Z

00 M00076 1932.. 1941(93) GATA-2 GATA-binding factor 2 1303..1312(92)-- 743..734( 92i 925. .9 16(90) M00099 1813..1798(92) S8 S8 1114..1129(90) MOO0104 28..37(92) -CDP cut-like homeodornain protein M00223 "547..539(92) STATx signal transducers and activators of transcription M00271 1955.. 1960(92) AML-la runt-factor AML- I M00254 1 831..1820(91) CCAAT cellular and viral CCAAT box M00042 649-..658(91) Sox-5 M00289 384..396(91) HFH-3 HNF-3/Fkh Homnolog 3 Freac-6) M00302 1384.. 1395(9 1) N-F-AT Nuclear fa'ctor of activated T-cells 841 830(90) M00155 367..382(91) AiRM- apolipoprotein Al regulatory protein 1 M00208 470. .459(90) NF-kappaB NF-kappaB b-in-ding site M00183 1030..1039(90) c-Myb c-Myb M00240 243..237(90) Nkx-2.S homeo domain factor Nkx-2.5/Csx, tinman Shomolog 1448(90) MOO] 88 1788.. 1798(90) AP- I activator protein 1 M00083 47..40(90) MZF1 MZFI MOO0184 273..282(90) MyoD) myoblast determining factor MOO0147 167..158(90) HSF2 heat shock factor 2 MOO0172 1788..1798(90) AP-1 activator protein 1 M00221 1860..1850(90) SREBP-1 sterol regulatory element-binding protein I FM00194 471..458(90) 1NIF-kappaB JNl-kappaB Table 2 1, putative transcription factor binding motifs within the DUB regulatory or promoter, region of hDUJB 8.9. The position is indicated by nucleotides.

00

;Z

00 M00083 M00241 M00272 M00253 MOO0100 M00042 M00096 1432..1438(93 743..737(92) 89..83(92) 592..586(92) 1280.. 1286(92) 444..450(92) -682..1688(9.1) 1688.. 1682(9 1) 779..772(100) 68..61(90 1800..1807(100) 1290.. 1299(96) 182..189(96) -794.A801 1893..1886(95) 1475..1482 94 768..775(94) 1506..1499(93) 13-49.13-42( 91 582. .589(91) 351..358(90) 1815..1808(90) 342..349(90) 1877..1870(90) 504..511(290 1322.. 1329(90) 1125..1119(96) 742..751(96) 669..678 92) 726..735(92) 1827..1819(96) ICV2'2 1C)Alf(0, MZF1I tMZFI N'kx-2-.5 p 5 3 c' p homeo domain factor N-kx-2.5ICsx., tinmran homfolog tumor su Ippressor p53 cap signal for transcription initiation Cdx,, -CdxA

I

Sox-5 1 Pbx- 1 CATA -I [Pbx-l M00045 1877..1888(95) E4BP4 E4BP4 M00054 489..480(95) NF-kippaB NF-kappaB M00OO141 476..484(94) Lyf-1 LyF-1 M00052 489..480(94) NF-kappaB NF-kappaB MOO0199 1797..1789(94) NP-i AP-1 binding site 1789.. 1797(91) M100 174 1788..1798(94) AP-l activator protein 1 M0U0053 489. .480(94) c-Rel c-Rel M00278 1933..1941(93) Lmo2 complex of Lmo2 bound to TaI-1, E2A proteins, and GATA-1, half-site 2 M00076 1932..1941(93) GATA-2 GATA-bindintg factor 2 1007.. 1016(92) 1701 1692(91) M00285 1734..1746(92) TCFI I ITCFIIKCR-FI./Nrfl homodimers, _______11135..1147(91) 00

;Z

00 M00099 1813..1798(92) S8 S8 34..1149(90)__ MOO 104 49..58(92) CDP cut-like homeodomnain protein M00223 567..559(92) STATx signal transducers arid -activators of transcription M00075 1701.. 1692(92) GATA-l GATA-binding factor 1 161..152(90) 1736..1745(90)- M00348 316..325(92) GATA-2 GATA-binding factor 2 MOO] 09 873..886(91) CIEBPbeta CCAAT/enhancer binding protein beta M00254 183 1..1820(91) CCAAT cellular and viral CCAAT box M00203 M00350 M00289 MOO0113 M00249 318.. 328(9 1) 316..325(91) 404..416(91) 833..822(90) 1165..1153(90)

(.ATA-X

GATA-3 HFH-3

CREB

CHOP-

C/EBPalpha NE-kappaB A I A binding si Ee M00208 1490. .479(90) MOO 19 0 M00349 MFO,40016 M00183 M00240 M001 88 M00302 M00184 M00147 M00087 M0O0172 M00221 M000O33 M00194 1263 .1250(90) 316. .325(90) 1263 1250(90) 1050.. 1059(90) 263. .25 7(90) 1477.. 147 1(90) 1788.. 1798(90) 1407.. 1418(90) 293. .302(90) 188..179(90) 1004.. 1015(90) 1788..1798(90) 1860..1850(90) 778..765(90) 49 1..478(90)

C/EBP

GATA-2 C/EBPalpha] c-Myb Nkx-2.5 AP-1

NF-AT

MyoD HSF2 Ik-2 AP-lI SREBP- 1 p300 N'F-kappaB GTATA-binding factor 3 I{NF-3/Fkh Homolog 3 (=Freac-6) cAMP-responsive element binding protein heterodimers of CHOP and CIEBPalpha NF-kappaB binding site CCAAT/enhancer binding factor GATA-binding factor 2 CCAAT/enhancer binding protein alpha c-Myb borneo domain factor Nkx-2.5ICsx, tinman homolog activator protein 1 Nuclear factor of activated T-cells myoblast determining factor heat shock factor 2 Ikaros 2 activator protein I sterol regulatory element-binding protein 1

P

3 0 0 INE-kappaB Table 22, putative transcription factor binding motifs within the DUB regulatory~or promoter, region of hIDUB 8.10. The position is indicated by nucleotides.

Transfac MOO0148 Position(Score) 1038..1032(100) 965. .959(96) 1550..1556(92) 725..731(90).

1382..1376(90) 3 10. .3 16(90) 1715..1709(90) 1824..1818(90) 112..18(90) Name

SRY

Description sex-determining region.Y gene product 00

;Z

00 413..407(90) 1630.. 1624(90) M00241 1800..1807(.100) Nkx-2.5 homeo domain factor Nkx-2.5/Csk, tiniman.

___homolog MOQIOG 1123..1117(100) dxA CdxA M00240 1 240..1234(100) Nkx-2.5 homeo domain factor Nkx-2.5/Csx, tinman ____262..256(90) M00141 474..482(rOo.) Lyf-1 .LyF-1 MO0l01 1123..1117(99) CdxA CdxA 540.. 546(97) 1429.. 1435(94) 982. .988(92) 88-.81(92) 741..735(92) 442. .448(92) M00075 1838..,1847(97) GATA-1 GATA-binding factor 1 1889..1898(93) M00253 766..773(96) cap cap signal for transcription initiation 181.. 188(96) 1794..1801(95) 1893 1886(95) 1210..1217(94) 816..823(94) 1506..1499(92) 357. .364(92) 1697..1704(92) 1090.. 1097(91) 1346..1339(91) 1877..1870(91) 71..78(90) 80. .5 87(90) 18 15.. 1808(90) 340..347(90) 502..509(90) 1319..1326(90) M00096 1827..1819(96) Pbx-I Pbx-1I M00285. 1734. A 746(95) TCFI I TCF I II/KCR-F1I/NrflI homnodimers 113 3o.114 5(91) 35..23(91) 1089001101(90) -M00134 325..343(94) HNF-4 hepatic nuclear factor 4' M00199 1797001789(94) AP-1I A.P-1 binding site 1789.1797(9 1) M00174 1788..1798(94) AP-1 activator protein I M00042 740..749( 4) Sox-5 00

;Z

00 163 1..1622(92) ___667..676(91) MOO0106 672..681(94) CDP cut-like homeodomain protein- M00158 340..327(93) COIJP-TF COUP/HNF-4 heterodimer M00076 .761 752(93) GATA-2 GATA-binding factor 2 1323..1332(92) 1005..1014(92) M00099 1813..1798(92) S8 S8 1132..1147(90) M00104 48..57(92) CDP cut-like homeodomain protein' M00223 565..557(92) STATx signal transducers and activators Of transcription M00033 826..813(92) p300 p300 M00271 1955..1960(92) AML-la runt-factor AML-1I M00254 1831..1820(91) CCAAT cellular and viral CCAAT box M00289 402..414(91) HFH-3 HNF-3/Fkh 1-omolog 3 Freac-6) M00217 160..153(90) USF USF binding site M00183 1048..1057(90) c-Myb c-Myb M00188 1788..1798(90)- AP-1 activator protein 1 M00083 67..60(90) MZF1 MZF1 MOO] 84 1292..301(90) MyoD) myoblast determining factor M00147 187..178(90) HSF2 heat shock factor 2 M00087 1002..1013(90) Ik-2 Tkaros 2 M00172 1788..1798(90) AP-1 activator protein 1 M 002 21 1860..1850(90) 1SREBP-l sero regulatory el ement -binding protein I Table 23, putative transcription factor binding motifs within the DUB regulatory or promoter, region of hDIJB 8.11. The position is indicated by nucleotides.

Transfac Position (Score) Name Description _M00348 71. .80(100) 1GATA-2 GATA-binding factor 2 M00350 71..80(100) GATA-3 jGATA-binding factor 3 M00349 71..80(100) GATA-2 GATA-binding factor 2 M00148 990..984(100) 1664.. 1658(100) 813..807(96) 917..911(96) 1858..1864(92) 1850..1856(92) 1836..1842(92) 1399..1405(90) 1514.. 1508(90) 680. .686(90) 2104..2098(90) 368..362(90) 721..715(90) 1002..996(90) SRY sex-determining region Y gene product 00

;Z

00 M00100

MOIOI

1910.. 1904(90) 274..280(90) 595..589(1 00) 1408..1402(100 1474..1480(96) 595..589(99) 1408.. 1402(99) 803..797(98) 1537.. 153 1(98) 1715..1721(92) 699. .693(92) 934. .940(92) 43..37(92) 495 501(92) .CdxA CdxA CdxA !CdxA M00141 M00347 M00272 M00253 1282.. 1274(98) 71..80(97) 1573..1582(96) 1137..1144(96) 136..143(96) 2074..2081(95) 457..464(95) 2173..2166(95) 72l.. 728(94) 1444.. 1437(94) 660..653(94) 1792.. 1785(92) 312..3,119(92) 1632..1625(91) 535..542(91) 2095..2088(91) 1358..,1365(91) 768..775(90) 295..302(90) Lyf-1I GATA-1 p 5 3 LvF- I GATA-binding factor I tumor suppressor p53 cap signal for transcription initiation _M0096 2107..2099(96). Pbx-1 Pbx-1I _M02 85 2014..2026(95) TCFI TCF11/KCR-Fl/Nrfl homodimers.

___1418..1430(91) M0O0130 1657..1668(95) HFH-2 1NF-3/Fkh Homolog 2 M000O77 2213..222](95) GATA-3 GATA-binding factor 3 -M00054 442. .433(95) NF-kappaB NE-kappaB _M00052 442. .433(94) NF-kappaB NF-kappaB _M00203 73..83(94) GATA-X GATA binding site M199 2077..2069(94) AP-1 NP-i binding site 2069..2077(91) ___1994..2002(90) jQO 1-74 2068..2078(94) A-P-1 activator protein 1 1446(90) _MO0075 895..886(94) GATA-1 ATA-binding factor 1 00

;Z

00 21.69..2178(93- 1091..1082(93) 1981..1972(92) ___201 6..2025(90) M00053 442. .433(94) c-Rel c-Rel M00241 2080..2087(94) Nkx-2.5 homeo domain factor Nkx-2.5/Csx, tirnan ___homolog M00076 716..707(94) GATA-2 GATA-binding factor 2 2212..2221(93) 1609..1618(92) 957. .966(92) 895..886(91) 1..1972(91) MOO 106 627..636(94) CDP cut-like homeodomain protein M00033 731..718(94) p300 p300 M00227 2149..2141(94) v-Myb 'v-Myb M00158 295..282(93) COUP-TF COUP/HNF-4 heterodimer MOO0162 2080..2093(93) Oct- I octamer-binding factor 1 M00278 2213..2221(93) Lmo2 complex of Lmo2 bound to Tal-1, E2A proteins, and GATA-.1, half-site 2 MOO1 34 1280..298(93) HNF-4 hepatic nuclear factor 4 M00032 1226..235(93) c-Ets-lI(p54) c-Ets- I(p54) MOO0172 1436..1446(92) AP-1 activator protein 1 .2078(90) MOOI 17 1089..1076(92) CIEBPbeta CCAAT/enhancer binding protein beta M00042 1911..1902(92) Sox-5 Sox-5 M 00223 1520..5 12(92) uc r a d ac i at r o ra s ri to M00073 1 3..23(92) deltaEFlI deltaEFI MOO018 8 1436..1446(91) AP-1I activator protein 1 .2078(90) M00254 2111..2100(91) CCAAT cellular and viral CCAAT box M00099 2093..2078(91) S8 S8 2076..2091(90) 11417.. 1432(90) M00289 1657.. 1669(9 1) HFH-3 -INF-3/Fkh Homolog3 Freac-6) 357..369(91) Mi014 7 752..743(91) HSF2 heat shock factor 2 M00208 443..432(90) NF-kappaB NE-kappaB binding site M00217 115..108(90) USF USF binding site Mj00183 1333..1342(90) c-Myb c-Myb M00173 1436..1446(90) AP-1 activator protein I M240 217..21 1(90) Nkx-2.5 homeo domain factor Nkx-2.5ICsx, tinman M001 84 1965.. 1974(90) MyoD) myoblast determining factor 1247..256(90) M00087 1954..965(90) s 00 MIOO0 128 70..82(90) GATA-1 GATA-binding factor I MOO 145 1347..1362(90) Brn-2. POU factor Brn-2 _MO00194 444..431(90) N-a aB NF-kappaB3 References: 00 1. Baek, K. Mondoux, M. Jaster, Fire-Levin, and D'Andrea, A. D. (2001).

DUB-2A, a new member of the DUB' subfamily of hematopoietic deubiquitinating enzymes, Blood 98, 63 6-42.

00 2. Jaster, Baek, K. and D'Andrea, A. D. (1999). Analysis of cis-acting sequences and trans-acting factors regulating the interleukin-3 response element of the DUB-I gene, Biochim Biophys Acta 1446, 308'-16.

o 3. Jaster, Zhu, Pless, Bhattacharya, Mathey-Prevot, and D'Andrea, A. D.

(1997). JAK2 is required forinduction of the murine DUB-i gene, Mol Cell Biol 17, 3364-72.

4. Migone, T. Humbert, Rascie, A.,'Sanden, D'Andrea, Johnston, J. Baek, K. Mondoux, M. Jaster, Fire-Levin, et al. (2001). The deubiquitinating enzyme DUB-2 prolongs cytokine-induced sighal trAnsducers and .activators of transcription activation and suppresses apoptosis following cytoki*ne withdrawal, Blood 98, 1935-41.

Zhu, Carroll, Papa, F. Hochstrasser, and D'Andrea, A. D. (1996a). DUB-I, a deubiquitinating enzyme with growth-suppressing activity,- Proc Nati Acad Sci U S A 93, 3275-9.

6. Zhu, Lambert, Corless, Copeland, N. Gilbert, D. Jenkins, N. and D'Andrea, A. D. (1997). DUB-2 is a member of a novel family of cytokine-inducible deubiquitinating enzymes, J Biol Chemn 272j 5 1-7.

7. Zhu, Pless, Inhorn, Mathey Prevot, and D'Andrea, A. D. (1 996b).* The murine DUB-I gene is specifically induced by the betac, subunit of interleukin-3 'receptor, Mol Cell Biol 16, 4808-17.

0OAqTHISHU4XDX SU'1DSIOIThWSOG~dJISS 09 AAS7.ENDSOC~lYIArdIOS~~c:aXAXIN).(dUrA IrIA)IVSMWlqLX S~VdIADH xoqa~~~r~O~sv~ariqdiaIHHD 0H~o IOHIqJLL DaS. iAVOd UDXIV~7"'Sq' H.aVdaI~llqVM~DIH IVJ.I SS7.dSOSd 09 aouarnbasa pTqdadAlod peonpap vlrvnaq st ~o 4001 vssoOvvq6 6O~~ 50 l41eOo- ve ;qJeOV ~0 B6 6 65 D B565~ E00 BES 6EBE6E BESBBEBE BBP~E5B~BE~e60E VT 569at 10BEB BEzn~ Beoaon B& BB D lBB ~0 e51 o loo; 6eS6qeroi 05E~ &m BS60 40 0 VSI 6110 3~ zv5eO5e pep~E p Je-4LO De r5IO O D1 005 ,1J 1o6 v~ e1e~s oqeSe oi ~,L5 e io0J~ e~ v) o e v J~ v 0 0 o l 0 16el i eZVaa io~uabs~pajn OD rr 0& anabs9~dcAEo ena TVMr Se ~5~555~ e5~5 e~ ~5e5D BE~.Opp6 00 qT tanq iaj Qunbs apo DnN ~Ar00 09 0 Ile60 p~evoe essvq1 lje6jV eovpe e 3q q 0 01 pl Bo E50 5e6 ;v e6 ee 5ee5D15e pv01 5olsv103l 55 Del5 0I~e 36 5s56 Os S9 or 0364 1*01e1 o41p ~jo oseDope~O1 sv e S01 v.Bq 366so I31oze3 qope 3-:oee:6ei 3 5o~)5ve aoS- 4-5 4l- e ooo o5loe ooeqqIoo~ le6oooqoo 65voev o qZ tnaq. IoJ;:ugnbzs pI1o~qonN 017 0OATIVdX sHxNDTomlsua doisvriLDL&wsaoiLdiss SqNTIS rI7Nrdllq~SN ,N)W~EVA~Hs~dUS3ldV70VAdVqaIIa AZLL3)S'Id S)adrIS.L SgSHfdaMES)AOI2 v1A7VOOSrIASJLI svja~a~i~avA d E)H)MV~IV IIrd)N OsW~dOWGdAOAIVINLASaH~rAr 1 II AISL'lI)S~'drZA)HVaENizdA'0rV 0AS0VVIaIWarIAdaa~as I I H H7XIOSUM)XD3 IOHIllGIXSHHAZ)XH~d-IZv)'flWVaALaWrIA2HVC aouanbas ap 1 ~dad~lod peonpap eZVnati ei po6e66oivoo6 6eP536 I5 opoeSo e S ieS o ooI ooloo e o e~ 6epoi 66oo eop55p Spe555566 Io e5p oo Pe o65ee P5~55 Se 555eee5 DO5 I e ou I ~o I6o v155s P Sesl 00061 31 O o~go oS o S~5S55~ee S5~55 e See6 e 0 o p e5 oo6 55ljeS S eroI o q656poSvpo I o u e ol61e Ioeo lo I o~jv665o~O Se1014- So1.0: e 11 eo1545 4040 us~e~e~n.50eS

J

;*06 DO06s Bev D 00 00 00 aaacactcgaacagtctcaaccctgcaccaaacgatct aaatgaatgtccggggggcgaacaagagaaaaacaagc ;Z ctgcttgtgtgccagtga hflUB4.2b deduced polypeptide sequence MEDDSLYLGGEWQFNI{FSKLTS SRPDAAFAEIQRTSLPEKS PLSCETRVDLCDDLAPVARQLAPREKLPLS

SRRP

AAGGQMNCVALCTYTLNMSESTHHGMCMAIRLNGVQSAL

00 AGFHRGKQEDAHEFLMFTDAMKKACLPGHKQHSKTTLIHQI FGGYWRSQI KCLHCHGISDTFDPYLDIAL o: DIQASQAELKELGNYSVLRPSKLLTAVIVKFDTNIKVYE LDMQPYMSQQNTGPLVYVLYAVLVHAGWS CHNGHYFSYVKAQEGQWYKMDDA EVTA~ AITSALSQQAYVLFYIQK SEWER iSESVSRGREPRALGTEDTDRRATQGELKRDHiPCLQAPELDEHLVERATQEST'LDHWKFLQEQNKTKPEF NRKVGTLPPDVLVIHQSKYKCGM1KM1HPEQQSSLLLS S STPTHQESNTGTLASLRGRARRSKGKSKA 00

LLVCQ

Nucleotide sequence for hflUB4 .3 atggagccccatgggtatgatcaccttaacccttccgc gagacttcgatcggatccccggataccccttaacggca z0 ctttagttgtcggcaaactcccgggactccggacgaac gcggtggcggtcgaaggatctcaggagtctgatctaaa accgcctcacaagttcgggattaaggctgccagcgagt tgagtcaccctaaggctccactgcctacaccccgctgc gctggcttccatagaggcaagcaggaagatgcccatgaat ttctcatgttcactgtggatgccatgaaaaaggca tgctcggaagaga~ct~ttagaac~ctacacatttggca tgaaccataggccatcagcttaaattgcctctgctgct gcttattggttttcggggcgctcaagtattacacacctctgccaaggtc ctactgataggtccgttaagacaatcagaggattcggg ctgctcgctctttacgaaagcttgcagctttcggtgca gcgggatgccagaatctttagcagtagagcagttaaga gagcagccgccactatcgctatacgctctccttctcga agtgaatgg gaaagaca cagtgagagtgtgtcaagaggcagggaaccaagagcccttggcgcagaagacacagac agcacagaga~ccaaaaccctctcgcccatgaggatgt gaaacatagagactgcgtgaatctaggaaga~cagcggt aagcgaatgagactctdgctcttatacacaaaagttgit aaacactcgaacagtctcaactttctgccgcctaggcat aaatgaatgtccggggggcgaacaagagaaaaacaagc ctgcttgtgtgccagtga hDtYE4.3 deduced polypeptide sequence MEDDSLYLGGEWQFNHFSKLTS SRPDAAFAE IQRTSLPEKS PLSCETRVDLCDDLAPVARQLAPREKLPLS

SRRP

AAVGAGLQNMGNTCYVNASLQCLTYTPPLANYMLSREHSQTCHRHKGCMLCTMQHITRALHNPGHVIQPSQALA

AGFHRGKQEDAHEFLMFTNKKACLPGHKQDHSKTTLIHQI FGGYWRSQIK CLHCHGISDTFDPYLDIAL D IQAAQSVQQALEQLVKPEELNGENAYHCGVCLQRAPASKTLTLHTSAKV I LVLKRFSDVTGNKIAQNVQYPP-C LDMQPYMSQQTGPLVYVLYAVLTHAGWSCHGHYFSQEGQWYDVTASITSVL.SQQAYVLFY

.IQK

SEWERHS ESVSRGREPRALGAEDTDRRATQGELKPRDHPCLQAPELDEHLVERATQESTLDRWKFLQEQNkT

.KPEF

NVRXKVEGTLPPDVLVIHQSKYKCGMN1QHHPEQQS SLLNLS SSTPTHQESMNTGTLASLRGRARRSKGKNKNsKRA

LLVCQ

Nucleotide sequence for hflUB4 atccaaacctatgaatttg Lggtggctcgactcgccga aaactggtcttcatgctggagccccatgggtatgatca Cattcaataacttsccagacttcgatcggatccccsga tccattagggccttgctttagttgtcggcaaactcccg gagaagcttcctctgagtaacaggagacctctgcggtggSgctggctccagaatatgggaaatacctgctac gtgaacgcttccttgcagtgcctgatatacacaccgccccttgccaactacatgctgtcccgggagcacctcaa 00

;Z

00 actgtcactaaggtctccttcagagtaaccaggctccactg cagctcgctaagatgtcgctctggcacgagtcctattt agtcatgtgcatgccgtCtaggcaCtgtcgggatgcacaagtacatctactctaagaaa acccctccaaatga catggttcataggccatcagcttaa acttactacgaacccgaacagaccgggcacactgacgt gtagcgaaccagaaatcttattggtgccaagccgctca actactaaaccgcag'cctctgataggtccgttaagaca atgcaattcaactatctgctagttctttaagatagctt gttttccagttcgtcccgggggttaacgcta~tttagca gccaagcatgaaatgtagcagtaccttgaccttgctata cagcagctttaacaagggaggagccggggggcaagaga hflUB4gadeced polypeptide sequengceacagagaaccaaaaccctct MRQgccHLKatLSggaggatgtgaggcccggagactgcatgatct ARQGQWYLKMDDAEVASS IS LSQQNLYIQKSDEEHSGEVSRGREPLGAERDDRFTOEQRHPE

QAPELDEHLVERATQESTLDHWKFLQEQNKTKPEFNRVGTLPPD-VIHQSKYKCGMKNH~HPEQQSSLLNLS

STPHEMTTALGARKKMKALCWQKYP

Nucleotide sequence for hDUB4. 6 atggaggacg actcactcta acatcttctc ggcccgatgc tcaccactct catgtgagac cagcttgctc ccagggagaa gggctccaga atatgggaaa acaccgcccc ttgccaacta aagggctgta tgctctgtac cacgtcatcc agccctcaca gcccatgaat ttctcatgtt aagcaggtgg atcatcactc tggagatctc aaatcaagtg ctggacatcg ccctggatat gtgaagcccg aagaactcaa gcgccggcct ccaagacgtt aagagattct ccgatgtcac cttgacatgc agccatacat gctgtgctgg tccacgctgg gct~caagaag gccagtggta tctgtcctga gtcaacaggc cacagtgaga gtgtgtcaag aggcgagcaa cgcaaggaga gacgagcact tggtggaaag caagagcaaa acaaaacgaa cccgacgtac ttgtgattca gaacagcaaa gctccctgct aacactggca cactcgcttc cacagcaaga gggctctgct cttgggaggt gagtggcagt tcaacc act t,.ttcaaaactc agcttttgct ccgtgtcgac gcttcctctg tacctgctac catgctgtCC gatgcaagct ggcat tggct cactgtggat taaggacacc tctccactgc ccaggcagct tggagagaat aactttacac aggcaacaag gtctcagacg gtggagttgt taaaatggat ctacgtcctc aggcdgggaa gctcaagaga agccactcag gcctgagttc tcaatcaaaa aa acc tc~t c t cctgcgaggg tgtgtgccag gaaatccagc ctctgtgatg..

agtagcagga gtgaacgctt cgggagcact cacatcacac gctggCttCC 9ccatgaaaa accctcatcc cacggcattt cagagtgtcc gcctatcatt acctctgcca.

attgccaaga aacacaggac cacaacggac ggac ttct Ct a ttztggctc gacctgctgc ccttgcagtg ctcaaacgtg gggccctcca atagaggcaa aggcatgcct accaaatatt cagacacttt agcaagcttt gtggtgtttg aggtcctcat atgtgcaata ctctcgtcta attacttctc tgtggcaaga ggtgggggct cctgacatac tcatcgtcac caatcctggc gcaggaagat tcccgggcac tggaggctac tgacccttac ggaacagttg tctccagagg cc ttgtattg tcctgagtgc tgtcctctat ttatgtcaaa tagcatcact atgggaaaga agacacagac ccccgagttg gaaattcctt taccctgcct ccatcatcct ggagtccatg gaagaacaaa gatgccgagg- tcaccgcctc ttttacatcc. agaagagtga ccaagagccc. ttggcgcaga gaccacccct gcctccaggc gaaagcacct tagaccactg aacgtcagaa aagtcgaagg, tacaagtgtg ggatgaagaa tcgacgaccc cgacacatca agggccagga gatccaaagg tga hflUB4.6 deduced polypeptide sequence

MEDDSLYLGG

QLAPREKLPL

KGCMLCTMQA

KQVDHHSKDT

VKPEELNGEN

LDMQPYMSQT

SVLSQQAYVL

DEHLVERATQ

EQQSSLLNLS

EWQFNHFSKL

S SRRPAAVGA 14ITRALHNPG TLIHQI FGGY

AYHCGVCLQR'

NTGPLvY'VLY

FYIQKSEWER

ESTLDHWKFL

STTPTHQESM

TSSRPDAAFA,

GLQNMGNTCY

HVIQPSQALA

WRSQI.KCLHC-

APASKTLTLH

AVLVHAGWSC

HSESVSRGRE

QEQNKTKPEF

NTGTLASLRG

EIQRTSLPEK

VNASLQCLTY;

AGFHRGKED

HGISDTFDPY

TSAKCVLILVL

HNGHYFSYVK

PRALGAEDTD

NVRKVEGTLP

RA.RRS KGKN~K S PLSCETRVD TPpL.ANYMLS

AHEFLMFTVD

LDIALDIQAA

KRFSDVTGN'K-

AQEGQWYKMD

RRATQGELKR

PDVLVIHQSK

HSKRALLVCQ

LCDDLAP VAR

RERSQTCHRH

AMK KACLPGH

.QSVQQALEQL

IAKNVQYPE]C.

DAEV-TAS SIT

DHPCLQAPEL

YKCGMKNHHP

00 00 Nucleotide sequence for hflUB4 .7 atggaggacg acatcttctc tca cc ac tc t cagcttgCtC gggctccaga acaccgCccc: aagggctgca cacgtcatcc gcccatgaat aagcaggtaqg tggagatctc ctggacatcg gtgaagcccg gcgccggcct aagagattCt cttgacatgc 0 gctgtgCtgg gctcaagaag tctgtcctga cacagtgaga aggcgagcaa gacgagcact caagagcaaa cccgacgtac gaacagcaaa aacactggca cacagcaaga actcactcta ggcccgatgc catgtgigac ccagggagaa atatgggaaa ttgccaacta tgctctgtac agccctcaca ttctcatgtt atcatcactc aaatcaactg ccctggatat aagaactcaa ccaagacgtt ccgatgtcac agccatacat tccacgctgg gccagtggta gtcaacaggc gtgtgtcaag cgcaaggaga tggtggaaag acaaaacgaa ttgtgattca gCtCCCtgCt cactcgcttc gggctctgct cttgggtggt agc ttt tgc t ccgtgtcgac: gcttcctctg tacctgctac: catgctgtcc tatgcaagct ggca ttggct cactgt ggat t aa gga-cac c tctccactgc ccaggcagct tggagagaat aactttaLac aggcaacaag gtctcagcag gtggagttgt taaaatggat ct a cgt cct c aggcagggaa lgctcaagaga *agccactcag gcctgagttc *tcaatcaaaa aaacctctct cctgcgaggS *tgtgtgccac gagtggcagt gaaatccagc ctctgtgatg agtagcagga gtgaacgctt cgggagcact.

cacatcacac qctggcttcC gccatgaaaa accctcatcc: 'cacggcat tt cagagtgtC gcctatcatt acctctgcca- 'attgccaaga aacacaggac cacaacggac: gatgccgagg ttttacatcc: ccaagagcc gaccacccct gaaagcacct aacgtcagaa Ltacaagtgtg tcgtcgaccc Iaggaccagga Itga tcaaccactt ggacttctct a-tttggctcc gacctgctgc ccttgcagtg c-tcaaacgtg ggg ccc tcc a at agaggcaa acjgcatgcct.

accaaatatt cagacacttt agcaagcttt gtggtgtttg aggtcctcat atgtgcaata ctcttgtcta attacttctc tcaccgccgc agaagagtga ttggcgcaga gcct cc agg c tagaccactg aagtCgaagg ggatgaagaa cgacacatca g atcc aaagg ttcaaaactc: ccctgagaag tgtggcaaga ggtgggggct cctgacatac tcatCgtCac.

caatcctggc gcaggaagat tcccgggcac tggaggctac: tga cc ct tac ggaac agttgtctccagagg ccttgtattg tcctgagtgc tgtcctctat ttatgtcaaa tagcatcact atgggaaaga agacacagac; .ccccgagttg gaaattcctt taccctgcct ccatcatcct ggaggccatg gaagaacaaa hflUB4.7 deduced polypeptide sequence MEDDSLYLGG EWQFHFSKL 'TSSRPDAAFA

EIQRTSLPEK

QLAPREKLPL

KGCMLCTMQA

KQVDHHSKDT

VKPEELNGEN

LDMQPYMSQQ

SVLSQQAYVL

DEHLVERATQ

EQQSSLLNLS

S SRRPAAVGA

HITRALHNPG

TLIHQIFGGY

AYHCGVCLQR

NTGPLVYVLY

FYIQKSEWER

ESTLDHWKFL'

SSTPTHQEAM

GLQNMGNTCY

HVIQPSQALA

WRSQINCLHC

APASKTLTLH

AVLVHAGWSC

HSESVSRGRE

QEQNJKTKPEF

N'TGTLASLRG

AGFHRGKQED

HGISDTFDPY

TSAKVLILVL

HNGHYFSYVK

PRALGAEDTD

NVRKVEGTLP

RTRRSKGKNK

SPLSCETRVD

*TPPLANYMLS

AHEFLMFTVD

LDIALDIQAA

KRFSDVTGNK

AQEGQWYKMD

RRATQGELKR.

PDVLVIHQSK.

HS KRALLVCQ

LCDDLAPVAR

REHSQTCHRH

AI4KIACLPGH

QSVQQALEQL.

IAKNVQYPEC

DA.EVTAASIT

DHPCLQAPEL

YKCGMKNH{P

Nucleotide sequence for hDUB4 8 atgcgccaga ctgCggtCCC ctctacttgg gatgcagctt gagacccgtg gagctcgtca tttgaagact ctctcggaag ggatagcgtc ttgctgcaaa agcagaaaaa ccttgtgatc: cttgttccag tcgacatgga ggacgactca gaggtgagtg gcagttcaac cacttttcaa aactcacatC ttctcggccc ttgctgaaat ccagcggact tctctccctg agaagtcacc: actctcatgt tcgacctctg tgatgatttg gctcctgtgg ca-agacagct tgctcccagg 00

;Z

00 gagaagcttc ggaaatacct aactacatgc tgtacgatgc tcacaggcat atgt tcactg cactctaagg aagtgtctcc ga tat cc agg ctcaatggag acgttaactt gtgacaggca tacatgtctc gctgggtgga tggtataaaa caggcctacg tcaagaggca ggagagctca gaaagagcca acgaagcctg attcatcaat c tg ct aa acc gcttccctgc CtgCttgtgt ctctgagtag gctacgtgaa tgtcccggga aagc tca cat tggctgctgg tggatgccat acaccaccct Actgccacgg cagctcagag agaatgccta tacacacctc a c aagat tgc ag cagaa ca c gttgtcacaa tggatgatgc tcctctttta gggaaccaag agagagacca ctcaggaaag agttcaacgt caaaatacaa tctc tCgtC gagggagggc gccagiga' caggagacct cgcttccttg gcactctcaa cacacgggcc cttccataga gaaaaaggca catccaccaa catttcagac tgtcc:agcaa tcattgtggt tgc'caaggtc caagaatgtgaggacctctt cggacattac cgaggtcac catccagaag agcccttggc cccctgcCtc caccttagac cagaaaagtc gtgtgggatg gaccccgaca caggagatcc gctgcggtgg cagtgcctga acgtgtcatc ctccacaatc ggcaagcagg tgccttcccg atatttggdg acttttgacc g c tttggaac gtttgtctcc ctcatccttg caatatctg gtctatgtcc ttctcttatg gccgctagca agtgaatggg gcagaagaca caggcccccg cactggaaat gaaggtaccc aagaaccatc catcaggagt aaagggaaga gggctgggct catacacacc gtcacaaggg ctggccacgt aagatgccca ggcacaagca gctactggag cttacctgga agttggtgaa 'agagggcgcc -tattgaagag agtgccttga t cta tgc tgt tcaaagctca tcacttctgt aaagacacag cagacaggcg agttggacga tccttcaaga tgcctcccga atcctgaaca ccatgAatcac acaaacacag ccagaatatg gccccttgcc ctgcatgctc catccagccc tgaatttctc ggtagatcat atctcaaatc catcgccctg gcccgaagaa ggcctccaagattctccgat catgcagcca gctggtccac agaaggccaa cctgagtcaa tgagagtgtg agcaacgcaa gcacttggtg gcaaaacaaa cgtacttgtg gcaaagctcc tggcacactc caagagggct hflUB4.8 deduced polypeptide sequence

MRQR.ARHLKT

DAAFAEIQRT

GNTCYVNASL

SQALAAGFHR

KCLHCHGISD

TLTLHTSA.KV

AGWSCHNGHY

SRGRE PRALG

TKPEFNVRKV

ASLRGRARRS

LSEGIASCCK

SLPEKSPLSC

QCLTYTPPLA

GKQEDAHEFL

TFDPYLDIAL

LILVLKRFSD

FSYVKAQEGQ

AEDTDRRATQ

EGTLPPDVLV

KGKN.KHSKRA

LRSQQKNLVI

ETRVDLCDDL

NYMLSREHSQ

MFTVDAMKKA

DIQAAQSVQQ

VTGNKIAKNV

WYKMDDAEVT

GELKRDHPCL

IHQSKYKCGM

LLVCQ

LVPVDMEDDS

APVARQLAPR

TCH-RHKGCML

CLPGHKQVDH

ALEQLVKPEE

QYPECLDMQP

AAS ITS VLSQ

QAPELDEHLV

KNI{HPEQQSS

LYLGGEWQFN

EKLPLSSRRP

CTMQAN ITRA

HSKDTTLIHQ

LNGENAYHCG

YMSQQNTGPL

QAYVLFYIQK

ERATQESTLD

LLNLSSSTPT

HFSKLTSSRP

AAVGAGLQNM

LHNPGHVIQP

IFGGYWRSQI

VCLQRAPAS K

VYVLYAVLVH

SE WERHSES V

HWKFLQEQNK

HQESMNTGTL

Nucleotide sequence foT hflUB4 atgtgcatac gaacagggtc actggcagac agcttatcga ccgatgccca gggaacatgt aactgcaatt ccaccataca cgatcgatgc gagaatccag gggccagtat taaaaatggt aggttatcgc tggaagggaa ctcaggtcag a aagcgcact gctgccaaaa ggatagcgtc ctcgttccagj ti:gacatgga cacttttcaa aactcacatc tctctccctg agaagtcacc gctcctgtgg caa gac agct gctgcggtgg gggctgggct cagtgc'Ztga catacacaac acgtgtcatc gtcacaaggg ctccacaatc ctggccacgt ggcaagcagg aagatgccca tgccttcccg ggca caagca atatttggag gctactggag tccgtgtgac t tgggc tccc ccactttcgg atgcgtaact gatatgcacg aatttcactc gaaaata~gc ttcgacttct tttctgcaiac ggacgac tca ttctcggccc actctcatgt tgctcccagg cc agaat atg gccccftgcc ctgcatgctc cat cc agccc tgaatttctc ggtagatcat atctcaaatc gtgtgtgaaa ctcaaaatcg cagcattaca ggaaatggag gcttattttg ggacagagaa tgtgctaaat' tgtccttccg ctgcggtccc ctctacttgg gatgcagctt gagacdcgtg gagaagcttc ggaaatacct aactacatgc tgtactatgc tcacaggcat atgttcacztg cactctaagg aagtgtctcc actacagtgt gatgagcatg gttatgagca tztcaagcaca attttggcac caaatgtgct gcaacatcgc cgatcctgaa gccttttccc actgaaacaa tcaataggct caacgtggaa actatacttc attgactatt, tcgctgagag gatgatggca agcagaaaaa ccttgtgatc gaggtgagtg 9cag3ttcaac .ttgctgaaat ccagcgga~ct tcgacctctg tgatgatttg.

ctc'tgagtag caggagacct gctacgtgaa cgcttccttg tgtCccggga gcactctcaa aagctcacat cacacgggc tggctgctgg cttccataga tggatgccat gaaaaaggca acaccaccct cat-ccaccaa .actgccacgg catttcagac 00 acttttgacc gctttggaac gtttgtctcc ctcatccttg caatatcctg gtctatgtcc ttctcttatg gccgctagca agtgaatggg acagaagaca caggcccccg cactggaaat gaaggtaccc aagaaccatc catcaggagt cttacctgga agttggtgaa agagggcgcc tattgaagag agtgccttga tctatgctgt tcaaagctca tcacttctgc aaagacacag cagacaggeg agttggacga tccttcaaga tgcctcccga atcctgaaca ccatgaacac catcgcccta, gatatccagg cagctcagag tgtccagcaa gcccgaagaa..ct~aatggag. agaatgccta, tcattctggt, ggcctccaag acgttaactt tacacacctc tgccaaggtc, attctccgat gtcacaggca acaagattgc caagaatgltg catgcagcca tacatgtctc agcagaacac aggacctctt gctggtccac gctgggtgga gttgtcacaa cggacattac., agaaggccag tggtataaaa tggatgatgc cgaggtcacc cctgagtcaa caggcctacg tcctctttta Catccaga ag tgagagtgtg tcaagaggca gggaaccaag agcccttggc agcaacgcaa ggagagctca agagagacca cccctgcctc gcacttggtg gaaagagcca ctcaggaaag caccttagac.

gcaaaacaaa acgaagcctg agttcaacgt cagaaaagtc cgtacttgtg attcatcaat caaaatacaa gtgt-ggatg gcaaagctcc ctgctaaacc tctcttcgtc gaccccgaCa tggcacactc gcttccctgc gagggagggc caggagatcc 00 r- 10 00 aaagggaaga acaaacacag caagagggct Ctgcttgtgt gccagtga.

hDUB4 .10 deduced polypep tide sequence

MCIRTGSPCD

NCNSTIQCVT

RLSLEGKKIR

LVPVDMEDDS

APVARQLAPR

TCHRHKGCML

CLPGHKQVDH

ALEQLVKPEE

QYPECLDMQ.P

VCENYSVMSM

GNGGN'IAflPE

CAKYYTSLTI

LYLGGEWQFN

EKL PLS SRR P

CTMQA.HITRA

HSKDTTLIHQ

LNGENAYHiSG

YMSQQNTGPL

TGRQLIDWAP

RSMRESRICT

LRSESALSTS

HFSKLTSSRP

AAVGAGLQNM

LHNPGHVIQP

IFGGYWRSQI

VCLQRAPASK

VYVLYAVLVH

SEWERHSESV

HWKFLQEQNK

LKIGYEHSST

AYFGLFPLKQ

CPSVA.ERMMA

DAAFAEIQRT

GNTCYVNASL

SQALAAGFHR

KCLHCHGISD

TLTLHTSAKV

AGWSCHNGHY

.SRGREPRALG

.TKPEFNVRKV

PMPREHVHFR

GPVLKMVISL

AAIASFCN~

SLPEKSPLSC

QCLTYTTPLA

.GKQEDAHEFL

TFDPYLDIAL

LILVLKRFSD

FSYVkA QEGQ

TEDTDRPA.TQ

EGTLPPDVLV

KGJKN1KHSKRA

QHYNFGTKCA

GQRINRLNVE

LRSQQKNLVI

ETRVDLCDDL

NYMLSREHSQ

MFTVflAMKKA

DIQA-AQSVQQ

VTGNKIAKNV

.WYKM1DDAEVT.,

GELKRDHPCL

IHQSKYKCGM

L LVCQ.-,

AASITSALSQ'.QAYVLFYIQK

QAPELDEHLV ERATQESTLD KgHHPEQQSS LLNLSSSTPT HOES MNTGTL ASLRGRARRS Nucleotide sequence for hDUB4. 11: atgtgcatac gaacagggtc actggcagac agcttatcga ccgatgccca ggacacttta catgaaaaga caagggaaag tatacttcat tgactattct gcggagagga tgatggcagc ggtgagtggc agttcaacca gctgaaatcc agcggacttc gtggcaagac agcttgctcc gtgggggctg ggctccagaa.

ctgacataca caccgcccct catcgtcaca agggctgcat aatcctggcc acgtcatcca caggaagatg cccatgaa-tt cccaggcaca agcaggtaga.

ggaggctact ggagatctca gacccttacc tggacatcgc gaacagttgg tgaagcccga: ctccagaggg cgccggcctc cttgtattga agagattctc cctgagtgcc ttgacatgca gtcctctatg ctgtgctggt tatgtcaaag ctcaagaagg agcatcactt ctgtcctgag tgggaaagac atagtgagag tccgtgtgac gtgtgtgaaa actacagtgt gatgagcatg ttgggctccc ctcaaaatCg gttatgagca. ttcaagcaca catccggcac aggaagcctt ctgatggagc acacctggcc aaacggggcc aaagggaaga aaatacgctg-* tgctaaatac.

caggtcagaa agcgcacttt cgtcttcttg tccttccgtc tgccaaaatc gacatggagg acgactcact :ctact tggga cttttcaaaa ctcacatctt ctcgg!=caga tgcagctttt tctccctgag ajagtcaccac tct~catatga tttggctcct..

cagggagaag c *ttcctctga gtagcaggag acctgctgcg.

tatgggaaat .acctgctacg tgaacgcttccttgcagtgc tgccaactaq atgqtgtccc gggagcactc tcaaacgigt gctctgtact. atgcaagctc acatcacacg ggccctccac gccctcacag gcattggctg ctggcttcca tagaggcaag tctcatgttc actgtggatg ccatgaaaaa. ggcatgcctt tcatcactct ,aaggacacca ccctcat~cca .ccaaatattt aatcaagtgt ctc cactgcc acggcatttc agacactttt cctggatatc. caggcagctc. agagtgtcca gcaag.*Ctttg agaactcaat ggagagaatg cctatcattg tggtgtttgtcaagacgtta actttacaca .cctctgccaa ggtcctcatc.

cgatgtcaca ggcaacaaga ttgccaagaa tgtgcaata~t gccatacatg.,tctcagcaga. acacaggac tcttgtctat ccacgctgag'-tggagttgtc acaacggaca ttacttctct ccagtggtat ,aaaatggatg atgccgaggt caccgccgct tcaacaggcc. .tacgtcctct tttacatcca gaagagtgaa tgtgtcaaga ggcaggaac-caagagccct tggcgcagaa 00 gacacagaca cccgagttgg aaattccttc accctgcctc catcatcctg gagtc catga aagaaca aaac ggcgagcaac acgagcactt aagagcaaaa ccgacgtact aac agcaaag acactggcac acagcaagag gcaaggagag ggtggaaaga caaaacgiaag tgtgattcat, ctccctgcta act cgc ttcc ggctctgctt ctcaagagag gccactcagg cctgagttca caatcaaaat aacctctctt ctgcgaggga gtgtgccagt hDUB4.11 deduced polypeptide sequence accacccctg aaagcacctt acgtcagaaa acaagtgtgg cgtcgacccc gggccaggag ga

PMPRTLYIRH

ABRMMAAAKI

VARQLAPREK

HRHKGCMLCT

PRHKQVDHHS

EQLVKPEELN

PECLDMQPYM

SITSVLSQQA

-PELDEH-LVER

HHPEQQSSLL

cctccaggcc agaccactgg agtcaaaggt gatgaagaac gacacatcag atccaaaggg

MCIRTGSPCD

HEKTRERNGA

GEWQFNHFSK

VGAGLQNMGN

NPGHVIQPSQ

GGYWRSQIKC

LQRAPASKTL

VLYAVLVHAE

WERHSESVSR

KFLQEQNJKTK

ESMNTGTLAS

VCENYSVMSM

KGKKIRCAKY

LTSSRPDAAF

TCYVNASLQC

ALAAGFHRGK

LHCHGISDTF

TLHTSAKVL I

WSCHNGHYFS

GREPRALGAB

PEFNVRKVKG

LRGRARRSKG

TGRQLIDWAP LKIGYEHSST YTSLTILRSE SALSSSCPSV AEIQRTSLPE KSPLSYDLAP LTYTPPLANY MLSREHSQTC QEDAI{EFLMF TVDANKKACL DPYLDIALDI QAAQSVQQAL LVLKRFSDVT GNKIAKNVQY YVKAQEGQWY KMDDAEVTAA DTDR.RATQGE .LKRDHPCLQA TLPPDVLVIH QSKYKCGMKN KbNKHSKRALL VCQ

RKPSDGAHLA

DMEDDSLYLG

LPLSSRRPAA

MQAHI TRALH

KDTTLIHQIF

GENAYHCGVC

SQQNTGPLVY,

YVLFYIQKSE.

ATQESTLDHW

NLSSSTPTHQ

Nucleotide sequence for hDUB8. 1 atgggggacgctcactctacttgggaggtgagtggcagttcaaccacttttcaaaactcacatcttctcggcca gatgcagcttttgctgaaatccagcggacttctctc~Ctgagaagtcaccactctcatctgagacccgtgtcgac ctttagttgtcggcaa~cccccaga'igtcttatga'aac gctgcggtgggggctgggctccagaatatgggaaatacctgctacgagaacgcttccctgcagtgcctgacatac acactgcccct tgccaactacatgctgtcccgggagcactctcaaacatgtcagcgtcccaagtgctgcatgctc tgattcaccctaaggctccgctgctta~accccgctgc gcgctctggcacgagttctatttagtattgtcagaagc tgctcgcaagagaactatcagccactacacatttggcg tgaaccataggccatcaggttaaattgcctctgctgct gaacagaccgggcacactgacatgtg accagatatggga gcctatcattgcggtcttgtctccagagggcgccggcctccaacacgttaactttacacacttctgccaaggtc ctcatcct tgtcttgaagagattctccgatgtcgcaggcaacaaacttgccaagaatgtgcaatatcctgagtgc ctgaagacaaagccgaaccggcttgcagctttcggtgca gcgggatgccagaatcttcagcagtagatcggttaaga gatgccgaggtcactgtctgtagcatcatttctgtcctgagtcaacaggcctatgtcctcttttacatccagaag aggaggagccggggggcaag~gga~aggctgccgaaaaa aggcgagcaaagcaaggagagctcaagagagaccacccctgcctccaggcacccgagttggacgagcacttggtg gaaacatagagact~catgatctcaacaaaacagcggt aacgtcggaaaagtcgaaggtaccctgcctcccaacgcactgtgattcatcaatcaaaatacaagtgtgggatg aaacactcgaacagtctcaaccctgcacgaaacgatct aaatgaatgtccgagggacgaacaagagaaaaacaagc ctgcttgtgtgccagtga bDUB8.1 deduced polypeptide sequence MGDDSLYLGGEWQFNHFS KITSSRPDAAFAE IQRTSLPEKSPLS SETRVDLCDDLAPVARQLAPREKLPLS

SRRP

AAVGAGLQNMGNTCYENASLQCLTTLPLAYMLSREHSQTCQRPKCCMLCTMQLITWALHSPGHVIQPSQALA

AGFHRGKQEDVHEFLMFTVDMKKACLPGHKQHCTTLIHQI FGGCWRSQ IKCLHCHGISDTFDPYLD lAL D IQAAQSVKQALEQLVKPEELNGENAYHCGLCLQPAPASNTLTLHTSAVL I LVLKRFSDVAGNKLAKNVQYPEC LDMPYMSQQNTGPLVYVLYAVLHAGWSCHDGHYFSYVQEVQWYDAVVCSII SVLSQQAYVLFY IQK

SEEHEVRRPAGETRAQEKDPCQPLELE-TETDWFQQKKE

NVGKVEGTLPPNALVIHQS KYKCGMKNHIPEQQSSLLNLS S TTRTDOESMNTGTLASLQGRTRRAKGKNKHS

KRA

LLVCQ

Nucleotide sequence for HDUB8.3 aougnbee apiqdadA~od paoupop S-8916H 6- -6-55vlqvL-s LL 'ln el6 1 l6V 6 oq0Drses s v~oIOe oq e qo SIs oL06eo40 -40Cto-LBse -0~esl SLlov06 ~0 ;1 ot S q a o z eb s S 0T n ozAii-xHi~cxuid)rsrjEiwa(lNl~Ir'S 00dHXD~)XOIq~dl~lUNaXINaqx~qLaz~aq2qd~~~u o qa~vuisoviaDS~S'aaXI~rPXO~ISESVLa~aXxO~O~AsX 003dM{&XW~)X7 ~00 0 00 -67-, 00 MEDDSLYLGGEWQFNFSKLTSSRPDAAFAE IQRTSLPEKSPLSSEARVDLCDDLAPVARQLAPRKKLPLS

SRRP

AAVGAGLQNMGTCYENASLQCLTYTPPLANYMLSREHSQTCQRPKCCMLCTQHITWALHSPGHVIQPSQALA

SAGFHRGKQEDAH-EFLMFTvDAmKKACLPGHK(QVDHHSKDTTLINQI FGGC WRSQI KCLI4CHG ISDTFDPYLDIAL ;ZDI QAAQSVKQALEQLVKPEELNGENAYBCGLCLQRAPVS KTLTLHTFAKER ILETQRPWVVTRHKLAKSVQYAES LDMQPYMSQQNTGPLVYVLYAVLV1{AGWSCHDGHYFSYVKAQEGQWYKMDDKTACS ITS VLSQQAYVLFYIQK ZtSEWERHS ESVSRGREPRALGAEDTDRRATQGELKRDHPCLQAPELDERLVERATQESTLDHWRFPQEQNKTKPEF SNVRKVEGTLP PNVLVIHQS KYKCGMKNHJ-PEQQS SLLNLS STTRTDQES VNTGTLAS LQGRTRRS KGKNIiS KRA

LLVCQ

N'ucleotide sequence for HDUB8.6 00 Atggaagacgaccactctatttgggaggtgactgcagttcaatcacttttcaaaactcacatcttctcggcta gagacttcgatcg gctttttaagccacccttaacgtca SctctgtgatgattggctcctgtggcaagacagcttctcccaggagaaGcttcctctgagtagcaggagacct gcggtggcggtcgagtgaaacttttacgtccgatctaaa SgctggcttccatagaggtgagcaggaggatgcccatgaatttCtcatgttTactgtggatgccatgaaaaaggca tgctcggaa~cgtgtacatcagccaccctccaatttggga Tggagatctcaaatcaagtatctccactgccacggcatttcagacacctttgacccttacctggacatcgccctg gaacagaccgggc~cactgacgtggaccagatatggga gcctatcattgtggtct ttgtctccagaaggc-gcct'4cctccaagacgttAactttacccacttctgccaaggtc ctattgataggtccgttaagacactcagaggattcagg Cggctcgctctttacgaaagcttgcagctttcggtgca gctgggtggagttgtcacaacggacAttacttctcttatgtdaaagdtcaagaaggccagtggtataaaatggat gagcagccgccgctaccgctatacgctttccttctcga aggaggagccggggg~caagagacaggctgtcgaaaaa Agcacagagaaccaaa~ccct'ctcgtccatgaggatgt gaaacatagagac~gcatgatcccaacaaaacagcggt aagcgaatgagactctcactcttatacacaaaagggtt aaacactcgaacagtctcaaccctgcaacaaacgatct Aaatgaatgtccgagggacgaacaagataaaaacaaac ctgcttgtgtgccagtga HDUB8.6 deduced polypeptidef'sequence MEDDSLYLGGDW4QFNHFS KLTSSRLDAAFAEIQRTSLS EKS PLSSETRFDLCDDLAPVAROLAPREKLPLS

SRRP

AAVGAGQKINTFYVSLQCLTYTLPLSNYMLSREDSQTCHLHKCCMFCTMQITWLYRPGVI

QPSQVLA

AGFHiRGEQEDAHEFLMFTVDAM~KACLPGHKQLDHHSDTTLIEQI FGAYWRSQI KYLHCBGI SDTFDPYLDIAL DIQAAQSVKQAIJEQLVKPKELNGENAYHCGLCLQKAPAS KTLTLPTSAKVL ILVTJKRFSDVTGNKLAKNIVQYPKC RDMPYMSQQNTGPLVVLYAVLVAGWSCHNGHYFSYVAQEGWYDDAVTASGI TSVLSQQAYVLFY IQK SEWERMS ESVSRGREPRLGAEDTDRPATGELKRDHPCLQVPELDEHLVETQESTLDKPQKQNTKEF NVRKVEGTLPPNVLVIHQSKYKCGMKNHHPEQQS SLLN'LS STKPTDQESMNTGTLASLQGSTRRSKGNNHSKRS

LLVCQ

Nucleotide sequence for HDUB8.7 Atggagccccatgggtatgatcaccttaacccttccgc gagacttcgatcg~atcccctaagc6ccccttagcggca ctttagttgtcggcaaactcccgagactccggacgaac gcggtggcggtcgaaggatctcaggagtccgatctaaa Accgcctcacaag~~ccga'accciaagcggccatcgagt tgattc gtaacct gctccgcfgctEacaccccgctgc gcg~tctggcacgagtcc~atttagtdttgtcagaagc tgccttcccggccacaagcaggtagatcatcactctaaggacaccAccctcatccaccaaatatttggaggctgc Tgaaccataggccatcaggttcgcdttactacgaaccct gaaccgcgtaattag-actgaiatgtag~cagatatggga gcctatcattgcggtctttgtctccagagggcgcca9cctccaagakcgt tAactttacacacttctgccaaggtc ctactgctaggtccgttaagacactcagaggattcggg 00 aggaggagccgtaattgcaagag acaacccggctgaagacacagac Agcacagagaaccaaaaccccgccagacggtgagggtgt gaaacatagagac~gcatggatccagacaaaacagcggt aagcgaatgagactctcactcttatacaacaaaaggggt aaacactcgaacagtctcaaccctgcacgaaacgatct aaatgactgtccgagggacgaacaagagaaaaacaagc 00 10 ctgcttgtgtgccagtga HD1Th8.7 deduced polypeptide sequence 00 15 MEDDSLYLGGEWQFNJFSKLTSSRPDAAFAEIQRTSLPEKS PLS SEARVDLCDDLA.PVARQLAPRKKLPLSSRRP AAVGAGLQNMGNTCYEASLQCLTYTPPLANYMLSRESQTQRPKCCMLCTMQHITWAHS

PGHVIQPSQALA

AGFHRGKQEDAlEFLMFTVKKACLPGHKQHSKTTLIHQI FGGCWRSQI KCLHCHGI SDTFDPYLD IAL DIcQVQLQVKE-GNYCLCQAAKLLTSKLL

RSVTNLKVYE

LDMQPYMSQQNTGPLVYVLYAVLVHAGWSCHDGHYFSKAQEGQWYDTACS

ITSVLSQQAYVLFYIQK

SEWRSSSGER

GETRRTGLRHCQPLELERTETDWFQQKKE

NVRKVEGTLPPNVLVIHQS KYKCGMKNHHPEQQS SLLNLS STTRTDQESVNTGTLASLQGRTRRSKGKt'1KHS

KRA

LLVCQ

Nucleotide sequence for HDUB8.8 Atgaagccccatgggtatgcgtatattcaacccttccgt gagacttcgatcg~atcccctaagccccccttaacgtca ctttagttgtcggc gcgtgcccgggactccggac~aac gcggtggcggtcgaaagatctcaggagtccgatctaaa Accgcctcacaagttcgggattaaggcttccatcgagt tgattcaccctaa~gcttcgctgcttacaccccgttgc gcgctctggtacgagtcctatttagtattgtcagaagc tgctcggaagacaactatcagccactacacatttggga Tggagatctcaaatcaagtatctccactgccacgcatttcagacacctttgacccttacctggacatcgccctg gatatccaggcagctcagagtgtcaAgcaagctttggaacagttggtgaacccaaagaactaatggagagaat gcctatcat tgtggtctttgt ctccagaaggcgcctgcctccaagacgttAactttacccacttctgccaaggtc ctattgataggtccgttaagacactcagaggattcagg Cgtgacatgcagccatacatgtctcagcagaacacaggacctcttgtctatgtcctctatgctgtgctggtccac ggggtggagttgtcacaacggacAttacttctctattcaaagctcaagaagccatgtataaaatggat gatgccgaggtcactgcctctggcatcacctctgtcctgagtcaacaggcCtatgtcctctttacatccagaag agtgaatgggaaagacacagtgagagtgtgtcaagaggcagggaae caagagcccttggtgctgaagacagac Aggccagcaacgcaaggagagctcaagagagaccaccttgcctccaggtacccgagttggacgagcacttggtg gaaagagccactcaggaaagcacctTagaccactggaaattcccccaaaagcaaaacaaaacgaagcctgagttc aagcgaatgagactqtcac~ctggtc~ataat agggtt aaaaaccatcatcctgaacagcaaagctccgtgctaaacctctcttcgacgaaaccgacagatcaggagtccatg aaatgaatgtccgagggacgaacaagataaaaacaaac ctgcttgtgtgccagtga s0 HDTB8.8 deduced polypeptide sequence.

mEDDSLYLGGDWQFNHFSKLTS SRLDAA.FAEIQRTSLSEKS PLS SETRFDLCDDLAPVARQLAPR.EKLPLSSRRP AAVGAGLQKIGNTFYVNVS LQCLTYTLPLSNYMLSREDSQTCHLEKCCMFCTMQAN ITWALYRPGHVIQ PSQVLA AGFHRGEQEDAHEFLMFTVDAMKKACLPGHKQLDHHS KDTTLIHQI FGAYWRSQI KYLHCMG ISDTFDPYLD IAL D IQAAQS VKQALEQLVKPKELNGENAYHCGLCLQKAPAS

KTLTLPTSAKVLILVLKRSDVTGNKLAKN.VQYPKC-

RDMQPYMSQQNTGPLVYVLYAVLVAGWSCHN.GHYFSYfVKAQEGQWYKMDDAEVTASGI

TSVLSQQAYVLFYIQK

SSWERHS ESVSRGREPRA-LGAEDTlRPATQGELKRlHPCLQVPELDEHLVERATQESTLDHWKFPQKQNKTKPEF NVRKVEGTLPPNVLVIHQS KYKCGMKNHHPEQQS SVLNLSSTKPTDQESMNTGTLASLQGSTRRSKGNNKHGS

KRS

LLVCQ

-69- 00

;Z

00 Nucleotide sequence for HDUB8.11 Atggagccccatgggtatgatcaccttaacccttccgc gagacttcgatcg~atccccggataacccataacggca tttcagttgccgg'agcgt~cccgggactccggacgaac gcggtggcggtcgaaggatctcaggagtccgatttaaa Atcgcc'gc'caa c tcgggattaaagctgccatcgagt tgactg~gtaacctgcccaatctgcttacaccccgctgc gcgctctggcagag'iagtcctatttagtattgtcagAagc tgctcggaagaactac:cttgaggtccgttaagacaatc Aaattcaactatctgctcgctctttacgaaagcttgca gtccagttcgtccgcgtggttaacgaatctttagcagtcaa gagcatgaaatgtagcaagggaggagccggggggcaag aggacaacccggtagccgcgcacagagaaccaaaatcc Tgccagacggtgcacctggaaacatagagactgcatga ttccaggaacaag~ctatcagcgaatgagactctcact cttgtgattctataatcattggtaaactac~aaacagtctcaa Ctttcagacgcgtaggcagaatgaatgtccgagggacg agatccaaagggaagaacaaacactgcaagagggctctgcttgtgtgccagtga HDUBB.ll deduced polypeptide sequence MEDDSLYLGGEWQFNHFSKLTSSRPDAAFAE IQRTSLPEKSQLSTETRVDFCDDLAAVARQTLAPRELPLS

SRRP

AAVGAGLQNMGNTCYVNASQQCLTYI PPLANYMLR9SQTCHRHKCCMLCTMEAHITPLHIPGIQPSQL

AGHGQALFMTDMKCPHQLLWRSVGKANQPCDQYSQTPV

VLYAVLVHAGWSCHNGHYFSYVKVQEGQWYKMDDAEKS

EWERHSESVSRGREPRALGAEDTDRPATQGELKRDYP

CLQVPELDEHLVERATQESTLDHWKFLQEQNKTKPEFRKEGT.LPPNVLVIHQS

KYKCGMKNI{NPEQQSSLLN

LSSTNPTDQESMNTGTLASLQGRTRRSKGKNKHCR.-LVCQ.

Nucleotide sequence for HDUB4 .4 sequence atggaggagg acatcttctc tcaccactct cagcttgctc gggctccaga acaccgcccc aagggctgca cacgtcatcc gcccatgaat aagcaggtag tggagatctc ctggacatcg gtgaagcccg gcgccggCCt aagagattct cttgacatgc gctgtgctgg.

gctcaagaag atctgtcctg acacagtgag caggcgagta gg acg ag ca~c tcaagagcaa t cccga cgt a tgaacagcaa actcactcta cttgggtggt 9 ggctcgatgc agcttttgct g catgtgagac ccgtgtcgac ccagggagaa gcttcctctg a atatgggaaa tacctgctac Ittgccaacta catgctgtcc

C

tgctctgtac tatgcaagct C agccctcaca ggcattggct ttctcatgtt cactgtggat atcaccctc taaggacacc aaatcaagtg tctccactgcc ccctggatat ccaggcagctc aagaactcaa tggagagaat ccaaqacgtt aactttacac ~agtggcagt tcaaccactt -ttcaaaactc ~aaatccagc ggacttctct ccctgagaag ctctgtgatg atttggttCC, .tgaggcaaga igtagcagga gacctgctgc ggtgggggct gtgfaacgctt ;ccttgcagtg cctgacatac.

:ggagcact ctcaaacgtg tcatcgtcac :acatcacac gggccctcca caatcctggc gctggcttcc .atagaggcaa gcaggaagat 3ccatgaaaa aggcatgcct tcccgggcaC accctcatct accaaatatt tggaggctac ~acggcattt cagacacttt tgacccttac :agagtgtcc agcaagcttt ggaacagttg ycctatcatt. gtggtgtttg.,ctccagagg icttctgcca aggtcctcat ccttgtattg a t a a t

C

ccgatgtcac aggcaacaag attgccaaga atgtgcaata tcctgagtgC gccatacat gtctcagcag aacacaggac ctcttgtcta tgtcctctat ccatgctgg gtggagttgt cacaacggac. attac.tt~c. ttatgt~caaa ccagtggta taaaatggat gatgccgagg .tcaccgcctc ttagc.atcac, gtcaacagq. cctacgtcct cttttacatc. cagaagagtg aatgggaaag agtgtgtcaa gaggcaggga accaagagcc cttggcgcag aagacacaga Lcgcaaggag agctcaagag agaccacccc. tgactccagg cccccgagtt ~tggtggaaa gagccactca ggaaagcacc ttagaccact ggaaattcct Lacaaaacga agcctgagtt caacgtcaga aaagtcgaag gtaccctgcc :ttgtgattc atcaatcaaa atacaagtgt gggatgaaga accatcatcc agctccctgc taaacctctc ttcgacgacc ccgacacatc'agcagtccat 00 00 00 00i gaacaatggc acactcgctt ccctgcgagg gagggccagg agatccaaag ggaagaacaa acacagcaag agggctctgc ttgtgtgcca gtga hfltB4 .4 Deduced polypeptide sequence

MEEDSLYLGG

QLAPREKLPL

KGCMLCTMQA

KQVDHPSKDT

VKPEELNGEN

LDMQPYMSQQ

EWQFN}!FSKL TSSR-LDAAFA EIQRTSLPEK SPLSCETRVD

LCDDLVPEAR.

SSRRPAAVGA GLQNNGNTCY VNASLQCLTY TPPLANYMLS

REHSQTCHRH

HITRALHNlPG HVIQPSQALA AGFH-RGKQED AHEFLMFTVDANKKACLPGH TLIHQIFGGY WRSQIKCLHCHGISDTFDPY LDIALDIQAA

QSVQQALEQL

AYHCGVCLQR APASKTLTLH TSAKVLI LVL KRFSDVTGN~K IAKNVQYPEC NTGPLVYVLY AVLVHAGWSC HNGHYFSYVK AQEGQWYKND

DAEVTAS

Nucleotide sequence for 1IDUB4 9* atggaggacg acatctcctc: tcaccactct .0 cagcttgCtc: gggctccaga acaccgccc aagggctgca cacgtcatcc gcccatgaat aagcaggtgg tggagatctc ctggacatcg gtgaagccg gcgccggcct aagagattct cttgacatgc gctgtgctgg gctcaagaag tctgtcctga cacagtgaga actcactcta cttgggaggt gagtggcagt tcaaccactt ttcaaaactc: ggcccgatgcagcttttgct gaaatccagc ggacttctct ccctgagaag catgtgagAc ccgtgtcgac Ictctgtgatt atttggctcctgtggcaaga ccagggagaa gcttcct'ctg agtagcagga gacctgctg*c: ggtgggggct atatgggaaa tacctgctac gtgaacgctt ccttgcagtg cctgacatac: ttgccaacta catgctgtcc cgggagcact ctcaaacgtg tcatcgtcac tgctctgtac tatgcaagct cacatcacac gggccctcca caatcctggc agccctcaca ggcattggct gctggcttcc: atagaggcaa gcaggaagat ttctcatgtt cactgtggat gccatgaaaa aggcatgcct tcccgggcac: atcatcactc taaggacacc accctcatcc accaaatatt tggaggctac aaatcaagtg tdtcdActgc cacggcattt cagacacttt..tgacccttac ccctggatat ccaggcagct cagagtgtcc agcaagC-ttt ggaacagt~tg aa6'aactcaa tggagagaat* gcctatcatt gtggtgtttg tctccagagg ccaagacgtt aactttacac acctctgcca aggtcctcat ccttgtattg.

ccgatgtcac: aggcaacaag -attgccaaga atgtgcaata..tcctgagtgc agccatacat gtctcagcag aacacaggac ctcttgtcta tgtcctctat tccacgctgg gtggagttgt cacaacggac attacttctc ttatgtcaaa gccagtggta taaaattgat gatgccgagg.-tcaccgcctc-tagcatcalCt ctcaacaggc: ctacgtcctc ttttacatcc agaagagtga atgggaaaga gtgtgtcaag aggcagggaa ccaagagccc -ttggctctga agactaa hDUB4 .9 deduced polypeptide sequence.

MEDDSLYLGG

QLAPREKLPL

KGCMLCTMQA

KQVDHfHS1QDT

VKPEELNGEN

LDMQPYMSQQ

SVLTQQAYVL

EWQFNHFSKL TS PRPDAAFA EIQRTSLPEK S PLSCETRVD LCDYLAPVAR SSRRPAAVGA GLQNMGNTCY VNASLQCLTY TPPLANYMLS

REHSQTCHRH

HITRALNNPG HVIQPSQALA AGFHRGKQED AREFLMFTVD ANKKACLPGH.

TLIHQIFGGY WRSQIKCLHC-HGISDTFDPY LDIALDIQAA QSVQQAJJEQL.

AYHCGVCLQR APASKTLTLH-TSAKVLILVL KRFSDVTGNK

IAKNVQYPEC.

NTGPLVYVLY AVINHAGWSC 1{NGHYFSYVK AQEGQWYKID

DAEVTASSIT

FYIQKSEWER- HSESVSRGRE 'PRALGSED Nucleotide sequence for hIUE B8,.2 sequence atgcggccag *agagcccgtc atttgaagac tcggaagaga tagcgtcttt ctgcaacctg cggtcccagc cgaaaaacct tgtgatcctt'gttccgggcg Acatggagga cgactcactc tacttgggag gtgagtggca gt tcaaccac ttttcaaaac: tcacatcttc tcggccagat gcagcttttg ctgaaatcca gcggActtct 'ctctctgaga agtcatcact ctcatctgag acccgcgtcg' acctctgtga tgatttggct cctgtggcaa gacAgctcgc tcccagggag aagcttcctc t .gagtagca g gagacctgct-gcggtggggg ctgggctcca gaatatggga..

aatacct9ct acgtgaacgc ttccctgcag tgcctgacat &cacatcgcc ccttgccaac-* tacatgctgt cccgg gagcia ctctcaaacg tgtcatcgtc 'acaagtgctg catgctctgt actatgcaag'Ctcacatcac atggccccti7 cacagtcctg gccatgtcat ccagccctca caggtgttgg, ctgct9gCtt ccEatagaggc gagcaggaag,- atgcccatga atttctcatg.

00

;Z

00 ttcactgtgg tctaaggaca tgtttccact atccaggcag aatggataaa ttaactttac acaggcaaca atgtctcagc gggtggagt ataaaatgga cctatgtcct taggcaggga tcatgaataa ttiaaccaat gtgtaaccat tttcagaatc ctcttcactc aagaattccc gattgcccct atgccatgaa aaaggcattc cttcccgggc acaagcattt agataatcac ccaccctcat ccaccaaata tttggagggt actggagatc tcacatcaac gccacgggat ttcagacacc tttgaccctt acctggacat cgccctggat ctcagagtgt caagcaagct ttgtaacagt tgg.tgaagcc cgaagaactc atgcctatca ttgtggtctt tg.tctccaga 'aggcgcctgc ctccaggacg acacttctgc caaggtcctc atccttgtat tgaagagatt ctctgaggtc aacttgccaa gaatgtgcaa tatcctgagt gccttgac -at gqagccatac agaacacagg acctcttgtc tatgtcctct atgctgtgct ggtccacgct gtcacaacgg acattactta tcttatgtca aactcaagaa ggccattggt tgatgccgag gtcactgcct ccggtat~cac ttctgtcctg agtcaacagg cttttacatc cagaagaatg aatttggaag acccagttac agtgtgtcca accaagagct ctttgcgtga aggcaagtga attgtgtgtg aaataaaatg atcttgcagt ggagtattta tttgtctcac tttgtaatca gtgaatgagc atcaatgcct agtgcctacc ccccagagat aagaactcc actctcttat ggcctctgga ttgcttatga ctctgaagat aattctcctt tcccccaacg acttcaggtg gtggtaacag ataacacatc ag tccctttc tctctctttt aggaaaactc tcactgagac aa aggaaaat cctatggttt actggggagg tcaggagtga aattggtggc tccttcctcc ctgtcaagtc ccttcctcag ttgtctcfltc aggaict hDtJB8.2 dedeuced polypeptide sequence MRPES PS FED AAFAE IQRTS

NTCYVNASLQ

QVLAAG FHRG

CFHCHGISDT

SEEIASFCNL RSQPKNLVIL VPGDMEDDSL YLGGEWQFNH FSKLTSSRPD LSEKSSLSSE TRVDLCDDLA PVARQLAPRE KLPLSSRRPA AVGAGLQNNG CLTYTPPLAN YMLSREHSQT CHRHKCCMLC TMQAHITWPL HSPGHVIQPS EQEDAHEFLM FTVDANKKAF LPGHKH-LDNH SKDTTLIHQI FGGYWRSHIN FDPYLDIALD IQAAQSVKQA L Nucleotide sequence for hDuB 8.9 atggaggaag acatcttctc tcaccactct cagcttgctc ggtctccaga acaccgcccc aagtgctgca ccatgtcatc tgcccatgaa caagcagcta ctagagatct cctggatatc ggtgaagccc ggcgcctgcc gaagagattC cgttgacatg tgctgttctc actcaagaag tctccttaga cccagt taca attgtggtga taatcagtga acttccagtt CcctgtCCC actcactcta cttgggaggt. gagtggcagt tcaaccactt. ttcaaaactc agccagatgc agcttttCct gaaatccagc ggacttctct ccctgagaag catcggagac ccgtgtcgac ctctgtgacg atttggctcc tgtgacaaga ccagggagaa gcttcctccg agtagcagga gacctgctgc ggtgggagct atatgggaaa tacctgccac ttgaatgctt ccctgcagtg cctgacatac ttgccaacta catgctgtcc tgggagctct ctcaaatgtg tcatcgtCCC tgctctgtat tatggaagct cacagcacac gggcacctcc accgtcctgg cagccctcac aggcattggc tgctgacttc catagagaca agcaggaaga tttctcatat tcactgtgga tgccattaga aaggcatgcc ttcccgggca gatcatcact gcaaggacac catcctcatc caccaaatat ttggagggta caaatcaagt gtctctactt ccacggcatt tcagacacct tcgaccctta gccctggata tccaggcagc tcagagtgtc aagcaagctt tggaacagtt gaagaactca atggagagaa tgcctatcat tgtggtcttt gtctccagaa gccaagacgt taactttacc cacttctgcc aaggtcctca tccttgtctt tccgatgtca caggcaacaa acttgccaag aatctgcaat. atcctgagtg cagccataca tgtctcagca gaacacagga cctcttttct atgtcctcta gtcatcaccg ggtggagttg tcacaacgga cattacttct cttgtgtcaa gccagtggta taaaatggat gatgccgagg tcactgcctc tggtatcact gtcaacaggc ctatgtcctc ttttacatcc agaagaatga. atttggaaga.

gggtgtccgc aggcagagaa ccaagagctc tttgtgctga agacaattga aataatatgt catgaataaa tcttgcagca gatttatttg tctcactttg atgagcttta acgaatatca atgcctagtg cctacccccc agagataaga tctcatgtgt aatcatggca tctggattgc tcatgattct. gaagataatt ccaaagtttc agaatcactt caggtggtag aaacagataa cacatcagtc.

cctttctctc tcttttctct tca hDUB8.9 Deduced polypeptide sequence MEDDS LYLGG

QLAPREKLPL

KCCMLCTMQA

KHLDNHSKDT

EWQFNHFSKL-TSSRPDAAFA

SSRRpAAVGA GLQNNGNTCY HIT.WPLHSPG HVIQPSQVI.A TLiHQIFGGY .WRSHINCFHC EIQRTSLSEK SSLSSETRVD LCDDLAPVAR VNASLQCLTY TPPLANYMLS REHSQTCHRH,.

AGFHRGEQED AHEFLMFTVD) ANKKAFLPGH HGISDT-FDPY LDIALDIQAA QSVKQALEQL VKPEELNG Nucleotide sequence for hDuB 8 00 00 atggaggacg acatcttctc tcatcactct cagctcgctc gggctccaga acaccgcccc aagtgctgca catgtcatCC gcccatgaat aagcatttag tggagatctc 0 ctggacatcg gtgaagcccg gcgcctacct aagagattct cttgacatgc gctgtgctgg ctcaagaagg ctgtcctgag ccagttacag tgtgtgtgaa o tgtaatcagt gaacttccac ttctcctttC tccctttctc tatggtttac 3 gtcaagtctc agatgccccc actcactcta cttgggaggt gagtggcagt tcaaccactt ttcaaaactc ggccagatgc agcttttgct gaaatccagc ggacttctct ctctgagaag catctgagac ccgcgtcgac ctctgtgatg atttggctcc tgtggcaaga ccagggagaa gcttcctctg agtagcagga gacctgctgc ggtgggggct .atatgggaaa tacctgctac gtgaacgctt ccctgcagtg cctgacatac ttgccaacta catgctgtcc cgggagcact ctcaaacgtg tcatcgtcac tgctctgtac tatgcaagct cacatcacat ggcccdtcca cagtcctggc agccttcaca ggtgttggct gctggcttcc atagaggcga gcaggaagat ttctcatgtt cact gtggat gccatgaaaa aagdattcct tcccgggcac ataatcactc taaggac-acc adcctcatcc accaaatatt tggagggtac acatcaactg tttccactgc catgggattt cagacacctt tgacccttac ccctggatat ccaggcagct cagagtgtca agcaagcttt ggaacagttg aagaactcaa tggataaaat gcctatcatt gtggtctttg tctccagaag ccaggacgtt aactttacac acttctgcc4 aggtcctcat ccttgtattg ctgatgtcac aggcaacaaa cttgccaaga atgtgcaata tcctgagtgc agccatacat gtctcagcag aacacaggac ctcttgtcta tgtcctctat tccacgctgg gtg gagttgt cacaacggac attacttatc ttatgtcaaa ccattggtat aaaatggatg atgccgaggt cactgcctcc ggtatcactt tcaacaggcc tatgtcctct tttacatcca gaagaatgaa tttggaagac tgtgtccata ggcagggaac cgagagctct ttgcgtgaag gcaagtgaat ataaaatgtc atgaataaat cttgcagtgg agtatttatt tgtctcactt gaatgagctt taaccaatat caatgcctag tgcctacccc ccagagataa tctcttatgt gtaaccatgg cctctggatt gcttatgact ctgaagataa ccccaacgtt tcagaatcac ttcaggtggt ggtaacagat aacacatcag tctcttttct cttcactcag gaaaactctc actgagacaa aggaaaatcc tggggaggaa gaattccctc aggagtgaaa ttggtggctc cttcctccct ttcctcagga ttgccccttt gtctcttcag gactctgctc atcaggccg tggttgtgca tacctggcct gtgaagaaat a hDUB*. 10 Deduced polypeptide sequence

MEEDSLYLGG

QLAPREKLPP

KCCMLCIMEA

EWQFNHFSKL TSSQPDAAFP EIQRTSLPEK SPLSSETRVD LCDDLAPVTR SSRRPAAVGA GLQNNGNTCH LNASLQCLTY TPPLANYMLS WELSQMCHRP H4STRAPPPSW PCNPALTGIG C Table 24. Deduced aAmino acid alignent of hDUB4.10 and hDUB4.I.1..

hDUB4 .10 MCIRTGSPCDVCENYSVMSMTGRQLIDWAPLKIGYEHSSTPMPREHVHFRQHYNFGTKCA hDUB4 .11 MCIRTGSPCDVCENYSVMSMTGRQLIDWA-PLKIGYEHSSTPMPRT-LYIRHRK-------- 52 hDUB4 .10 NCNSTIQCVTGNGGNIADPERSMRESRICTAYFGLFPLKQGPVLKMVISLGQRINRLNVE 120 TRE 66 hDUB4 .10 RLSLEGKKIRCAKYYTSLTILRSESALSTSCPSVAERMAAAKRIASFCNLRSQQKNLVI 180.

hDUB4 .11 RNGAKGKKIRCAKYYTSLTILRSESALSSSCPSVAERM.AAAl 109 hDUB4 .10 LVPVDMEDDSLYLGGEWQFNHFS1K-JSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDL 240.- 00

;Z

00 hDTJB4.11 -IDMEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLS--------- YDL 158 hDUS4.10 AP**ARKPSRPAVALNGTYNSQL.YTLNMSES 0 hDUB4.10 APVARQLAPREKLPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYTTPLANYMLSREHSQ 300 hDUB4. 10 TCRKCLTQHTAHPHIPSAAGHGQDHFMTDMK 360 hDIB4 11 TCHRHKGCMLCTMQAHITRALHNPGHVI QPSQALAAGFHRGKQEDAHiEFLMFTVDANKKA 278 hDUB4 .10 CLPGHKQVDHHSKDTT.LIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQ 420 hDUB4. 11 CLPRHKQVDHHSKDTTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVQQ 338 hDUB4 .10 ALQVPENEAHGCQAPSTTHSKLLLRSVGKAN 480 hDUB4 .11 ALQVPENFNYCVtRPSTTHSKLLLRSVGKAN 398 hDUB4. 10 QYPECLDMQPYMSQQN TGPLVYVLYAVLVHAGWSCHNGHYFSYTKAQEGQWYKMDDAEVT 540 hDUB4 .11 QYPECLDMQPYMSQQNTTGPLVYVLYAVLVHAEWSCNGHYFSYVKQEGQWYKMDDA.EVT 458 hDUB4 .10 AAISLQAVFIKEEHEVRRPAGETRATGLRHC 600 hDU4 12. AASITSV SQQAYVLFYIQKSEWERHSESVSRGREPRALGAEDTDRRATQGELKRDHPCL 518 hDt3B4 .10,QAPELDEHLVER-ATQESTLPDHWKFLQEQNKTKPEFNVRKVEGTLPPDVLVIHQS KYKCGM 660 hDUB4. 11 QAPELDPEHLVERAT QESTLDHWKFLQEQ14KTKP IEFNVRKVKGTLPPD'JLVIHQSKYKCGM 578 hDUB4 .10 KNHHPEQQS SLLNLSS STPTHQESMNTGTLASLRGRARRSKGKNKHSKRALLVCQ 715 hDUB4 .11 KNHEQSLLSTTQSNGTALGARK~4HKALC 632 Table 25. Nucleotide sequence alignment of hDIJB4.5, hDUTB4.8 and hDUB8.2 in frame termnination codons in hDUB8.2 are underlined hDIJB4.5 hDUB4 8 hDUB8. .2 hDUB4.5 hDUB4 .8 hDUB8 .2 hDUB4.5 hDUB4 8 hDUB8 .2 hDUB4.5 hDUB4 .8 hDUB. .2 hDUB4.5 hDUB4 .8 hDUB8. .2 A TGCG- CCAGAGAGCTCGTCATTTG AGACTCT CTCGGAAGGGATAGCGTCTTTCTGCA 59 ATGCG -CCAGAGAGCTCGTCATTTGAAGACTCTCTCGGAAGGGATAGCGTCTTGCTGCA 59 ATGCGGCCAGAGAGCCCGTCATT.TGAAGA CTCGGAAGAGATAGCGTCTTTCTGCA 56 CCTGCGGTCCCAGCA GAAAACCTTGTGATCCTTGTTC C ACGACATGAGGAAGACTC 119 ACTGCGGTCCCAGCAGAAAACCTTGTGATCCTTGTTCCAGTCGATGACGACTC 119 CCTGCGGTCCCAGCCGAAAAACCTTGTGATCCTTGTTCCGGGCGACATGGAGGACGACTC 116 17 ACTCTACTTGGGAGGTGAGTGGCAGTTCAACCACTTTCAACTCACTCTTCCCC 179 ACTCTACTTGGGAGGTGAGTGGCAGTTCACCACTTTTCAACTCACATCTTCCGGCC 179 CATCACTTGATGAGATGCAGGG CACTT TCTAAAGCTCACATTCG 176 CGATGCAGCTTTTGCTGAATCCAGCGGACTCTCTCCCTGAGAGTCACCCTCTCATG 239 AGTGACTTCGATCGGATCCCCGGATACCCCT 236 TGAGACCCGTGTCGACCT:CTGTGATGATTTGGCTCCTGTGGCAAGACAGCTTGCTCCCAG 299 TGAGACCCGTGTCGACCTCTGTGATGATTTGGCTCCTGTGGCAAGACAGCTTGCTCCCAG 299 TGAGACCCGCGTCGACTTGTGATGATTTGGCTCTGGGCAAGACAGCTCGCTCCCAG 296 00 GGACTCCGGACGAACGtCGGGGTGCCAAAA 359 ;Z DtJB4 .8 GGAGAAGCTTCCTCTGTAGCAGGAGACCTGCTGCGG T GGGGCTGGGCTCCAGAAA 356 hDUB8 .2 hDU4. GGAATACTC*CGTA**CTCTTGAGG*TG**TCAACG*CC*GC41 hDUB4. 5 GGGAAATACCTGCTACGTGAACGCTTCCTTGCAGTGCCTGACATACACACCGCCCCTG 419 hDUB4. 8 GGGAAATACCTGCTACGTGAACGCTTCCTTGCAGTGCCTGACATACACACCGCCTG 419 00) hDUB4 SCACTACATGCTGTCCC GGGAGCACTCTCACGTGTCATCGTCGGGCTGC-TC 479 hDUB4 .8 CAACTACATGCTGTCCCGGGAGCACTCTACGTGTCACTCAGGCTGCAGT 7 hDUB8.2 CAACTA CATCTTCCCGGGAGCACT CTCGTGTCATC GTCACAGTGCTGCTT 476 00 hDUB4 CTGTACGATGCAAGCTCACATACCGGGCCCTCCACATCCTGGCCACGTCACAC 539 hDUB4. 8 CTTCAGAGTAACCCGCCTCCACTGCCTACAC S39 C1 hDJB 8.2 CTGTACTATGCAAGCTCACATCACATGCCCCTCCAAGTCCTGGCCATGTCAT CAG 536 hDUB4 .5 CTCACAGGCATTGGCTGCTGGCTTCCATAGAAGCGGAAGATGCCCATGAATT 599 hDUB4 .8 CTCACAGGCATTGGCTGCTGGCTTCCATAGAGGCAGGGAAGATGCCCATGATC C 599 hDUB6 .2 CTCACAGGTGTTGGCTGCTGGCrTCCATAGAGGCGAGCAGGAAGATGCCCATGATTTCT 596 CTGTCACT TGAT CP~d) GGCATGCCTTCCCGGGCACAAGCAGGTGGATCA 659 hDUB4 .5 CATG.-T ACTGTGGATGCCATGAAAGCTCTCCGCCA.AGGTA65 hDUB4 .8 CATGTTCACTGTGGATGCCATGAAAGGCATCC-CCCGGGCCGCATTGAT 659 bDUB48.2 CATCACT GTAGGA GCCATc cAATTTGAGTATGGACCA 1 hDUB4 .8 TCACTCTAGGACACCACCCtCT)TCCACCATATTTGGAGGCTACTGGAGATCAT 719 hDUB8 .2 TCACTCTAAGGACACCACCCTCATCCACCATATTGGAGGGTACTGGAGATCTCACA 716 hDU4. CAGGCC***CtGAtCGAATTGCq 779 hDUB4 SCAGTGTCTCCACTGCCACGGCATTGACACTTTTGACCCTTACCTGACATCGCCC 779 hDUBB .2 CACTGTTTCACTGCCACGGGATTTCGACACCTTGACCCTTACCTGGACATCGCCCT 776 GATATCAGGAGCTAGAGGTCCAGCAGCTTTGGAACAGTTGGTGAAGCCCGAAGA 839 hDU34 .5 GGATATCCAGGCAGCTCAGAGT.TCGAGTTGAATTGGACCAG 3 hDUB4 B GGATATCCAGGCAGCTCAGAGTGTCAAGCAGCTTTGTAACAGTTGGTGAAGCCCGAAGA 839 CTCA~dGAAGAAG.CTATCATTGTGGTGT .TTGTCTCCAGAGGGCGCCGGCCTCCAA 899 hDUB4 .5 ACTCAATGGAGAGAATGCCTTTTTGGTGCCAAGCCGCTCA89 hDUB 8.2 ACCAGAAATCTTATTGTTTTTCGAGGCGCCA 896 w w hDUB4 .5 GACGTTAACTTTACACACCTCTGCCAAGGTCCTCATCCTTGTATTGAGAGATTCTCCGA 959 hDUB4 .8 GACGTTAACTTTACCACTCTGCCAGGT66CTTCCTTGTATTGAGAGATTCTCCGA 959 hDUB8 .2 GACGTTAACTTTACACACTTCTGCCAAGGTCCTCATCCTTGTATTGAAGAGATTCTCTGA 956 t hDUB4. S TGTCACAGGCAACAAGATTGACAAGAATGTGCATATCCTGAGTGCCTTGAATGAGC 1019 hDUB4 .8 TGGCGCAAGTGCAATTGATTCGGGCTAAGAC 1019 hDUB8 .2 GGTCACAGGCAACAACTCAAGAATGTGCATATCCTGAGTGCCTTGACTGCAGCC 1016 **4I hDUB4 ATACATGTCTCAGACGAAC TCAGGACCTCTCGTCTATGTCCTCTATGCTGTGCTGGTCCA 1079 hDIJB4. 8 ATACATGTCTCAGCAGAACACGACCTCTGTCTATGTCCTCTATGCTGTCTOTCC 1079 hDUB8 .2 ATACATGTCTCAGCAGAACACAGGACCTCTTGTCTATGTCCTCTATGCTGTGCTGGTCCA 1076 hDUB4. 5 hB .SCGCTGGGTGGATTGTCACAACGGACATTACTTCTCTTATGTCAGCT CAGAAGGCCA 1139 00

;Z

00 hDUB4 .8 hDUB8. 2 hDJB4. 5 hDUB4. 8 hflUB 8. 2 hDUB4 5 hDUB4 8 hDJB8 2 hDUB4 5 hDUB4 8 hDUB. .2 hDUB4 5 hDUB4 .8 hDUB8. .2 hDUB4 .5 hDJB4 8 hDUB 8. 2 hDUB4 .5 hDUB4 8 hDUB8 .2 h.DUB4 5 hDUB4 .8 hDUB8. .2 hDUB4 .5 hDUB4 .8 hDUB8 .2 CGCTGGGTGGAGTTGTCACAACGGACATTACTTCTCTTATGTCAAAGCTAGAAGGCCA 1139 'CGC'rGGGTGGAGTTGTCACAACGGACATTACTTATCTATGTCA- CTCAAGAAGGCCA 1135 GTGGTATAAAATGGATGATGCCGAGGtCACCGCCTCTAGCATACTTCTGTCCTGAGTCA

ATGGTATAAAATGGATGATGCCGAGGTCACCGCCGCTAGCATCACTTCTGTCCTGAGTCA

TTGGTATAAAATGGATGATGCCGAGGTCACTGCCTCCGGTATCACTTCTGTCCTGAGTCA

ACAGCTAGTCTCTTACACCGAGAGGATGGAAG**CGT*GAT*

ACAGGCCTACGTCCTCTTTTACATCCAGAAGAGTGAATGGGAGCACAGTGAGAGTGT

ACAGGCCTACGTC CTCTTTTACATCCAGAAGAATGAATGGGGACCCAGTGAGAGTGT GAAGGCAGGTAccTACTTTTATCGAGAATTGGAGACGCAGTAGGT GTCAAG AGGCAGGGAACCAAGAGCCCTTGGCGCAGAAGACACAGACAGGCGAGCAACGCA

GTCCATAGGCAGGGAACCAAGAGCTCTTTGCGTGAAGGGTGATTGTGTGTGATA

1199 1199 1195 1259 1259 1255 1319 1319 1315 AGGAGAGCTCAAGAGAGACCACCCCTGCCTCCAGGCCCCCGAGTTGGACGAGCACTTGGT 1379 AGGAGAGCTCAAGAGAGACCACCCCTGCCTCCAGGCCCCCGAGTTGGACGAGCACTTGT 1379 AAATG- -TCATGA- -ATAAATCTTGCAGTGGAGTATTT -ATTTGTCTCACTTTGTAAT 1368, GG **CACTAGGAAGC* CTTGACCC*GG* ATCCT* ACAAA* A143 GGAAAGAGCCACTCAGGAAGCACCTTAGACCACTGG TTCCTTCGAGCACA 1439 CAGTGAATGAGCTTTAACCATATCAATGCCTAGTGCCTACCCCCCAGAGATAGAACT 1428, ***CCGA GTA TTGT 149 AACGAAGCCTGAGTTCAACGTCAGAAAAGTCGAAGGTACCCTGCCTCCCGACGTACTTGT 1499 CCACTCTCTTATGTGTAAC CAtGGCCTCTGGATtGCTTATGACTCTGAAGATATTCT 1486 S* GATTCATCAATCAAAATACAAGTGTGGGATGGACTCTCCTG -AACAGCAAAGCT 1558 GATTCATCAATCAAATACAAGTGTGGGATGGACATCTCCTG-AACAGCAAAGCT 1558 CCTT -TCCCCCAACGTTTCAGAATCACTTCAGGTGGTGGTAACAGATAACACATCAGTC 1544.

**GGTCATAAC CTGCAAC 61 CCCTGCTAAACCTCTCTTCGACGACCCCGACACATCAGGAGTCCATGAACACTGGCACAC 1618 CCTTTCTCTCTCTTTTCTCTTCACTCAGGAAACTCTCACTGAGACGAAATCCTA 1604 TCGCTTCCCTGCGAGGGAGGGC- CAGGAGATCCAAGGGAAGAACAACACAGCA 1673 TCGCTTCCCTGCGAGGGAGGGC--CAGGAGATCCAAGGGAAGAACAALACACAGCA 1673 TGG TTTACTtGGGGAGGAGATTCCCTCAGGAGATGGTGCTCCTTCCTCCCTGT 1664 GAGGGCTCTGCTTGTGTG CCAGTGGTCTCAGTGGAAGTACCGACCCACA 1722 GAGGGCTCTGCTTGTGTG 1698 CAAGTCtCTTCCTCAGGATTGCCCCTTTGTCTCTTCAGGACT------------- 1706 hDUB4.5 hDUfl4 .8 hDUB8. .2 hDUB4.5 hDUB4 8 hDUB8. .2 Table 26. Deduced amino 'acid alignment of hDUB4.5, hDUB4.8 and hDUB8.2.

N-terminal potential mitochondrial targeting sequences are und6rili ned.

hDUB4. 5 hDUB4.8 hDUB8 .2 hDUB4 .5 hDUB4.8 hDUB8 .2 MRQRRHLTLSGIASFCLRSOKNLILVVD1EEDLYLGEWQNHFKLTSRP60 MRQRARHLKTLSEGIASCCKLRSOQQ0NLVI LVPVDMEDDSLYLGGEW0FNHFS KLTS SRP MRPESPS FED -SEE IAS FCNLRSQP KLVILVPGDMEDDSLYLGGEWQFHFS KTS SRP 59 DAAFAEI *..**CDLPVRQPE*PSNRP***GLN DAFEOTLE-PSERDCDAVRLPELLSRAVALN 120 DAFEQTLESLSTVLDLAVRLPELLSRAVALN 120 00 hDUB4 5 GNTCYNASLQCLTYTPLANYMLSREHSTP{{KCMLCHTMQ-ITJPGffIQP 180.

;Z hDtJB48 GNCVALCTTPAYLRHOTHHGMCMAIRLNGVQ 180 hDUBB .2 GNCVALCTTPAYLRHOTHHCMCMAIWLSGVQ 179 ohDUB4 .5 SOALAGFHRGKQEDAHiEFLMFVDAMKACLPGHKQVHHSDTTLIHQI FGGYWRSQI 240 hDIJB4 SQALAAGFMRGKQEDAHEFLMFTVDAMKACLPGHKQVDHHSDTTLI 1401FGGYWRSQI 240 hDUB8 .2 SQVLAAGFHRGEQEDAHE FLMFT\TDAMKAFLPGHHLDNHS IOTTLI 1401FGGYWRSMI 239 00 0 tt* KCLHCGISDTFDPYLDIALDI0AA0SVQAJELVKPEELGENAYHCG\FCLQRAPASK 300 hDUB4.8 KCCGISDTFDPYLDIAIDI0A0QSV0QQAELVKPEELNGENAYHCGVCLQAPAK 300 O hDUB8.2 NCFHCHGISDTFDPYLDIALDI0AAQSVK0A----------------------------- 271 00 ohDUB4 .5 TLLTAVIVKFDTNIKVYE.DKYSTSPVVYVV 360 ohDUB4 .8 TLTLHTSALILVLKGFSDVTGNKIAKNbQYPECLDMPYMSQNTGPLVYLYAVLVM 360 hDU B S.2 0 hDUB4 AGWSCHNGMYFSVKAQEG0WYKMDAEVTASSITSVLS0QdAWLFYIQkEWERHSEOt 42 hDUB4.8 AGWSCNGHYFSY-KAQEG0WYt4DAEVTAAS ITSVLSQQAYVLFY IQKS2WERHSESV 420 hD U B 8.2 hDUB4 .5 SRGREPRALGAEDTDRRATGELDPCLAPEDEHLVERATQESThDHKFLQEQNK 480 hDUB4.8 SRGREPRAGAEDTDRRATQGELKRHPCLQAPELDEHLVERAT0ESTLDHKFLQNK 480 hD U B 8.2 hDUE4 TKPEFNVRKEGTLPPDVLVIQ SKYKCGM1QMPEQSSLNLSSTTPThESNGTL 540 hDUB4. 8 TKENRVGLPVVHSYCMKHPdSLNSSPHEMT 540 hDUB 8.2 hDtJB4 ASLRGRARRSKGK4KHSKPALLVCQWSQWKYRPT 574.

hDUB4 .8 ASLRGRARRSKGKNKHSKRALLVCQ 565 hDUBS.2 $0 Table 27. Upstream of initiation codon nucleotidle sequence (putative promoter region) alignment of hDUB4.5, hDUB4.8 and hDUBS.2 Numbering is initiated from initiation ATG.

bDUB4 .5 CACACGAACACAATCACACACACACACTCACACGGTTT9CTACGTMAAGATTTCTTCCCT -276 hDUB4 .8 CACACGAACACAATCACACACACACACTCACACGGTTTCCTACGTAGAfl'TCTTCCCT -276 hDUBS .2 GGGAGAAMACACACACACACACACACACACACGGTTTCATAGGTAAAGATrCTTCCCT -276 hDt7B4 GCCATTGCTTTACCTAAAATAAGGCAACTGTGTGGCCATGTCCACCCGGnTACCTC -216 ?XDUB4 .8 GCCATTGCTTTACCTAAAATAAGGCAACTGTGTGGCCACTGTCCCACCCGGTTACACTC -21.6 hDUBS .2 CACATTCTTTTACCTAAAATAAGGCAACTGTGTGGCCACTGTCCCAACCCGGTACACTC -216 hDtJB4 .5 CTATTATATGTGCCTATCATCCTGAjGGAGTAATTTGATTCAGGTGTTCTPGAAGTPATGC -156 hDJB4 .8 CTATTATATGTGCCTATCATCCTGAGGAGTAATTTGATTCAGGTG CTGGAGTCATGC -156 hDUB8 .2 ATATTACATGTGTCTATCAGCCTGAGGATAGTTTGAnTCAGGTGTTCTAGAAGTCATGA -156 hDtJB4. S TGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTCCTTCC -96 hDtJB4 .8 TGTGGGCTGTGTCTGTTGAATACCCAGCGATGCAAGGGGACACACCTGTACTCCTTCC -96 hDUB8 .2 TGTGGGCTGTGTCTGTTGAArICCCAGCGATGCAAGGGGACACACCCTGTCACTCATTCC -96 1iDUB4 .5 TGATTGAGTGCTGATATTTGATTGGCTTATCGCGCACCTGATGAGTTGGTGTTC '-36 00 hDUB4 TGAATTGAGTGCTGATATTTGATTGGCTTATCGCGCACCTGATGAGTGGGTGGGGTGTTC -36 hDUB8 .2 TTAATTGAGTGCTGATATTTGATTGGTTTATCGCGCACCTGATGGGTGGGTGGGGTGTTC -36 hDUB4 .5 GCGGTTGGTGGGGTTGACTTACAGAAGGGCTGATG 0 hDUB4 .8 GCGGTTGGTGGGGGTGACTTACAGAAGGGCTGATG 0 hDUB8 .2 GCGGTTGGTGGcGGTGAGTTAtATAA GGGCTGATG 0 00 Table 28 CLUSTAL W (1.8 1) multiple sequence alignment of core arrino acids of hDUBs 8 .5 MEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSSEARVDLCDDLAPVAR 8M 7MDSYGEQNFKTSPAFAIRSPKPSERDCDAVR6 8.71 MGDDSLYLGGEWQFNiFSKLTSSRDAAFAEIQRTSLPEKSPLSSEARVDLCDDLAPVAR 804.1 2 DDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVAR 0 4 .2 MEDDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRT.SLPEKS.PLSCET.RVDLCDDLAPVAR 4.35 MEEDSLYLGGEWQFNHFSKLTSSRPDAAFAEIQRTSLPEKSPLSCETRVDLCDDLAPVAR 4.51 MEDDSLYLGGEWQFNFSKLTSSRPDAAFAEIQRTSLPEKSPLSCE.TRVDLCDDLAPVAR 4.13 MEDDSLYLGGEWOFNJFSYLTSSRPDAAFAE IQRTSLPEKSQPLSTETRVDFCDDLAPVAR 8.11 MEDDSLYLGGEWQFN{FSKLTSSRPDAAFAEIQRTSLPEKSQLSTETRVDFCDDLAAVAR 8.118DSYGEQNFKTSPAFEQ SPK TTVFDLAA 8 .6 MEDDSLYLGGDWQFHFSKLTSSRLDWAAEIQRTSLSEKSPLSSET.RPDLCDDLAPVAR 8. ME R* 6 8 .5 QLAPRKKLPLSSRRPAAVGAGLQNMGNTCYENASLQCLTYTPPLjANYMLSREHSQTCQRP 120 8.7 QLAPRKKLPLSSRRPAAVGAGLQNMGNTCYENASLQCLTYTPPLANYMLSREHSQTCQRP 120 8.1 QLAP REKLPLSSR PAAVGAGLQNMGNTCYENA.SLQCLTYTLPLANYMLSREHSQTCQRP 120 4 .2 QLAPREKLPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYTTPLANYMLSREHSQTCHRH 120 4 3 QLAPREKLPLSSRRPAAVGAGLQNMGNTCYVNASLQCLTYTPPLANYMLSREHSQTCHRH 120 4 .S QLAPREKLPLSN RRPAAVGAGLQNMNTCYASLOCLTYTPPLANYMLSREHSOTCP 120 4 .1 QLAPREKPPLSSRRPA AVGAGLQNMGTCYNASLQCLTYKPPLANYMLFRHSQTCHRH 120 8.3 QLAPREKLPLSSRRAAVGAGLQNMNTCYVNASQQCLTYTPPLANYMLSREHSQTCHRH~ 120 8.11 QIARKP~RPAGGQMNCVAQCTIPAYLRHQCR 120 8.8 QLA4PREKLPLSSRRAAGAGLQKIGNTFYVNVLCLTYTLPLSNYMLSREDSQTCHLH 120 8. .6 QLAPREKLPLSS RRPAAYGVAGLQKIGNTFYVNVS .LQCLTYTLPLSNYMLSREDSQTCHLH 120 8 .5 KCCMLCTMQAHI TWAU.KSPGHVIQPSQALAAGFHRGKQEDAHEFLMFTVDAMKKACLPGH 180 8 .7 KCCMLCTMQAHI TWALHSPGHVIQPSOALAAGFHRGkQEDAHEFLMFVDAMKKACLPGH 180 8 .1 KCCMLCTMQAHI TWALHS PGHVIQPSQAI.AAGFHRGKQ. EDVHE FLMFTVDAM~KKACLPGH 180 4 .2 KGCMLCTMQAITRALHNPGHVIQPSALAHRKEHFMFVMKCPG18 4 .3 GCMLTMQAITRALN06HIO'Q'ALAAGFMHRG'KQEDAHEFLMFTVDAMKKACLPGH 180 4 .3 KGCMLCTMQAHITRAHNPGHVIPSQAAGFHRGKQEDAHEFLMFTVDAKKCLPGH 180 4 .1 KGCMLCTMQAHITRALHI PGHVIQPSQALAAGFHRGKQEDAI-EFLNFTVDAMRKACLPGH 180 8 .3 KCCNLCTMEAHI TWPLHI PGHVIQPSQA.AAGFHRGKQEAALEFLMFTVDAMKKACLPGH 180 8 .11 KCCMLCTMEAITWPLHI PGHVIQPSQALAAGFHRGKQEAALEFLMFTVDAM~KKACLPGH 180 8.8 KCCMFCTMQAHI TWALYRPGHVIQPSQVLAAGFHRZGEQEDAHEFLMFTVD AMKKACLPGH 180 8 .6 KtCMFCTMQAHITWALYRPGVIQPSQAAGF GEQEDAHEFLMDMKKCLPGH 180 8 .7 KQVDH}SDTTLIHQI FGGCWRSQI KCLHCHGISDTFDPYLDIALDIOAAQSVKOALEQL 240 8.7 KQVDHCSITTLIHQIFGGCWRSQIKCLHCHGISDTFDPYLDIALDIQAAQSVKQALEQL 240 4.2 KQVDHHKDTLIHQIFGGYWRSQIKCLHCHGISDTFDPYLDIAIQAAQSVQQALEQL 240 4.32 KQVDHHtSKDTTLIHQI FGGYWRSQI KCL}ICHGI SDTFDPYLDIAI.DIQAAQSVQQALEQL 240 4.53 KQVDHI-SKDTTLIHQI FGGYWRSQI KCLHCH-GI SDTFDPYLDIALDIQAAQSVQQALEQL 240 4 .5 KOVDRHSKDTTLIHQIFGGYWRSQIKCLHCHGISDFDPYLDIALDIQAAQSVQOALQL 240 8 .3 KQVDHHSKDTTLIHQIFGGYWRS0IKCLHCHGISDTFGPYLDIALDIQEAQSVKQALEQL 240 8.11 196 8.8 KQLDHHSKDTTLIHQIFGAYWRSQIKYLHCHGISDTFDPYLDIALDIQAQSVKQALEQL 240 8 .6 KQLDHHSKDTTLIHQIFGAYWRSQIKYLXiCHGISDTFDPYLDIALDIQAAQSVKQALEQL 240 J 8.5 8.7 8.1.

4.2 4.3 4.1 8.3 8.11 8.8 8.6 8.7 8.1 4.2 4 .3 4.1 8.3 8 .11 8.8 8.6 8.7 8.1 4.2 4.3 4.1 8.3 8. 11 8.8 8.6 0 8.7 8.1 4.2 4.3 4 .1 8.3 8. 11 8.81 8.6 VKPEELNGENAYHCGL LQAPVSKTLTLTFAERI LETQRPWVVTRHKI.AKSVQYAES 300 VKELGNYCLLRPSTTMSKLL.KFDTNLKVYE 300 VKELGNYHGC AANTTHSKLLVLKRFSDVAGNKLAKNVQYPEC 300 VKELGNYSVLPAAKLLTAVIVIFDTNIKVYE 300 VKPEELNGENAYHCGVCLQAPASTTHSAVIVKRSVGKIKVY 300 VKPEELNGENAYHCGVCLQAPASKTLTLHTSAVLI LVLKRFSDVTGNKI DKNJVQYPEC 300 VKELGNYCVLRPSTTHNAVIVKFDTNIKVYE 300 GNKIAKNVQYPEC 267 NKIAKNVQYPEC 208 VKPKLNGNAYCG.CLQAPAKTLLPTSKVLLVLRFSVTGKLANVQPKC300 VKPKELNGENAYCGLCLQKAPASKTLTATSLILVLFSDVTGAKVQYK 300 VKMPYMEL NE PAYVCLCLQKAWSTLTLTSYVLILFSWKMD ~AKVACT36 LDMQP MSQNTGPLVYVLYAVLVHAGHGYS'GHYFQEQWYKMDDAETA 360 LDKYSTSPVVYVVAWCHGYSYAEQY.DAETSI 360 LDdYSQ~PVVYVVAWCN.,SVKQGWKDAETSI 360 LDMQP.MSQQNGPLVYVLYVAVLSCHGHYS)HYFQEQWYtDAEVTI 3607 LDMQ MSQQ P Y Q QLYVVHGSHNHFY-.VQGWlaDA LDMPYMSQQNTGPLVYVLYAVLAGWSCHGHYFSYQEGQWYDAVAT 327 SVLSQOAYVLFYIQKSEWERSESVSRGREPRALGAEDDRRATQGELKRD)HPCLOAE 420 -SLQAVFIKEEHEVRRI~~ PiTRAQEKDPLAE 420 SVSQY~YQS'EHEV-S.RGERLVrTRAQEKDPLAE 420 -KSEWERSESVSRGEPRALGATDPTQGELRYPCLQVPEL 307 SVLSQQAYVLFYIQKEE SSSGRPAGETRAQGLR)PLVE 420 SVSQYLYQSWRSSSGERLADDPTGLPDPLVE 420 DFLE-TtTD*RPENTPF~RVGLPVVHSYCMNH 480 PELEAQS~HKLENTPFTGVGLPAVHSYCMNH 480 DEHLVERATQESTLDHWKFLOEQINKTKPEFVGIEGTLPPAIYIHQSKYKCGMKQNHHP 480 .DEHLVERATQSTDWKF LQENKTKPEFVREGTLPPDVLVIHQSKYKCGMgHP 480 DELE-TE'~H F.LENT~tNRVqLPVVHSYCMNH 480 DELEAQSLH'FL QK.TKEWRYGVPVVHSYCMNH 480 DELEAQSLHKPKNTPFNRVGLPVVHSYCMNH 480 DELETETDWFQQKKEFVKETPNLIQKKGMH 480 -79- 00 EQQSSLLNLSSTTRTDQESVNTGTLASLQGRTRRSKG1KIGISKRALLVCQ 530 8 .7 EQQSSLLNLSSTTRTDQESVNTGTLASLQGRTRRSKGKNKHS}K.ALLVCQ 530 8.1 EQQSSLLNLSSTTRTDQES4NTGTLASLQGRTRRAKGQNKHSKRALLVCQ 530 5 4 .2 EQQSSLLNLSSSTPTHQESMTGTLASLRGRARRSKGKNKH~SKRALLVCQ 530 4 .3 EQQSSLLNLSSSTPTHQESMbJTGTLASLRGRARRSKGKNKHSKRALLVCQ 530 4 .5 EQQSSLLNLSSTTPTHQESMNTGTLASLRGRARRSKGIQJIGSKRALLVCO 530 4 .1 EQQSSLL1ThSSTTPTDQESMNTGTLASLRGRTRRSKG1NKHSKPALLVCQ 530 8.3 EQQSSLLNLSSTNPTDQESMflTGTLASLQGRTRRAKGIQJKHCKR-ALLVCO 497 8.11 EQQSSLLNLSSTNPTDQESMThTGTLASLQGRTRRSKGKNKHCKRALLVCQ 417 00 8.8 EQSSVLNLSSTKPTDQESMNTGTLASLGSTRRSKGNNIG{SKRSLLVCQ 530 8 .6 EQQSSLLNLSSTKPTDQESTGTLASLQGSTRRSKGNKSKRSLLVCQ 530 00 00 Table 29 CLUSTAL W (1.81) multiple sequence alignment of putative Promoter sequences of hDUBS (upstream of ATG initiation codon) 8.9 8.10 8.3 8 .11 4 .2-a 0 4.3 4 .2_b 4.4 4.1_b 8.1 8.7 8.6 8.8 8.2 !0 4.1_a 8.9 8.10 8.3 8.11 4.2 a 4.3 4.2-b 4 .4 4. 1_b 8.1 8.7 8.6 8:*8 8.2 4.1_a.

8.9 8.10 8.3 8.11 4.2 a 4.3 4.2_b 4.4 4. 1_b 8.1 8.7 8.6 8.8 8.2 4. 1-a TGACGTGTGTGAAAACTACAGTGTGATGAGCATGACTTGCAGACAGGTTATCGATTGGGC GACGTGTGTGAAALACT1ACAGTGTGACGAGCATGACTCGCAGACAGGTTATCGATTGGGC 59 GATATCAATACGGC 14 GATATCAATACGGC 14 TTATCGATTGGGC 13 TGAGCATGACTGGCAGACAGCTTATCGATTGGGC 34 GATGAGCATGACTGGCAGACAGCTTATCGATTGGGC 36 GTGATGAGCATGACTGGCAGACAGTTATCGATGGC 38 GTGATGAGCATGACTGGCAGACAGCTTATCGATTGGC 38 AGTGCAATGAGCATGACACGCAGGCAGGATATCAATTCGGC 41 CAATGAGCATGACACGAAGACAGAATATCAATTCGGC 37 CAATGAGCATGACATGCAGGCAGGACATCAATTCGGC 37 TGTGATGAGCATGACTCGCAGACAGGTTATCGATTGGGC 39 TGTGATGAGCATGACTCGCAGACAGGTTATCGATTGGGC 39 TCTCTGTCAGAACCATGGTACTCTGTTGTGGTGTGAGTAGC 43 TCACATCTTCTCGGCCAGATGCAGCCTTTGCTGTCAGCGACTTCTC 51 -AGTATAGCAGAGCAGAGAGCTG GAGGGACC 31 T-CCCAA-ATAGGATAGAACAGC AGGTCCCGGCTG 115 T -CCC CTCAAAAT- CAGTTATGAGCATTAAAGCACACCGATGCCC AGGTCCCGGCTC 114 T- CACCTCAAAAG-CAGTTATGAGCATTAAAGGACACCCATGCCT -AGGTCCCGCTTA 69 T-CACCTCAAAAG-CAGTTATGAGCATTAGGACACCCATGCCT -AGGTCCCGGTTA 69 T-CCCCTCAAAAT-CGGTTATGAGCATTCAAGCACACCGATGCCC -AGGTCCCGGCTG 68 T-CCCAA-GTAGGATAGAACAGC -AGGTCCCGGCTG 89 T-CCCCTCAAAAT-CGGTTATGAGCATTCAGCACACCGATGCCC -AGGTCCCGGCTG 91 T- CCCCTCAAAAT- CGGTTATGAGCATTCAAGCACACCGATGCCC -AGGTCCCGGCTG 93 T-CCCCTCAAAAT-CGGTTATGAGTATTCAGCACCCGATGCCC AGGTCCCGGCTG 93 T -CCCCTCAAAAG -CTGTTATGAGCATTAAAGGACACCAATGCCT AGTTCCCGGTTA 96 T -CACCTCAAAT -CAGTTGTGAGCATTAAAGAA.AACCAATTCCT AGGTCCCGCTTA 91 T-ACCAA-ATAGGATAGAACATC AGGTCCCGCTTA 92 T- CCCCTCAAAAT -CAGTTAGGAACATGAAAGCACACCGATGCCC AGGTCCTGGCTG 94 T-CCCCTCAAAATCAGTTAGGAACATGAAAGCACCGATGCCC -AGGTCCTGGCTG 94 CACAGATCATCTG-TAGAT-TAAGGGGTGTGGCTTTGTTCACA AAGCTTTATTTA 98 TCCCTGAGAAGTCACAACTCTCAACTGAGACCCGCGTCGACTTCTGCGATGATGGCGC 111 TGCATCCCTAAT--- GATATAAGAAAGTATCTGTACTAGCCCTGA--ATGGTATAACTA CAGAAGC *CCGCTTGGGACAGC *TTGTGTAG 7 CAGGAATAAGAC- CCTCCGCGTCTTGTGTGA-AGCCACGGC ATCTGGATTGCTCATGC 172 CAGGATAAGAC -TCCCACCCCTGTGTGAAGCCACGGC- -ATGTGGATTGCTCATGC 171 AAGAGATAAGAC- TCTCCCACACCCTGTGTGAAGCCACGGC ATGTGGATTGCTCATGC 126 CAGGATAAGAC CCTCCCAGGACCTGTGTGAAGCCACGGC ATGTGGATTGCTCATGC 126 CAGGAATAAGAC- CCTCCAGCGTCTTGTGTGAAGCCTCGGC ATCTGCATTGCTCATGC 125 CAGGAATAAGAC -CCTCCAGGGTCTTGTGTGAAGCCTCGGC ATCTGCATTGCTCATGC 146 CAGGAATAAGAC CCTCCAGGGTCTTGTGTGA.AGCCTCGGC ATCTGCATTGCTCATGC 148 CAGGAATAAGAC -CCTCCAGGGTCTTGTGTGAAGCCTCGGC ATCTGCATTGCTCATGC 150 CAGGATAAGAC- CCTCGACGCTTGTGTGAAGCCTCGGC--ATCTGCATTGCTCATGC 150 AAAGATAAGAC -CTCCACACCCTGTGGGAAGCCACGGC ATCTGGATTGCTCATGC 153 AAGAGATAAGAC CATCCAACAACCTGTGTGAAGCCACCGC- ATCTGGCTTGCTCATGA 148 AGAATAAGA CCTCCGAACCTCTTGTGAAGCCACGAC ATCTGGATTGCTCATGT 149 CAGGAATAAGAT -CCTCCGACGTCTTGTGTGAAGCCACGAC--ATCTGCATTGCTCATGC 151 CAA.ACACAGGCTGTGGGCTGGATTTGGCCTGCAGCTGTAGT TTGTG- ATCCTTGA 152 CTGTGGCAAGAC AGCTTGCTCCCAGGGAGAAGCTTCCTCTGAGTAGCAGGAGACCTGC 169 CAG- GTTAAATT TACGTGAAAAAGAAATCAACTTCTGCCTTGTTTAAGCACTTA- 140 00 8.9 8 .10 8.3 8.11 4 .2 a 4 .5 4 .3 4 .2 b 4 .4 4 .1_-b 00 8.1 8.7 8.6 8.8 8 .5 8.2 00 4 .l1a CI 8.9 8.10 8.3 8.11 4 .2_a 4. 3 4 .2_b 4 .4 4.1_b 8.1 8.7 8.6 8.8 8.2 4.1_-a 8.9 8.10 8 .3 8.11 4 .2_a 4 .5 4 4 .2_b 4 .4 4 b 8.1 8.7 8.6 8.8 8.2 4. la TTCTG- G -GGATCATTCTCCTGAAAATG GGGCTCCTTCCTGCCTGTGGAGCACCTCT TTCTG- G- GGATCATTCTCCTGAAAACG- -GTGGCTCCTTTCTCCCTGTGGAGCACCTTT TTCTG- G- GGATCATTCTCCTGAAAATG- -GTGGCTCCTTTCTCACTGTGGAGCATCTTT TTCTG- G -GGATCATTCTCCTGAAAATG -GTGGCTCCTTTCTCACTGTGGAGCATCTTT TTCTG- G -GGATCATTCTCCTGAAAATG -GTGGCTCCTTTCTCCCTGTGGAGCATCTTT TTCTG- G-GGATCATTCTCCTGAAAATG- -GTGGCTCCTTTCTCCCTGTGGAGCATCTTT TTCTG- G-GGATCATTCTCCTGAAAATG- -GTGGCTCCTTTCTCCCTGTGGAGCATCTTT TTCTG- G- GGATCATTCTCCTGAAAATG- -GTGGCTCCTTTCTCCCTGTGGAGCATCTTT TTCTG- G -GGATCATTCTCCTGAAAATG- -GTGGCTCCTTTCTCCCTGTGGAGCATCTTT TTCTG-G- GGATCATTTTCCTGAAAATC- -GTGGCTGCTTTCTCCCTGTGTAGCATCTTT TTCTG-G- GGATCATTCTCCAGAAAATG- -GTGGCTCCTTTCTCCCTGTGGAGCATCTTT TTCTG- G- GGAACATTCTTCTGAAAATG- -GCGGCTCCTTTCTCCCTGTGGAGCATCTTT TTCTG- G -GGATCATTC1TCCTGAAAATG- -GTGGCTTCTTTCTCCCTG'IGGAGCATCTTT TTCTG- G GGATCATTCTCCTGAPAATG GTGGCTTCTTTCTCCCTGTGGAGCATCTTT TTCAG- ACAGTTTAGCAAGGCTGAAAAG AACACCCACACCCCCTTGTTACCCACAGAT TGCGGTGGGGGCTGGGCTCCAGAATATG- -GGAAATACCTGCTACGTG AACGCTTCC TTCAG3--- GCATTAATTTTATAAATATGTAGAGAATACATACTCCTTAT- GAGCAGA-- CT-ACAGGCCC*TTCACCGAC*TTAA*AGCCA* AGCTC CTA -AGCA-GTGC -CCTTTCTTCACCCAGGACACTTTACATCAGGCACAGAAAGCCTTCT CTA -AGCA- GTG CCTTTCTTCACCCAGGACACTTTACTTCAGGCACAGGAAGCCTTCT CTA -AGCA- GTGT- CCTTTCTTCCCCCAGGACACTTTACTTCAGGCACAGGAAGCCTTCT CTA-AGCA -GTGCTCTTTTCTTCCCCCAGGACACTTTACTCGGCA-AGGAAGCCTTCT CTA- AGGA -GTGCTCTTTTCTTCCCCCAGGACACTTTACATCCGGCACAGGAAGCCTTCT CTA-AGCA -GTGCTCTTTTCTTCCCCCAGGACACTTTACATCCGGCACAGGA-AGCCTTCT CTA- AGCA- GTGCTCTTTTCTTCCCCGAGGACACTTTACATCCGGCACAGGAAGCCTTCT CTA- AGGA- GTGCTCTTTTCTTCCCCCAGGACACTTTACATCCGGCACAGGAAGCCTTCT CTA- AGCA- GTGCTCTTTTCTTCCCCACAGGACACTTTACATCCGGCACAGGAAGCCTTCT CTA- AGCA- GTGC-CCTTTCTTCCCAC-AGGACACTTACATGAGGTGCAGGAAGCCTTCT CTA- AGCA- GTGC- CCTTTCTTCCCCCAGGACACTTTACATGAGGCTAGGAAGCCTTCT CTA- AGCA- GTGCTCCTTTCTTCCCCCAGGACACTTTACATCAGGCGAAGAAGCCTTCT CTA- AGCA -GTGCTCCTTTCTTCCCCCAGGACACTTTACATCAGGCGCACGAAGCCTTCT GGGTGGGA -CTGTGTTGGCCAGAGACCGAGAGACGGGTGCTCACAGGGGAACGTACAGCA

CAGCAGTGTCTGACATACACACCGCCCCTTGCCAACTACATGCTGTCCCGGGAGCACTCT

-AACAATGTTTGCGCCATATGGTCCATGATGGGTGTTCAATAATGTGTGATGATGATAAT

GAGACAACGGCAGAAGCAGGTAGACGGCAA*TAA

GATGGAGCACACCTGGCCCATGAA-AAGACAAGGGATAAGAAACGGGGCCAAACATCACAG

GATGGAGCACACCTGGCCCATGAAAAAACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG

GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAATGGGGCCAAAGGTCACAG

GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAATGGGGCCAAAGGTCACAG

GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG

GATGGAGCACACCTGGCCCATGAAALAGACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG

GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG

GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA- AAGAAACGGGGCCAAAGGTCACAG

GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG

GATGGAGCACACCTGGCCCATGAAAAGACAAGGGA-AAGAAATGGGGCCAAAGGTCACAC

GATGGAGTACACCTGGCCCATGAAAAGACAAGGA-AAGAAAAAGGGCCAAAGGTCACAG

GATGAAGTACACCTGGCCCATGAAAAGACA.AAGGA-AAGAAACAGGGCCAAAGGTCACAG

GATGGAGCAC-ACCTGGCCCATGAAAAGACAAGGGA-AAGAAACGGGGCCAAAGGTCACAG

TGTAGAGGCCGGAAGGTGCTCCAGGGCACAAGTGT -GGGAAAGTGGGACATACGGGGA-AG CAAACATGTCATC- -GTCACAAGTGCTGCATGCTCTGTACC-ATGGAAGCTCACATCACAT

AATGAAGACAATAGTGACAAATAAAAGAAAATAAA-AAGCAGTGAAACAAAGTGGTTTAA

00 8.9 OJ~ 8.10 ;Z 8.3 8.11 4 .2 a 4 .5 4.3 4.2_b 4.4 00 0 4.1 b 8.1 8.7 8.6 8.8 8.5 00 8.2 4.1_a 0 8.9 8.10 8.3 8.11 4.2_a 4.S 4.3 4 .2_b 4.4 4.1_b .0 8.1 8.7 8.6 8.8 8.2 4. 1_a 8.9 8.10.

8.3 8.11 4.2_a 4.3 4.2_b 4.4 4.1_b 8.1 8.7 8.6 8.8 8.2 4 .1_a TCCTCTCATTCCACCGTCCTCCTTAAAATCATCCTAATTTCATGGGCTCT

GCGGCCACG

TCCTCTCATTCCATCATCCTCCTTAAAATCATCCTAATTTCATGGGCCCT

-GAGGCCACG

TCCTCTCATTCCATCATCCTCCTTAAAATCATCCTAATTTCGGCCCT-GAAGCCAGG

TCCTCTCATTCCATCATCCTCCTTAAAATCATCCTAATTTCATGGGCCCT

-GAGGCCACG

TCCTCTCATCCCATCATCCTCCTTAAATCATCCTAATTTCTGGGCCCT-

GAAGCCAGG

TCCTCTCATCCCATCATCCTCCT'rAAAATCATCCTAATTTCATGGGCCCT-

GAAGCCAGG

TCCTCTCATCCCATcATCCTCCTTAAAATCATCCTAATTTCATGGGCCCT

-GAAGCCAGG

TCCTCTCATCCCATCATCCTCCTTAAAATCATCCTAATTTC-ATGGGCCCT

-GAAGCCAGG

TCCTCTCATCCCATCATCCTCCTTAAAATCATCCTAATTTCTGGGCCCT

GAAGCCAGG

TCCTCTCATTCCATCATACTCCTTAAAATCATCCTAATTTCATGGTCCT

-GAAGCCAGG

TCCTCTCATTACATCATCATCCTTAAAATCATCCTAATTTCATGAGCCCT

-GAAGACAGG

CCCACTCATTTCATCACCATCCTTAAAATCATCCTAATTTCATGGGCAT

-GAAGCCAGG

TCCTCTCATTCCATCATCCTCCTTAAATCATCCGAATTTATGAGCCCTTGAGCCAGG

TCCTCTCATTCCATCATCCTCCTTAAATCATCCGATTTCATGAGCCCTTGAGCCAGG

T'rTCCAGAAAGCATGATGTCAAGTTGGAG

-GTGGAGCGCTGCTGGGCTTGTGAAGGGTCT

GGCCCC- TCCA-CATTCCTGGCCATGTCATCCAGCCCTCACAGGCATT----------

G

TAGCTATACATAGTTATT -TTTGAGTCTCGTAATATATTT

GCTGTTTCTTTACACCTCGAGACCTTGGCGCCAGGCCTCAATTCTGCCCCGGTGCTTACT

GCTGTTTCTTTACACCTCGAGACCTTGGCGCCGGGCCTCAATTCTGCTCCAGTGCTTACT

GCTGTTTCTTTAAA.ACTAGAGGCCTTGGCGCCGTGCCTCAATTCTGCCCTGTTCCTTACT

GCTGTTTCTTTAAACTAGAGGCCTTGGCGCCGGGCCTCAATT'rTGCCCTGTTCCTTACT GCTGTTTCTTTAr-ACCTAGAGGCCTTGGCGCCGGGCCTCAATTCCGCCCTGTTCCTTACC

GCTGTTTCTTTACACCTAGAGGCCTTGGCGCCGGGCCTCAATTCCGCCCTGTTCCTTACC

GCTGTTTCTTTACACCTAGAGGCCTTGGCGCCGGGCCTCAATTCCGCCCTGTTCCTTACC

GCTGTTTCTTACACCTAGAGGCCTTGGCGCCGGGCCTCAATTCCGCCCTGTTCCTTACC

GCTGTTTCTTTACACCTAGAGGCCTTGGCGCCGGGCCTCAATTCCGCCCTGTTCCTTACC

GCTGTTTCTTTACACCTAGAGGCCTTGGCGCCGGGCCTCAATTCTGCCCTGTTGCTTACT

GCTGTTTCTTTACACCTAGAGGCCTTGGCGCCGGGCCTCAATTCTGCCCTGTTCCTTACT

GCTGTTTCTTTACACCCAGAGGCCT1TGGCGCCGGGCCTCAATTCTGCCCTGTTCCTTACT

GCTGTTTCTTTACACCCAGAGGCCTTGGCGCCGGGCCTCAATTCTGCCCTGTTCCTTACT

GCTGTTTCTTTACACCCAGAGGCCTTGGCGCCGGGCCTCAATTCTGCCCTGTTCCTTACT

CGAGTCCAAGTGAGGGCGGGTTGTGAAGGGTCTCCTCTCAAAGCTGACCGACTTCGGGAC

GCTGCTGGCTTCCATAGAGGCAAGCAGGAAGCTGCCCTTGA.ATTTCTCATGTTCACTGTG

TATGCTGGC- GCAAATAAGGAAATTTACATCGTCTAATAAAAATTATTTATCAATTTAT GTTAACTTGGA*TCCAAG-TG

TCTACTGAGCGG

GTCTAAGACATTTTGGGAAAATCCCTAGAGC

-CTAGATCTTCAATCCTGGTAAGCCAGAG

GTCTAAGAATTTTGGGAGAATCCCTAGAGC-

CAGATCTTCAATCCTGGTAAGCCAGAG

GTCTAAGAAAGGTTGGGAAAATCCCTAGAGC-

CAGGATCTTCATTCCTGGTAAGCCAGAG

GTCTAAGAAGTTGGGAAAATCCCTAGAGC-

CAGGATCTTCATTCCTGGTAAGCCAGAG

GTCTAAGACATGTTGGGAAAATCCCTAGAGC-

CAGGATCTTCATTCCTGCTAGCCAGAC

GTCTAAGACATGTTGGGAAAATCCCTAGAGC-

CAGGATCTTCATTCCTGCTAAGCCAGAC

GTCTAAGACATGTTGGGAAAATCCCTAGAGC-

CAGGATCTTCATTCCTGCTAAGCCAGAC

GTCTAAGACATGTTGGGAAAATCCCTAGAGC

-CAGGATCTTCATTCCTGCTAAGCCAGAC

GTCTAAGACATGTTGGGAAAGTCCCTAGAGC

-CAGGATCTTCATTCCTGCTAAGCCAGAC

CTCTAAGACATGTTTGGGAAAATCCAGAGC

-CAGGACCTTCATTCCTGGTAAGCCAGAG

GTCTAAGACATTTTGGGAAAATCACTAGAGC- CAGGACCTTCATTCCTGGTAAGCCAGAG GTCTAAGACATTTTGGGAAAATCCCTAGAGC-

CAGGATCTTCATTCCTGGTAAGCCAGAG

GTCTAAGACATTTTGGGAAAATCCCTAGAGC

-CAGGATCTTCATTCCTGGTAAGCCAGAG

TTCCCAGGGATTGTTGTTGAGTCCACGGCTCACGTCGTCCACACTC

TGAGGTCCCATGG

GATGCCATGAAAAAGGCATGCCTTCCCGGGCACAAGCAGGTAGATC

ATCACTCCAAGG

AAAACAGTAAAAATTTCATAG- -AATGGGGCTAAGAATCTGCACTGCAAACTAACTCTTT 00 8.9 8.10 ;Z 8.3 8.11 4 3 .2_a 4.3 4.2_b 4.4 4.1lb 00 8.1 8.7 8.6 8.8 CK~ 8.5 00 8.2 00 4.1la CK) 8.9 8.10 8.3 8.11 4.2_a 4.3 4 .2_b 4 .4 4.1_b 8.1 8.7 8.6 8.8 8 8.2 4. 1_a B89 8.10 8.3 8 .11 4.2_a 4 .5 4 .3 4 .2_b 4 .4 4.1_b 8.1 8.7 8.6 8.8 8.2 4 .1_a AGCCTGGAGACACACCCAAATTATGTCCCTCT'rAGTTCAGGGAACATGTCCATTTTCGTC 583 AGCCTGAAGACACACCCAAATTATGTCCCTCTTAGTTCAGGGAACATGTCCATTTTCGTC 581 AGCCTGAAGACACACCCAAATTCTGTCCCTCTTACTTCAGGGAACATGTCCACTTTCGTC 536 AGCCTGAAGACACACCCAAATTCTGTCCCTCTTACTTCAGGGAACATGTCCACTTTCGTC 536 AGCCGCAAGACACACCCAAATTCTCTCCCTCTTACTTCAGGGAACATGTCCACTTTCGGC 536 AGCCGGAAGACACACCCAAATTCTGTCCCTCTTACTTCAGGGAACATGTCCACTTTCGGC 557 AGCCGGAAGACACACCCAAATTCTGTCCCTCTTACTTCAGGGAACATGTCCACTTTCGGC 559 AGCCGGA.AGACACACCCAAATTCTGTCCCTCTTACTTCAGGGAACATGTCCACTTTCGGC 561 AGCCGGAAGACACACCCAAATTCTGTCCCTCTTACTTCAGGGAACATGTCCACTTTCGGC 561 AGAATGAAGACACACCAAAATTCTGTCCCTCTTAATTCAGGGAACGTGTCCACTTTCGTC 564 AGCCGAAAGACACACCCAAATTCTGTCCCTCTTAGTTCAGGGAACAGGTCTACTTTCGTC 558 AGCCTGAAGACACACCCAAATGCTGTCCCTCTTAGTTCAGGGAACATGTCCACTTTCGTC 560 AGCCTGAAGACACACCCAAATGCTGTCCCTCTTAGTTCAGGGAACATGTCCACTTTCGTC 563 AGCCTGAAGACACACCCAAATGCTGTCCCTCTTAGTTCAGGGAACATGTCCACTTTCGTC 563 ATTCGCCACCCACATTCATCTACTCTCCTCTCTCTCTrCCTTACCTCCTTTGATCCCCTC 565 ACACCACCCTCATCCACCAAATATTTGGAGGGTACTGGAGATCTCAAATCAAGTGTCTCC 567 CAGTTGATTTTATGCACAGAAATTATTGAGAATCCCCTTATCTAGATCCAACAGATCTGG 546 AGATAATTGCCAAGTCACGAATCCA*AAGAAAT 643* AGCACTAAA.ATTTTTGCACCAAATGTGCTAACTGCAATTCCACCATGAATGCGTAACTG 643 AGCACTACAATTTTTGCACCAAATGTGCTAACTGCAATTCCACCATGCAATGCATAACTG 56 AGCATTACAATTTTTGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCATAAATG 596 AGCATTACAATTTTTGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCATAAATG 596 AGCATTACAATTTGGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCGTAACTG 56 AGCATTACAATCTTGGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCGTAACTG 617 AGCATTACAATTTTGGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCGTAACTG 621 AGCATTACAATTTTGGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCGTAACTG 621 AGCATTAAATTTTGGCACCAAATGTGCTA?.CTGCAATTCCACCATACAATGCGTAACTG 621 AGAATTAAAATTTTTGCACCAAATGTGCTAACTGGAATTCCACCATACAATGCATAACTG 624 AGCATTACAATTTTTGCACCAAATGTGCTAACTGCAATTCCACCATACAATGCATAACTG 618 AGCATTACAATTTTTGCACCAAATGTACTAACTGCAATTCCACCATACAATGCATAACTG 620 AGCATTACAATTTTTGCACCAAATGTACTAACTGCAATTCCACCATACAATGCATAACTG 623 CCCA-TATGCTACCCCCCGCTACCAAACCTCTGCCAAGCATACCACCCTATCGGCAGCTA 624 ACTGCCACGGCATTTCAGACACTTTTGGCCCTTACCTGGACATCGCCCTGGATATCCAGG 627 GCTTACATAGGTGCTATCAAGACTTAAGGAAGAAAATTTTCCTGACTCTATCCATACCTC 606 GAAAAGACTTATTCGAATCTT *ATTGAA 9 TAAATAGAGGCAACATCTCATATCCTGAACAATCATGTG AGAATCTAGGAGAC 697 TAAATGGAGGCAACATCTCAGATCCTGAACAATCGATGCG AGAATCCAGGAGAC 650 GAAATGGAGGGAACATCTCAGATCCTGAACAATCGATGCG AGAATCCAGGAGAT 650 GAAATGGAGGGAACATCTCCGATCCTGAACAATCGATGCG AGAATCCAGGAGAT 650 GAAATGGAGGCAACATCTCCGATCCTGA.ACGATCGATGCG AGAATCCAGGATAT 650 GAAATGGAGGCAACATCTCCGATCCTGAACGATCGATGCG AGAATCCAGGATAT 671 GAAATGGAGGCAACATCTCCGATCCTGAACGATCGATGCG AGAATCCAGGATAT 673 GAAATGGAGGCAACATCTCCGATCCTGAACGATCGATGCG AGAATCCAGGATAT 675 GAAATGGAGGGAACATCCCGATCATGAACGATCGAAGCG AGAATCCAGGATAT 675 GAAATGGAGGGAAAATCCC-AGATCATGAACAATCATAGG---AGAATCCAGGAGAC 678 GAAATGGAGGGAACATCTCAGATCATGAACAATGATGCG AGAATCCAGGAGAT 672 GAAATGGAGGGAACATCTCAGAGCATGAACAACGATGCG AGAATCCAGGAGAT 674 GAAATGGAGGGAACATCTCAGACCATGAACAATCGATGAG AGALATCCAGGAGAC 677 CTCTTCACTCCCA-ACTACATCGGCCGCATCN1NNNNNN N NNNN NNNN 677 AAGCTCAGAGTGTCAAGCAAGCTTTGGAACAG'flGGTGAAGCCCGAAGAACTCAATGGAG 687 CAATTAGTAATAGATCTAGAGATTTAAAACTGAAATCCAGACCTC-CTGCTTCCATGTGC 665 00 8.9 8.10 ;Z 8.3 8.11 4 .2 a 4 .3 4.2_b 4.4 00) 4.1lb 8.1 8.7 8.6 8.8 S 8.5 00 8.2 4. la L~8.9 8.10 8.3 8.11 4.2_a 4.5 4.3 4. 2_b 4.4 4.1_b 0 8.1 8.7 8.6 8.8 8.2 4. 1_a 8.9 O 8.10 8.3 8.11 4.2 a 4.3 4. 2_b 4.4 4.1_b 8.1 8.7 8.6 8.8 8.2 4.lIa ACACCGCTTATTTTTGCCTTTTCCCACTGACATGGCTAGTATTAACATGTTATGCT 757 ACCGTATTGCTTCATAACAGCATTACACTTC 755 ACCGTATTGGTTCTTAACAGCATTAAAGTTC 710 ACCGTATTGGTTCTTAAAGGCGATAAAGTTC 710 GCACGGCTTATTTTGGCCTTTTCCCACTGAAACAAGGGCAGTATTAAATGGCACGCT 710 GCCGTATTGCrTCCCGACAGCATTAAAGCCC 731 GCCG7rTTGCTTCCCGAAAAGCATTAAAGCCC 733 GCCGTATTGCTTCATAACAGCATTAAAGTCC 735 GCCGTATTGCTTCATAACAGCATTAAAGCCC 735 ACCGTATTGCTTCATAACAGCATTAAAGTTC 738 ACCGTATTGCTTCTTAACAGCATTAAATTTC 732 ACACGGTTTATTTTTGCCATTTCCGTGACAGCCGTATTAAAAGGTTATGCT 734 ACCGTATTGCTTCTTAACAGCACTAAAGTTC 737 ACCGTATTGCTTCTTAACAGCACTAAAGTTC 737 737 AGAATGCCTATCATTGTGGTCTTTGTCTCAGAGGGCGCCGGCCTCGACGTACTT 747 AGTGTCCTTTCACTGTCCTGTTTTGCTTACTTGATGGAGGATTTGAGATATGAC 725 ATCCTTGGTTTCACTCCCCACTTTTATCTCTCGGATGTTTACTTCT -TGAGACAGG 814 ATCCTGGGTTTCACTCTCTGCTTTTTCTCTCATGTTTTCTTCT-TGAGACAGG- 812 ATCCTCTGTTTCACTCCCTGCTTTTAAGTCTCC--GATGTTT- CTTCT-TAAGACAGG- 764 ATCCTCTGTTTCACTCCCTGCTTTTAAGTCTCC GATGTTT -CTT CT- TAAGACAGG 764 ATCCTCTGTTTCACTCCCTGCTTTTAAACGTCTCCGATGT-TTCTCCC-TGAGACAGG-- 766 ATCCCTGTTTCACTCCCTGCTTTTAACGTCTCCGATGT-TTCTCCC -TGAGACAGG 787 ATCCTCTGTTTCACTCCCTGCTTTTACGTCTCCGATGT -TTC1'CCC -TGAGACAGG- 789 ATCCTCTGTTTCACTCCCTGCTTTTACGTCTCCGATGT-TTCTCCC -TGAGACAGG-- 791 ATCCTCTGTTTCACTCCCTGCTTTTACGTCTCTGATGT -TTCTCCC -TGAGACAGG 791 ATACTCTGTTTCACTCCCTGCTTTTAAACGTCTCCGATGT -TTCTTCT -TGAGACAGG 794 GTCTTCTATTTCACTGCCTGCTTTTACGTCTCCGATGTATTCTTCTTGAGAGG-- 789 ACCCTCTGTTTCACTCACTGCTTTTACGTCTCCGATGTTTTCTTCT -TCAGACAGG 791 ATCTTCTGTTTCACTCCCTGCTTTTA-CGTCTCCGATGTTTTCTTCT-TCAGACAGG- 794 ATCTTCTGTTTCACTCCCTGCTTTTACGTCTCCGATGTTTTCTTCT -TCAGACAGG 794 NNNNN~NNJNNNCTGCTTTTAAACGTCTCCGATGTTTTCTTCT -TCAGACAGG 794 TACACACTTCTGCCAAGATCCTCATCCTCGTATTGA-GAGATTCTCCGATGTCACAGGCA 807 CACATGATTCAACTCCTCCTCAGC1CTGAGAT ATAGCCCTGTCCTGGC ACAAGAA 784 GCGTC- ACTGCCGTCACCCACGCTTTTCTACGGT GTAATTTTTGTTGTTCGCTT 867 GCCTC- ACT CCCGTCACCAGGGCTTTTCTACGGT GCAATTTTCGGTGTTTGCTT 865 GCCTC -ACTTCCTTCCCCCTGACTTTTCTACGT ATAATTTTCGTTGTTTGCTT 817 GCCTC-ACTTCCTTCCCCCTGACT'ATTCTACGGT---A TAATTTTCGTTGTTTGCTT 817 GCCTC- ACTTCCGTCAGCCGGGCTTTTCCACGGT ATAATTTTCCTTGTTTGCTT 819 GCCTC-ACTTCCGTCAGCCGGGCTTTTCCACGGT ATAATTTTCCTTGTTTGCTT 840 GCCTC- ACTTCCGTC-AGCCGGGCTTTTCTACGT ATAATTTTCCTTGTTTGCTT 842 GCCTC-ACTTCCGTCAGCCGGGCTTTTCTACGGT ATAATTTTCCTTGTTTGCTT 844 GCCTC -ACTTCCGTCAGCCGGGCTTTTCTACGGT ATAATTTTCCTTGTTTGCTT 844 GCCTC-ACTGCCGTCCGCCGGGCTAT-CTAGAGT ATAATTTTCAGTGTTTGCTT 846 GCCTrC- ACTACTGTCACCTGGGCTTTTCTAAGGT 7- ATAATTTTCCTTGTTTGCTT 842 GCCTC-ACTCCCGTCACCCGGGCTTTTCTACGGT ATAATTTTCtTTGTTTGCTT 844 GCCTC- ACTCCCGTCACCCGGGCTTTTCTACGGT ATAATTTTCCTTGTTTGCTT 847 GCCTC-ACTCCCGTCACCCGGGCTTTTCTACGGT ATAATTTTCCTTGTTTGCTT 847 GCCTC-ACTCCCGTCACCCGGGCTTTTCTACGGT ATAATTTTCCTTGTTTGCTT 847 ACAAA-ATTGCCAAGAATGTGCAATATCCTGAGTGCCTTGACATGCAGCCATACATGTCT 866 GCTCCTGCAGTAGTAGAGGAGGCAAATATACGTT CACTAATCTAACATACAAG 837 00 00 00 8. 9 8. 10 8.3 8.11 4.2 a 4.3 4.2_b 4.4 o 4.1lb 8.1 8.7 8.6 8.8 8.5 8.2 4.1_-a o 8.9 8.10 8.3 8.11 4.2_a 4.5 4.3 4.2_b 4 .4 4 .1_b o 8.1 8.7 8.6 8.8 8.2 4. 1-a TTGTCAAATTTAGAAATTTTCATTTCA TCTCTATCAAATGTTGCTCCATT- ATCA TTGTCAAATTTAGAACTTTTCATTTCA TCTCTATCAAATGTTGATCCATT

ATCA

TTGTCAAAATTAGAACTTTTTATTTCA TCTCTATGAAATGTTGATCCATT

ATCA

TTGTCAAAATTAGAACTTTTTATTTCA- -TCTCTATGAAATGTTGATCCATT- ATCA TTGTCCAAATTAGAACTTTTTATTTCA- -CCTCTAGGAAACG7TGATCCATT- ATCA TTGTCCAA.ATTAGAACTTTTTATTTCA- -CCTCTAGGAAACGTTGATCCATT- ATCA TTGTCCAA.ATTAGAACTTTTTATTTCA TCTCTAGGAALACGTTGATCCATT ATCA TTGTCCAAATTAGAACTTTTTA CA- -TCTCTAGGAAACGTTGATCCATT ATCA TTGTCCAAATTAGAACTTTTTATTTTA -TCTCTAGGAAACGTTGATCCATT- ATCA TTGTCAACCTTAGAACATTTTATTTCG- -TCTCTATGAAATGTTGATCCATT ATCA TTGTCAAAATTAGAACATTTTATTTCA- -TATCTATGAAATCTTGATCCATT ATCA TTGTCAAAATTAGAACTTTTTATTTCA- -TCTCTATGAAATGTTGATCC-ATT---- -ATCA TTGTCAAAATTAGAACT=TTTATTTCA- -TCTCTATGAAATGTTGAGCCATT- ATCA TTGTCAAAATTAGAACTTTTTATTTCA- -TCTCTATGAAATGTTGAGCCATT- ATCA TTGTCAAAATTAGAACTTTTTATTTCA- -TCTCTATGAAATGTTGATCCATT ATCA CAGCAGAkACACAGGACCTCTTGTCTATGTCCTCTATGCTGTGCTGGTCCACGCCGGGTGG -GCAGTAGGCACTGTACCATAAACAAG-ACACTGTGGGGGTTCAGACCAGG

GGCAA

CAAGAGAAAATTCCCTCTTAAAGTGTTATTCT*

CATACGTATGA -AAATATTATCACCGTGCTGTGAGATACGTTGTTTTTATTTTCATCAA CATACGTATGA- AAATATTATCACCCATGCTGTGAGATACGTTGTTTTTATTTTCATCAA

CATACGTATGG-AAAGACTATCACCCATGTGTGAGATACGTTGTTTTTATTTTCATCAA

CATACGTATGG-AAATATATCACCATGTGTGAGATACGTTGTTTTTATTTCATCA

CATACGTATGG -AAATATTATCACACATGCTGTGAGATACGTTGTTTTTATTTTCATCAA CATACGTATGG -AAATATTATCACACATGCTGTGAGATACGTTGTTTTTATTTTCATCAA CATACGTATGG -AAATATTATCACACATGCTGTGAGATACGTTGTTTTTATTTTCATCAA CATACGTATGG -AAATATTATCACACATGCTGTGAGATACGTTGTTTTTATTTTCATCAA CATACGTATGG -AAATATTATCACCACGCTGTGAGATACGTTGTTTTTATTTTCATCAA CATACACATG AAATATTATCACCACTGTCAGATACGTTGT=TTTATTTTCATCAC CGTACGTATGG -AAATAGTATCAGCCAATGCTGTGAGATAAGTTGTTTTTATTTTCGTCAA CGTAAGTATGG -AAATAGTATCACCCACGCTGTGAGATACGTTGTTTTTATTTTCATCAG CATACGTATGG- AAACAGTATCACCCATGCTGTGAGATACGTTGTTTTTATTTTCATCAG CATACGTATGG -AAACAGTATCACCCATGCTGTGAGATACGTTGTTTTTATTTTCATCAG

AGTTGTCACAACGGACATTACTTCTCTTATGTCAAAGTTCAAGAAGGCCAGTGGTATAAA

AGTGGGGATTG ATAGGGCTAGTAAAGTCTAGGAAGTGTTCACTAACAAAATGTCTAA

*GTAATTGATCTTTATTTCATTTTGT

TTCTTTAATAAACCAAAGGTTATAGTTGGGATACCTTCTGATTTCTCAAGTTTTTTGTTT

TTCTTTAATAAACCAAAGGTTATAGTTGGGATACCTTCTGATTTCTCAAGTTTTTTGTTT

TTCTTTAATAAACCAAAGGTTATAGTTGGGATACCTTCCGATTTCTCTAGTTTTTGTTT

TTCTTTAATAAACCAAAGGTTATAGTTGGGATACCTTCCGAGTTCTCTAGTTTTTTGTTT

TTCTTTAATAAACAAACGGTTATAGCTGGGATACCTTCTGAGTTCTCAAGTTTTTTGTTT

TTCTTTA.ATAAACAAACGGGTATAGCTGGGATACCTTCTGAGTTCTCAAGTTrTTTGTTT

TTCTTAATAAACAAAAGGGTATAGCTGGGATACCTTCTGAGTTCTCAAGTTTTTTGTTT

TTCCTTAATAAACAAAAGGTTATAGCTGGGATACCTTCTGAGTTCTCAAGTTTTTTGTTT

TTC TAATAAAAAAAGGTTATAGCTGGGATACCTTCTGAGTTCTCAAGTTTTTGTTT TTCT- -AAGAAAAAAAGCTATAGTTGGGATACCTTCTGATTTCTCAAGGTTTTTGTTT

TTCTTTAATAAACAAAAGCTTATAGTTGGGATACCTTTGATTTCTCAAGTTTTTTGTTT

TTATTTAATAAACAAAAGCTTATAGTTGGGATACCTTTGGATTTCTCALAGTTTTTTGTTT

TTCTTTAATAAACAAAAGCTTATAGTTGGGATACCTTTGGATTTCTCAAGTTTTTTGTTT

TTCTTTAATAAACAAAAGCTTATAGTTGGGATACCTTTGGATTTCTCAGTTTTTT

ATGGATGATGCCGAGGTCACTGCCTCTGGCATCACCTCTG

TCCTGAGTCAACAGGCC

TTATTAACTAAACTAAATGGTTTC- TCAACATGACCTAATTAATTGTAACTTACTATAAA 921 919 871 871 873 894 896 898 898 900 896 898 901 901 901 926 891 980 978 930 930 932 953 955 957 957 959 955 957 960 960 960 986 948 1040 1038 990 990 992 1013 1015 1017 1016 1016 1015 1017 1020 1020 1020 1043 1007 8.9 0 8.10 8.3 8.11 4 .2_a 4 .3 4.2_b 4 .4 4.1 Ib 8.1 8.7 8.6 8.8 8.2 4. 1_a 00 8.9 8.10 8.3 8.11 j) 4.2a 4 .3 4.2_b 4.4 00J 4 .1Ib 8.1 8.6 o 8.8 (i 8.5 00 8.2 8.1 8.3 8.11 4.2_a 4.5 4 .3 4 .2_b 4 .4 4 4.1_b o 8.1 8.7 8.6 8.8 8.2 4 .1-a 8.9 8.10 8.3 8.11 4.2 a 4 .5 4.3 4.2_b 4 .4 4.1_b 8.1 8.7 8.6 8.8 8.2 4 .l1a CATGTTTTCTT-- CAGGTTTTCTT-- CATGTTTTCTTTCTTTTTTTTTTTTTTTTTTTT GAGACGGGGTCTCGCTCT

CATGTTTTCTTTCTTTTTTTTTTTTTTTTTTTTTTTTTTTTGAGACGGGGTCTCGCTCT

CGTGTTTTCTT-- CGTGTTTTCTT-- CGTGTTTTCTT-- CGTGTTTTCTT-- CGTGTTTTCTT-- CATATTTTCTT-- CATGTTTTCTT-- CAAGTTTTCTT-- CATGTTTTCTT-- CATGTTTTCTT-- CAAGTTTTCTT-- TATGTCCTCTTTTACATCC-- TGGTTGTTTGTTCA 1051 1049 1041 1050 1003 1024 1026 1028 1027 1027 1026 1028 1031 1031 1031 1062 1021 GTCGCCCAGGCCGGACTGCGGACTGCAGTGGCGCATCTCGGCTCCTGCAAGCTCCGCT 1101 GTCGCCCAGGCCGGACTGCGGACTGCAGTGGCG TaTCGGCTCACTGCA-GCTCCGCT 1110 TCCCGGGTTCACGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGACTACAGGCGCCC 1161 TCCCGGGTTCACGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGAaTACAGGCGCCC 1170 00

;Z

0 0

CA

8.9 8.10 8.3 8.11 4.2_a 4.3 4.2 b 4.4 4.1_b 8.1 8.7 8.6 8.8 8.2 4.-1_a 8. 9 8.10 8.3 8.11 4 .2_a 4.3 4.2_b 4.4 4.1_b 8.1 8.7 8.6 8.8 8.2 4 .1-a A

GCCACCGCGCCCGGCTAATTTTTTGTATTTTTAGTAGAGACGGGGTTTCACTTTGTTAGC

GC -ACCGCGCCCGGCTAATTTTTTGTATTTTTAGTAGAGACGGGGTTTCACCTTGTTAGC 1052 1050 1221 1229 CAGGATGGTCTCGATCTCCTGACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGG 1281 CAGGATGGTCTCGATCTCCTGACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGG 1289 8.9 8.10 8.3 8.11 4.2_a 4.3 4.2_b 4 .4 4.1_b 8.1 8.7 8.6 8.8 8.2 4 .l1a

APACTGCCGTCGCAC

AACTGCCGTCGCAC

GATTACAGGCGTGAGCCACCGCGCCCGGCCGTTTCATGTTTTCTTAAACTGCCATCGCAC

GATTACAGGCGTGAGCCACCGCGCCCGGCCGTTTCATGTTTTCTTAAACTGCCATCGCAC

AAACTGCCGTCGCAC

AAACTGCCGTCGCAC

AAACTGCCGTCGCAC

AAACTGCCGTCGCAC

AAACTGCCGTCGCAC

AAACTGCCCTCCCAC

AAACTGCCGCCGCAC

AAACTGCCGCCGC-AC

AAACTGCCGCCGCAC

AAACTGCCGCCGCAC

AAACTGCCGCCGCAC

ACAAGAGTGAATGGGAAAGACAC

TAAACCTTAATCTTTT

1066 1064 1341 1349 1018 1039 1041 1043 1042 1042 1041 1043 1046 1046 1046 1085 1037 00 8.9 OJ~ 8.10 ;Z 8.3 8 .11 4 .2 -a 4 .3 4 .2_b 4.4 00) 4.1 b 8.1- 8.7 8.6 8.8

CK

5 8.5 00 8.2 4 .l1a o 8.9 8.10 8.3 8.11 4 .2_-a 4.5 4.3 4 .2_b 4 .4 4.1_b o 8.1 8.7 8.6 8.8 8.2 4. 1_a 8.9 8.10 8.3 8.11 4-2_a 4 .3 4.2_b 4.4 4.1_b 8.1 so 8.7 8.6 8.8 8.2 4.l1a GTCCAAAACCACTCGCTATGCAATGTCTTG -ACCATCTCTCTTTTCTGGCAAATATAT 1125 GTCCGAAACCATTCACTATACAATGTCATT -TTCATCTCTCTTTTCTGGCACACATAT 1123 ATCCGAAATCATTCACTTACAATGTCATGACCATCTCTCTTTCCTGGCCATAT 1400 ATCCGAAATCATTCACTATACAATGTCATG-ACCATCTCTCTTTTCTGGCAAACATAT 1408 GTCCGAAACCGCTCACTATGCAGTGTCATGACCGTCTCTCTTTTCTGGCACATAT 1077 GTCCGAAACCGCTCACTATGCAGTGTCATG -ACCGTCTCTCTTTTCTGGCAAACATAAAT 1098 GTCCGAAACCGCTCACTATGAGTGTCATG-ACCGTCTCTCTTrTCTGGCAAACATAT 1100 GTCCGAACCGCTCACTATGCAGTGTCATGACCGTCTCTTTTCTCAACATAT 1102 GTCCGAACCGCTCACTATGCAGTGTCATGACCGTCTCTCTTCTCCATAT 1101 GTCAGAAACTACTCACTATACAATGTCGTG-ACAATCTACATTTTCGGGCA.AACACAAT 1101 GTCCGAAACCACTCACTATACAATGTCAGG-ACCATCTCTCTTTTCTGGCACACATAT 1100 GTCCGAACCACTCACTATACAATGTCAGACCATCTCTCTTTTCTGGACACATAT 1102 GTCCGAAACCACTCACTATACAATGTC-AGG -ACCATCTCTCTTTTCTGGTACACATAT 1105 GTCCGAAACCACTCACTATACATGTCAGG -ACCATCTCTCTTTTCTGGTACACATAT 1105 GTCCGAAACCACTCACTATACAATGTCAGG -ACCATCTCTCTTTTCTGGCACACAT.AAT 1105 AGTGAGAGTGTGTCAAGAGGCAGGGAACC-AGAGCCCTCGGCGCTGA-AGACACAGAC 1142 GCA;AATGACTTTCCTTAAGTTCGTAACGGA 1097 TTTCGGAATGTCATCATTAGTCTCTCGGTGATTGCATTATTTCCCCAAGTCTTTTACA 1185 TTGCGGAATGTCATCAATTAGTCTCTCGGTGATTGCATGATTTCCCCAGTCTTACACA 1183 TTGGTGCTATATTTATGCGAGTTCCAGCTCC 1460 TTGGGATTGTCATCAATTAGTCTCTCGGTGACTGAATGATTTCCACA-GTCmCACA 1468 TTGGTGCTATATTTGGGTGAGTTCCAGC CC 1137 TTGGTGCTATATTTGGGTGAGTTCCAGCTCC 1158 TTGGGGATTGTCATCAATTAGTCTCTCGGGGATTGTGATTTCCCCGGCTTCA 1160 TTGGTGCTATATTTGGGTGAGTTCCAGCTCC 1162 TTGGGGATTGTCATCATTAGTCTCTCGGGGATTGCATGATTTCCCCGGCTTCT 1161 TTGGGGAATGTCATCAAATAGTCTCCCGCTGATTGCATGATT -CCACAAAGTCCTACACA 1160 TTGGGGATGTCATCAATTAGTCTCTCGGTGATTGCATGA CCCGTCmTCAA 1160 TTGGGGAATGTCATCAATTAGTCTCTCGGTGATTGCATGATTTCCCCAGTCTTTCACA 1162 TTGGAGCTATATTTGTGTGAGTTCCAGCTCC 1165 TTGGGGAAGTCATCAATTAGTCTCTCGGTGATTGATGATTTCCCCAAGTCTTTCACA 1165 TTGGGGAATGTCATCAATTAGTCTCTCGTGATTGTGATTTCCCCAGTCTTTCACA 1165 A- GGCGAGCAACG -CAAGGAGAGCTCAAGAGAGACTACCCCTGCCTCCAGG TACCCGA 1198 CCACATCATTCTAATGAACTTAGTGTCCAATAACATGACTCTCAGTCGTCCCACGGA 1157 GTTGTGGATATTTTCAATCGGAGTCAGCTAG 1245 CTCTACATTGTGCACTGAGTATCTCTTCAGACTTTAGTGCATGTTTCTACCACTTGATGC 1243 GTCTACTTTGTGCACTGAGTATCTCTTCAAACTTCAGTGT -GTTTCTACCATATGATGC 1518 GTCTACTTTATGCACTGAGTATCTCTTCAAACTTCAGTGTATGTTTCTACCATTTGATGC 1528 GTTCTGGATATTTTCAATCGGAGTCACTTAT 1197 GTCTACTTTGTGCACTGAGTATCTCT'TCAAACTTCAGTGCATGTTTCTACCATTTCATGC 1218 GTCTACTTTGTGCACTGAGTATCTCTTCAAACTTCAGTGCATGTTTCTACCATTTGATTC 1220 GTCTACTTTGTGCACTGAGTATCTCTTCAA.ACTTCAGTGCATGTTTCTACCATTTGATCC 1222 GTCTACTTTGTGCACTGAGTATCTCTTCAACTTCAGTGCATGTTTCACCATTTGATGC 1221 GTCTACATTGTGCACTGAGTATCTCTTCAAACTTCAGTGCTTCTTTCTACCATATGATGC 1220 GTCTACTTTGTGCAATGAGTATCTCTTCAAACTTCAGTGCATATTTCTACCATTTGATGC 1220 GCCTACTTTGTGCACTGAGTATCTCTTCAAACTTTAGTGCATGTTTCTACCATTTGATGC 1222 GTCTACTTTGTGCACTGAGTAACTCTCCAAACTTCAGTGCATGTTTCTACCATTTGATGC 1225 GTCTACTTTGTGCACTGAGTAACTCTCCAACTTCAGTGCATGTTTCT~ACCATTGATGC 1225 GCCTACTTrGTGCATGAGTATCTCTTCAAACTTTAGTGC-ATGTTTTACCA=GATGC 1225 GTTGGACGAGCACTTGGTGGAAAGAGCCACTCAGGAAGCAC-CTTAGACCACTGGAAAT 1257 AGTTATTTTGTGTGCATAGTACATCTCTGTGAATATGCCTTGAOTATGGAGGACAC 1217 00 8.9 CI 8.10 8.3 ;Z 8.11 4 .2 a 4.3 4.2 b 4.4 D 4.1lb 00 8.1 8.7 8.6 8.8 8 .5 8.2 00 4.lIa S 8.9 8.10 8.3 8.11 4.2_a 4 .5 4 .3 4 .2-b 4.4 4.1_b 2 8.1 8.7 8.6 8.8 8.2 4.1 Ia 8.9 0 8.10 8.3 8.11 4.2_a 4.3 4. 2_b 4.4 4. 1_b 8.1 8.7 8.6 8.8 8.2 4.1la TTTATTATTCAGCAATCTAGCTTCCACAAGAGCATTTAATGTAAAGACTTGTCT

-TTTTC

TTTATTACTT- GCCATCTAGCTTCCACAAGAGCATTTCATGCAAAGACTTCTCT -TGTTC TTTATTATTTGGCAACCTAGCTTCCAAAAGAGCATTTCATGCAAAGACTTGTCT

-TGTTA

TTTATTATTTGGCAACCTAGCTTCCAAAAGAGCATTTCATGCAAAGACTTGTCT

-TGTTA

TTTCTTATTTGGCAATCTAGCTTCCACAAGAGCATTTCACGCAAAGACTTGTCT

-TGTTC

TTTCTTATTTGGCAATCTAGCTTCCACA.AGAGCATTTCATGCAAAGACTTGTCT

-TGTTC

TTTCTTATTTGGCAATCTAGCTTCCACAAGAGCATTTCATGCAAAGACTTGTCT -TGTTC TTTATTATTTGGCAATCTAGCTTCCACAAGAGCATTTCATGCAAAGACTTGTCT

-TGTTC

TTTATTATTTGGCAATCTAGCTTCCACAAGAGCATTTCATGCAAAGACTTGTCT

-TCTTC

TTTATCATTTGGCAATCTAGCTTCCACAAGAGCATTTCATGCAAACACTTGTCT

-TGTTG

TTTATTATTTGGCAACCTAGCTTCCACAAGAGCATGTCAGGCAAAGAGTTCTCT -TGTTC TTTATTATTTGGCAGCCTAGCTTCCACA-AGAGCATTTCATGCAAAGACTTGTCT -T'GTTC TTTATT- TGGCAGCCTAGCTTCCACALAGAGTATTTCATGCAAAGACTTGTCT -T'GTTC TTTATT- TGGCAGCCTAGCTTCCACAAGAGTATTTCATGCAAAGACTTGTCT -TGTTC TTTATTATTTGGCAGCCTAGCTTCCACA-AGAGCATTTCATGCAAAGACTTGTCT -TGTTC

TCCTCCAAGAGCAAAACAAAACGAAGCCTGAGTTCAACGTCAGAAAACTTGAAGGTACCC

TT-ATTATCCAAACAGAGACATTCCACTGGTGCTAGAGAGCCACAGAC CGAAGTTTTC TCACGCAGTATTATCGAAAGACATAGTGA*TG

AGTA

TCCACTGGCAGGTAATTTCACTCGGATAGAGAATCATTAGGCTGAACATGGAAAGGTTAT

TCCACTGGCAGGTAATTTCACTCGGATAGAGAATCAATAGGCTGAACGTGGAAAGCTTAT

TCCACTGGCAGCTAATTTCATTCGGATAGAGAATCAATAGGCTGAACGTGGAAAGCTTAT

TCCACTGGCAGGTAATTTCACTCGGATAGAGAATCAATAGGCTCAACGTGGAAAGCTTAT

TCCACTGGCAGGTAATTTCACTCGGATAGAGAATCAATAGGCTCAACGTGGAAAGCTTAT

TCCACTGGCAGGTAATTTCACTCAGATAGAGAATCAATAGGCTCAACGTGGAAAGCTTAT

TCCACTGGCAGGTAATTTC-ACTCGGACAGAGAATCAATAGGCTCAACGTGGAAAGGTTAT

TCCACTGGCAGGTAATTtCACTCGGACAGAGAATCAATAGGCTCAACGTGGAAAGGTTAT

TCCACTGGCAGTAATTCAACTCGGATAGAGAATCAATAGGCTCAACGTGGAAAGGTTAT

TCCACTGGAAGTAATTCACCATAGAGAATCAATAGGCTCAACGTGGAAAGGTTAT

TCCACTGGAAGTAATTTCACTCGGACAGAGAATCAATAGGCTGAACGTAGAAAGGTTAT

TCCACTGGCAGTAATTTCACTCGGATAGAGAGTCAATAGTCTGAACGTGGAAAGGTTAT

TCCACTGGCAGGTAATTTCACTCGGATAGAGAATCAATAGTCTGAACGTGGAAAGGTTAT

TCCACTGGCAGTAATTTCACTCGGATAGAGAGTCAATAGTCTGAACGTGGAAAGGTTAT

TGCCTcccAACGTACTTGTGATTCATCAATCAAAATACAAGTGTGGGATGAAAAA-

CCAT

TCTGCCTACTGGAAATAAAGC--CAAGCTTTCTTCTTTCCTCAGCCGTGAGGATTGC

CGTGAGTTTTGTCCCGTTCC* TTTGAGAAAAAG

CGCTGGGAGGTCTGTTTGATTCCACGGATCTCTCCTTTTTTATTAGGAAAAAAATATC

CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTCTTATTAGGGAAAAAATACAC

CGCTGGAAGGTTTGTTTGTTTCCACGGATCTCTCCTTTCTTATTAGGGAAAAAAATACGC

CGCTGGAAGGTCTGTTTGTTTCCACGGATC1'CTCCTTTCTATTAGGGAAGAAAATACC CGCTGGAAGGTCTGTT'rGATTCCACGGATCTCTCCTTTCTCATTAGGGAAGAAAATACGC

CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTCTC.ATAGGGAAGAATACGC

CGCTGGAAGGTCTGTTTGAT'rCCACGGATCTCTCCTTTCTCACTAGGGAAGAAAATACGC

CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTCTCACTAGGGAAGAAAATACGC

CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTCTCATAGGGAAGAAAATACGC

CGCTGGAAGGTCTG CATTCCACGGATCTCTCCTTTCTATTAGGAAGAAAAATACGC

CCCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTCTTATTAAGGAAGAAAATACGC

CCCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTATTATTAAGGAAGAAATATACGC

CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTATTATTAAGGAAAAATATACGC

CGCTGGAAGGTCTGTTTGATTCCACGGATCTCTCCTTTATTATTAAGGAAAAAATACGC

CATCCTGAA- -CAGCAA.AGCTCCCTGCTAAACCTCTCTTCGACGAACCCGACAGATCAGG TGACCTCC- -TCTTTATCATTCTCTCTCTCTCTTTTTTTTTAATGAGCCAAGCTCCACCA 1304 1301 15 77 1587 1256 1277 1279 1281 1280 1279 1279 1281 1281 1281 1284 1317 1274 1364 1361 16 37 1647 1316 1337 1339 1341 1340 1339 1339 1341 1341 1341 1344 1376 1329 1424 1421 1697 1707 1376 1397 1399 1401 1400 1399 1399 1401 1401 1401 1404 1434 1387 00 00) 00) CAi 8.9 8.10 8.3 8.11 4.2_a 4 .5 4 .3 4 .2_b 4 .4 4. 1_-b 8.1 8.7 8.6 8.8 8.2 4.1 a TGTGCTAATTACTGTACTTCATTGCCTATTCTGGTAGAG

CGCACTTCAGA

TGCGCTAATTACTATACTTCATTGAATTCTGGTAGAG

CGCACTTCCGA

TGTGCTAAATACTATACTTCATTGACTATTTCAGGTCAGAG

CGCACTTCCGA

TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTAGAG

CGCACTTCCGA

TGTGCTAAATACTATACTTCATTGACTATTCTCAGTCAGAG

CGCACTTTCGT

TGTGCTAAATACTATACTTCATGACTATTCTCAGGTAGAG

CGCACTTTCGA

TGTGCTAA-TACTATACTTCATTGACTATTCTCAGTCAGAG

CGCACTTTCGA

TGTGCTAMTACTAACTTCATTGATATTCTCAGGTAGAG

CGCACTTTCGA

TGTGCTAATATATACTTCATTGACTATTCTGGTAGAG

CGCACTTTCGA

TGTGCTAAATATTATACTTCATTGACTATTCTAGGTCAGAG

CACACTTCCGA

TGTGCTAAATACCATACTTCATTGACTATCTCAGGTCAG-G

CACACTTCCGA

TGTGCTAAATACTATACTTCATTGACTATTCAGGTAGAG

CGCACTTCAGA

TGTGCTAAATACTATACTTCATTGACTATCTCAGGTAGAG

TGCACTTCAGA

TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTAGAG--TGCACTTCAGA

TGTGCTAAATACTATACTTCATTGACTATTCTCAGGTCAGAG--CGCACTTCAGA

AGT-CCATGAACACTGGCACACTCGCTTCTCT -GCAAGGGAG--GAC-

CAGGAGA

AATAATAAGATAAACTTTGTGCA.AGACTTGGTAAGAGTAGAGTGTCTGACACCTTATGGT

1 1 1 1 1 1 1 1 1 a a

I

2 o 8.9 8. 10 8.3 8.11 4.2_a 4.5 4 .3 4. 2_b 4 .4 4.1_b o 8.1 8.7 8.6 8.8 8.2 4. 1_a 8.9 ~O 8.10 8.3 8.11 4.2_a 4.3 4. 2_b 4.4 4.1_b 8.1 8.7 8.6 8 .8 8.2 4.l1a CTTCT- CCTTCTATCGCTGAAAGGAT -GATGGTATCTGCCAAA.AGCACATAC

-TCGGA

CTTCTTGTCCTTCCATCGCTGAGAGGAT-GATGGTATCTGCCAAA.AGCACATAT-

TTGGA

CTTCTTCTCTTTCCGTCGCTGAGAGGAT-GATGGTAGCTGCCAAAAGCACATAC-TTGGA

CTTCTTCTCTTTCCGTCGCTGAGAGGATGATGGTAGCTGcCAAGCTAC

-TTGGA

CTTCTTGTCCTTCCGTCGCGGAGAGGAT-GATGGCAGCTGCCAAAAGTACATAC-TTGGA

CTTCTTGTCTTTCCGTCGCTGAGAGAT-GATGGCAGTTGcCAAAAGTACATAC

-TTGGA

CTTCTTGTCCTTCCGTCGCTGAGAGGAT-GATGGCAGCTGCCAAAAGTACCTAC-TTGGA

CTTCTTGTCCTTCCGTCGCTGAGAGGAT-GATGGCAGCTGCCAAA.AGTACCTAC-TTGGA

CTTCTTGTCCTTCCGTCGCTGAGAGGAT-GATGGCAGCTGCCAAAAGTAACTAC-TTGGA

ATTCTTGTCC'rTCGGTCACTGAGAGGAT- GATGGTAGCTGCCAAAAGTACATAC-

TTGGA

TTTCTTGTCCTTCTGTCGCTGAGAGGAT-GATGATAGCTGCCAAAAGTACATAC

-TTGGA

CTTCTTGTCCTTCCGTTGATGAGAGGAT-GACGGTAGCTGCCAAAAGTACATAC-TTGGA

CTTC'=TGTGCTTCCATCGCTGAGAGGAT-GATGGTAGCTGCCAAAAGTACATAC-

TTGGA

CTTCTTGTGCTTCCATCGCTGAGAGGAT-GATGGTAGCTGCCAAAAGTACATAC-TTGGA

CTTCTTGTCCTTCCGTTGATGAGAGGAT-GACGGTAGCTGCCAAAAGTACATAC-TTGGA

GCCAAAGGGAAGA- ACAAACACTGCAAGAGGGCTCTGC-TTGTG

GCTATAATACTCAAAGCA.AGCAAAATCGCCTAGGACCAGAAGGGAGTCACATAGGA

AGT~~ ACTCACCACCCCC*C

*CA

AGT- ACATCCCAGCACAAACACACACACACACA----------------

CACGCACACA

CATCCCGGCACAALACACACACACACACA----------------

CACACACACA

GGT- TCATCCCAGCACAAACACACACACACAAA

CACACAAACA

GGT- TCATCCCAGCACAAACACACACACACAAA---------------CACACAAACA AGT--- TCATCCCAGCACAAACACACACACACACGCG-CCCCCCCCACACACACACACACG AGT TCATCCCAGCACAAACACACACACACACACGCCCCCCCC---CACACACACACA GGT- TCATCCCAGCACAAACACACACACACACACGCCCCCCCC

CACACACACA

GGT- TCATCCCAGCACAAACACACACACACACACGCCCCCCCC

CACACACACA

GGT- TCATCCCAGCACAAACACACAACACACACGCCCCCCCC

CACACACACA

AGT TCATCCCAGCACCAAACACACATAACACACAC

CCACACACACA

AG- TCATCCCAGCACAAGCACACACACACATAAACCACACA--CACACACACA AGT TCATCCCAGCACAAGCACACACACACACA-

-CACAAACA--CACACACACA

AGT- TCATCCCAGCACAAGCACACACACACACA-

-CACAAACA---CACACACACA

AGT- -TCATCCCAGCACAAGCACACACACACACA

-CACAAACA---CACACACACA

TGCCAGTGATCTCAGTGGAAGTGCCGACCCACACGTAGGGGAGA---AAACACACA

AATCTAGAAGACCTATTGGCTGAGAGACCTGCAGCCTCATAGTCATTAGCTCTC

-CATA

479 476 752 762 431 452 454 456 .455 .454 454 .456 .456 .456 .459 .484 .447 1534 1534 1810 1820 1489 1.510 1.512 1514 1.513 1512 1.512 1514 1514 1514 1517 1526 1507 1576 1576 1852 1862 1544 1567 1566 1566 1566 1564 1564 1564 1564 1564 1567 1580 1566 00 8.9 CI 8.10 O 8.3 8.11 4.2 a 4 .5 4 .3 4 .2 b 4 .4 4 .1_b 00 8.1 8.6 8.8 S 8.5 8.2 00 4 .l1a CK~ 8.9 8.10 8.3 8.11 4 .2_a 4 .3 4.2_b 4.4 4.1_b 8.1 8.7 8.6 8.8 8.2 4 .1_a 8.9 8.10 8.3 8.11 4.2_a 4 .5 4 .3 4.2_b 4.4 4.1_b 8.1 8.7 8.6 8.8 8.2 4 .lIa AACACACATACTCACAC------------- GGTTTCA- -TAGGTAAAGATTTCTTCCCTGA CACACACACACACACAC------------- GGTTTCA- -TAGGTAAAGATTTCTTCCCTGA CACACACA GGCTTCA- -TAGGTAAAGATTTCTTCCCTGA CACACACA GGCTTCA- -TAGGTAAAGATTTCTTCCCTGA AACACACTCACACACACACACGCACAC GGTTTCC- -TAGGTAA.AGATTTCTTCCCTGC AACACAATCACACACACACACTCACAC -GGTTTCC- -TACGTAAAGATTTCTTCCCTGC AACACACTCACACACACACACGCACAC GGTTTCC- -TAGGTAAAGATTTCTTCCCTGC AACACACTCACACACACACACGCACAC GGTTTCC- -TAGGTAAAGATTTCTTCCCTGC AACACACTCACACACACACACGCACAC -GGTTTCC- -TAGGTAAAGATTTCTTCCCTGC AACACACTCACACACACACACACACACACGGTTTCC- -AAGGTAAAGATTTCTTCCCTGC CACACACACACACACACAGACACACACAGGGTTTCA- -TAGGTAAAGATTTCTTCCCTGA CACACACACACAGAGAGAGATACACACACGGTTTCA- -TAGGTAAAGATTTCTTCCCTGA CACACACACACACACACAGACACACACACGGTTTCA- -TAGGTAAAGATTTCTTCCCTGA CACACACACACACACACAGACACACACACGGTTTCA- -TAGGTAAAGATTTCTTCCCTGA CACACACACACAGAGAGAGATACACACACGGTTTCA- -TAGGTAAAGATTTCTTCCCTGA C-ACACACACACACACAC------------- GGTTTCA- -TAGGTAAAGATTTCTTCCCTGA GCAACTCTCACATGAAATGAAGTCAGTGGTGTTTCAAGTGCTTGAAACCCTCTTTACT- C CATTTTCTAATA GCA ***GTG*CATGTCCA ***GTTCC* CATTCTTTTACCTAAAATAAG GCAACTGTGTGGCCACTGTCCCAACCCGGTTACCT CATTGTTTTACCTAAAATAAG GCAACTGTGTGGCCACTGTCCCAACCCGGTTACACT CATTGTTTTACCTAAAATAAG- GCAACTGTGTGGCCACTGTCCCAACCTGGTTACACT CATTGTTTACCTAAAATAAG GCAACTGTGTGGCCACTGTCCCAACCTGGTTACACT CATTGCTTTACCTAAAATAAG GCAACTGTGAGGCCACTGTCCCAACCCGGTTACACT CATTGCTTTACCTAAAATAAG- -GCAACTGTGTGGCCACTGTCCCAACCCGGTTACACT C.ATTGCTTTACCTAAAATAAG GCAACTGTGAGGCC.ACTGTCCCAACCCGGTTACACT CATTGCTTTACCTAAAATAAG- GCAACTGTGAGGCCACTGTCCCAACCCGGTTACACT CATTGCTTTACCTAAAATAAG- GCAACTGTGAGGCCACTGTCCCAACCCGGTTACACT CATTCTTTACCTAAAATAAG GCAACTGTGTGGCCACTGTCCCAACCCGGTTACACT CATTCTTTTACCTAAAATAAG GCAACTGTGCGGCCACTGCCCAACCCGGTTACACT CATTCTTTTACCTAAAATAAG GCAACTGTGTGGCCACTGTCCCAACCCGGTTACACT CATTCTTTTACCTAAAATAAG GCAACTGTGTGGCCACTGTCCCAACCCGGTTACACT CATT-CTTTACCTAAAATAAG--- GCAACTGTGTGGCCACTGTCCCAACCCGGTTACACT CATT-TGTACCTAAAATAAG GCAACTGTGTGG-CCACTGTCCCAACCCG- TTACACT TACTTCTAAATGTGAATTAATTATGCAAATTTACTAGCAGTTGCTAGACCT -CAAAAGC CATATTATATGTGCCTATCATCCTGAGGAGTAATTT- GATGAAGGTGTTTTAGAAGT CATATTACATGTGTCTATCAGCCTGAGGAGTAGTTT GATTCAGGTGTTCTAGAAGT CATATTACATCTGCCTATCATCCTGAGGAGTAATGT---- GATTCAGGTGTTCTAGAAGT CATATTACATCTGCCTATCATCCTGAGGAGTAATGT GATTCAGGTGTTCTAGAAGT CCTATTATATGTGCCTATCATCCTGAGCAGTAATTT- GATTCAGGTGTTCTGGAAGT CCTATTATATGTGCCTATCATCCTGAGGAGTAATTT- GATTCAGGTGTTCTGGAAGT CCTATTATATGTGCCTATCATCCTGAGGAGTAATTT GATTCAGGTGTTCTGGAAGT CCTATrATATGTGCCTATCATCCTGAGGAGTAATTT GATTCAGGTGTTCTGGA.AGT CCTATTATATGTGCCTATCATCCTGAGGAGTAATTT- GATTCAGGTGTTCTGGAAGT CCTATTATATGTGCTTATCATCCTGAGGAGTAATCT- GATTCAGGTGTTCTGGAAGT CATATTATATGTGCCTATCACCCTGAGGAGTAATTT- GATTCAGGTGTTCTAGALAGT CATATTATATGTGCCTATCACCCTGAGGAGTAATTT- GATTCAGGTGTTCTAGAAGT CATATTACATGTGTCTATCAGCCTGAGGAGTAATTT- GATTCAGGTGTTCTAGAAGT CATATTACATGTGTCTATCAGCCTGAGGAGTAATTT- GATTCAGGTGTTCTAGAAGT CATATTATATGTGCCTATCACCCTGAGGAGTAATTT- GATTCAGGTGTTCTAGAAGT CATATTACATGTGTCTATCACCTAGGAGTAGTTT GATTCAGGTGTTCTAGAAGT

AAAATAATCAGGCATTATTCTACTAAGTATTGGTCTCCATAACTCCTCTATTTTCTTTAG

1622 1622 1892 1902 1600 1623 1622 1622 1622 1622 1622 1622 1622 1622 1625 1626 1625 167 9 167 9 1949 1959 1657 1680 1679 1679 1679 1679 1679 1679 1679 1679 1679 1683 1683 1735 1735 2005 2015 1713 1736 1735 1735 1735 1735 1735 1735 1735 1735 1735 1739 1743 00 8.9 8.10 ;Z 8.3 8.11 4.2 a 4 .3 4 .2_b 4 .4 00 0 4.1 b 8.1 8.7 8.6 8.8 8 .5 00 8.2 0 B-9 8 .10 8.3 8.11 4 .2_a 4 .5 4 .3 4 .2_b 4 .4 4.1_b 8.1 8.7 8.6 8.8 8.2 4 .1_a 8.9 8.10 8.3 8.11 4.2_a 4.3 4 .2_b 4.4 4.1_b 8.1 8.7 8.6 8.8 8.2 4. 1_a CATGATGTGGACTGTGTCTGTTGAATCCCAGCGATGCAGGGGAACACCCTGTGACTC 1795 CATGATGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCGGGACAACCCTGTGACTC 1795 CATGATGTGGGCTGTGTCTGTTGATTCCCAGCGATGCAAGGGGAACACCCTGTGACTC 2065 CATGATGTGGGCTGTGTCTGTTGATTCCCAGCGATGCAAGGGACACACCCTGTGACTC 2075 CATGCTGTGGGCTGTGTCTGTTGPLTTCCCAGCGATGCCAGGGGAACACCCGTGACTC 1773 CATGCTGTGGGCTGTGTCTGTTGATTCCCAGCGATGAGGGGACACCCCTGTGACTC 1796 CATGCTGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCCAGGGGACACP.CCCTGTGACTC 1795 CATGCTGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCCAGGACACCCTGTGACTC 1795 CATGCTGTGGGCTGTGTCTGTGTTCCCAGCGATGCCAGGAACACCCTGTGACTC 1795 CATGATGTGGGCTGTGTCTGTTGATTCCCAGCGATGAGGGGACACCCCTGTGACTC 1795 CATGATGTGGGCTGTGTCTGTTGAAMTCCCAGCGATGCAAGGGGACACACCCTGTGACTC 1795 CATGATGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACAACCCTGTGACTC 1795 CATGATGTGGGCTGTGTCTGTGATTCCCGCGATGCAAGGGGAACACCCTGTGACTC 1795 CATGATGTGGGCTGTGTCTGTTGAATTCCCAGCGATGCAAGGGGACACACCCTGTGACTC 1795 CAGTTGCGGCGTATCCACAGAGGAAACTTAT 1795 CATGATGTGGGCTGTGTTGTTGATTCCCGCGATGCAGGGGACCACCCTGTGACTC 1799 GAAAGTTAGTCTAAGACATTTGGCATAAGGCTATGCAGCTTGGTGGGTCAGCC 1803 ATT *TT* TGATG*TA*A* TGATG* TTATTCC* CC*TTGTGGGGGGGG185 ATTCCTTATTGGTGCTGATATTTGATTGGTTTATTGCGCACCTGATGGTGGGTGGGG 1855 ATTCCTTAATTGAGTGCTGACATTTGATTGGTTTATCGCGCACCTGATGGTGGGTGGGG 2125 ATTCCTTAATTAAATGCTGATATTTGATTGGCTTATCGCGCACCTGATGAGTGGGTGAGG 2125 CTTCCTGAATTATGCTGATATTTGATTGGCTTATCGCGCACCTGATGAGTAGGTGGGG 1835 CTTCCTGAATTGAGTGCTGATATTTGATTGGCTTATCGCGCACCTGATGAGTGTGG 1833 CTTCCTGATTGAGTGCTGTTATTTGATTGGTTATCGCGCACCTGATGAGTGGTGGGG 1856 CTTCCTGAATTGAGTGCTGTTATTTGATTGGCTTATCGCGCACCTGATGAGTGGGTGGGG 1855 CTTCCTGAATTGAGTGCTGATATTTGATTGGCTATCGCGCACCTGATGAGTGGGTGGGG 1855 CTTCCTGAATTGAGTGCTGATATTTGATTGGCTATCGCGCACCTGATGAGTGGGTGGGG 1855 ATTCCTTAGAGTGCTGATATTTGATTGTTTTCGCGCACCTGATGGGTGGGTGGGG 1855 ATTCCTTAATTGAGTGCTGATATTTGATTGGTTTTATCGCACACTGATGGGTGGGTGGGG 1855 ATCTATGGGTAATGTGGTACCCCTAGGGGGG 1855 ATTCCTTAATTGAGTGCTGATATtTGATTGGTTTATCGCAACCTGATGGGTGGGTGGGG 1855 ATTCCTTATTGAGTGCTGATATtTGATTGGTTTATCGCACACCTGATGGGTGG 3 GTGGGG 1855 ATTCCTTAATGAGTGCTGATATTTGATTGGTTTATCGGCCCTGATGGGTGGGTGGGG 1855 AGGAAGGATTCGTGGGGGTCTCCTTGAATACTGCTAATCTAGATCTTCAACC 1862 TGTTCGCTCTTGGTGCGGGTGAGTTATGTAGGGCTGATTTGGCCAGAGA.CTCGTTATT 1915 TGTTCGCGGTTGGTGGGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGAGCTCGTCATT 1915 TGTTCGCCGTTGGTGGGGGTGAGTTATATA.AGGGCTGATGCGGCCAGAGAGCTCGTCATT 2185 TGTTCGCCGTTGGTGCGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGAGCTCGTCATT 2195 TGTTCGCGGTTGGTGGGGTGACTACAGAAGGGCTGATGTGGCCAAGAGCTCGTCATT 1893 TGTTCGCGGTTGGTGGGGTTGACTTACAGAAGGGCTGATGCG -CCAGAGAGCTCGTCATT 1915 TGTTCGCGGTTGGTGGGGGTGACTTATAGAAGGGCTGATGCGGCCAGAGAGCTCGTCATT 1915 TGTGTTGTGGTATAAAAGCGTCGCGGGTGCT 1915 TGTTCGCGGTTCGTGGGGTGACTTACAGAGGGCTGATGCGGCAGAAGCTCGTCATT 1915 TGTTCGCGTTGGTGTGGGTGAGTTATAGAAGGGC]TGATGCGGCCAGAGAGCTCGTCATT 1915 TGTTCGCGGTTGGTGGGGGTGAGTTCTATAAGGGATGATGCGGCCAGAGAGCTCGTCATT 1915 TGTTCGCGGTTGGTGGGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGAGCTCGTCATT 1915 TGTTCGCGGTTGGAGGGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGAGCTGGTCATT 1915 TGTTCGCGGTTGGAGGGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGAGCTGGTCATT 1915 TGTTCGCGGTTGGTGGGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGACTCGTATT 1915 TGTTCGCGGTTGGTGGGGGTGAGTTATATAAGGGCTGATGCGGCCAGAGAGCCCGTCATT 1919 TATTGCCCCTCAGTACTGTTG-GTCCCCTGTACTTGACTTTTCCCCTTAAGTTTG--ATT 1919 00 00 0 8.9 8.10 8.3 8.11 4.2_a 4 .5 4 .3 4.2_b 4.4 4.1_b 8.1 8.7 8.6 8.8 8.2 4. 1-a

TGAAGACTCTCTCGGAAGAGATAGCGTTTTTCTGCAACCTACGGTCCCAGCAGAAAAACC

TGAAGACTCTCTCGGAAGAGATAGCATCTTTCTGCAACCTGCGGTCCCAGCCGAAAAACC

TGAAGACTCTCTCGGAAGAGATAGAGTCTTTCTGCAACATAAGGTCCCAGCCGAAAAACC

TGAAGACTCTCTCGGAAGAGATAGCGTCTTTCTGCAACATAAGGTCCCAGCCGAAAAACC

TGAAGACTCTCTCGGAAGGGATAGCGTCTTTCTGCAACCTGTGGTCCCAG-AGACAAACC

TGAAGACTCTCTCGGAAGGGATAGCGTCTTTCTGCAACCTGCGGTCCCAGCAGAAAAACC

TGAAGACTCTCTCGGAAGGGATAGCGTCTTTCTGCAACCTGCGGTCCCAGCAGAAAAACC

TGA.AGACTCTCTCGGAAGGGATAGCGTCTTTCTGCAACCTGCGGTCCCAGCAGAAAAACC

TGAAGACTCTCTCGGAAGGGATAGCGTCTTTCTGCAACCTGCGGTCCCAGCAGACAAACC

TGAAGACTCTCTCGGAAGAGATAGCGTCTTTCTGCAACCTGCGGTCCCAGCAGAAAAACC

TGAAGACTCTCTCGGAAGAGATAGCGTCTTGCTGCAACCTGCGGTCCCAGCAGAAAAACC

TGAAGACTCTCTTGGAAGAGATAGCGTCTTGCTGCAACCTGCGGTCCCAGCAGAAAACC

TGAAGACTCTCTCGGA.AGAGATAGCGTCTTGCTGCAACCTGCGGTCCCAGCAGAAAAACC

TGAAGACTCTCTCGGAAGAGATAGCGTCTTGCTGCAACCTGCGGTCCCAGCAGAAAAACC

TGA-AGACTCTCTTGGAAGAGATAGCGTCTTGCTGCAACCTGCGGTCCCAGCAGAAAAACC

TGAAGACTC GGAAGAGATAGCGTCTTTCTGCAACCTGCGGTCCCAGCCGAAAAACC

CCATTTCCTA-ATATTATCCTTCCCTCTTCCTCCTCAGCAACTAGTCTTCTAAATTAGAAC

TT T A C T G TG G G G C T

TTGTGATCCTTGTTCCAGTCGACATGGAGGACGACTCACTCTACTTGGGAGGTGAGTGGC

TTGTGATCCTTGTTGCGGGCGACATG TTAAACACAATG AGCAGATATG 1975 1975 2245 2255 1953 1975 1975 1975 1975 1975 1975 1975 1975 1975 1975 1975 1979 2001 2001 2271 2281 2013 2001 2001 2001 2001 2001 2001 2001 2001 2001 2001 2001 2001

C,

8.9 8.10 8.3 8.11 4.2_a 4.3 4 .2-b 4.4 4.1_b 8.1 8.7 8.6 8.8 8.2 4. 1_a 8.9 8.10 8.3 8.11 4.2 a 4.3 4 .2_b 4 .4 4.1_-b 8.1 8.7 8.6 8.8 8.2 4.1I_a 00 0 0

CA

8.9 8.10 8.3 8.11 4.2_a 4.5 4.3 4.2_b 4.4 4.1_b 8.1 8.7 8.6 8.8 8.2 44_ Ia 8.9 8.10 8.3 8.11 4.2_a 4.3 4. 2_b 4.4 4 .1_b 8.1 8.7 8.6 8.8 8.2 4 .1_a 8.9 0 8.10 8.3 8.11 4 .2_-a 4.3 4. 2_b 4.4 4.1 b 8.1 0 8.7 8.6 8.8 8.2 4 .1 a A T G A T T T G G C T C C T G T G G C- G A C A G C T T G C T C C- G- A G- G C T T C C T C T G G-2 1 9 3 HDUB4.6 putative promoter sequence upstream of initiation ATG gcatgactgg gcacaccgat ctcggcatct c tccc tgtg~g ggcacaggaa gggccaaagg ggtcctgaag c agac ag tt gcccaggtcC gcattgctca agcatctttc gccttctgat tcacagtcct ccagggctgt atcgattggg cggctgcagg tgcttctggg taagcagtgc ggagcacacc ctcatcccat ttctttacac ctcccctcaa aataagaccC gatcattctc tcttttcttc tggcccatqa catcctcctt ctagaggcct aatcqgttat tccagggtct ctgaaaatgq ccccaggaca aaagacaagg aaaatcatcc tggCgCCgg gagcattcaa tgtgtgaagc tggctccttt ctttacatcc gaaagaaacg taatttcatg cctcaattcc 00 00 00 gccctgttcc ctgctaagcc tgtccacttt acaatgcgta caggatatgc: ggcacgctat cagggcctca tccaaattag ggaaatatta aacaaacggt taaactgccg ctggcaaaca ccaaaggctt tctaccattt gacttgtctt cgtggaaagg ggaagaaaat cactttcgac acttggaagt cacgaacaca gccattgctt ctattatatg tgtgggctgt tgaattgagt gcggt tggag actctctcgg atccttgttc ttaccgtcta agacagccg cggcagcatt actggaaatg acggcttatt cctctgtttc cttccgtcag aactttttat tcacacatgc tatagctggg tcgcacgtcc taAatttggg tcacagtcta catgctttct gttctccact ttatcgctgg acgctgtgct ttcttgtctt tcatcgcaga atcacacaca tacctaaaat tgcctatcat gtctg ttgaa.

gctgatattt ggggtgactt aagggat agc cagtcgacat agacatgttg a ag a ca cacc acaattttgg gaggcaacat ttggcctttt actccctgct ccgggctttt ttcacctcta tgtga gatac atac c ttctg gaaaccgctc gattgtcatc ctttgtgcac tafttggcaa ggcaggtaat aaggtctgtt aaatactata tccgtcgctg aaaaacacac cacacactca.

ggaaaatccc tagagccagg caaattctgt ccctcttact caccaaatgt gctaactgca ctccgatcct gaacgatcga cccactgaaa caagggccag tttaaacgtc tccgatgttt ccacggtata attttccttg ggaaacgttg atccattatc gttgttttta ttttcatcaa agttctcaag ttttttgttt' actatgczagt"'gtcatgaccg ziattagtctc tcggggattg tgagtatctc ttcaaacttc tctagcttcc acaagagcat ttcactcaga. tagagaatca tgattccacg gatctctcct cttczattgaC tattctcagg agaggaigat ggcagctgcc acacacacgc gcccccccca atcttcattc tcagggaaca attccaccat tgcgagaatc tattaaaaat ctccctgaga tttgcttttg a cat acg tat ttctttaata cgtgttttct tctctctttt catgatttcc agtgcatgtt ttcatgcaaa .ataggctcaa ttctcattag tcagaaagcg aaaagtacat cacacacaca cacggtttcc..tacgtaaaga .tttcttccct aaggcaactg tgtggcicact. gtcccaiaccc cc .tg aggagt .aattt~attdcaSggtgttctg ttcccagcga .tgc aa~ggga *cacaccctgt gattggctta tcgcg cacct gatgagtggg acagaagggc tgjatgc gcc agagagctcg gtctttctgc aacctgcggt cccagcagaa ggttacactc gaagt~catgc gactdcttcc, tg tgg tgt tc tcatttgaag aaaccttgtg HDUB34.7 putative promoter sequence upstream of initiation ATG tcctcagcgt cggtttttag ccatcatctt tggcctagtt ttttcctcat cccactgatc: cctaatggag atttaatgcc cattcactta. catacttgca actttgggaa gccgaggtgg catggtgaaa. ccccgtctct tgtaatccca gctactcagg gttgcagtga gccaagatta agaaaacaaa. aaacccaaaa tgatccaatg ccttcctttt tgtcttgtga tatttacaat gttctgagat gtctgctgtg tgctggaaag caggtcttgg attggttggc cagaagccca tccctccctc cctccctccc ggctctgctg gctgccaaga.

agaagagata. agaaattcca tttcacgcct gtaatcccag tccacaagag catttcacgc: ggatagagaa. tcaataggct acggatctct cctttctcat gactattctc aggtcagaaa gatggcagct gccaaaagta cacgcccccc cacacacaca taggtaaaga tttcttccCt gtcccaaccc ggttacgctc aggtgitctg gaagtcatgt cacaccctgt gactccttcc gatgagtggg tggggtgttc gcctggcata aacacctccc ccaaacccag attaaatcag gagtcggcca gtggatcacg actaaaaata aggctgaggc tgccattgca acttgcagag tctctttctc ctaggagaag tttgcaggta cgctatattt attgtcactc tctccaagat tgggccacca cagggctgat cacttgggag aaagacttgt caacgtggaa tagggaagaa gcgcactttc catacttgga cacacaaaca gccattgctt ctattatatg tgtgggctgt tgaattgagt gcggt tggtg agctgtttga ctccgtgtgt.

g aca cc ct a aag6aattc t ggtgtgteggaggtcaagaA caaaaattaa: aggcgatttg ctccagcctg tgaat ttagg aaata ttt tg.

gcaggagaga ccttccctca ataccatggt tctctctctg atccagtaac gcaaaaaggg aagaaagacc aacccaggaa ggtggtttgg agctgctgac gattctcagg ctcadacctg ttcgagacca ctggtgtagc cttgaacctg ggcaacagag aaaccatgaa agccaggtac gaactaagaa attt cc cta c acttcccctc ictccctctc tgactgatca aaaattggtt atgggcttcc cgtaccccac agaacctgct caggattaaa gac tgaca-tt taatcccagc ,tcctggccaa tgtgdgtgcc ggaggtggag cgagactctc gtacacagtt tatcctagac cagagagcat t cact ggcc a cctatactca gctccctccc gctgggggtg gtgagtgaga aggcgcggtg, caatctagct aatttcactc gtttaattcc atacttcatt ctgagaggat c a ca cac ac a cacggtttcc tgaggccact aatttgattc tgccagggga tcgcgcacct tgatgcggcc gccaggatgg-tcggatttgg cttgttctcc actggcaggt aggttatcgc-tggaaggtct aatacgctgt gctaaatact gacttcttgt ccttccgtcg agttcatccc agcacaaaca cactcacaca. cacacacgca tacctaaaat aaggcaactg tgcctatcat cctgaggagt gtctgttgaa. ttcccagcga gctgatattt-gattggptta ggggtgactt acagaagggc -96-.

00 t agagagctcg tcatttgaag actctct-cgg aagggatagc gtccttctgc aacctgcggt cccagcagac aaacctt gtg atccttgttc cagtcgacat 9 HDUB4.8 putative promoter sequence upstream of initiatiol..ATG 00 00 0 CAGGGCTCCG

TACGAACAGG

GACAGCTTAT

CCAGGTCCCG

ATTGCTCATG

CATCTTTCTA

CTTCTGATGG

ACAGTCCTCT

AGGGCTGTTT

ACCGTCTAAG

!0 ACAGCCGGAA

GCAGCATTAC

TGGAAATGGA

GGCTTATTTT

TCTGTTTCAC

TCCGTCAGCC

CTTTTTATTT

ACACATGCTG

TAGCTGGGAT

GCACGTCCGA

AATTTGGGGA

ACAGTCTACT

TGCTTTATTA

TCTCCACTGG

ATCGCTGGAA

GCTGTGCTAA

CTTGTCCTTC

ATCCCAGCAC

CACACACACA

TAAAATAAGG

TATCATCCTG

GTTGAATACC

A~TATTTGATT

TGACTTACAG

TAGAACCACA

GAATCTTGGG

.CGCAACCCTG.CTCAA.GCACC

.CAAATGTGCA.

I'GTGATGAGC 2

GTCTCCGTGT,

CGATTGGGCT

.,CTGCAGGAA

CTTCTGGGGA

AGCAGTGCTC

AGCACACCTG

CATCCCATCA

CT TACACCT

ACATGTTGGG

GACACACCCA

AATTTTGGCA

GGCAACATCT.

GGCCTTTTCC

TCCCTGCTTT

GGGCTTTTCT

CACCTCTAGG

TGAGATACGT

ACCTTCTGAG

AACCGCTCAC

TTGTCATCAA

TTGTGCACTG

TTTGGCAATC

CAGGTAATTT

GGTCTGTTTG

ATACTATACT

CGTCGCTGAG

AAACACACAC

CACTCACACG

CAACTGTGTG

AGGAGTAATT

CAGCGATGCA

GGCTTATCGC

GACGTGTGTG. AAAACTACAG CCCCTCAAAA

TCGGTTATGA

TAAGACCCTC

!CAGGGTCTTG

TCATTCTCCT

.GAAAATGGTG

TTTTCTTCCC

CCAGGACACT

GCCCATGAAA

AGACAAGGGA

TCCTCCTTAA

.AATCATCCTA

AGAGGCCTTG GCGCCGGGCC AAAATCCCTA.

,GAGCCAGGAT

AATTCTGTCC

,CTCTTACTTC

CCAAATGTGC

TAACTGCAAT

CCGATCCTGA -ACGATCGATG.

CACTGAAACA

.AGGGCCAGTA

TAAACGTCTC

CGATGTTTCT

ACGGTATAAT

TTTCCTTGTT

AA.ACGTTGAT.

.CCATTATCAC

TGTTTTTATT

TTCATCAATT

TTCTCAAGTT

TTTTGTTTCG

TATGCAGTGT

CATGACCGTC

TTAGTCTCTC

GGGGATTGCA

AGTATCTCTT

'CAAACTTCAG

TAGCT.TCCAC

AAGAGCATTT

CACTTGGACA GAGAATCAAT.

ATTCCACGGA-

.TCTCTCCTTT

TCATTGACTA.

TTCTCAGGTC

AGGATGATGG:CAGCTGCCAA

ACACACGCGC.

CCCCCCCACA

GTTTCCTACG

TAAAGATTTC

GCCACTGTCC

CAACCCGGTT

TGATTCAGGT

GTTCTGGAAG

AGGGGACACA CCCTGTGACT GCACCTGATG

AGTGGGTGGG

3CATTCAAGC rGTGAAGCCT

GCTCCTTTCT

rTACATCCGG

A.AGAAACGGG

A.TTTCATGGG

rCAATTCCGC

CTTCATTCCT

AGGGAACATG.

TCCACCATAC

CGAGAA TCCA TT AAAAATGG

CCCTGAGACA

TGCTTTTGTC

ATACGTATGG

CTTTAATAAA

TGTTTTCTTA

TCTCTTTTCT

TGATTTCCCC

TGCATGTTTC

CATGCAAAGA

AGGCTCAACG

CTCATTAGGG

AGAAAGCGCA

AAGTACATAC

CACACACACA

TTCCCTGCCA

ACACTCCTAT

TCALTGCTGTG

CCTTCCTGAA

GTGTTCGCGG

%.CACCGATGC

CGGCATCTGC

CCCTGTGGAG

CACAGGAAGC

GCCAAAGGTC

CCCTGAAGCC

CCTGTTCCTT

GCTAAGCCAG

TCCACTTTCG.

AATGCGTAAC

GGATATGCAC

CACGCTATCC

GGGCCTCACT

CA.AATTAGAA

AAATATTATC.

CAAACGGTTA

AACTGCCGTC

GGCAAACATA

AAAGGCTTTC

TACCATTTGA

CTTGTCTTCT

TGGAAAGGTT

AAGAAAATAC,

CTTTCGACTT.

TTGGAGGTTC

CGAA CACAAT

TTGCTTTACC

TATATGTGCC

GGCTGTGTCT

TTGAGTGCTG

TTGGTGGCGG

AAGGGCTGAT G HDUB4. 9 putative -promoter sequence upstream of .initiation

ATG

gcatctttct ccttctgatg ca cag tcct c agggctgttt accgtctaag acagccggaa gc~agcattac tggaaatgga.

ggcttatttt tctgtttcac tccgtcagcc ctttttattt acacatgctg agttagcgct gagc a cacc t tcctcccatc ctt:tacacct* acatgttggg gacacaccca aatitttggCa ggcaacatct ggc cttttcc tccctgCttt gggcttttct catctctagg tgagatacgt cttttcttcg ggcccatgaa atcctcctta, agaggccttg a-aaat ccct a aattctgtcc: ccaaatgtgc ccgatcctga cccaggacac tttacatccg.. gcacacg -aag aagccaaggg aaatcatcct gcgccgggcc gagccaggat ctcttacttc .taactgcaat acgatcgatg aatttcctgg tcaattccgc cttcattcct agggaacatg tccac catac cgagaatcca t taaaaatgg ccctgagaca tgcttttgtc atacgtatgg ccctgaagcc.

*cctgttc~ctt.

gctaagccag tccactttcg aatgcctaac ggatatgcac cacgctatcc ggacctcact caaattagaa aaatattatc cactgaaaca .agggccagta taaacgtctc .Cgat~gtt9Ct acggtataat tttccttgtt aaacgttgat ccattatcac tgtttttatt ttcatcaatt: ctttaataaa caaaaggtta 00 tagctgggat accttctgag gcacgtccga aaccgctcac aatttgggga ttgtcat caa acagtctact 'ttgtgcactg tgctttatta 'tttggcaatc ttcgctggaa actgtgctaa cttgtccttc 00 atcccagcac 1- acacacacaa ~t aataaggcaa M catcctgagg gaattcccag 00atttgattgg Sacttacagaa C1 acatg caggtacttt ggtctgtttg atactatact cgtcgctgag aaacacacac tcacacggtt ctgtgtgacc agtaatttga cgatgccagg ct tatcgcgc gggctgatgc ctgcaacctg ttctcaagtt.

tatgcagtgt ttagtctct c agtatctctt tagcttccac cactcggaca attccacgga tcattgacta aggatgatgg acacgcgccc tcctaggtaa actgtcccaa ttcaggtgtt gggacacacc acctgatgag gg ccagagag cggtcccagc ttttgttcg catgaccgtc ggggattgca caaacttcag..

aagagcattt gagaatc aat ttctcaggtc cagctgccaaccccacacac agatttcttc cccggttaca ctggaagtca ctgtgactcc tgtgggg9t ctcg tcattt.

agaaaaac'Ct tgttttctta aactgccgtc, tctcttttct ggcaaacata ,tgatttcccc aaaggctttc tgcatgtttc tacaatttga catgcaaaga*cttgtcttgt aggctcaacg~ tggaaaggtt ctcattaggg aagaa'aatac agaaagcgca ctttcgactt aagtacatac ttgga'agttc acacacaaac acaatcacac cctgccatgg ctttacctaa ctcctattat atgtgcctat tgctgtggga tgtgt~ctgtt ttcctgaatt gagtgctgat gttcgcggtt...ggtgggggtg gaagactctc tcggaaggga tgtgatcctt gttccagtcg- HDUB4.1O putative promoter sequence upstream of initiation ATG agcaagcttt gtggtgtttg aggtcctcat atgtgcaata ctcttgtcta attacttctc.

tcaccgccgc agaagagtga ttggcgcaga gcctccaggc tagaccac tg aagtcaaagg ggatgaagaa cgacacatca gatccaaagg ggaagtaccg aactacaccc aatcctacat agtgatggct agtcttccga gtgtgtattt gactcggttt gaaggtgaaa gaaactggaa tttttacact ccacataacg agtccaaacg aataaaggaa gaaatcaatc ccagctgcga ccgacgtggt ctgattagac gaggaaagct ccctgctcaa ggaacagttg gtgaagcccg aagaactcaa tctccagagg gcgccggcct ccaagacgtt ccttgtattg aagagattct ccgatgtcac tcctgagtgc cttgacatgc agccatacat tgtcctctat gctgtgctgg tccac~ctga ttatgtcaaa gctcaagaag gcc agtg .gta' tagcatcact tctgtcctga gtcaacaggc atgggaaaga catagtgaga gtgtgtca'ag* agacacagac aggcgagcaa cgcaaggaga ccccgagttg gacgagcact tggtggaaag gaaattcctt caagagcaaa acaaaacgaa taccc'tgcct cccgSacgtac ttgtgatt .ca ccatcatcct gaacagcaaa gctccctgct 99a9tccat9 aacactggca cactcgcttc gaagaacaaa cacagcaaga gggctctgct acccacacgt aggggtgcac acacacacgc agaagcgcgc acgcaaacac .acacacaccc aaactaatga ggagcccaag tttctgtctc acatctcagg atgagcccgc atatgggaaa acctctggag ggactgtctg agtgtttgtg ctgaatatga cctaccgacg tgtaggtttg cgtattttct cttggggtgt gtttcattcg tgtggctcat gtgggacatc cgtggatcat.

tgcatttgga agagaagaac ggtgctcttc ggttcctgaa tggacctcag gcgccctggg ccggaagcgg acagaccgac ttgcctgttt gaaaattttc ccacgggcat gtaagtcatc agcaaacaca ggagtgtgtg tattcaactg tcactgggtg tgtttaaaaa tggcatttgg aagctgcatc tctgaagcac agtccctgtc gtttccgtgg aaatgattgt gggaaatggc ttcatggtcc ctttctcgtc aggtacagtg gcccagggca caactcaggg ctccgtagaa gcacccaaat g tggagagaat gcctatcatt aactttacac aggcaacaag gtctcagcag gtggagtgt taaaatggat ctacgtcctc 6ggcagggjaa 9.c icaagaga agccac t cag gcctgagttc tcaatcaaaa aaacctctct cc tgcgaggg tgtgtgccag acacacacag acacaaacac tacaacaggg catcaagttt ttcatgatag cgtgtgaggt tcagttgttg tctcgccacc tttcttcccc acttgtgctc cacggtgccc tggaagtaag aaataaattc ggaatttCtg ccgcagtgag cccttccttt atcaaagttg ccacagaatc acctctgcca attg cc aag a aacacaggac cacaacggac gatgccgagg ttttacatcc cdaagagccc gaccacccct g aa agc ac CC aacgtcagaa t ac aagtgtg t cgtcgaCccc agggccagga tgatctcagt acacacacat gaacaccgtc acaactggat tggggtcgtg gtgacattca aat tgcaggg gtcggcatga ttgaatagtg gggc tcg Ccg ttgctggaac gctc c a tg ctgtattgat agaaagccct ggtcatttgt acttattgat tctctatttg accagcccca ttgggcgcaa HDUB4.11 putative promoter sequence upstream of initiation ATG 00

;Z

00 cagcaagctt tgtggtgttt aaggtcctca aatgtgcaat cctctcgtct cattactcct gtcaCCgCCt cagaagagtg cttggcgtag tgcctccagg ttagaccact agagtcgaag cggatgaaga ccgacagatc agatccaaag tggaagtacc taactacacc caatcctaca tagagatggc o gagtcttCCg agtgtgtatt ggactcggtt agaaggtgaa ggaaactgga gtttttacac cccacataac gagtccaaac taataaagga tgaaatcaat o tccagctgcg tccgacgtgg gctgactaga agaggaaagc accctgctca t aott catqaagccc qaagaactca atggagagaa tgcctatcat :;cagZ)g Laactttaca gtctccagag ggcgCCggcc tccttgtatt gaagagattc.

atcctgagtg ccttgacatg atgtcctcta,-tgctgtgctg cttatgtcaa. agctcaagaa ctagcatcac ttCtgtcctg aatgggaaag..aCacagtgag aagacacaga caggcgagca.

cccccgagtt ggacgagcac ggaaattcct -tcaagagcaa gtacggtgcc tcccgacgta accatcatcc tgaaCagcaa aggagtccat gaacactggc ggaagaacaa acacagcaag gaccacacg taggggtgca cagaagcgcg cacgcaaaca taaactaatg aggagcccaa tacatctcag gatgagcccg aacctctgga ggg- ctgtt tatgaatatg acctaccgac tcgtattttc tcttggggtg atttggctca tgtggga,c~at atgcatttgg aagagaag~a tagttcctga atggac ct-ca gccggaagca gacagaccqga ggaaaatttt cccacgggca aagcaaacac aggagtgtgt ctcactgggt gtgtttaaaa aaagctgcat ctctgaagca .tgtttccgtg ga aatgattg.

cttgatggtc cctt-ctcgt tgcccagggc acaactcagg a9cacccaaa tg.

cccgatgt:ca cagccataca gtccacgctg ggccagiggt agtcaacagg.

agqtgtgtcaa acgcaaggag ttggtggaaa aacaaaacga cttgtgattc.

agctcctgc acactcgctt 4gggctctgc tacacacaca cacacacacc gtttctgtct catatgggaa gagtgtttgt.

gtgt Aggttt tgtttc.attc ccg tggatca c gtq ctctt ggcg Cc ctgg c6tt gcctgtt tgtaagt cat gtat.tcaaca i tqgcatttg cagtccctgt tgggaaatgg Cagg tacagt gc tcca taga caggcaacaa tgtctcagca ggtggagttg ataaaatgga cctacgtcct, ga gg caggg a agctcaagag gagccactc a agc~ctgagtt atcaatcaaa t aaacct ct c ccctacgagg ttgtgtgcca cacacacaca cacacaaaca gtacaacagg acatcaagtt gttcatgata g cgtgtg agg gacagttgtt ttc c gccac cfttcttCcc gacttgtgct tcacggtgcc ctggaagtaa gaaataaat t gggaa tttCt cccgcagtga qcccttcctt gatcaaagtt accacagaat aattgccaag gaacacagga tcacaacgga tgatgccgag cttttacatc acc aagagcc agaccacccc ggaaagca~cc caacgtcaga atacaagtgt ttcgacgacc gaggaccagg gtgatctcag cacacacaca cgaacaccgt gacaactgga ttggggtcgt ggtgacattC taattgc.ag!4' ggtcggcacg cttg'aatagt dCgggctcgcc cttgctggaa cgct tc CCat gctgtattga cagaaagccc gggtcatttg gacttattta t t Ctctat tt gaccaacccc C ttgggagc a

Claims (6)

1. An isolated polynucleotide encoding a human deubiquitinating protease selected. Sfrom the group consisting of hDUB 4.1a, hDUB 4.1b, hDUB 4.2a, hDUB 4.2b, hDUB 4.3, hDUB 4.4, hDUB 4.5, hDUB 4.6, hDUB 4.7, hDUB 4.8, hDUB 4.9, hDUB 4.10, hDUB 4.11, 00 hDUB 8.1, hDUB 8.2, hDUB 8.3, hDUB 8.5, hDUB 8.6, hDUB 8.7, hDUB 8.8, hDUB 8.9, cC hDUB 8.10, and hDUB 8.11. 00

2. A polypeptide encoding a human deubiqititinating protease selected from the group S consisting of hDUB 4.1a, hDUB 4.lb, hDUB 4.2a, hDUB 4.2b, hDUB 4.3; hDUB 4.4, hDUB hDUB 4.6, hDUB 4.7, hDUB 48, hDUB 4.9, hDUB 4.10, hDUB 4.11, hDUB 8.1, hDUB

8.2, hDUB 8.3, hDUB 8.5, hDUB hDUB 8.7,'hDUB 8.8, hDUB 8.9, hDUB 8.10, and hDUB 8.11. 3. A method of using a polynucleotide according to claim 1, wherein the polynucleotide is used in an assay to identify an inhibitor of a hDUB of claim 1. 4. A method of using a polypeptide according to claim 2, wherein'the polypeptide is used in an assay to identify an inhibitor of a hDUB of claim 2. A method of reducing inflammation by regulating proinflammatory cytokine signaling, by administering a compound capable of inhibiting a polypeptide according to claim 2. 6. A method of modulating an autoimmune disease by altering cytokine receptor signaling involved in lymphocytes proliferation, by administering a compound capable of inhibiting a polypeptide according to claim 2. 7. A method of modulating an immune reaction during infection, by administering a compound capable of inhibiting a polypeptide according to claim 2. -100- 00 C 8. A method of reducing inflammation by regulating proinflammatory cytokine signaling, by administering a compound capable of altering regulation of transcription of a polynucleotide of claim 1.

9. A method of modulating an autoimmune disease by altering cytokine receptor signaling involved in lymphocytes proliferation, by administering a compound capable of n altering regulation of transcription of a polynucleotide of claim 1. 00 O 10. A method of modulating an immune reaction.during.infection, by administering a 0 compound capable of altering regulation of.transcription of a polynucleotide of.claim 1.

11. A method of identifying a modulator of a human deubiquitinating protease, wherein a compound is added to the reporter assay comprising a polynucleotide immediately 5' to a human deubiquitinating protease selected from the group consisting of hDUB 4.la, hDUB 4.1b, hDUB 4.2a,ihDUB 4.2b, hDUB 4.3, hDUB 4.4,.hDUB 4.5, hDUB 4.6, hDUB 4.7, hDUB 4.8, hDUB 4.9, hDUB 4.10, hDUB 4.11, hDUBi8.1, hDUB 8.2, hDUB 8.3, hDUB hDUB 8.6, hDUB 8.7, hDUB 8.8, hDUB 8.9, hDUB 8.10, and hDUB 8.11 operatively linked to a reporter gene; and the effect of the compound is determined. 00 00 00 SEQUENCE LISTING <110> Hahn, Chang Liu, Hong <120> Human Analogs of Murine Deubiquitinating Protease Genes <130> USAV2001/0185 <160> 54 <1'70> Patentln version 3.1 <210> <211> <212> <213> 1 19 DNA Homo sapiens <4300> 1 atggaggacg actcactct 19 <210> 2 <211> 16 <212> DNA <213> Homo sapiens <400> 2 ctggcacaca agcaga <210> 3 <211> 3051 <212> DNA <213> Homo sapiens 2/99 00 <220> OJ<221> <<223> misc-feature human DUB4.la <400> 3 atgaccctgC aggaactgcg gacctaactg atcctggggc tcaaacctc gcccacgtca cgccgcttcc ttaagagact cccgtgtgtg atcaaaaagg gacgagctgt cggagctatt tcccatggta atcgagaacc ctcacaggcc cacagccggg gcagacatca gggacgagga acccctgcca gtcccagccc gccagcagac gaagccatcc caggctcctc- accaccgagc atccttgttc aaccactttt acttctCtC( aacagagcat agagtgcct~a gccccgcctc ccgcccctgg cgcagtccag tggcgcccga tggcggcgCg catcagattc tgaagcaccc gtgcatctgt acgaggtgc t tgctgccctC ctacaggcct cagcagcctt tggccatctg tcctcgagca ctgccaactt cagggccctt gcacactcag tgaaacccac caaacggcag Itgtcactggt Iaggtctacct tagagatagc cagtcgacat caaaactcac ctgagaagtc gcccttctgC cgttagccca ccgggcccca ccccgcgtcg gcccggcttc ggagaacgcg ctcactgcgc tgagctgctg gccatcagtc ggtcaccagc gg cgg aga Ct gggaggctcg ggtcacatgg cactaacagg caagatgtgt qctccgaggg agacgcccca gagaaaaggt tcccctctct aggtcca9cg acacctgaaa cggggtcctg ggcctttacc gtctttctgc ggaggacgac atcttctcgg accactctca attgagcatg c aggcctgacc c aacccggact gaagaccatg ctccaggtct gggacagaac tccttcccct cgggatattt aagtatgccc agcacgaggg ctgatggcca ttcacacttt gacgccaccc ggtgtcctag cgcccccagg aatgtccttc ggagaccaca ggtgtttggc ggtggaacag gtggccaggg caagaagttc cggaggctgg gtccgcaacc aacctgcggt tcactctact ccagatgcag tgtgagaccc :aatcatgaa t :gacgatccc a :ggCcCCC c 3gctcgctcc ccaggcaacg :ctggctgca ggcagagctt tgcagaagac ggtgctttct ctgtccacac aggagtccac ccgagatcac tctaccttgc agcttggcag catacatctt t ca atggcc t ggagaaaaac tgggccaccg agctctgcct acacaggccc acgacgtgct ctgcctgccg cagagacgtg cccagcagaa tgggaggtga cttttgctga gtgtcgacct :cacag9cgg lgggaccctc ;aagctccgg :gggccttcc :tgcggctcc 3ggtttcgag agaggcaaag tgtgaagcat ctcagaactc ggagcctttg ccagggccac agccatcatc agaatgggcc tggcgctggc cagcgactgt ctcattagag aaccacttct aaaacccctc gtg9CCCt99 acccctgcaa gt at tgccc a ggagcacaag ccagctgttc aaaccttgtg gtggcagttC aatccagcgt ctgtgatgat 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 ttggctcctg tggcaagaca gcttgctccc agggagaagc ctcctctgag ta9caggaga 00 ;Z 00 cctgctgcgg ctgcagtgcc caaacgtgtc gccctccaca agaggcaagc gcatgccttc caaatatttg gacacttttg caagctttgg ggtgtttgtc gtcctcatcc gtgcaatatc ctcgtctatg tactcctctt accgcctcta aagagtgaat ggcgtagaag ctccaggccc gaccactgga gtcgaaggta atgaagaacc acagatcagg tccaaaggga tgggggctgg tgacatacaa atcgtcacaa ttcctggcca aggaagatgc ccgggcacaa gaggctactg acccttacct aacagttggt tccagagggc ttgtattgaa ctgagtgcct tcctctatgc atgtcaaagc gcatcacttc gggaaagaca acacagacag ccgagttgga aattccttca cggtgcctcc atcatcctga agtccatga& agaacaaaca gctccagaat accgccactt gggctgcatg tgtcatccag ccatgaattt gcaggtagat gagatctcaa ggacatcgcc gaagcccgaa gccggcctcc gagattcccc tgacatgcag tgtgctggtc tcaagaaggc tgtcctgagt cagtgagagt gcgagcaacg cgagcacttg agagcaaaac cgacgtactt acagcaaagc cactggcaca cagcaagagg atgggaaata gccaactaca ctctgtacta ccctcacagg ctcatgttca cgtcactcta atcaagtgtc ctggatatcc gaactcaatg aagacgttaa gatgtcacag ccatacatgt cacgctgggt cagtggtata caacaggcct gtgtcaagag caaggagagc gtggaaagag aaaacgaagc gtgattcatc tccctgctaa Ctcgcttccc gctctgcttg cctgctacgt tgctgttccg tgcaagctca cattggctgc ctgtggatgc aggacaccac tccactgcca aggcagctca gagagaatgc ct tt ta caca a gcaacaaaat ctcagcagaa ggagt tgtca aaatggatga acgtcctctt gcagggaacc tcaagagaga ccactcagga ctgagttcaa aatcaaaata acctctcttc tacgagggag tgtgccagtg gaacgcttcc ggagcactct catcacaagg tggcttccat catgagaaag cctcatccac cggcatttca gagtgtccag ctatcattgt ctctgccaag tgccaagaat cacaggacct caacggacat tgccgaggtc ttacatccag aagagccctt ccacccctgc aagcacctta cgt cagaaga caagtgtcgg gacgaccccg gaccaggaga a 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3051 <210> <211> <212> <213> <220> <221> <223> 4 1016 PRT Homo sapiens MISCFEATURE human DUB4.la <4et Thr Leu Gin Gin 5 Ser Met Pro Phe Cys 1.0 Ile Glu His Ala Ile Met rksn His Arg Arg Arg Asn Cys Glu Ser 25 Ala Tyr Val Ser Pro Arg Pro Ala Ser Arg Asp Pro Thr 00 SAla Pro Asn Ile Pro Gly Thr Le u Asp Leu Thr Gly Pro Asp Ser Pro Pro Lys Leu Arg Ile Leu Gly Pro Ala Pro Gly Pro Ala Giu Asp His Gly Ala Pro Gly Pro Ser Ser Asn Pro Pro Ser Arg Pro Gly Leu Gin Val Ser Ary Gin Arg Cys Gly Giu Leu Trp 115 Ser 100 Ala His Val Met Al a 105 Pro Giu Giu Asn Ala Gly Thr 110 Ala Arg Ser Leu Gin Gly Phe Giu 120 Arg Arg Phe Leu Ala 125 Leu Arg 130 Ser Phe Pro Trp Gin 135 Ser Leu Giu Ala Lys 140 Leu Arg Asp Ser Ser 145 Asp Ser Giu Leu Leu IS0 Arg Asp Ile Leu Gin Lys Thr Val Lys His 155 160 Pro Val Cys Val His Pro Pro Ser Lys Tyr Ala Arg Cys Phe 1.75 Leu Ser Giu Arg Ala Val 195 Leu 180 Ile Lys Lys Gly Ser Val Val Thr Ser Ser Thr 190 Val Leu Ala His Thr Glu Pro Leu 200 Asp Glu Leu Tyr Giu 205 Giu Thr 210 Leu Met Ala Lys Ser Thr Gin Giy His 220 Arg Ser Tyr Leu Leu 225 Pro Ser Gly Gly Ser Phe Thr Leu Ser Glu Ile Thr Ala Ile Ile 235 240 5199 00 er His Gly Thr Thr 245 Gly Leu Val Thr Trp 250 Asp Ala Tnr Leu Tyr Leu 255 kla Glu Trp Ala 260 Leu Glu Leu Gly 275 Ile Glu Asn Pro Ala 265 Ala Phe Thr Asn Arg Gly Val 270 Ile Cys Lys Ser Gly Ala Gly 280 Leu Thr Gly Leu Ala 285 00 4Iet Cys 290 Cl. 00 .,eu Glu 305 Arg Pro Gin Ala Ile Phe Ser Asp His Ser Arg Val Gin Leu Arg Asn Val Leu Leu Gly Leu Ser Leu Glu kla Asp Ile Thr Asn Leu Asp Ala Pro Gly Asp His Arg 330 Arg Lys 335 rhr Thr Thr Ser 340 Gly Thr Arg Thr Gly Pro Leu Arg Lys Gly Gly Val 350 Leu Ser Pro rrp Leu Gly His Arg Lys Pro Leu 360 Thr Pro Ala Ser Thr 365 Leu Ser 370 Gly Gly Thr Glu Leu 375 Cys Leu Trp Pro Trp 380 Val Pro Ala Leu Pro Thr Gly Pro Val Ala Arg Asp Thr 395 Gly Pro Pro Leu Ala Ser Arg Pro Gly Arg His Leu Gin Giu Val His Asp Val 415 Leu Tyr Cys Leu Ala Ala 435 Glu Ala Ile Val Leu Val Gly Val Leu Arg Arg 430 Tyr Leu Ala Cys Arg Glu His Gin Ala Pro Glu Phe Thr 450 Val Arg As Pro Thr Cys Gin Leu Thr Thr Glu Leu Glu 465 Ile Ala Ser Phe Asn Leu Arg Ser Gin Lys Asn Leu lIe Leu Val Pro Val Asp Met Giu Asp 485 Asp 490 Ser Leu Tyr Leu Gly Gly 495 00 0 3u Trp Gin Phe la Ala Phe Ala 515 Asn His Phe Ser Lys Leu 505 Thr Ser Ser Arg Pro Asp 510 Lys Ser Pro Giu Ile Gin Arg 520 Thr Ser Leu Pro Glu 525 Leu Ser 530 Cys Glu Thr Arg Val1 535 Asp Leu Cys Asp Leu Ala Pro Val 00 "-Ala 545 00Pro Arg Gin Leu Ala Pro 550 Arg Giu Lys Pro Leu Ser Ser Arg Arg 560 Ala Ala Val Gly 565 Ala Gly Leu Gin Met Gly Asn Thr Cys Tyr 575 Vai Asn Ala Tyr Met Leu 595 Leu Gin Cys Leu Thr 585 Tyr Lys Pro Pro Leu Ala Asn 590 His Lys Gly Phe Arg Glu His Gin Thr Cys His Arg 605 Cys Met 610 Leu Cys Thr Met Ala His Ile Thr Ala Leu His Ile Gly His Val Ile Gin 630 Pro Ser Gin Ala Ala Ala Gly Phe His 640 Arg Gly Lys Gin Asp Ala His Glu Leu Met Phe Thr Vai Asp 655 Ala Met Arg Ser Lys Asp 675 Ala Cys Leu Pro Gly 665 His Lys Gin Vai Asp Arg His 670 Tyr Trp Arg Thr Thr Leu Ilie Gin Ile Phe Gly Giy 685 Ser Gin 690 Ile Lys Cys Leu Cys His Gly Ile Asp Thr Phe Asp Tyr Leu Asp Ile Ala 710 Leu Asp Ile Gin Ala Gin Ser Val Gin 720 Gin Ala Leu Giu Ala Tyr His Cys 740 Gin 725 Leu Val Lys Pro Giu Leu Asn Gly Giu Asn 735 Giy Val Cys Leu Gin Arg Ala Pro 745 Ala Ser Lys Thr 750 00 ~eu Thr Leu CK1 755 His Asn Ser Ala Lys Val 760 Leu Ile Leu Val. 765 Leu Lys Arg ;Z )he Pro 770 Asp Val Thr Gly Asn 775 Lys Ilie Ala Lys Asn Val Gin Tyr Pro 780 Cys Leu Asp Met Pro Tyr Met Ser Gin Asn Thr Gly .eu Vai Tyr Val Leu 805 Tyr Ala Val Leu Val1 810 His Ala Gly Trp Ser Cys 815 iis Asn Gly C'yr Lys Met 835 His 820 Tyr Ser Ser Tyr Lys Ala Gin Glu Giy Gin Trp 830 Asp Asp Ala Giu Thr Ala Ser Ser Ile Thr Ser Val 845 eu Ser 850 Gin Gin Ala Tyr Leu Phe Tyr Ile Lys Ser Glu Trp Arg His Ser Giu Ser 870 Val Ser Arg Gly Giu Pro Arg Ala 31y Vai Giu Asp Thr 885 Asp Arg Arg Ala Gin Gly Giu Leu Lys Arg 895 ksp His Pro Ary Ala Thr 915 Leu Gin Ala Pro Leu Asp Giu His Leu Val Giu 910 Leu Gin Giu Gin Glu Ser Thr Leu 920 Asp His Trp Lys Gin Asn 930 Lys Thr Lys Pro Glu 935 Phe Asn Val Arg Vai Glu.Gly Thr Pro Pro Asp Val Leu 950 Val Ile His Gin Lys Tyr Lys Cys Arg 960 Met Lys Asn His Pro Giu Gin Gin Ser Leu Leu Asn Leu Ser 975 Thr Leu Ala 990 Ser Thr Thr Thr Asp Gin Glu Met Asn Thr Gly Ser Leu Arg Gly Arg Thr Arg Arg Ser Lys Gly Lys Asn Lys His Ser 995 1000 1005 8/99 00 SLys Arg Ala Leu Leu Val Cys Gin 1010 1015 <210> <211> 1593 <212> DNA 00<213> HOMO sapiens (Nl<220> 00 S<221> misc-feature C]<223> human DUB4.1b <400> 5 atggaggacg acatcttctc tcaccactct cagcttgctc gggctccaga aaaccgccac aagggctgca catgtcatcc gcccatgaat aag cagg tag tggagatctc ctggacatcg gtgaagcccg gcgccggCCt aagagattcc cttgacatgc gctgtgCtgg gctcaagaag tctgtcctga cacagtgaga aggcgagcaa actcactcta ggccagatgc catgtgagac ccagggagaa atatgggaaa. ttgccaacta tgctctgtac agccctcaca ttctcatgtt atcgtcactc aaatcaagtg ccctggatat aagaactcaa. ccaagacgtt ccgatgtcac agccatacat tccacgctgg gccagtggta gtcaacaggc gtgtgtcaag cgcaaggaga cttgggaggt gagtggcagt tcaaccactt ttcaaaactc agcttttgct ccgtgtcgac gcctcctctg tacctgctac catgctgttc tatgcaagct ggcattggct cactgtggat taaggacacc tctccactgc ccaggcagct tggagagaat aactttacac aggcaacaaa gtctcagcag gtggagttgt taaaatggat ctacgtcctc aggcagggaa gctcaagaga gaaatccagc ctctgtgatg agtagcagga gtgaacgctt cgggagcact cacatcacaa gctggcttcc gccatgagaa accctcatcc cacggcattt cagagtgtcc gcctatcatt aactctgcca attgccaaga aacacaggac cacaacggac gatgccgagg ttttacatcc ccaagagccc gaccacccct gtacttctct atttggctcc gacctgctgc ccctgcagtg ctcaaacgtg gggccctcca atagaggcaa aggcatgcct accaaatatt cagacacttt agcaagcttt gtggtgtttg aggtcctcat atgtgcaata ctctcgtcta attactcctc tcaccgcctc agaagagtga ttggcgtaga gcctccaggc ccctgagaag tgtggcaaga ggtgggggCt cctgacatac tcatcgtcac cattCctggC. gcaggaagat tcccgggcac tggaggctac tgacccttac ggaacagttg tctccagagg ccttgtattg tcctgagtgc tgtcctctat ttatgtcaaa tagcatcact atgggaaaga agacacagac ccccgagttg 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 00 3-I acgagcact :aagagcaaa <:ccgacgtac g aacagcaaa aacactggca 00 :acagcaaga tggtggaaag acaaaacgaa ttgtgattca gctccctgct cactcgcttc gggctctgct agccactcag gcctgagttc tcaatcaaaa aaacctctct cctacgaggg tgtgtgccag gaaagcacct tagaccactg gaaattcctt aacgtcagaa gagtcgaagg tacggtgcct tacaagtgtc ggatgaagaa ccatcatcct tcgacgaccc cgacagatca ggagtccatg aggaccagga gatccaaagg gaagaacaaa tga 1320 1380 1440 1500 1560 1593 ,210> c211> c212> c:213 r220> -:22i1> r,223 6 530 PRT H-omo sapiens MISCFEATURE human DUB4.1b <400> 6 14et Glu Asp Asp Ser Leu Tyr Leu Gly Gly Glu Trp Gin Phe 1 5 10 Asn His Phe Ser Lys Gin Arg Thr Thr Ser Ser Arg Asp Ala Ala Phe Ala Giu Ile Giu Thr Arg Ser Leu Pro Giu Lys 40 Ser Pro Leu Ser Cys Val Asp so Leu Cys Asp Asp Leu 55 Ala Pro Val Ala Arg Gin Leu Ala Pro Giu Lys Pro Pro Ser Ser Arg Arg Ala Ala Val Gly Gly Leu Gin Asn Met Gly Asn Thr Cys Val Asn Ala Ser Leu Gin Cys Leu Thr His Ser Gin 115 Tyr 100 Lys Pro Pro Leu Asn Tyr Met Leu Gly Cys Met Leu 125 110 Cys Thr Met Thr Cys His Arg His Lys 120 10/99 tlGin Ala ;Z 130 His Ile Thr Arg Ala 135 Leu His Ile Pro Gly His Val Ile Gin 140 Pro 145 Ser Gin Ala Leu Al a 150 Ala Gly Phe His Arg 155 Gly Lys Gin Giu Asp 160 Ala His Glu Phe Met Phe Thr Val Asp 170 Ala Met Arg Lys Ala Cys 175 Leu Pro Gly Ile His Gin 195 Lys Gin Val Asp His Ser Lys Asp Thr Thr Leu 190 Lys Cys Leu Ile Phe Gly Gly Trp Arg Ser Gin Ile 205 His Cys 210 His Gly Ile Ser Thr Phe Asp Pro Tyr Leu Asp Ile 220 Ala Leu Giu Gin Al a Leu 240 Leu 225 Asp Ilie Gin Ala Gin Ser Val Gin Gin 235 Val Lys Pro Glu Giu 245 Leu Asn Gly Giu Asn 250 Ala Tyr His Cys Gly Val 255 Cys Leu Gin Arg Ala Pro Ala Ser Lys 260 265 Thr Leu Thr Leu His Asn Ser 270 Val Thr Gly Ala Lys Val 275 Leu Ile Leu Val Leu 280 Lys Arg Phe Pro Asp 285 Asn Lys 290 Ilie Ala Lys Asn Gin Tyr Pro Giu Leu' Asp Met Gin Pro 305 Tyr Met Ser Gin Asn Thr Gly Pro Leu Val Tyr Val Leu Tyr Ala Val Leu Val Ala Gly Trp, Ser Cys 330 His Asn Giy His Tyr Ser 335 Ser Tyr Val Lys 340 Ala Gin Giu Gly Trp Tyr Lys Met Giu Val Thr Ala Ser Ser Ilie 355 Val Leu Phe Tyr Ilie Gin Lys 370 375 Thr 360 Ser Val Leu Ser Gin 365 Asp Asp Ala 350 Gin Ala Ty Ser Glu Ser Ser Giu Trp, Giu Ary His 380 11/99 00 Val 3 85 ~tArg Ser Arg Gly Arg Glu 390 Pro Arg Ala Leu Gly 395 Val Glu Asp Thr Asp 400 Arg Ala Thr Gin 405 Gly Giu Leu Lys Arg 410 Asp His Pro Cys Leu Gin 415 Ala Pro Glu Thr Leu Asp 435 Asp Giu His Leu Val1 425 Glu Arg Ala Thr 430 Thr Lys Pro His Trp Lys Phe Gin Glu Gin Asn Lys 445 Giu Phe 450 Asn Val Arg Arg Giu Gly Thr Val Pro 460 Pro Asp Val Leu Val1 465 Ile His Gln Ser Tyr Lys Cys Arg Lys Asn His His Pro 480 Giu Gin Gin Ser Leu Leu Asn Leu Ser 490 Ser Thr Thr Pro Thr Asp 495 Gin Giu Ser Arg Arg Ser 515 Asn Thr Gly Thr Ala Ser Leu Arg Gly Arg Thr 510 Lys Gly Lys Asn Lys His Ser Lys Arg Ala Leu Leu. Vai Cys Gin 530 <210> <211> <212> 213;> 7 3066 DNA H-omo sapiens <220> <221> misc-feature <223> human DUB4.2a <400> 7 atgggaaata cctgctacgt gaacgcttcc ttgcagtgCC tgacatacac accgcccctt gccaactaca tgctgtcccg ggagcactct caaacgtgtc atcgtcacaa gggctgcatg 12/99 00 ;Z 00 ctctgtacta tgcaagctca catcacacgg g~cctccaca atcctggcca cgtcatccag ccctcacagg ctcatgttca catcactcta atcaagtgtc ctggatat~c gaactcaatg aagacgttaa gatgtcacag ccatacatgt cacgctgagt cagtggtata caacaggcct gtgtcaagag caaggagagc gtggaaagas aaaacgaagc ccccagagg2 cgcaaccctc- gtccactttC caatgcgtai agqatatgC cagaaaaac( ggtgagtggc gctgaaatCl gacctctgt, ctgagtagc. tacgtgaac, tcccgggag gctcacatc gctgctggc cattggctgc ctgtggatgc aggacaccac tccactgcca aggcagctca gagagaatgC ctttacacac 9 caacaagat ctcagcagaa ggagttgtca aaatggatga acgtcctctt gcagggaacc tcaagagaga ccactcagga ctgagttcaa Laagctgccca Ictcaagcacc ggcagcatta i ctggaaatg(3 :ttgtgatcct agttcaacce agcggacttc 3 atgatttggC a ggagacctgC g cttccttgci c actctcaaa( a cacgggccc, t tccatagagi tggcttccat a catgaaaaag g cctcatccac c cggcatttca g gagtgtccag c ctatcattgt g ctctgccaag 9 tgccaagaat cacaggacct c caacggacat tgccgaggtc ttacatccag aagagccctt ccacccctgc aagcacctta cgtcagaaaa gggcacaact caaatgtgca caattttggc Iaggcaacatc tggccttttc cgttccagtc Lcttttcaaaa tctccctgag tcctgtggca tgcggtgggg I gtgcctgaca gtgtcatcgt :ccacaatcct gaggcaagc a catgccttc c aaatatttg g acacttttg a :aagctttgg a jtcctcatcc t ~tgcaatatc c :ttgtctatg t accgccgcta aagagtgaat ggcgcagaag ctccaggccc gaccactgga gtcaaaggta cagggctccg tacgaacagg accaaatgtg gccgatcctg ccactgaaac gacatggagg ctcacatctt aagtcaccac agacagcttg gctgggctcc tacacaacgc cacaagggct ggccacgtca ggaagatgc c caggcacaa g aggctactg g cccttacct g acagttggt g ccagagggc g tgtattgaa 9 :tgagtgcctt :cctctatgc itgtcaaagc ~catcacttc 3 ggaaagaca acacagacag ccgagt tgga aattccttca cagtgatcaa tagaaccaca gtctccgtgt ctaactgcaa aacgatcgat aagggccagt acgactcact ctcggcccga tctcatgtga ctcccaggga agaatatggg cccttgccaa gcatgctctg tccagccctc aatttctcat catgaat tt caggtagat agatctcaa gacatcgcc [aagcccgaa ~ccggcctcc ;agattCtcc :gacatgcag :gtgctggtc tcaagaaggc tgtcctgagt tagtgagagt gcgagcaacg cgagcacttg agagcaaaac agttgaccag gaatcttggg gacggaacat ttccaccata gcgagaatcc attaaaaatg ctacttggga tgcagctttt gacccgtgtc gaagcttcct aaatacctgc ctacatgctg tactatgcaa acaggcattg gttcactgtg 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 caagcaggaa gatgcccatg gatgccatga aaaaggcatg ccttcccggg cacaagcagg .tagatcatca ctctaaggac 13/99 00 00 00 accaccctca tgccacggca gctcagagtg aatgcctatc cacacctctg aagattgcca cagaacacag tgtcacaacg gatgatgccg ctcttttaca gaaccaagag agagaccacc caggaaagca ttcaacgtca aaatacaagt tcttcgtcga gggagggcca cagtga tccaccaaat tttcagacac tccagcaagc attctggtgt ccaaggtcct agaatgtgca gacctcttgt gacattactt aggtcaccgc tccagaagag cccttggcac cctgcctcca ccttagacca gaaaagtcga gtgggatgaa ccccgacaca ggagatccaa at ttggaggc ttttgaccct tttggaacag ttgtctccag catccttgta atatcctgag ctatgtcctc ctcttatgtc cgctagcatc tgaatgggaa agaagacaca ggcccccgag ctggaaattc aggtaccctg gaaccatcat tcaggagtcc agggaagaac tactggagat tacctggaca ttggtgaagc agggcgccgg ttgaagagat tgccttgaca tatgctgtgc aaagctcaag acttctgccc agacacagtg gacaggcgag ttggacgagc cttcaagagc cctcccgacg cctgaacagc atgaacactg aaacacagca ctcaaatcaa tcgccctaga ccgaagaact cctccaagac tctccgatgt tgcagccata tggtccacgc aaggccagtg tgagtcaaca agagtgtgtc caacgcaagg acttggtgga aaaacaaaac tacttgtgat aaag~ctccct gcacactcgc agagggctct gtgtctccac tatccaggca caatggagag gttaacttta cacaggcaac catgtctcag tgggtggagt gtataaaatg ggcctacgtc aagaggcagg agagctcaag aagagccact gaagcctgag tcatcaatca gctaaacctc ttccctgcga gcttgtgtgc 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3066 <210> 8 <211> <212> <213> <220> <221> <223> 1021 PRT Homo sapiens MISC FEATURE human DUB4.2a <400> 8 Met Gly Asn Thr Cys Tyr Val Asn Ala Ser Leu Gin Cys Leu Thr Tyr 1 5 10 is Thr Pro Pro Leu Ala Asn Tyr Met Leu Ser Arg Glu His Ser Gin Thr 25 14/99 tlsHis Arg ;Z 35 His Lys G2.y Cys Met 40 Leu Cys Thr Met Gin Ala His Ile rhr Arg Ala Leu His Asn Pro Gly His Val Ile Pro Ser Gin Ala 00 e Leu 00 Lys Ala Ala Gly Phe His Arg Giy Lys Gin Asp Ala His Giu Met Phe Thr Asp Ala Met Lys Ala Cys Leu Pro Arg His Gin Val Asp 100 His His Ser Lys Thr Thr Leu Ile His Gin Ilie 110 Cys His Gly Phe Gly Gly 115 Tyr Trp Arg Ser Gin 120 Ile Lys Cys Leu Ile Ser 130 Asp Thr Phe Asp Tyr Leu Asp Ile Ala 140 Leu Asp Ile Gin Ala Gin Ser Val Gin 150 Gin Ala Leu Giu Gin 155 Leu Val Lys Pro Giu Leu Asn Gly Giu 165 Asn Ala Tyr His Cys Gly Val Cys Leu Gin Arg 170 175 Ala Pro Aia Ile Leu Val 195 Lys Thr Leu Thr His Thr Ser Ala Lys Val Leu 190 Lys Ile Ala Leu Lys Arg Phe Asp Val Thr Giy Asn 205 Lys Asn 210 Val Gin Tyr Pro Cys Leu Asp Met Gin 220 Pro Tyr Met Ser Gin 225 Gin Asn Thr Gly Leu Val Tyr Val Leu 235 Tyr Ala Val Leu His Ala Giu Trp Aia Gin Giu Gly 260 Ser Cys His Asn Gly His Tyr Phe Ser Tyr Val Lys 245 250 255 Gin Trp Tyr Lys Met Asp 265 Asp Ala Glu Ala Tyr Val 285 Val Thr Ala 270 Leu Phe Tyr Ala Ser Ilie Thr Ser 275 Val Leu Ser Gin Gin 280 15/99 00 Ile Gln OJ~ 290 Lys Ser Giu Trp Arg His Ser Glu Ser Val Ser Arg Gly .:-Arg S305 Giu Pro Arg Ala Leu Gly Ala Giu Asp 310 Thr 315 Asp Arg Arg Ala Gin Giy Glu Leu Lys 325 Arg Asp His Pro Cys 330 Leu Gin Ala Pro Giu Leu 335 Asp Glu His 00 STrp Lys Phe CK1 355 Val Giu Arg Ala Thr 345 Gin Glu Ser Thr Leu Asp His 350 Phe Asn Val Leu Gin Giu Gin Lys Thr Lys Pro Arg Lys 370 Vai Lys Gly Thr Ile Lys Val Asp Pro Gin Arg Lys Ala Gin Gly Thr Gin Gly Ser Val Giu 395 Pro Gin Asn Leu Arg Asn Pro Ala Gin 405 Ala Pro Lys Cys Ala Tyr Giu Gin Gly 410 Leu Arg 415 Val Thr Glu Cys Ala Asn 435 Val. His Phe Arg Gin 425 His Tyr Asn Phe 430 Asn Giy Gly Cys Asn Ser Thr Ilie Gin Cys Val Thr Asn Ile 450 Ala Asp Pro Giu Ser Met Arg Giu Arg Ile Cys Thr Ala 465 Tyr Phe Gly Leu Phe 470 Pro Leu Lys Gin Gly 475 Pro Val Leu Lys Gin Lys Asn Leu Val 485 Ile Leu Val. Pro Asp Met Giu Asp Asp Ser 495 Leu Tyr Leu Ser Ser Arg 515 Gly 500 Gly Glu Trp Gin Phe Asn His Phe Ser 505 Lys Leu Thr 510 Thr Ser Leu Pro Asp Ala Ala Phe Ala Giu Ile Gin

520- Pro Giu Lys Ser Pro Leu 530 Cys Glu Thr Arg Asp Leu Cys Asp 16/99 tO~sp Leu Ala Pro I'-eu ser Ser Arg Val Ala Arg Gin 550 Leu Ala Pro Arg Glu Lys Leu Pro c c r560 Pro Ala Ala 00 31y Asn Thr Thr Pro Leu 00 His Arg His Cys Tyr Val Asri Ala 580 Val Gly Ala Gly 570 Ser Leu Gin Cys 585 Ser Arg Glu His Leu Gin Asn Met 575 Leu Thr Tyr Thr 590 Ser Gin Thr CYs 605 Ala His Ile Thr Ala Asn Tyr Met Lys Gly Cys Leu Cys Thr Met Arg 625 Ala Leu His Asn Pro 630 Gly His Val Ile Pro Ser Gin Ala Ala Ala Gly Phe Arg Gly Lys Gin Glu 650 Asp Ala His Glu Phe Leu Met Phe Thr Gin Val Asp 675 Val1 660 Asp Ala Met Lys Lys 665 Ala Cys Leu Pro 670 Gin Ile Phe His His Ser Lys Asp 680 Thr Thr Leu Ilie His 685 Gly Gly 690 Tyr Trp Arg Ser Ile Lys Cys Leu His 700 Cys His Gly Ile Asp Thr Phe Asp Tyr Leu AspIle Al a 715 Leu Asp Ile Gin Al a 720 Ala Gin Ser Val Gin Aia Leu Giu Gin 730 Leu Vai Lys Pro Giu Glu 735 Leu Asn Gly Pro Ala Ser 755 Giu 740 Asn Ala Tyr His Gly Vai Cys Leu Lys Thr Leu Thr Leu 760 His Thr Ser Ala Lys 765 Gin Arg Ala '750 Val Leu Ile Ile Ala Lys Leu Val 770 Leu Lys Arg Phe Ser 775 Asp Val Thr Leu Asp Met Gly Asn Lys 780 Asn Val Gin Tyr Pro Giu Cys 785 790 Gin Pro Tyr Met Ser Gin 795 800 17/99 00 kl~a Asn Thr Gly Leu Val. Tyr Val Leu 810 Tyr Ala Val Leu Val His 815 Gly Trp Cys His Asn Gly Tyr Phe Ser Tyr Val Lys Ala 830 Thr Ala Ala 31n Giu Gly 835 Gin Trp Tyr Lys Met 840 Asp Asp Ala Giu Ser Ile 850 0 (f)ml Lys C-K1 865 Thr Ser Ala Leu Ser 855 Gin Gin Ala Tyr Leu Phe Tyr Ile Ser Giu Trp Arg His Ser Giu Val Ser Arg Gly Siu Pro Arg Ala Gly Thr Giu Asp Asp Arg Arg Ala Thr Gin 895 31y Giu Leu Giu His Leu 915 Arg Asp His Pro Leu Gin Ala Pro Giu Leu Asp 910 Asp His Trp Val Giu Arg Ala Gin Giu Ser Thr Lys Phe 930 Leu Gin Giu Gin Asn 935 Lys Thr Lys Pro Phe Asn Val Arg Lys 945 Val Giu Gly Thr Leu 950 Pro Pro Asp Val Val Ilie His Gin Ser 960 Lys Tyr Lys Cys Met Lys Asn His Pro Giu Gin Gin Ser Ser 975 Leu Leu Asn Leu Ser Ser Ser Thr 980 Thr His Gin Giu Ser Met Asn 990 Thr Gly Thr 995 Leu Ala Ser Leu Arg Gly Arg Aia Arg Arg Ser Lys Gly 1000 1005 Lys Asn Lys His Ser Lys Arg Ala Leu Leu Val. Cys Gin 1010 1015 1020 <210> 9 <211> 1593 <212> DNA 18/99 00 M 23> Homo sapiens e220> :t c221> misc_feature 223> human DUB4.2b <:400> 9 atggaggacg acatcttCtC tcaccactct cagcttgctc gggctccaga acaacgcccc aagggctgca cacgtcatcc gcccatgaat aagcaggtag tggagatCtC ctggacatcg gtgaagcccg gcgccggcct aagagattct cttgacatgc gctgtgctgs Sct ca ag a a tctgccctge cacagtgage aggcgagcaz gacgagcact caagagcaaz cccgacgta( gaacagcaai aacactgqc actcactcta ggcccgatgc catgtgagac ccagggagaa atatgggaaa ttgccaacta tgctctgtac agccctcaca ttctcatgtt atcatcactc aaatcaagtg ccctagatat aagaactcaa ccaagacgtt ccgatgtcac agccatacat tccacqctgg Igccagtggta Lgtcaacaggc kgtgtgtcaag icgcaaggaga :tggtggaaag iacaaaacgaa :ttgtgattca a gctccctgCt a cactcgcttc cttgggaggt agcttttgCt ccgtgtcgac gcttcCtCtg tacctgctac catgCtgtcC tatgcaagct ggcattggct cactgtggat taaggacacc tctccactgC ccaggcagct tggagagaat aactttacac aggcaacaag gtctcagcag gtggagttgt taaaatggat ctacgtcctc aggcagggaa gctcaagaga agccactcac gcctgagttc tcaatcaaaz aaacctctct cctgcgagg gagtggcagt gaaatccagc ctctgtgatg agtagcagga gtgaacgCtt cgggagcact cacatcacac 9 ctggC tt CC gccatgaaaa accctCatcc cacggcattt cagagtgtCC gcctatCatt acctctgCCa attgCCaaga aacacaggac cacaacggac gatgccgagg ttttacatcc ccaagagCCC gaccacccct IgaaagCacct :aacgtcagaa itacaagtgtc :tcgtcgaccc 3agggCCagga tcaaccaCtt gg act tc tCt atttggCtCC gacctgctgc ccttgcagtg ctcaaacgtg gggccctCCa atagaggCaa aggcatgcct accaaatatt cagacacttt agcaagcttt ctggtgtttg agg tcct cat atgtgcaata ctcttgtcta attacttctc tcaccgccgc agaagagtgz t tggcacagE gcctccaggc tagaccactc Laagtcgaag Iggatgaagai :cgacacatC tgatccaaag, ttcaaaactc ccctgagaag tgtggcaaga ggtgggyggCt cctgacatac tcatCgtcac caatcctggc gcaggaagat tcccgggcac tggaggctac tgacccttac ggaacagttg tctccagagg ccttgtattg *tcctgagtgC L tgtcctctat ttatgtcaaa tagcatcact iatgggaaaga xagacacagac :ccccgagttg SgaaattCCtt Staccctgcct a ccatcatcct a ggagtccatg g gaagaacaaa 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 19/99 00 S:acagcaaga gggctctgct tgtgtgccag tga 210> :2 11 530 :212> PRT :1>Homo sapiens 1593 :220> 00 :221> S:2 23 MISCFEATURE human DUB4.2b .4 00 let Glu Asp Asp Ser Leu Tyr Leu Gly Glu Trp Gin Phe Asn His ?he Ser Lys Leu Thr Ser Ser Arg Pro 25 Asp Ala Ala Phe Ala Giu Ile ;ln Arg Thr Ser Leu Pro Glu Ser Pro Leu Ser Cys Glu Thr Arg Jal Asp Leu Cys Asp Asp Leu Ala Pro Val Ala Arg Gin Leu Ala Pro Glu Lys Leu Pro Leu Ser Ser Arg Arg Pro 75 Ala Ala Val Gly Al a Gly Leu Gin Asn Met Gly Asn Thr Cys Val Asn Ala Ser Leu Gin Cys Leu Thr His Ser Gin 115 Thr Thr Pro Leu Al a 105 Asn Tyr Met Leu 110 Cys Thr Met Thr Cys His Arg Lys Gly Cys Met Gin Ala 130 His Ile Thr Arg Leu His Asn Pro Gly His Val Ile Gin 140 Pro 145 Ser Gin Ala Leu Ala Gly Phe His Gly Lys Gln Glu 00 20/99 Ala His Glu Phe Leu Met Phe Thr Val Asp Ala Met Lys r~l165 170 Leu Pro Gly His Lys Gln Val Asp His His Ser Lys Asp ~j..180 185 Lys Ala Cys 175 Thr Thr Leu 190 Lys Cys Leu Ile His Gin 195 Ile Phe CGiv Gly Tyr Trp Arg Ser Gln Ile 200 205 His CYS 210 His Gly Ilie Ser Thr Phe Asp Pro Leu Asp Ile Ala Leu 225 Asp Ile Gin Ala Al a 230 Gin Ser Val Gin Ala Leu Giu Gin Val Lys Pro Glu Leu Asn Gly Glu Ala Tyr His Ser Gly Val 255 Cys Leu Gin Ala Lys Val 275 Ala Pro Ala Ser Thr Leu Thr Leu His Thr Ser 270 Val Thr Gly Leu Ilie Leu Val Lys Arg Phe Ser Asn Lys 290 Ile Ala Lys Asn Gin Tyr Pro Giu Leu Asp Met Gin Pro 305 Tyr Met Ser Gin Gin 310 Asn Thr Gly Pro Val Tyr Val Leu Ala Val Leu Val Ala Gly Trp Ser His Asn Gly His Tyr Phe 335 Ser Tyr Val Glu Val Thr 355 Ala Gin Giu Gly Gin Trp Tyr Lys Met Asp Asp Ala 345 350 Ala Ala Ser Ile Thr 360 Ser Ala Leu Ser Gin Ala Tyr Val Leu 370 Phe Tyr Ile Gin Lys 375 Ser Glu Trp Glu His Ser Glu Ser Ser Arg Gly Arg Giu 390 Pro Arg Ala Leu Thr Glu Asp Thr Arg Arg Ala Thr Gin Gly Glu Leu Lys 405 Arg Asp His Pro 410 Cys.Leu Gin 2 1/99 00 Ala Pro Giu Leu. 420 ;Z Thr Leu Asp His 43 Asp Glu His Leu Giu Arg Ala Thr Gln Glu Ser 430 Thr Lys Pro Trp Lys Phe Leu 440 Gin Giu Gin Asn Lys 445 Giu P'ne 450 iAsf vaJ. irg Lys Val 455 Giu Gly Thr Leu Pro Asp Val Leu 00 Val 465 00Gi Ile His Gin Ser Tyr Lys Cys Gly Lys Asn His His Gin Gin Ser Leu Leu Asn Leu Ser Ser Thr Pro Thr His 495 Gin Giu Ser Arg Arg Ser 515 Met Asn 500 Thr Gly Thr Ala Ser Leu Arg Gly Arg Ala 510 Leu. Leu Val Lys Gly Lys Asn His Ser Lys Arg Cys Gin 530 <210> 11 <211> 1593 <212> DNA <213> HOMnO sapiens <220> <221> misc-feature <223> human DUB4.3 <400> 11 atggaggacg acatcttctc tcaccactct cagcttgCtC gggctccaga acaccgcccc aagggctgca actcactcta. ggccc(3atgc catgtgagac cc aggy ag aa atatgggaaa. ttgccaacta tgctctgtac cttgggaggt agcttttgct ccgtgtcgac gcttcCtg tacctgctac catgctgtcc gatgcaagct gagtggcagt gaaatccagc ctctgtgatg agtagcagga. gtgaacgctt cgggagcact cacatcacac tcaaccactt ggacttctct atttggctcc gacctgctgc ccttgcagtg ctcaaacgtg gggccctcca ttcaaaactc ccctgagaag tgtggcaaga ggtgggggct cctgacatac tcatcgtcac caatcctggc 22/99 00 C1cacgtcatcc agccctcaca. ggcattggct gctggcttcc atagaggcaa gcaggaagat gcccatgaat aagcaggtag tggagatctc ctggacatcg gtgaagcccg gcgccggcct aagagattct cttgacatgc gctgtgctgg gctcaagaag tctgtcctga cacagtgaga aggcgagcaa gacgagcact caagagcaaa. cccgacgtac gaacagcaaa aacactggca cacagcaaga ttctcatgtt atcatcactc aaatcaagtg ccctggatat aagaactcaa. ccaagacgtt ccgatgtgac agccatacat tccacgctgg gccaatggta gt caacaggc gtgtgtcaag cgcaaggaga tggtggaaag acaaaacgaa ttgtgattca gctccctgct cactcgcttc gggctctgct cactgtggat taaggacacc tctccactgc ccaggcagct tggagagaat aactttacac aggcaacaag gtctcagcag gtggagttgt taaaatggat ctacgtcctc aggcagggaa gctcaagaga agccactcag gcctgagttc tcaatcaaaa aaacctctct cctgcgagg t gtgtgc cac gccatgaaaa accctCatCC cacggcattt cagagtgtcc gcctatcatt acctctgcca attgccaaga aacacaggac cacaacggac gatgccgagg ttttacatcc ccaagagccc gaccacccct gaaagcacct aacgtcagaa tacaagtgtg tcgtcgaccc Iagggccagga Itga aggcatgcct accaaatatt cagacacttt agcaagCttt aggtcctcat atgtgcaata ctcttgtcta. attacttctc tcaccgccgc agaagagtga ttggcgcaga gcctccaggc tagaccgctg aagtcgaagg ggatgaagaa cgacacatca gatccaaagq tcccgggcac tggaggctac tgacccttac ggaacagttg tctccagagg ccttgtattg tcctgagtgc tgtcctctat ttatgtcaaa tagcatcact atgggaaaga agacacagac ccccgagttg gaaattcctt taccctgcct ccatcatcct ggagtccatg Igaagaacaaa 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1593 <210> <211> <212> <213> <220> <221> <223> 12 530 PRT. Homo sapiens MISCFEATURE human DUB4.3 <400> 12 Met Glu Asp Asp.Ser Leu Tyr Leu Gly Gly Glu Trp Gin Phe Asn His 1 5 10 23199 00 Phe Ser Lys Leu Gin Arg Thr Ser 00 Val Asp Leu Cys 50 SArg Glu Lys Leu 00 Gly Leu Gin Asn Thr Ser Ser Arg Leu Pro Glu Lys Pro 25 Asp Ala Ala Phe Ala GiU Ile Glu Thr Arg Ser Pro Leu Ser Asp Asp Leu Ala Pro Val Ala Gin Leu Ala Pro Pro Ser Ser Arg Arg Pro Ala Ala Val Gly Gly Asn Thr Cys Tyr Val Asn Ala Ser Leu Gin Cys Leu Thr Thr Pro Pro Leu Al a 105 Asn Tyr Met Leu 110 Cys Thr Met His Ser Gin Thr Cys His Arg Lys Gly Cys Met Gin Ala 130 His Ile Thr Arg Leu His Asn Pro His Val Ile Gin Pro 145 Ser Gin Ala Leu Al a 150 Ala Gly Phe His Gly Lys Gin Glu Asp 160 Ala His Giu Phe Met Phe Thr Val Ala Met Lys Lys Ala Cys 175 Leu Pro Gly Ilie His Gin 195 Lys Gin Val Asp His 185 His Ser Lys Asp Thr Thr Leu 190 Lys Cys Leu Ile Phe Gly Gly Tyr 200 Trp Arg Ser Gin Ile 205 His Cys 210 His Gly Ile Ser Thr Phe Asp Pro Leu Asp Ile Ala Leu 225 Asp Ilie Gin Ala Al a 230 Gin Ser Val Gin Ala Leu Glu Gin Leu 240 Val Lys Pro Giu Cys Leu Gin Arg 260 Leu Asn Gly Giu Ala Tyr His Cys Gly Val 255 Ala Pro Ala Ser Thr Leu Thr Leu His Thr Ser 270 24/99 b-kl ys Val ;Z 275 Leu Ile Leu Val. Leu Lys 280 Arg Phe Ser Asp Val. Thr Giy 285 Asfl Lys 290 Ile Ala Lys Asn Val. 295 Gin Tyr Pro Glu Cys 300 Leu Asp Met Gin 0 0 Pro 305 ciAla 00 Ser Tyr Met Ser Gin Asn Thr Giy Pro Val Tyr Val Leu Val Leu Val Tyr Val Lys 340 His 325 Ala Gly Trp Ser His Asn Gly His Tyr Phe 335 Ala Gin Glu Gly Trp Tyr Lys Met Asp Asp Ala 350 Gin Ala Tyr Giu Val Thr 355 Ala Ala Ser Ile Ser Val Leu Ser Gin 365 Val Leu 370 Phe Tyr Ile Gin Ser Giu Trp Giu Arg 380 His Ser Giu Ser Ser Arg Gly Arg Pro Arg Ala Leu Ala Glu Asp Thr Arg Arg Ala Thr Gin 405 Giy Glu Leu Lys Arg 410 Asp His Pro Cys Leu Gin 415 Ala Pro Giu Thr Leu Asp 435 Asp Giu His Leu Giu Arg Ala Thr Gin Giu Ser 430 Arg Trp Lys Phe Gin Giu Gin Asn Lys Thr Lys Pro 445 Giu Phe 450 Asn Val Arg Lys His Gin ser Lys 470 Giu Gly Thr Leu Pro 460 Pro Asp Val Leu Ile Tyr Lys Cys Gly Lys Asn' His 'His Pro 480 Glu Gin Gin Ser Ser 485 Leu Leu Asn Leu Ser Ser 490 Ser Thr Pro Thr His 495 Leu Arg Gly Arg Ala 510 Gin Glu Ser Arg Arg Ser 515 Asn Thr Gly Thr Leu Ala Ser 505 Lys Gly Lys Asn Lys 520 His Ser Lys Arg Ala Leu Leu Val. 525 25/09 00 Cys Gir OJ~ 530 <210> 00 00 <211> <212> <213> <220> <221> <223> 13 1722 DNA H-omo sapiens misc feature human <400> 13 atgcgccaga ctgcggtccc ctctacttgg gatgcagctt gagacccgtg gagaagct tc ggaaatacct aactacatgc tgtacgatgc tcacaggcat atgttcactg cactctaagg aagtgtctcc gatatccagg ctcaatggag acgttaact gtcacaggca tacatgtctc gctgggtgga tggtataaaa gagctcgtca agcagaaaaa gaggtgagtg ttgctgaaat tcgacctctg ctctgagtaa gctacgtgaa tgtcccggga aagctcacat tggctgctgg tggatgccat acaccaccct actgccacgg cagctcagag agaatgccta tacacacctc acaagattga agacgaactc gttgtcacaa tggatgatgc tttgaagact ccttgtgatc gc a9t t ca ac ccagcggact tgatgatttg caggagacct cgc t tcc tt g gcactctcaa cacacgggcc cttccataga gaaaaaggca catccaccaa catttcagac tgtccagCaa tcattgtggt tgccaaggtc caagaatgtg aggacctctc cggacattac cgaggtcacc ctctcggaag cttgttccag cacttttcaa tctctccctg gctcctgtgg gctgcggtgg cagtgcctga acgtgtcatc ctccacaatc ggcaagcagg tgccttcccg atatttggag acttttgacc gctttggaac gt ttgtctcc ctcatccttg caatatcctg gtctatgtcc ttctcttatg gcctctagca ggatagcgtc tcgacatgga aactcacatc agaagtcacc caagacagct gggctgggct catacacacc 9tcacaaggg ctggccacgt aagatgccca ggcacaagca gctactggag cttacctgga agttggtgaa agagggcgcc tattgaagag agtgccttga tctatgctgt tcaaagctca tcacttctgt tttctgcaac ggaagactca ttctcggccc actctcatgt tgctcccagg ccagaatatg gccccttgcc ctgcatgctc catccagccc tgaatttctc ggtggatcat atctcaaatc catcgccctg gcccgaagaa ggcctccaag attctccgat catgaagcta gctggtccac agaaggccag cctgagtcaa 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 26/99 00 caggcctacg ;tcaagaggca ggagagctca gaaagagcca 00 acgaagcctg attcatcaat ctgctaaacc 00 gcttCCCt9C tcctctttta gggaaccaag agagagacca ctcaggaaag agttcaacgt caaaatacaa tctcttcgac gagggagggc gccagtggtc catccagaag agcccttggc cccctgcctc caccttagac cagaaaagtc gtgtgggatg gaccccgaca caggagatcc tcagtggaag agtgaatggg gcagaagaca caggcccccg cactggaaat gaaggtaccc aagaaccatc catcaggagt aaagggaaga taccgaccca aaagacacag cagacaggcg agttggacga tccttcaaga tgcctcccga atcctgaaca ccatgaacac acaaacacag ca tgagagtgtg agcaacgcaa gcacttggtg gcaaaacaaa cgtacttgtg gcaaagctcc tggcacactc caagagggct 1260 1320 1380 1440 1500 1560 1620 1680 1722 <210> <211> <212> <213> <220> <221> <223> 14 574 PRT Homo sapiens MISCFEATURE human <400> 14 Met Arg G: 1 ln Arg Ala 5 Arg His Leu Lys Leu Ser Giu Gly Ile Ala Ser Phe Cys Pro Val Asp Asn Leu Arg Ser Gin Lys Asn Leu Val Met Giu Giu Asp Leu Tyr Leu Gly Gly Ile Leu Val Glu Trp Gin Ala Ala Phe Phe Asn His Phe Ser Lys Thr Ser Ser Arg Pro Asp Al a Giu Ile Gln Arg Ser Leu Pro Glu Lys Ser Pro Leu Ser Glu Thr Arg Val Asp Leu Cys Asp Asp Leu. Ala Pro Vai 90 Ala Arg Gin 27/99 00 Leu Ala Pro Arg C 100 Val Gly Ala Gly S115 Glu Lys Leu Pro Leu Ser 105 Asn Arg Arg Pro Ala Ala 110 Val Asn Ala Leu Gin Asn Gly Asn Thr Cys Tyr 125 Ser Leu Gin Cys Leu Thr Thr Pro Pro Leu Asn Tyr Met Leu Arg Glu His Ser Gin 150 Thr Cys His Arg His 155 Lys Gly Cys Met Cys Thr Met Gin His Ile Thr Arg Leu His Asn Pro Gly His 175 Val Ile Gin Gin Glu Asp 195 Pro 180 Ser Gin Ala Leu Ala Ala Gly Phe His 185 Met Phe Thr Val Asp 205 Arg Gly Lys 190 Ala Met Lys Ala His Glu Phe Leu 200 Lys Ala 210 Cys Leu Pro Gly Lys Gin Val Asp His Ser Lys Asp Thr 225 Lys Thr Leu Ile His Cys Leu His Cys 245 Gin 230 Ile Phe Gly Gly Tyr 235 Trp Arg Ser Gin His Gly Ile Ser Thr Phe Asp Pro Tyr Leu 255 Asp Ile Ala Glu Gin Leu 275 Leu 260 Asp Ile Gin Ala Gin Ser Val Gin Gin Ala Leu 270 Ala Tyr His Val Lys Pro Glu Leu Asn Gly Glu Asn 285 Cys Gly 290 Val Cys Leu Gin Arg 295 Ala Pro Ala Ser Lys 300 Thr Leu Thr Leu His 305 Thr Ser Ala Lys Val 310 Leu Ile Leu Val Leu 315 Lys Arg Phe Ser Asp 320 Val Thr Gly Asn Lys 325 Ile Asp Lys Asn Val 330 Gin Tyr Pro Glu Cys Leu 335 Asp Met Lys Leu 340 Tyr Met Ser Gin Thr 345 Asn Ser Gly Pro Leu Val Tyr 350 28 /99 00 Jal Leu Tyr Ala qs ryr Phe Ser 370 Val Leu Val His Ala Gly Trp Ser Cys His Asn Gly Tyr Val Lys Ala Gin Glu Gly Gin Trp 375 380 Tyr Lys Met Asp 385 Asp Ala Glu Val Thr Ala Ser Ser 390 Phe Tyr Ilie Gin Ile Thr 395 Ser Val Leu Ser Gin 400 GIn Ala Tyr Val 00Ser Giu Ser Val 420 Ser Giu Trp Giu Arg His 415 Ser Arg Giy Arg Giu 425 Pro Arg Ala Leu 430 Asp His Pro Asp Thr Asp 435 Arg Arg Ala Thr Gly Giu Leu Lys Arg 445 Cys Leu 450 Gin Ala Pro Giu Asp Giu His Leu Val 460 Glu Arg Ala Thr Giu Ser Thr Leu His Trp, Lys Phe Gin Giu Gin Asn Lys 480 Thr Lys Pro Giu Phe Asn Vai Arg Lys 485 Giu Gly Thr Leu Pro Pro 495 Asp Val Leu His His Pro 515 Val 500 Ile His Gin Ser TPyr Lys Cys Giy 510 Ser Thr Thr Glu Gin Gin Ser Leu Leu Asn Leu Pro Thr 530 His Gin Glu Ser Asn Thr Gly Thr Ala Ser Leu Arg Arg Ala Arg Arg Ser 550 Lys Gly Lys Asn His Ser Lys Arg Ala 560 Leu Leu Val Cys Gin Trp 565 Ser Gin Trp Tyr Arg Pro Thr <210> <211> 1593 <212> DNA <213> Homo sapiens 29/99 00 <220> <221> misc-feature <223> human DUB4.6 <400> atggaggacg acatcttctc tcaccactct cagcttgctc gggctccaga acaccgcccc aagggctgta cacgtcatcc gcccatgaat aagcaggtgg tggagatctc ctggacatcg gtgaagcccg cgccggcct aagagattct cttgacatgc gctgtgctgg gctcaagaag tctgtcctga cacagtgaga aggcgagcaa gacgagcact caagagcaaa cccgacgtac gaacagcaaa aacactggca cacagcaaga actcactcta gg cccg at go catgtgagac ccagggagaa atatgggaaa ttgccaacta tgctctgtac agccctcaca ttctcatgtt atcatcactc aaatcaagtg ccctggatat aagaactcaa ccaagacgtt ccgatgtcac agccatacat tccacgctgg gccagtggta gtcaacaggc gtgtgtcaag cgcaaggaga. tggtggaaag acaaaacgaa ttgtgattca gctccctgct cactcgcttc gggctctgct cttgggaggt agcttttgct ccgtgtcgaC gcttcctctg tacctgctac catgctgtcc gatgcaagct ggcattggct cactqtggat taaggacacc tctccactgc ccaggcagct tggagagaat aactttacac aggcaacaag gtctcagacg gtggagttgt taaaatggat ctacgtcctc aggcagggaa gctcaagaga agccactcag gcctgagttc tcaatcaaaa aaacctctct cctgcgaggg tgtgtgccag gagtggcagt gaaatccagc ctctgtgatg agtagcagga gtgaacgctt cgggagcact cacatcacac gctggcttcc gccatgaaaa accctcatcc cacggcattt cagagtgtcc gocctat cat t acctctgcca attgccaaga aacacaggac cacaacggac gatgccgagg ttttacatcc ccaagagccc gaccacccct gaaagcacct aacgtcagaa tacaagtgtg tcgacgaccc agggccagga tga tcaaccactt ggacttctct atttggctcc gacctgctgc ccttgcagtq ctcaaacgtq gggccctcca atagaggcaa aggcatgcct accaaatatt cagacacttt agcaagcttt gtggtgtttg aggtcctcat atgtgcaata ctctcgtcta attacttctc tcaccgcctc agaagagtga ttggcgcaga gcctccaggc tagaccactg aagtcgaagg ggatgaagaa cgacacatca gatccaaagg ttcaaaactc ccctgagaag tgtggcaaga ggtgggggct cctgacatac tcatcgtcac caatcctggc gcaggaagat tcccgggcac tggaggctac tgacccttac ggaacagt tg tctccagagg ccttgtattg tcctgagtgc tgtcctctat ttatgtcaaa tagcatcact atgggaaaga agacacagac ccccgagttg gaaattcctt taccctgcct ccatcatcct ggagtccatg gaagaacaaa 120 180 240 300 360 4 480 540 600 660 720 780 640 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1593 30/99 <210> 16 <211> 530 <212> PRT <213> HOMO sapiens <220> <221> MISCFEATURE <223> human DUB4.6 <400> 16 met Glu Asp Asp Ser 1 5 Leu Tyr Leu Gly Gly 10 Glu, Trp Gin Phe Asn His Phe Ser Lys Gin Arg Thr 3S Thr Ser Ser Arg Asp Ala Ala Phe Ala Glu Ile Glu Thr Arg Ser Leu Pro Glu Ser Pro Leu Ser Val Asp so Leu Cys Asp Asp Ala Pro Val Ala Arg Gin Leu. Ala Pro Arg Glu Lys Leu Pro Leu 70 Ser Ser Arg Arg Pro Ala Ala Val Gly Gly Leu Gin Asn Met Gly Asn Thr Cys Tyr 90 Val Asn Ala Ser Leu Gin Cys Leu Thr His Ser Gin 115 Thr Pro Pro Leu. Asn Tyr Met Leu Ser Arg Glu 110 Thr Cys His Arg Lys Gly Cys Met Leu Cys Thr Met 125 Gin Ala 130 His Ile Thr Arg Al a 135 Leu His Asn Pro Gly 140 His Val Ile Gin Pro 145 Ser Gin Ala Leu Ala Ala Gly Phe His Arg 155 Gly Lys Gin Glu Ala His Glu Phe Leu Met Phe Thr Vai Asp Ala Met Lys Lys 165 170 Ala Cys 175 3 1/99 00 Leu Pro Gly Ile His Gin 1.95 His 180 Lys Gin Val Asp His 185 His Ser Lys Asp Thr Thr Leu 190 Lys Cys Leu Ile Phe Giy Gly Tyr 200 Trp Arg Ser Gin Ile 205 His 00 Leu C1225 00 Val Cys 210 His Gly Ile Ser Thr Phe Asp Pro Tyr 220 Leu Asp Ile Ala Asp Ilie Gin Ala Ala 230 Gin Ser Val Gin Ala Leu Giu Gin Lys Pro Giu Leu Asn Gly Gau Ala Tyr His Cys Gly Vai 255 Cys Leu Gin Ala Lys Val 275 Ala Pro Ala Ser Lys 265 Thr Leu Thr Leu 270 Val Thr Gly Leu Ile Leu Val Leu 280 Lys Arg Phe Ser Asp 285 Asn Lys 290 Ilie Ala Lys Asn Gin Tyr Pro Giu Cys 300 Leu Asp Met Gin Pro 305 Tyr Met Ser Gin Thr 310 Asn Thr Gly Pro Val Tyr Val Leu Ala Val Leu Val His 325 Ala Gly' Trp Ser His Asn Gly His Tyr Phe 335 Ser Tyr Val Giu Vai Thr 355 Ala Gin Giu Gly Gin 345 Trp Tyr Lys Met 350 Gin Ala Tyr Ala Ser Ser Ile Ser Val Leu Ser Vai Leu 370 Phe Tyr Ilie Gin Ser Glu Trp Giu His Ser Giu Ser Ser Arg Giy Arg Pro Arg Ala Leu Ala GJlu Asp Thr Asp 400 Arg Arg Ala Thr Ala Pro Giu Leu 420 Gin Gly Giu Leu Lys Arg Asp His Pro Cys Leu Gin 405 410 415 Asp Giu His Leu Val Glu Arg Ala Thr Gin Glu Ser 425 430 3 2/9 9 t0Thr Glu L~eu Asp His Trp Lys Phe Leu Gin Giu Gin Asn Lys Thr Lys Pro A A A445 Phe Asn 450 Val Arg Lys Val1 455 Glu Gly Thr Leu Pro 460 Pro Asp Val Leu Val1 465 Ile His Gin Ser Lys 470 Tyr Lys Cys Gly Met 475 Lys Asn His His Pro 480 Giu Gin Gin Ser Ser 485 Leu Leu Asn Leu Ser 490 Ser Thr Thr Pro *Thr His 495 Gin Giu Ser Arg Arg Ser 515 Asn Thr Gly Thr Ala Ser Leu. Arg Gly Arg Ala 510 Leu Leu Val Lys Gly Lys Asn His Ser Lys Arg Cys Gin 530 <210> <211> <212> 1*7 1593 DNA <213> Homo sapiens <220> <221> misc feature <223> human DUB4.7 <400> 17 a tggaggacg acatcttctC tcaccactct cagcttgctc gggctccaga acaccgcccc aagggctgca cacgtcatcc actcactcta ggcccgatgc cat g gagac ccagggagaa. atatgggaaa. ttgccaacta tgctctgtac agccctcaca cttgggtggt agcttttgct ccgtgtcgac gcttcCtctg tacctgctac catgctgtcc tatgcaagct ggcattggct gagtggcagt gaaatccagc ctctgtgatg agtagcagga gtgaacgctt cgggagcact cacatcacac gctggcttcc tcaaccactt ggacttctct atttggctcc gacctgctgc ccttgcagtg ctcaaacgtg gggccctcca atagaggcaa ttcaaaactc ccctgagaag tgtggcaaga ggtgggggct cctgacatac tcatcgtcac caatcctggc gcaggaagat 120 180 240 300 360 420 480 33/99 00 00 00 gcccatgaat aagcaggtag tggagatctc ctggacatcg gtgaagcccg gcgccggcct aagagattct cttgacatgc gctgtgctgg gctcaagaag tctgtcctga cacagtgaga aggcgagcaa gacgagcact caagagcaaa cccgacgtac gaacagcaaa aacactggca cacagcaaga ttctcatgtt atcatcactc aaatcaactg ccctggatat aagaactcaa ccaagacgtt ccgatgtcac agccatacat tccacgctgg gccagtggta gtcaacaggc gtgtgtcaag cgcaaggaga tggtggaaag acaaaacgaa ttgtgattca gctccctgct cactcgcttc gggctctgct cactgtggat taaggacacc tctccactgc ccaggcagct tggagagaat aactttacac aggcaacaag gtctcagcag gtggagttgt taaaatggat ctacgtcctc aggcagggaa gctcaagaga agccactcag gcctgagttc tcaatcaaaa aaacctctct cctgcgaggg tgtgtgccag gccatgaaaa accctcatcc cacggcattt cayagtgtcc gcctatcatt acctctgcca attgccaaga aacacaggac cacaacggac gatgccgagg ttttacatcc ccaagagccc gaccacccct gaaagcacct aacgtcagaa tacaagtgtg tcgtcgaccc aggaccagga tga aggcatgcct accaaatatt cagacacttt agcaagcttt gtggtgtttg aggtcctcat atgtgcaata ctcttgtcta attacttctc tcaccgccgc agaagagtga ttggcgcaga gcctCcaggc tagaccactg aagtcgaagg ggatgaagaa cgacacatca gatccaaagg tcccgggcac tggaggctac tgacccttac gga aca t tg tctccagagg ccttgtattg tcctgagtgc tgtcctctat ttatgtcaaa tagcatcact atgggaaaga agacacagac ccccgagttg gaaattcctt taccctgcct ccatcatcct ggaggccatg gaagaacaaa 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1593 <210> 18 <211> 530 <212> PRT <213> Homo sapiens <220> <221> <223> MISCFEATURE human DUB4.7 <400> 18 Met Glu Asp Asp Ser Leu Tyr Leu Gly Gly Glu Trp Gin Phe Asn His 1 5 10 34/99 00 ']Phe ;Z3 Ser Lys Leu Thr Ser Ser Arg Pro Asp Ala Ala Phe Ala Glu Ile 25 Arg Thr Ser Leu Pro Glu Lys Ser Pro Leu Ser Cys Glu Thr Arg Val Asp Leu Cys Asp Asp Leu Ala Pro Val Ala Gin Leu Ala Pro mArg 00 SGly Glu Lys Leu Pro Ser Ser Arg Arg Ala Ala Val Gly Leu Gin Asn Gly Asn Thr Cys Val Asn Ala Ser Leu Gin Cys Leu Thr His Ser Gin 115 Tyr 100 Thr Pro Pro Leu Asn Tyr Met Leu Ser Arg Glu 110 Cys Thr Met Thr Cys His Arg Lys Gly Cys Met Gin. Ala 130 His Ile Thr Arg Leu His Asn Pro Gly 140 His Val Ile Gin Ser Gin Ala Leu Ala Gly Phe His Gly Lys Gin Giu Asp 160 Ala His Glu Phe Met Phe Thr Val Asp 170 Ala Met Lys Lys Ala Cys 175 Leu Pro Gly Ilie His Gin 195 His 180 Lys Gin Val Asp His 185 His Ser Lys Asp 190 Asfl Cys Leu Ile Phe Gly Gly Trp Arg Ser Gin His Cys 210 His Gly Ile Ser Thr Phe Asp Pro Tyr 220 Leu Asp Ile Ala Leu 225 Asp Ile Gin Ala Gin Ser Val Gin Ala Leu Giu Gin Leu 240 Val Lys Pro Giu Leu Asn Gly Giu Asn Ala 250 Tyr His Cys Gly Val 255 Cys Leu Gln yS euGn Ala Pro Ala Ser Lys Thr Leu Thr Leu His Thr Ser 35/99 00 kia Lys Val 275 Zsn Lys Ile 290 Leu Ile Leu Val Leu 280 Lys Arg Phe Ser Asp 285 Vai Thr Gly Ala Lys Asn Val 295 Gin Tyr Pro Glu Cys 300 Leu Asp Met Gin Tyr Met Ser Gin Gin 310 Asn Thr Gly Pro Vai Tyr Vai Leu Tyr 320 00 00 kla Val Leu Val His 325 Ala Gly Trp Ser His Asn Giy His Tyr Phe 335 Ser Tyr Val Glu Val Thr 355 Ala Gin Giu Gly Gin 345 Trp Tyr Lys Met Asp Asp Ala 350 Gin Ala Tyr Ala Ala Ser Ile Ser Val Leu Ser Val Leu 370 Phe Tyr Ile Gin Ser Giu Trp Glu His Ser Giu Ser Val 385 Ser Arg Gly Arg Pro Arg Ala Leu Ala Giu Asp Thr Asp 400 Arg Arg Ala Thr Gly Giu Leu Lys Asp His Pro Cys Leu Gin 415 Ala Pro Glu Thr Leu Asp 435 Asp Giu His Leu Val 425 Glu Arg Ala Thr Gin Giu Ser 430 His Trp Lys Phe Leu Gin Giu Gin Asn Lys Thr Lys Pro Glu Phe 450 Asn Val Arg Lys Val 455 Glu Gly Thr Leu Pro Pro Asp Val Leu 460 Ile His Gin Ser Lys 470 Tyr Lys Cys Gly Lys Asn His His Pro 480 Glu Gin Gin Ser Gin Glu Ala Met 500 Ser 485 Leu Leu Asn Leu Ser 490 Ser Ser Thr Pro Thr His 495 Asn Thr Gly Thr Ala Ser Leu Arg Gly Arg Thr 510 Arg Arg Ser Lys Gly Lys Asn Lys His Ser 515 520 Lys Arg Aia Leu Leu Val 525 36/99 00 Cys Gin C1 530 <210> 19 <211> 1698 <212> DNA 00 <213> H-omo sapiens <220> <221> <223> misc-feature human DUB4.8 <400> 19 atgcgCcaga ctgcggtccc c t ctact tgg gatgcagctt gagacccgtg gagaagcttc ggaaatacct aactacatgc tgtacgatgc tcacaggcat atgttcactg cactctaagg aagtgtctc gatatccagg ctcaatggag acgttaactt gtgacaggca tacatgtctc gctgggtgga tggtataaaa gagctcgtca agcagaaaaa. gaggtgagtg ttgctgaaat tcgacctctg ctctgagtag gctacgtgaa tg tcc cggg a aagctcacat tggctgctgg tggatgccat acaccaccct actgccacgg cagctcagag agaatgccta tacacacctc acaagattgc agcagaacac gttgtcacaa tggatgatgc tttgaagact ctctcggaag ggatagcgtc ttgctgcaaa ccttgtgatc gcagttcaac ccagcggact tgatgatttg caggagacct cgcttccttg gcactctcaa. cacacgggcc cttccataga gaaaaaggca catccaccaa. catttcagac tgtccagcaa, tcattgtggt tgccaaggtc caagaatgtg aggacctctt cggacattac cgaggtcacc cttgttccag cacttttcaa tctctccctg gctcctgtgg gctgcggtgg cagtgcctga acgtgtcatc ctccacaatc ggcaagcagg t gc c ttcc cg atatttggag acttttgacc gctttggaac gtttgtctcc ctcatccttg caatatcctg gtctatgtcc ttctcttatg gccgctagca tcgacatgga aactcacatc agaagtcacc caagacagct gggctgggct catacacacc gtcacaaggg ctggccacgt aagatgccca ggcacaagca gctactggag cttacctgga agttggtgaa agagggcgcc tattgaagag agtgccttga t cta tgc tgt tcaaagctca tcacttctgt ggacgactca. ttctcggccc actctcatgt tgctcccagg ccagaatatg gccccttgcc ctgcatgctc cat cc agc cc tgaatttctc ggtagatcat atctcaaatc catcgccctg gcccgaagaa ggcctccaag attctccgat catgcagcca gctggtccac agaaggccaa. cctgagtcaa 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 caggcctacg tcctctttta catccagaag agtgaatggg aaagacacag tgagagtgtg 37/99 00 00 00 t ca a gagg ca ggagagctca gaaagagcca acgaagcctg attcatcaat ctgctaaacc gcttccctgc ctgcttgtgt gggaaccaag agagagacca. ctcaggaaag agttcaacgt caaaatacaa tctcttcgtc gagggagggc gccagtga. agcccttggc cccctgcctc caccttagac cagaaaagtc gtgtgggatg gaccccgaca. caggagatcc gcagaagaca caggcccccg cactggaaat gaaggtaccc aagaaccatc catcaggagt aaagggaaga cagacaggcg agttggacga tccttcaaga. tgcctcccga atcctgaaca ccatgaacac acaaacacag agcaacgcaa gcacttggtg gcaaaacaaa cgtacttgtg gcaaagctcc tggcacactc caagagggct 1320 1320 1440 1500 1560 1620 1680 1698 <210> <211> <212> <213> <220> <221> <223> 565 PRT Homo sapiens MISCFEATURE human DUB4.8 <400> Met Arg 1 Gin Arg Ala 5 Arg His Leu Lys Leu Ser Glu Gly Ile Ala Ser Cys Cys Pro Val Asp Leu Arg Ser Gin Lys Asn Leu Val Glu Trp Gin Met Giu Asp Asp Ser 40 Leu Tyr Leu Gly Gly Phe Asn s0 His Phe Ser Lys Thr Ser Ser Arg Asp Ala Ala Phe Al a Giu Ile Gin Arg Ser Leu Pro Glu Ser Pro Leu Ser Giu. Thr Arg Val Leu Cys Asp Asp Ala Pro Val Ala Arg Gln Leu Ala Pro Arg Glu Lys Leo Pro Leu Ser Ser Arg Arq Pro Ala Ala 38/99 O Val Gly Ala 115 Gly Leu Gin Asn Met Gly 120 Asn Thr Cys Tyr Val Asn Ala 125 Ser Leu 130 Gin Cys Leu Thr Tyr 135 Thr Pro Pro Leu Ala Asn Tyr Met Leu 140 Ser 145 Arg Giu His Ser Gin 150 Thr Cys His Arg His 155 Lys Gly Cys Met Leu 160 Cys Thr Met Gin His Ile Thr Arg Leu His Asn Pro Gly His 175 Vai Ile Gin Gin Giu Asp 195 Ser Gin Ala Leu Ala Gly Phe His Arg Gly Lys 190 Ala Met Lys Ala His Giu Phe Leu 200 Met Phe Thr Val Asp 205 Lys Ala 210 Cys Leu Pro Gly His 215 Lys Gin Val Asp His Ser Lys Asp Thr 225 Thr Leu Ile His Ile Phe Gly Gly Tyr 235 Trp Arg Ser Gin Lys Cys Leu His His Gly Ilie Ser Asp 250 Thr Phe Asp Pro Tyr Leu 255 Asp Ilie Ala Giu Gin Leu 275 Asp Ile Gin Ala Gin Ser Val Gin Gin Ala Leu 270 Aia Tyr His Val Lys Pro Giu Leu Asn Gly Giu Asn 285 Cys Gly 290 Val Cys Leu Gin Ala Pro Ala Ser Lys 300 Thr Leu Thr Leu Thr Ser Ala Lys Vai 310 Leu Ile Leu Val Lys Arg Phe Ser Asp 320 Val Thr Gly Asfl Lys 325 Ile Ala Lys Asn Gin Tyr Pro Giu Cys Leu 335 Asp Met Gin Pro 340 Tyr Met Ser Gin Asn Thr Gly Pro 350 His Asn Gly Val Leu Tyr Ala 355 Val Leu Val Ala Giy Trp Ser 39/99 00 4is Tyr 0J) 370 kj sp Asp S385 Phe Ser Tyr Val Lys 375 Ala Gin Giu Gly Trp Tyr Ly's Met Ala Giu Val Ala Ala Ser Ile Ser Val Leu Ser 31n Ala Tyr Val Phe Tyr Ile Gin Ser Glu Trp Giu Arg His 415 3er Glu Ser 00 0 %sp Thr Asp N 43 Ser Arg Gly Arg Pro Arg Ala Leu Gly Ala Glu 430 Asp His Pro Arg Arg Ala Thr Gly Giu Leu Lys Arg 445 2ys Leu 450 Gin Ala Pro Glu Asp Glu His Leu Giu Arg Ala Thr Giu Ser Thr Leu Asp 470 His Trp Lys Phe Gin Giu Gin Asn Thr Lys Pro Giu Phe Asn Val Arg Lys 485 Val1 490 Glu Giy Thr Leu Pro Pro 495 Asp Vai Leu His His Pro Val1 500 Ile His Gin Ser Tyr Lys Cys Gly Met Lys Asn 510 Ser Ser Thr Glu Gin Gin Ser Leu Leu Asn Leu Ser 525 Pro Thr His Gin Giu Ser 530 Met 535 Asn Thr Gly Thr Leu Ala Ser Leu Arg 540 His Ser Lys Arg Ala Gly 545 Arg Ala Arg Arg Ser 550 Lys Gly Lys Asn Leu Leu Val Cys Gin 565 <210> 21 <211> 2148 <212> DNA <213> Homo sapiens 40/99 00 <220> <221> <223> misc-feature human OUB4.10 <400> 21 atgtgcatac actggcagac ccgatgccca aactgcaatt cgatcgatgc gggccagtat aggttatcgc ctcaggtcag gctgccaaaa ctcgttccag cacttttcaa tctctccctg gctcctgtgg gctgcggtgg cagtgcctga acgtgtcatc ctccacaatc ggcaagcagg tgccttCCC9_ atatttgga9 acttttgacc gctttggaaC gtttgtCt~c ctcatccttc caatatCCtc gtctatgtcl ttctcttat' gaacagggtc agcttatcga gggaacatgt ccaccataca gagaatccag taaaaatggt tggaagggaa aaagcgcact ggatagcgtc tcgacatgga aactcacatc agaagtcacc caagacagct gggctgggCt catacacaac gtcacaaggs ctggccacgt aagatgcccz Iggcacaagcz gctactggac cttacctgg agttggtgai agagg9gcgc ;tattgaagal, 3 agtgccttg tctatgctg Stcaaagctc tccgtgtgac ttgggctcC ccactttcgg atgcgtaact gatatgcacg aatttcactc gaaaatacgc ttcgacttct tttctgcaac ggacgactca ttctcggccc actctcatgt tgctcccagg ccag a atat 9 gccccttgCC Ictgcatgctc catccagcc itgaatttctc Iggtagatcal 3 atctcaaat( a catcgccct a gcccgaaga. :ggcctccaa, g attctccga a catgcagc t gctggtcca a agaaggcca gtgtgtgaaa ctcaaaatcg cagcattaca ggaaatggag qcttattttg ggacagagaa tgtgctaaat tgtcCttCCg ctgcggtccc ctctacttgg gatgcagctt gagacccgtg Igagaagcttc Iggaaatacct aactacatgc tgtactatgc tcacaggcat atgttcactc cactctaag aagtgttcM a gatatccag a ctcaatgga4 g acgttaact t gtcacaggc a tacatgtct C gctgggtg g tggtataaa actacagtgt gttatgagca attttggcac gcaacatcgc gccttttccc t ca at aggc t actatacttc tcgctgagag agcagaaaaa gaggtgagtg ttgctgaaat tcgacctctg ctctgagtag gctacgtgaa tgtCCCggga aagctcacat tggctgCtg 3 tggatgccat 3 acaccaccct -actgccacg g cagctcaga(. g agaatgcct; t tacacacct, a acaagattg agcagaaca a gttgtcaca a tggatgatg gatgagcatg ttcaagcaca caaatgtgct cgatcctgaa actgaaacaa caacgtggaa attgactatt gatgatggca ccttgtgatc gcagttcaac ccagcggact tgatgatttg caggagacct cycttccttg gcactctcaa cacacgggc cttccataga gaaaaaggca catccaccaa 3catttcagac 3 tgtccagcaa c tgccaaggtc c caagaatgtg c aggacctctt a cggacattac c cgaggtcacc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 gccgCtagca tcacttctgc cctgagtcaa caggcctacg .tcctctttta catccagaag 41/99 00 Sagtgaatggg tacagaagaca <caggcccccg Scactggaaat gaaggtaccc 00 >aagaaccatc Mf* catcaggagt N' aaagggaaga aaagacacag cagacaggcg agttggacga tccttcaaga tgcctcccga atcctgaaca ccatgaacac acaaacacag tgagagtgtg agcaacgcaa gcacttggtg gcaaaacaaa cgtacttgtg g ca aagctcc tggcacactc ca agagggCt t caagaggca ggagagctca. gaaagagcca acgaagcctg attcatcaat ctgctaaacc gcttccctgc ctgCttgtgt gggaaccaag agagagacca ctcaggaaag agttcaacgt caaaataca~a tctcttcgtc gagggagggc gccagtga agcccttggc cccctgcCtC caccttagac cagaaaagtc gtgtgggatg gaccccgaca caggagatcc 1740 1800 1860 1920 1980 2040 2100 2148 <210> <211> <212> <213> <220> <221> <223> 22 715 PRT Homo sapiens MISCFEATURE human DtTB4.10 <400> 22 Met Cys Ilie Arg Thr Gly Ser Pro Cys Asp Val Cys GlU Asn Tyr Ser Val Met Ser met Thr Gly Arg Gin Leu 25 Ile Asp Trp Ala Pro Leu Lys His Val His Ile Gly Tyr Giu His Ser Ser Thr Pro Met Pro Arg Phe Arg Gin His Tyr Asn Phe Gly Thr Lys Cys Ala Asn. Cys Asn Ser 55 Thr Ile Gin Cys Val Gly*Asn Gly Gly Asn Thr Ala 90 Ile Ala Asp Pro Arg ser Met Arg Glu Pro Leu Lys Gin Gly 100 Ser Arg Ilie Cys Tyr Phe Gly Leu Phe Pro Val Leu Lys 105 Met Val Ile Ser Leu Gly Gin 110 42/99 00 tJ3krg Ile Asn Arg 115 Leu Asn Val Glu Arg Leu Ser Leu Glu Gly Lys Lys Ile Arg 130 Cys Ala Lys Tyr Tyr 135 Thr Ser Leu Thr Ile 140 Leu Arg Ser Glu 00 Ser 145 Ala 00 Asn Ala Leu Ser Thr Ser 150 Cys Pro Ser Val Ala 155 Glu Arg Met Met Ala 160 Ala Lys Arg Leu Val Ile 180 Ile 165 Ala Ser Phe Cys Asn 170 Leu Arg Ser Gin Gin Lys 175 Leu Val Pro Val Asp 185 Met Glu Asp Asp Ser Leu Tyr 190 Thr Ser Ser Leu Gly Gly 195 Glu Trp Gin Phe Asn 200 His Phe Ser Lys Arg Pro 210 Asp Ala Ala Phe Glu Ile Gin Arg Ser Leu Pro Glu Lys 225 Ser Pro Leu Ser Glu Thr Arg Val Asp 235 Leu Cys Asp Asp Leu 240 Ala Pro Val Ala Gin Leu Ala Pro Arg 250 Glu Lys Leu Pro Leu Ser 255 Ser Arg Arg Thr Cys Tyr 275 Ala Ala Val Gly Gly Leu Gin Asn Met Gly Asn 270 Thr Thr Pro Val Asn Ala Ser Leu 280 Gin Cys Leu Thr Tyr 285 Leu Ala 290 Asn Tyr Met Leu Ser 295 Arg Giu His Ser Thr Cys His Arg Lys Gly Cys Met Leu 310 Cys Thr Met Gin His Ile Thr Arg Ala 320 Leu His Asn Pro His Val Ile Gin Ser Gin Ala Leu Ala Ala 335 Gly Phe His Arg 340 Gly Lys Gin Glu Ala His Giu Phe Leu met Phe 350 Lys Gin Val Thr Val Asp Ala Met Lys Lys Ala Cys Leu Pro Gly His 365 43/99 00 Asp His OJ~ 370 His Ser Lys Asp Thr Leu Ilie His Ile Phe Gly Gly 385 Trp Arg Ser Gin Lys Cys Leu His Cys His Gly Ile Ser 395 Asp 400 Thr Phe Asp Pro Tyr 405 Ala Leu Asp Ile Aia Leu Giu Gin Leu 425 Asp Ile Gin Ala Ala Gin 415 Ser Val Gin Giy Giu Asn 435 Val Lys Pro Giu Glu Leu Asn 430 Ala Pro Ala Ala Tyr His Ser Gly Val Cys Leu Gin Ser Lys 450 Thr Leu Thr Leu Thr Ser Ala Lys Leu Ile Leu Val Leu Lys Ar9 Phe Ser 465 Asp 470 Val Thr Gly Asn Ly s 475 Ile Ala Lys Asn Gin Tyr Pro Giu Cys 485 Leu Asp Met Gin Tyr Met Ser Gin Gin Asn 495 Thr Gly Pro Vai Tyr Vai Leu Tyr 505 Ala Vai Leu Val His Ala Gly 510 Ala Gin Glu Trp Ser Cys His Asn Gly His Tyr 520 Phe Ser Tyr Val Gly Gin 530 Trp TPyr Lys Met Asp Ala Glu Val Ala Ala Ser Ile Thr Ser Ala Leu Ser 545 Gin 550 Gin Ala Tyr Vai Leu 555 Phe Tyr Ile Gin Ser Giu Trp Giu Arg 565 His Ser Giu Ser Ser Arg Gly Arg Giu Pro 575 Arg Ala Leu Leu Lys Arg 595 Gly 580 Thr Giu Asp Thr Arg Arg Ala Thr 590 Asp Giu His Asp His Pro Cys Leu 600 Gin Ala Pro Giu Leu Val Giu Arg Ala Thr 610 Glu Ser Thr Leu Asp His Trp Lys Phe 620 44/99 00 OLeu Gin ;Z 62 5 Glu Gly Giu Gln Asn Lys Thr Lys Pro Giu Phe Asn Val Arg Lys Val 630 635 640 Thr Leu Pro Pro Asp Val Leu Val 645 650 Ile His Gin Ser Lys Tyr Lys Cys Gly Asn Leu Ser 675 Met 660 Lys Asn His His Pro Giu 665 Gin Gin Ser Ser Leu Leu 670 Asn Thr Gly Ser Ser Thr Pro Thr 680 His Gin Giu Ser met 685 Thr Leu 690 Ala Ser Leu Arg Gly 695 Arg Ala Arg Arg Lys Gly Lys Asn Lys His Ser 705 Lys Arg Ala 710 Leu Leu Val Cys Gin 715 ':210> '211> ':212> <213> 23 1902 DNA Homo sapiens <220> <221> misc-feature <223> human DUB4.li <400> 23 atqtgcatac actggcagac ccgatgccca catgaaaaga tatacttcat gcggagagga ggtgagtggc gctgaaatcc gtggcaagac gtgggggCtg gaacagggtc agcttatcga ggacacttta caagggaaag tgactattct tgatggcagc agttcaacca agcggacttc agcttgCtcC ggctccagaa tccgtgtgac ttgggctcCC catccggcac aaacggggcc caggtcagaa tgccaaaatc cttttcaaaa tctccctgag cagggagaag tatgggaaat gtgtgtgaaa ctcaaaatcg aggaagcctt aa agggaaga agcgcacttt gacatggagg ctcacatctt aagtcaccac cttcctctga acctgctacg actacagtgt gttatgagca ctgatggagc aaatacgctg cgtcttcttg acgactcact ctcggccaga tctcatatga gtagcaggag tgaacgcttc gatgagcatg ttcaagcaca acacctggcc tgctaaatac tccttccgtc ctacttggga tgcagctttt tttggctcct acctgctgcg cttgcagtgc 120 240 300 360 420 480 540 600 45/99 00 rNctgacataca catcgtcaca <aatcctggcc Scaggaagatg cccaggcaca 00 >ggaggctact M1 gacccttacc N1 gaacagttgg 00 ctccagaggg C1cttgtattga cctgagtgcc gtcctctatg tatgtcaaag agcatcactt tgggaaagac gacacagaca cccgagttgg aaattccttc accctgcctc catcatcctg gagtccatga aagaacaaac caccgcccct agggctgcat acgtcatcca cccatgaatt agcaggtaga ggagatctca tggacatcgc tgaagcccga cgccggcctc agagattctc ttgacatgca ctgtgctggt ctcaagaagg ctgtcctgag atagtgagag ggcgagcaac acgagcactt aagagcaaaa ccgacgtact aacagcaaag acactggcac acagcaagag tgccaactac gctctgtact gccctcacag tctcatgttc tcatcactct aatcaagtgt cctggatatc agaactcaat caagacgtta cgatgtcaca gccatacatg ccacgctgag ccagtggtat tcaacaggcc tgtgtcaaga gcaaggagag ggtggaaaga caaaacgaag tgtgattcat ctccctgcta actcgcttcc ggctctgctt atgctgtccc atgcaagctc gcattggctg actgtggatg .aaggacacca ctccactgcc caggcagctc ggagagaatg actttacaca ggcaacaaga tctcagcaga tggagttgtc aaaatggatg tacgtcctct ggcagggaac ctcaagagag gccactcagg cctgagttca caatcaaaat aacctctctt ctgcgaggga gtgtgccagt gggagc act C acatcacacg ctggcttcca ccatgaaaaa ccctcatcca acggcattt c agagtgtcca cctatcattg cctctgccaa ttgccaagaa acacaggacc acaacggaca atgccgaggt tttacatcca caagagccct accacccctg aaagcacctt acgtcagaaa acaagtgtgg cgtcgacccc gggccaggag ga tcaaacqtgt ggccctccac tagaggcaag ggcatgcctt ccaaatattt agacactttt gcaagctttg tggtgtttgt ggtcctcatc tgtgcaatat tcttgtctat ttacttctct caccgccgct gaagagtgaa tggcgcagaa cctccaggcc ag acc act gg agtcaaaggt gatgaagaac gacacatcag atccaaaggg 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1902 <210> <211> <212> <213> <220> <221> <223> 24 633 PRT Homo sapiens MISCFEATURE human DUB4.11 00 46/99 <400> 24 Met Cys Ilie Arg Thr Gly Ser Pro Cys Asp Val Cys Glu Asfl Tyr Ser 1Z 5 10 1s Val Met Ser Met Thr Gly Arg Gin Leu Ile Asp Trp Ala Pro Leu Lys Ile Gly Tyr Giu His Ser Ser Th r 40 Pro Met Pro Arg Thr Leu Tyr Ile Arg His Arg Lys Pro Ser Gly Ala His Leu Aia His Giu Lys Thr Arg Glu Arg Asn Gly Ala Lys Gly LYS Lys Ilie Arg Cys Ala Lys Tyr 70 75 so Tyr Thr Ser Leu Thr Ile Leu Arg Ser Ser Ala Leu Ser Ser Ser Cys Pro Ser Glu Asp ASP 115 Ala Giu Arg Met Ala Ala Ala Lys Ile Asp Met 110 Asn His Phe Ser Leu Tyr Leu Gly 120 Gly Giu Trp Gin Ser Lys 130 Leu Thr Ser Ser Pro Asp Ala Ala Phe 140 Ala Glu Ile Gin Arg 145 Thr Ser Leu Pro Lys Ser Pro Leu Tyr Asp Leu Ala Pro 160 Val Ala Arg Gin Ala Pro Arg Glu Leu Pro Leu Ser Ser Arg 175 Arg Pro Ala Tyr Val Asfl 195 Asn Tyr Met 210 Gly cys Met 225 Val Gly Ala Gly Leu 185 Gin Asn Met Gly Asn Thr Cys 190 Pro Leu Ala Ala Ser LeU Gin Leu Thr Tyr Thr Leu Ser Arg His Ser Gin Thr His Arg His Lys Leu Cys Thr Met Gin Ala His Ile Thr Arg Ala Leu His 230 235 240 His Val Ile Gin Pro Ser Gin Ala Leu Ala Ala Gly Phe 245 250 255 Asn Pro Gly 4 7/99 00 His Arg Gly Lys OJ2~ 260 Asp Ala Met Lys 275 Gin Giu Asp Ala Giu Phe Leu Met Phe Thr Val 270 Val Asp His Lys Ala Cys Leu 280 Pro Arg His Lys His Ser 290 Lys Asp Thr Thr Ile His Gin Ile Gly Gly Tyr Trp Arg 305 00 Asp Ser Gin Ile Lys Pro Tyr Leu Asp 325 Leu His Cys His Gly 315 Ile Ser Asp Thr Ilie Ala Leu'Asp Gin Ala Ala Gin Ser Val 335 Gin Gin Ala Asn Ala Tyr 355 Giu Gin Leu Val Lys 345 Pro Giu Giu Leu *Asn Gly Giu 350 Al Ser Lys H*is Cys Gly Val Leu Gin Arg Ala Thr Leu 370 Thr Leu His Thr Ala Lys Val Leu Leu Val Leu Lys Arg 385 Phe Ser Asp Val Gly Asn Lys Ile Lys Asn Val Gin Tyr 400 Pro Giu Cys Leu Met Gin Pro Tyr Ser Gin Gin Asn Thr Gly 415 Pro Leu Val Cys His Asn 435 Val Leu Tyr Ala Leu Val His Ala Glu Trp Ser 430 Giu Gly Gin Gly His Tyr Phe Ser Tyr Val Lys Ala 440 Gin 445 Trp Tyr 450 Lys Met Asp Asp Ala Giu Val Thr Ala Ala Ser Ile Thr Ser Leu Ser Gin Gin Ala 470 Tyr Val Leu Phe Tyr 475 Ilie Gin Lys Ser Giu 480 Trp, Giu Arg His Ser 485 Giu Ser Vai Ser Arg Gly 490 Arg Glu Pro Arg Ala 495 Leu Gly Ala Giu Asp 500 Thr Asp Arg Arg Ala Thr G.in Gly Glu Leu Lys 51*0 48/99 00 Arg Asp His Pro Cys Leu Gin Ala Pro Glu Leu Asp Glu His Leu 'Val 525 Glu Arg Ala Thr Gin Glu Ser 530 535 Thr Leu Asp His Trp Lys 540 Phe Leu Gin Glu 545 Gin Asn Lys Thr Pro Glu Phe Asn Val 555 Arg Lys Val Lys Thr Leu Pro Pro Val Leu Val Ile Gin Ser Lys Tyr Lys Cys 575 Gly Met Lys Ser Ser Ser 595 His His Pro Glu Gin Ser Ser Leu 590 Gly Thr Leu Thr Pro Thr His Glu Ser Met Asn Thr 605 Ala Ser 610 Leu Arg Gly Arg Al a 615 Arg Arg Ser Lys Lys Asn Lys His Lys Ar9 Ala Leu Val Cys Gin <210> <211> <212> <2232> <220> <221> <223> 1593 DNA HIomo sapiens misc feature human DUB8.l <400> 25 atgggggacg acatcttctc tcaccactct cagctCgCtC gggctccaga acactgcccc actcactcta ggccagatgc catctgagac ccagggagaa atatgggaaa ttgccaacta cttgggaggt agcttttgct ccgtgtcgac gcttcctctg tacctgctac catgctgtcc gagtggcagt gaaatccagc ctctgtgatq agtagcagga gagaacgctt cgggagcact tcaaccactt ggacttctct atttggctcc gacctgctgC ccctgcagtg ctcaaacatg ttcaaaactc ccctgagaag tgtggcaaga ggtgggggCt cctgacatac tcagcgtcc 120 180 240 300 360 49M,9 00 aagtgctgca OJcatgtcatcc tccatgaat aagcaggtag tggagatctc 00ctggacatcg gtgaagcccg (]gcgccggcct 00 Saagagattct ~-Icttgacatgc gct g tgc tgg gctcaagaag tctgtcctga cacagtgaga aggcgagcaa gacgagcact caagagcaaa cccaacgcac gaacagcaaa aacactggca cacagcaaga tgctctgtac agccctcaca ttctcatgtt atcatcactg aaatcaagtg ccctggatat aagaactcaa ccaacacgtt ccgatgtcgc agccatacat tccacgctgg tccagtggta gtcaacaggc gtgtgtcaag agcaaggaga tggtggaaag acaaaacgaa ttgtgattca gctccctgct cactcgcttc gggctctgct tatgcaagct ggcattggct cactgtggat caaggacacc tctccactgc ccaggcagct tggagagaat aactttacac aggcaacaaa gtctcagcag gtggagttgt taaaatggat ctatgtcctc aggcagggaa gctcaagaga agccactcag gcctgagttc tcaatcaaaa aaacctctct tctgcaaggg tgtgtgccag cacatcacat gctggcttcc gccatgaaaa accctcatcc cacgggattt cagagtgtca gcctatcatt acttctgcca cttgccaaga aacacaggac cacgacggac gatgccgagg ttttacatcc ccaagagccc gaccacccct gaaagcacct aacgtcggaa tacaagtgtg tcgacgaccc aggaccagga tga gggccctcca cagtcctggc atagaggcaa aggcatgcct accaaatatt cagacacttt agcaagcttt gcggtctttg aggtcctcat atgtgcaata ctcttgtcta attacttctc tcactgtctg agaagagtga tcggcgctga gcctccaggc tagaccactg aagtcgaagg ggatgaaaaa ggacagatca gagccaaagg gcaggaagat tcccggccac tggaggctgc tgacccttac ggaacagttg tctccagagg ccttgtcttg tcctgagtgc tgtcctctat ctatgtcaaa tagcatcatt atgggaaaga agacacagac acccgagttg gaaattcctg taccctgcct ccatcatcct ggagtccatg gaagaacaaa 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 13B0 1440 1500 1560 1593 <210> 26 <211> 530 <212> PRT <213> Homno sapiens <220> <221> <223> MISCFEATURE human DUB8.1 <400> 26 00 50/99 4et Gly Asp Asp Ser Leu Tyr Leu Gly Gly Glu CL 5 ?he Ser Lys Leu Thr Ser ser Arg Pro Asp Ala 25 Trp Gin Phe Asn His Al a Phe Ala Giu Ile -ln Arg Thr Ser Leu Pro Giu Lys Ser 40 Pro Leu Ser Ser Glu Thr Arg 00 :tJal Asp 00 SArg Glu Leu Cys Asp Asp Leu Ala 55 Pro Val Ala Arg Gin Leu Ala Pro Lys Leu Pro Ser Ser Arg Arg Ala Ala Val Gly Gly Leu Gin Asn Met Gly Asn Thr Cys Tyr Giu Asn Ala Ser Leu Gin 90 Cys Leu Thr His Ser Gin 115 Tyr 100 Thr Leu Pro Leu Asn Tyr Met Leu Ser Arg Giu Cys Thr Met Thr Cys Gin Arg Lys Cys Cys Met Gin Ala 130 His Ile Thr Trp Leu His Ser Pro Gly 140 His Val Ile Gin Ser Gin Ala Leu Ala Gly Phe His Arg 155 Gly Lys Gin Glu Asp 160 Val His Glu Phe met Phe Thr Val Asp 1,70 Ala Met Lys Lys Ala Cys 175 Leu Pro Gly Ile His Gin 195 Lys Gin Val Asp His Cys Lys Asp Thr Thr Leu 190 Lys Cys Leu Ile Phe Gly Gly Trp Arg Ser Gin His Cys 210 His Giy Ile Ser Asp 215 Thr Phe Asp Pro Leu Asp Ile Ala Leu Asp Ile Gin 225 Val Lys Pro Glu Ala Ala 230 Gln Ser Val Lys Ala Leu Glu Gin Leu 240 Glu Leu Asn Gly Giu Asn 245 250 Ala Tyr His Cys Gly Leu 255 51/99 00 Cys Leu Gin Arg Ala Pro Ala Ser Asn C-A1 260 265 Thr Leu Thr Leu His Thr Ser 270 Val Ala Gly Ala Lys Val 275 Leu Ile Leu Val Leu 280 Lys Arg Phe Ser Asp 285 Asn Lys 290 Leu Ala Lys Asn Val1 295 Gin Tyr Pro Glu Leu Asp Met Gin 00 Pro 305 00 Ala Tyr Met Ser Gin Asn Thr Gly Pro Val Tyr Val Leu Tyr 320 Val Leu Val His 325 Ala Giy Trp, Ser His Asp Gly His Tyr Phe 335 Ser Tyr Val Glu Val Thr 355 Ala Gin Giu Val Trp Tyr Lys Met 350 Gin Ala Tyr Vai Cys Ser Ile Ser Val Leu Ser Val Leu 370 Phe Tyr Ile Gin Ser Giu Trp Glu His Ser Giu Ser Val1 385 Arg Ser Arg Gly Arg Arg Ala Lys Gin 405 Pro ArgAla Leu Ala. Glu Asp Thr Asp 400 Gly Glu Leu Lys Asp His Pro Cys Leu Gin 415 Ala Pro Glu Thr Leu Asp 435 Asp Giu His Leu Giu Arg Ala Thr 430 Thr Lys Pro His Trp Lys Phe Gin Glu Gin Asn Giu Phe 450 Asn Val Giy Lys His Gin Ser Lys 470 Giu Gly Thr Leu Pro 460 Pro Asn Ala Leu Ile Tyr Lys Cys Gly Lys Asn His His Pro 480 Giu Gin Gin Ser Ser Leu Leu Asn Leu 485 Ser Thr Thr Arg Thr Asp 4 Gin Glu Ser Met 500 Asn Thr Giy Thr Ala Ser Leu Gin Gly Arg Thr 510 52199 00 Arg Arg Ala Lys Gly Lys Asn Lys His Ser Lys Arg Ala Leu Leu Val! rl515 520 525 Cys Gin 530 00 00 <210> 27 <211> 1494 DNA <213> Homo sapiens <220> <221> misc-feature <223> human DUB8.3 <400> 27 atggaggacg acatcttctc tcacaactct cagcttgctc gggctccaga acaccgcccc aagtgctgca catgtcatCC gccct tgaat aagcaggtag tggagatctc ctggacatcg gtgaagcccg aatgtgcaat cctcttgtct cattacttct gtcactgCCt cacaagagtc actcactcta cttgggaggt gagtggcagt tcaaccactt ttcaaaactc ggccagatgc caactgagac ccagggagaa atatgggaaa ttgccaacta tgctctgtac agccctcaca ttctcatgtt atcatcactc aaatcaagtg ccctggatat aagaactcaa atcctgagtG atgtcctCta cttatgtcaE ctggcatcac aatgggaaac agcctttgct ccgcgtcgac gcttcctctg tacctgctac catgctgtcc catggaagct ggcattggct cactgtggat caaggacacc tctccactgc ccaggaagct tggagagaat I ccttgacatc LtgctgtgCtc kagttcaagaz -ctctgtcctc Sacacagtga<. gaaatccagc ttctgcgatg agtagcagga gtgaacgct t cgggagcact cacatcacat gctggcttcc gccat9aaaa accctcatcc cacggcattt cagagtgtca gcctatcatt cagccataca Igtccacgccc iggccagtggt 3 agtcaacag 3 agtgtgtca ggacttctct ccctgagaag atttggcgcc gacctgctgc cccagcagtg ctcaaacatg gg ccc ct cca atagaggcaa aggcatgcct accaaatatt cagacacttt agcaagcttt gtggcaacaa tgtctcag ca Iggtggagttg ataaaatgga cctatgtcct igaggcaggga :gtggcaaga ggtgggg9Ct tctgacatac tcatcgtcac cattcctggc gcaggaagct tcccgggcac tggagggtac tggcccttac ggaacagttg aattgccaag gaacacagga tcacaacgga tgatgccgag cttttacatc accaagagcc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 ctcggcgctg aagacacaga caggcgagca acgcaaggag agctcaagag agactacc 53 /99 00 tbtagaccact aacttgaag 3 ggatgaaaa -cgacagatc 0 gagccaaag c210> 28 00 c211> 497 c 212> PRT <213> Horn tacccgagtt ggaaattcct gtaccctgcc accatcatcc aggagtccat ggaagaacaa ggacgagcac ccaagagcaa tcccaacgta tgaacagcaa gaacactggc acactgcaag ttggtggaaa. aacaaaacga cttgtgattc agctccctgc acactcgctt agggctctgc gagccactca agcctgagtt atcaatcaaa taaacctctc ctctgcaagg ttgtgtgcca gg aaa gca cc caacgtcaga atacaagtgt ttcgacgaac gaggaccayg gtga 1200 1260 1320 1380 1440 1494 o sapiens <220> <221> <223> MISCFEATURE human DUB8.3 <400> 28 Met Glu Asp Asp Ser Leu Tyr Leu Gly Gly Glu Trp Gin Phe Asn His Phe Ser Lys Gin Arg Thr Val Asp Phe Arg Glu Lys Leu Thr Ser Ser Arg Asp Ala Ala Phe Glu Thr Arg Ser Leu Pro Glu Ser Gin Leu Ser CYS Asp ASP Ala Pro Val Ala Arg Gin Leu Ala Pro Ala Ala Val Gly Ala Leu Pro Leu Ser 70 Ser Arg Arg Pro 75 Gly Leu Gin Asn Met Gly Asn Thr Cys Tyr Val Asn Ala 90 Ser Gin Gin Cys Leu Thr Tyr Thr Pro Pro Leu Ala Asn Tyr Met Leu Ser Arg Glu 100 105 110 His Ser Gin Thr Cys His Arg His Lys Cys Cys Met Leu Cys Thr Met 115 120 125 54/99 00 Giu Ala 130 His Ile Thr Trp Pro 135 Leu His Ile Pro Gly His Val Ile Gin Pro 145 Ser Gin Ala Leu Al a 150 Ala Giy Phe His Arg 1s55 Gly Lys Gin Giu Ala Leu Giu Phe Leu 165 Met Phe Thr Val Asp 170 Ala Met Lys Lys Ala Cys 175 Leu Pro Gly Ile His Gin 195 His 180 Lys Gin Val Asp His 185 His Ser Lys Asp Thr Thr Leu 190 Lys Cys Leu Ile Phe Gly Gly Tyr 200 Trp Arg Ser Gin His Cys 210 His Gly Ile Ser Asp 215 Thr Phe Gly Pro Leu Asp Ile Ala Leu 225 Asp Ile Gin Glu Gin Ser Val Lys Ala Leu Giu Gin Val Lys Pro Giu Leu Asn Gly Giu- Agn 250 Ala Tyr His Cys Gly Asn 255 Lys Ilie Ala Tyr Met Ser 275 Asn Vai Gin Tyr Pro 265 Glu Cys Leu Asp Met Gin Pro 270 Leu Tyr Ala Gin Gin Asn Thr Gly 280 Pro Leu Vai Tyr Val Leu 290 Vai His Ala Gly Trp 295 Ser Cys His Asn His Tyr Phe Ser Tyr 305 Val Lys Val Gin Giy Gin Trp Tyr Met Asp Asp Ala Glu 320 Val Thr Ala Ser Gly 325 Ile Thr Ser Val Ser Gin Gin Ala Tyr Val 335 Leu Phe Tyr Ser Arg Gly 355 Arg Ala Thr 370 His Lys Ser Glu Giu Arg His Ser* 350 Thr Asp Arg Arg Giu Pro Arg Leu Gly Ala Giu Asp 365 Gin Gly Giu Leu 375 Lys Arg Asp Tyr Cys Leu Gin Val 5i.5/9 00 C-1ro Giu Leu Asp Glu His Leu Val Giu Arg 390 Thr Gin Giu Ser. *eu Asp His Trp Phe Leu Gin Giu Asn Lys Thr Lys Pro Giu 415 he Asn Val 00 M le His Gin 435 00 In Gin Ser 450 Lys Leu Giu Giy Thr 425 Leu Pro Pro Asn Vai Leu Val 430 His Pro Giu Ser Lys Tyr Lys Cys 440 Gly Met Lys Asn His 445 Ser Leu Leu Asn 455 Leu.Ser Ser Thr Pro Thr Asp Gin Ser Met Asn Thr Thr Leu Ala Ser Gin Gly Arg Thr .rg Ala Lys Gly Asn Lys His Cys Arg Aia Leu Leu Val Cys 495 210> 211> :212> :213> <220> <221> <223> 29 1593 DNA Homno sapiens misc-feature human <400> 29 atggaggacg actcactcta acatcttctc ggccagatgc tcaccactct catctgaggc cagcttgctc ccaggaagaa gggctccaga atatgggaaa acaccgcccc ttgccaacta cttgggaggt agcttttgct ccgtgtcgac gcttcCtctg tacctgctac catgctgtcc gagtggcagt gaaatccagc ctctgtgatg agtagcagga gagaacgctt cgggagcact tcaaccactt ggacttctct atttggctcc gacctgctgc ccctgcagtg ctcaaacatg ttcaaaactc ccctgagaag tgtggcaaga ggtgggggCt cctgacatac tcagcgtccc 56/99 00 00 00 aagtgctgca catgtcat~c gcccatgaat aagcaggtag tggagatctc ctggacatcg gtgaagcccg gcgccagtct cagagaccat cttgacatgc gctgtgctgg gctcaagaag tctgtcctga cacagtgaga aggcgagcaa gacgagcgct caagagcaaz cccaacgtac gaaca9Ccaai aacactggCi tgctctgtac agccctcaca ttctcatgtt atcatCactc aaatcaagtg ccctggatat aagaactcaa ccaagacgtt gggtggtcac agccatacat tccacgctgg gccagtggta gtcaacaggc gtgtgtcaag cgcaaggaga tggtggaaas iacaaaacgaa :ttgtgattcz I gctccctgct aL ccctCgCttC tatgcaagct ggcattggct cactgtggat taaggacacc tctccactgc ccaggcagCt tggagagaat aactttacac acgccacaaa gtctcagcag gtggagttgt taaaatggat ctatgtcctc aggcagggaa gctcaagaga Iagccactcac Lgcctgagtt c Ltcaatcgaai aaacctctCl cacatcacat gctggCttCC gccatgaaaa accctcatcc cacgggattt ca gagtgt ca gcctatcatt act tttgcca ctagccaaga aacacaggac cacgatggac gatg cc aagg ttttacatcc ccaagagccc Lgaccacccct gaaagcacct aacgtcagaE Stacaagtgtc tcgacgaccc gggcCCtcca c atagaggcaa g aggcatgcct t accaaatatt t cagacacttt t agcaagcttt gcggtctttg aggaacgcat gtgtgcaata ctcttgtcta attacttctc tcactgcctg agaagagtga tcggcgctga gcctccaggc tagaccactg iaagtcgaagg 3ggatgaaaaa gacagatca a gatccaaagg agtcctggt caggaagat .cccggccac .ggaggctgc gacccttac 3 gaacagttg :cttcagagg acttgaaacg tgctgagagc tgtcctctat ttatgtcaaa tagcatcact atgggaaaga agacacagac acccgagttg gagattcCCC taccctgcct ccatcatcct ggagtcCgtg gaagaacaa 420 480 540 600 660 720 780 840' 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1593 tctgcaaggg aggaccagg cacagcaaga gggctctgct tgtgtgccag tga <210> <211> <212> <213> <220> <221> e223> 530 PRT Homo sapiens MISC FEATURE human <400> 7/99 00 Met (N 1 Giu Asp Asp Ser 5 Leu Tyr Leu Gly Giu Trp, Gin Phe Asn His Phe Ser Lys Leu Thr Ser Ser Arg Pro 2S Asp Ala Ala Phe Ala Glu Ile Gin Arg Thr Ser Leu Pro Giu Lys 40 Ser Pro Leu Ser Ser Glu Ala Arg Val Asp Leu Cys Asp Asp Leu 55 Ala Pro Val Ala Arg Gin Leu Ala Pro Arg Lys Lys Leu Pro Leu Ser Ser Arg Arg Ala Ala Val Gly Gly Leu Gin Asn Gly Asn Thr 'Cys Tyr Giu Asn Ala Ser Leu Gin Cys Leu Thr His Ser Gin 115 Thr Pro Pro Leu Asn Tyr Met Leu Ser Arg Giu 110 Cys Thr Met Thr Cys Gin Arg Pro 120 Lys Cys Cys Met Gin Ala 130 His Ile Thr Trp Leu His Ser Pro His Val Ile Gin Pro Ser Gin Ala Leu 145 Ala Gly Phe His Gly Lys Gin Glu Ala His Glu Phe Met Phe Thr Val Asp 170 Ala Met Lys Lys Ala Cys 175 Leu Pro Gly Ile His Gin 195 Lys Gin Val Asp His Ser Lys Asp Thr Thr Leu 190 Lys Cys Leu Ile Phe Gly Gly Trp Arg Ser Gin His Cys 210 His Giy Ile Ser Thr Phe Asp Pro Leu Asp Ile Ala Asp Ile Gin Ala Ala 230 Gin Ser Val Lys Ala Leu Giu Gin Vai Lys Pro Giu Giu 245 Leu Asn Gly Glu Asn Ala 250 Tyr His Cys Gly Leu 255 -58/99 00 0Cys Leu Gin Arg NK 260 <Ala Lys Giu Arg 275 Ala Pro Val Ser Lys Tftr Leu Tflr Leu his Thr Ph-e 265 270 Ile Leu Glu Thr Gin Arg Pro Trp Vai Vai Thr Arg 13 Q n285 His Lys 290 Leu Ala Lys Ser Val1 295 Gin Tyr Ala Giu Ser 300 Leu Asp Met Gin Pro 305 Tyr Met Ser Gin Asn Thr Gly Pro Leu 315 Val Tyr Val Leu Ala Val Leu Val Ala Gly Trp Ser His Asp Gly His Tyr Phe 335 Ser Tyr Val Lys Val Thr 355 Ala Gin Giu Gly Trp Tyr Lys Met 350 Gin Ala Tyr Ala Cys Ser Ile Thr 360 Ser Val Leu Ser Val Leu 370 Phe Tyr Ile Gin Lys 375 ser Giu Trp Glu Arg 380 His Ser Giu Ser Ser Arg Giy Arg Pro Arg Ala Leu Ala Giu Asp Thr A'rg Arg Aia Thr Gin 405 Giy Giu Leu Lys Arg 410 Asp His Pro Cys Leu Gin 415 Ala Pro Giu Thr Leu Asp 435 Asp Glu Arg Leu Val1 425 Giu Arg Ala Thr 430 Thr Lys Pro His Trp Arg Phe Gin Glu Gin Asn Ly s 445 Giu Phe 450 Asn Val Arg Lys Val 455 Giu Gly Thr Leu Pro Asn Val Leu Ile His Gin Ser Tyr Lys Cys Gly Lys Asn His His Glu Gin Gin Ser Ser 485 Leu Leu Asn Leu Ser Ser Thr Thr Arg Thr Asp 490 495 Gin Glu Ser Val Asn Thr Gly Thr Leu Ala Ser Leu Gin Gly Arg Thr 500 505 510 .19/99 00 0 rg Arg Ser Lys Gly Lys Asn Lys His Ser Lys Arg Ala Leu Leu Val 515 520 525 ;Z ys Gin 530 r110>U ,211> :2 12 c13> 1593 DNA Homo sapiens c220> c221> misc-feature c223> human DUBB.6 c400> 31 atggaagacg acatcttctc tcaccactct zagcttgctc gggctccaga acactgccgc aagtgctgca catgtcatcc gcccatgaat aagcagctag tggagatctc ctggacatcg gtgaagccca gcgcctgcct aagagattct cgtgacatgc gctgtgctgg gctcaagaag act cactcta qgctagatgc catctgagac ccagggagaa agataggaaa tttccaacta tgttctgtac agccctcaca ttctcatgtt atcatcactc aaatcaagta ccctggatat aagaactcaa ccaagacgtt c cgat g tca c agccatacat tccacgctgg gccagtg~gta tt tgggaggt agcttttgct ccgtttcgac gcttcctctg taccttctat catgctgtcc tatgcaagct ggtattggct tactgtggat caaggacacc tctccactgc ccaggcagct tggagagaat aactttaccc aggcaacaaa gtctcagcag gtggagt tgt taaaatggat gactggcagt gaaatccagc ctctgtgatg agtagcagga gtgaacgttt cgggaggact cacatcacat gctggcttcc gccatgaaaa accctcatcc cacggcattt cagagtgtca gcctatcatt acttctgcca cttgccaaga aacacaggac cacaacggac gatgccgagg tcaatcactt ggacttctct atttggctcc gacctgctgc ccctgcagtg ctcaaacgtg gggccctcta atagaggtga aggcatgcct accaaatat t cagacacctt agcaagcttt gtggtctttg aggtcctcat atgtgcaata ctcttgtcta. attacttctc tcactgcctc ttcaaaactc ctctgaaaag tgtggcaaga ggtgggggct cctgacatac tcatcttcac ccgtcctggc gcaggaggat tcccgggcac tggagcgtat tgacccttac ggaacagttg tctccagaag tcttgtattg tcctaagtgc tgtcctctat ttatgtcaaa tggcatcacc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 tctgtcctga gtcaacaggc ctatgtcctc ttttacatcc agaAgagtga atgggaaaga 60/99 00 cacagtgaga Saggccagcaa gacgagcact 0 caaaagcaaa cccaacgtac 00 >gaacagcaaa M aacactggca N cacagcaaga gtgtgtcaag cgcaaggaga tggtggaaag acaaaacgaa ttgtgattca gctccctgct cactcgcttc gatctctgct aggcagggaa gctcaagaga agccactcag gcctgagttc tcaatcaaaa aaacctctct t ctgc aaggg tgtgtgccag ccaagagccc gaccaccctt gaaagcacct aacgtcagaa tacaagtgtg tcgacgaaac agcaccagga tga ttggtgctga gcctccaggt tagaccactg aagttgaagg gtatgaaaaa cgacagatca gatccaaagg agacacagac acccgagttg gaaattcccc taccctgcct ccatcatcct ggagtccatg gaataacaaa 1200 1260 1320 1380 1440 1500 1560 1593 <210> <211> <212> <213> <220> <221> <223> 32 530 PRT Homo sapiens MISCFEATURE human DUB8.6 <400> 32 Met Glu Asp 1 Phe Ser Lys Gin Arg Thr Asp Ser Leu Tyr Leu Gly Gly Asp Trp Gin Phe Asn His Leu. Thr Ser Ser Arg Leu. Asp Ala Ala Phe Ala Glu Ile Ser Leu Ser Glu Ser Pro Leu Ser Ser 4S Glu Thr Arg Phe Asp Leu Cys Asp Asp Leu Ala Pro Val Ala Gin Leu Ala Pro Arg Glu Lys Leu. Pro Ser Ser Arg Arg Pro 75 Ala Ala Vai Gly Al a Gly Leu. Gin Lys Gly Asn Thr Phe Tyr 90 Val Asn Val Ser Leu. Gin Cys Leu Thr Tyr Thr Leu Pro Leu. Ser Asri Tyr Met Leu Ser Arg Giu. I W) 105 110 61/99 00 0 Asp Ser SGin Ala 130 Gin 115 Thr Cys His Leu Lys Cys Cys Met Phe Cys Thr Met 125 His Val Ile Gin His Ile Thr Trp Ala 135 Leu Tyr Arg Pro Gly 140 Pro O0 145 Ser Gin Val Leu Ala Gly Phe His Arg 155 Gly Glu Gin Glu Asp 160 Ala His Glu Phe 00 Leu Pro Gly His rC- 180 Met Phe Thr Val Ala Met Lys Lys Ala Cys 175 Lys Gin Leu Asp His 185 His Ser Lys Asp Thr Thr Leu 190 Lys Tyr Leu Ile His Gin 195 Ile Phe Gly Ala Trp Arg Ser Gin lie 205 His Cys 210 His Gly lie Ser Thr Phe Asp Pro Leu Asp Ile Ala Asp lie Gin Ala Ala 230 Gin Ser Val Lys Ala Leu Glu Gin Leu 240 Val Lys Pro Lys Leu Asn Gly Glu Ala Tyr His Cys Gly Leu 255 Cys Leu Gin Ala Lys Val 275 Ala Pro Ala Ser Thr Leu Thr Leu Pro Thr Ser 270 Val Thr Gly Leu Ile Leu Val Leu 280 Lys Arg Phe Ser Asn Lys 290 Leu Ala Lys Asn Gin Tyr Pro Lys Arg Asp Met Gin Tyr Met Ser Gin Gin 310 Asn Thr Gly Pro Val Tyr Val Leu Tyr 320 Ala Val Leu Val Ala Gly Trp Ser His Asn Gly His Tyr Phe 335 Ser Tyr Val Glu Val Thr 355 Ala Gin Glu Gly Gin 345 Trp Tyr Lys Met Asp Asp Ala 350 Ala Ser Gly Ile Ser Val Leu Ser Gin Gin Ala Tyr 365 02/99 to jVal Leu 370 Phe Tyr Ile Gin Lys 375 Ser Glu Trp Giu Arg His 380 Ser Glu Ser Val 385 Ser Arg Gly Arg Glu 390 Pro Arg Ala Leu Gly 395 Ala Glu Asp Thr Arg Pro Ala Thr Gin 405 Gly Glu Leu Lys Arg 410 Asp His Pro Cys Leu Gin 415 Val Pro Giu Thr Leu Asp 435 Leu 420 Asp Giu His Leu Glu Arg Ala Thr Gin Giu Ser 430 Thr Lys Pro His Trp, Lys Phe Gin Lys Gin Asn Lys 445 Giu Phe 450 Asn Val Arg Lys Giu Gly Thr Leu Pro 460 Pro Asn Val Leu Val Ile His Gin Ser 465 Giu Gin Gin Ser Ser 485 Lys 470 Tyr Lys Cys Gly Lys Asn His His Leu Leu Asn Leu Ser 490 Ser Thr Lys Pro Thr Asp 495 Gin Giu Ser Arg Arg Ser 515 Met 500 Asn Thr Gly Thr Leu 505 Ala Ser Leu Gin Gly Ser Thr 510 Leu Leu Vai Lys Giy Asn Asn His Ser Lys Ary Ser 525 Cys Gin 530 <210> 33 <211> 1593 <212> DNA <213> Homo sapiens <220> <221> misc-feature <223> human DUB8.7 63/99 00 400> 33 tggaggacg OJcatcttctc <caccactct agcttgctc ggctccaga 00caccgccC agtgctgca r atgtcatcc 00 Scccatgaat C1agcaggtag ggagatctc tggacatcg tgaagcccg lcg3ccagcct iagagattct :ttgacatgc lctgtgctgg )ctcaagaag .ctgtcctga -acagtgaga aggcgagcaa gacgagcgct caagagcaaa cccaacgtac gaacagcaaa aacactggca cacagcaaga actcactcta ggccagatgc cat ctgagg c ccaggaagaa atatgggaaa ttgccaacta tgctctgtac agccctcaca ttctcatgtt atcatcactc aaatcaagtg ccctggatat aagaactcaa ccaagacgtt ccgatgtcac agccatacat tccacgctgg gccagtggta gtcaacaggc gtgtgtcaag cgcaaggaga tggtggaaag acaaaacgaa ttgtgattca gctccctgct ccctcgcttc cttgggaggt agcttttgct ccgtgtcgac gcttcctctg tacctgctac catgctgtcc tatgcaagct ggcattggct cactgtggat taaggacac tctccactgc ccaggcagct tgagag aa t aactttacac aggcaacaaa gtctcagcag gtggagttgt taaaatggat ctatgtcctc aggcagggaa gctcaagaga agccactcag gcctgagttc tcaatcgaaa aaacctctct tctgcaaggg gagtggcagt gaaatccagc ctctgtgatg agtagcagga gagaacgctt cgggagcact cacatcacat gctggcttcc gccatgaaaa accctcatcc cacgggattt cagagtgtca 9 cctatcatt acttctgcca cttgccaaga aacacaggac cacgatggac gatgccaagg ttttacatcc ccaagagccc gaccacccct gaaagcacct aacgtcagaa tacaagtgtg tcgacgaccc tcaaccactt ggacttctct atttggctcc gacctgctgc ccctgcagtg ctcaaacatg gggccctcca atagaggcaa aggcatgcct accaaatatt. cagacacttt agcaagcttt qcggtctttg aggtcctcat atgtgcaata ctcttgtcta attacttctc tcactgcctg agaagagtga tcggcgctga gcctccaggc tagaccactg aagtcgaagg ggatgaaaaa ggacagatca ttcaaaactc ccctgagaag tgtggcaaga ggtgggggct cctgacatac tcagcgtccc cagtcctggt gcaggaagat tcccggccac tggaggctgc tgacccttac ggaacagttg t ctccagagg ccttgtcttg tcctgagtgc tgtcctctat ttatgtcaaa tagcatcact atgggaaaga agacacagac acccgagttg gagattcccc taccctgcct ccatcatcct ggagtccgtg 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1593 aggaccagga gatccaaagg gaagaacaaa gggctctgct tgtgtgccag tga <210> 34 <211> 530 <212> <2.13> PRT Homo sapiens 64/99 t 220> <221> MISC_FEATURE 223> human DUB8.7 <400> 34 Met Glu Asp Asp Ser 5 Leu Tyr L eu Gly Gly 10 Giu Trp Gin Phe Asn His is Phe Ser Lys Gin Ary Thr Leu Thr Ser Ser Arg Asp Ala Ala Phe Ala Glu Ile Giu. Ala Arg Ser Leu Pro Glu Ser Pro Leu Ser Val Asp Leu Cys Asp ASP Ala Pro Val Ala Gin Leu Ala Pro Arg Lys Lys Leu Pro Ser Ser Arg Arg Ala Ala Val Gly Gly Leu Gin Asn Met Gly Asn Thr Cys Giu Asn Ala Ser Leu Gin Cys Leu Thr His Ser Gin 115 T'yr 100 Thr Pro Pro Leu Ala 105 Asn Tyr Met Leu Ser Arg Giu 110 Cys Thr Met Thr Cys Gin Arg Pro 120 Lys Cys Cys Met Leu 125 Gin Ala His Ilie Thr Trp 130 Leu His Ser Pro Gly His Val Ile Gin 140 Pro 145 Ser Gin Ala Leu Ala 150 Ala Giy Phe His Arg 155 Gly Lys Gin Glu Asp 160 Ala His Giu Phe Leu Met Phe Thr Val 165 Asp 170 Ala Met Lys Lys Ala Cys 175 Leu Pro Gly Ile His Gin 195 His 180 Lys Gin Val Asp His Ser Lys Asp Thr Thr Leu 190 Lys Cys Leu Ile Phe Gly Gly Cys 200 Trp Arg Ser Gin 65/99 00 His Cys C1 210 His Gly Ile Ser Thr Phe Asp Pro Tyr 220 Leu Asp Ile Ala teu <225 Asp Ile Gin Ala Gin Ser Vai Lys Aia Leu Giu Gin Vai Lys Pro Giu Leu Asn Giy Giu Ala Tyr His Cys Gly Leu 255 00 Cys Leu Gin 00 Ala Lys Val 275 Ala Pro Ala Ser Thr Leu Thr Leu His Thr Ser 270 Val Thr Gly Leu Ile Leu Val Leu 280 Lys Arg Phe Ser Asp 285 Asn Lys 290 Leu Ala Lys Asn Gin Tyr Pro Glu Cys 300 Leu Asp Met Gin Pro 305 Tyr Met Ser Gin Asn Thr Giy Pro Val Tyr Vai Leu Tyr 320 Ala Val Leu Val Ala Gly Trp Ser His Asp Gly His Tyr Phe 335 Ser Tyr Val Ala Gin Giu Gly Trp Tyr Lys Met Asp Asp Ala 350 Gin Ala Tyr Lys Vai Thr Ala Cys Ser Ile 355 Ser Val Leu Ser Val Leu 3*70 Phe Tyr Ile Gin Lys 375 Ser Giu Trp Glu His Ser Giu Ser Ser Arg Gly Arg Pro Arg Ala Leu Ala Glu Asp Thr Arg Arg Ala Thr Gly Glu Leu Lys Asp His Pro Cys Leu Gin 415 Ala Pro Glu Thr Leu Asp 435 Asp Giu Arg Leu Val1 425 Giu Arg Ala Thr Gin Giu Ser 430 His Trp Arg Phe Pro Gin Giu Gin Asn Lys Thr Lys Pro 440 445 Giu Phe Asn Val Arg Lys 450 Val 455 Giu Gly Thr Leu Pro 460 Pro Asn Val Leu 66/99 00 Val C1465 ~Glu Ile His Gin Ser Lys 470 Tyr LYS Cys Gly Met 475 Lys Asn His His Gin Gin Ser Ser 485 Leu Leu Asn Leu Ser 490 Ser Thr Thr Arg Thr Asp 495 Gin Giu. Ser Arg Arg Ser 515 Val1 500 Asn Thr Gly Thr Leu 505 Ala Ser Leu Gin Gly Arg Thr 510 Leu. Leu Val Lys Gly Lys Asn His Ser Lys Arg Cys Gin 530 <210> <211> 1593 <212> PRT <213> Homo sapiens <220> <221> MISCFEATURE <223> human DUB8.8 <400> Aia Thr Gly Giy Aia Aia Gly Aia Cys Gly 10 Ala Cys Thr Cys Aia Cys Thr Cys Thr Cys Thr Giy Ala Thr Thr Thr Gly Gly Ala Gly Gly Thr Gly Ala Cys Ala Cys Gly Cys Ala Gly Thr 40 Thr Cys Ala Ala Thr Thr Thr Thr Thr Cys Ala s0 Ala Ala Cys Thr Cys Ala Cys Ala Thr Cys Thr Thr Cys Thr Cys 70 Gly Gly Cys Thr Ala Gly Ala Thr Gly Ala Gly Cys Thr Thr.Thr Thr Gly Cys Thr Gly Ala Ala Ala Thr Cys 90 6 7/99 00 Cys Ala Gay Cys Gly Gly Ala Cys Thr Thr Cys Thr Cys Thr Cys Thr 100 105 110 Cys Thr Gay 115 Ala Ala Ala Ala Thr Cys Ala Cys Cys 125 Ala Cys Thr Cys Thr 130 Cys Ala Thr Cys Thr 135 Gly Ala Gly Ala Cys Cys Gay Thr 00 Thr (~145 00 Ala Thr Cys Gly Ala Cys Thr Cys Thr Thr Gly Ala Thr Thr Thr Thr Gly Cys Thr Cys Cys 170 Thr Gly Thr Gly Gly Cys 175 Ala Ala Gly Ala 180 Cys Ala Gly Cys Thr Gay Cys Thr Cys Cys Cys 190 Ala Gly Gly Gay Ala Gay Ala Ala Gly Cys Thr Thr Cys Cys Thr Cys 195 200 205 Thr Gay 210 Ala Gay Thr Ala Gay 215 Cys Ala Gly Gly Gay Ala Cys Cys Thr Gay Cys Thr Gay Cys 230 Gay Gay Thr Gay Gly 235 Gly Gly Gay Cys Sly Gay Gly Cys Th r 245 Cys Cys Ala Gay Al a 250 Ala Gay Ala Thr Ala Gay 255 Sly Ala Ala Gay Ala Ala 275 Thr Ala Cys Cys Thr Cys Thr Ala Thr G1 y Thr 270 Cys Ala Gay Cys Gay Thr Thr Cys Cys Cys Thr Gly 285 Thr Gly Cys Cys Thr Gly Cys Ala Thr Ala Ala Cys Ala Cys Thr Gay Cys Cys Gly Cys 310 Thr Thr Thr Cys Cys 31S Ala Ala Cys Thr Al a 320 Cys Ala Thr Gay Gay Ala Cys Thr 340 Cys 325 Thr Gay Thr Cys Cys 330 Cys Gay Gly Gly Ala Gly 335 Cys Thr Cys Ala Ala 345 Cy h ysAaAaAla Cys Gly Thr Gly Thr Cys 345 350 68/99 00 Ala Thr Cys Thr C355 -e cys Ala Thr Gly 370 Thr Cys Ala Cys Ala 360 Ala Gly Thr Gly 365 Cys Tflr Gly Thr Thr Thr Gly Thr Ala Cys 380 Thr Ala Thr Gly Cys 385 Ala Ala Gly Cys Cys Ala Cys Ala Cys Ala Cys Ala Thr 400 00 00 Gly Gly Gly Cys Cys Cys Thr Cys Thr Ala Cys Cys Gly Thr Cys Cys 405 410 415 Thr Gly Gly Cys Cys Cys 435 Cys Ala Thr Gly Cys Ala Thr Cys Cys Ala Gly 430 Thr Gly Gly Thr Cys Ala Cys Gly Gly Thr Ala Cys Thr 450 Gly Cys Thr Gly Gly 455 Cys Thr Thr Cys Cy S 460 Ala Thr Ala Gly Gly Gly Thr Gly Ala Gly Cys Ala Gly Gly Ala Gly Gly Ala Thr 470 4*75 480 Gly Cys Cys Cys Al a 485 Thr Gly Ala Ala Thr 490 Thr Thr Cys Thr Cys Ala 495 Thr Gly Thr Cys Ala Thr 515 Thr 500 Thr Ala Cys Thr Gly 505 Thr Gly Gly Ala Thr Gly Cys 510 Thr Gly Cys Gly Ala Ala Ala Al a 520 Ala Gly Gly Cys Al a 525 Cys Thr 530 Thr Cys Cys Cys Gly Gly Gly Cys Ala Cys Ala Ala Gly Cys 535 540 Ala Thr.Cys Ala Thr CysAla Cys Thr Cys 555 560 Gly Cys Thr Ala Gly 550 Cys Ala Ala Gly Gly 565 Ala Cys Ala Cys Cys 570 Ala Cys Cys Cys Thr Cys 575 Ala Thr Cys Gly Ala Gly 595 Ala Cys Cys Ala Ala Ala Thr Ala Thr 585 Thr Thr Gly 590 Ala Thr Cys Cys Gly Thr Ala Thr Gly Gly Ala Gly 605 69/99 00 0Thr Cys 0 610 Ala Ala Ala Thr Ala Ala Gly Thr Ala 620 Thr Cys Thr Cys ;ZCys <625 Ala Cys Thr Gly Cys 630 Cys Ala Cys Gly Cys Ala Thr Thr Cys Ala Gly Ala Cys Ala Cys Cys Thr 645 Thr Gly Ala Cys Cys Cys 655 00 Thr Thr Ala 00Cys Thr Gly 00 675 Cys Thr Cys 690 Cys 660 Cys Thr Gly Gly Ala Cys Ala Thr Cys 665 Gly Cys Cys 670 Cys Ala Gly Gly Ala Thr Ala Cys Cys Ala Gly Ala Gly Ala Thr Gly Thr Cys Ala Ala Gly Cys Ala 700 Ala 705 Gly Cys Thr Thr Gly Gly Ala Ala Ala Gly Thr Thr Gly 720 Gly Thr Gly Ala Ala 725 Gly Cys Cys Cys Ala Ala Gly Ala Ala Cys 735 Thr Cys Ala Cys Thr Ala 755 Ala 740 Thr Gly Gly Ala Gly 745 Ala Gly Ala Ala 750 Cys Thr Thr Thr Cys Ala. Thr Thr 760 Gly Thr -Gly Gly Thr Gly 770 Thr Cys Thr Cys Ala Gly Ala Ala Gly 780 Gly Cys Gly Cys Cys 785 Thr Gly Cys Cys Thr 790 Cys Cys Ala Ala Ala Cys Gly Thr Ala Ala Cys Thr Thr Ala Cys Cys Ala Cys Thr Thr Cys Thr 815 Gly Cys Cys Al a 820 Ala Gly Gly Thr Cys Thr Cys Ala 830 Ala Thr Thr Thr Thr Gly Thr Ala Thr Thr Gly Ala Ala Gly Ala Cys Thr Cys Cys Gly Ala 850 Thr Gly Thr Cys Ala 855 Ala Gly Gly Cys 70/99 00 kla Ala Cys Ala C1365 la Thr Gly Thr Ala Ala Cys Thr Thr Gly Cys Cys 870 875 Gly Cys Ala Ala Thr Ala Thr Cys 885 890 Ala Ala Gly Ala 880 Cys Thr Ala Ala 895 sly Thr Gly Cys Cys Ala 915 Cys 900 Cys Gly Thr Gly Ala Cys Ala Thr Gly Cys Ala Gly 910 Ala Gly Cys Thr Ala Cys Ala Thr 920 Gly Thr Cys Thr Ala Gly 930 Ala Ala Cys Ala Ala Gly Gly Ala Cys Thr Cys Thr Gly Thr Cys Thr Ala Thr Gly Thr Cys Cys Thr Cys Thr Ala Thr 950 955 960 Gly Cys Thr Gly Thr 965 Gly Cys Thr Gly Gly 970 Thr Cys Cys Ala Cys Gly 97 Cys Thr Gly Gly Gly Thr Gly Gly Ala Gly Thr Thr Gly Thr Cys Ala 980 985 990 Cys Ala Ala 995 Cys Gly Gly Ala Cys Ala Thr Thr Ala Cys Thr Thr Cys 1000 1005 Thr Cys Thr Thr Ala Thr Gly Thr Cys Ala.Ala 1010 1015 Ala 1020 Cys Ala 1025 Thr Ala 1040 Gly Cys 1055 Thr Cys 1070 Gly Thr 1085 Gly Cys 1100 Ala Gly Ala Ala Thr Ala Ala Ala Cys Gly Ala Gly Thr Gly Gly Cys Cys Cys Thr Gly Gly 1030 Al a 1045 Gly 1060 Ala 1075 Ala 1090 Gly Cys Cys Ala Thr Gly Gly Ala Thr Cys Ala Cys Thr Cys Ala Cys Gly Thr Cys Ala Gly 1035 Thr 1050 Thr 1065 Cys 1080 Ala 1095 Gly Cys Thr Thr Gly Gly Gly Ala Thr Gly Cys Cys Thr Cys Thr Cys Ala Gly Cys Thr Ala Thr Gly Thr Cys Cys Thr 1105 Cys Thr Thr Thr 1110 71/99 00 :hr Ala 1115 ;ly Ala S 1130 kla Gly 1145 00 d ia Gly 1160 00 la Gly 1175 'ly Ala 1190 :ys Cys 1205 ,ly Ala 1220 :ys Ala 1235 'ly Thr 1250 Sly Ala 1265 Ala Gly 1280 Ala Gly 1295 Thr Gly 1310 Ala Ala 1325 Cys Ala Thr Cys Ala Thr Gly Gly Thr Gly Ala Gly Ala Gly Gly Cys Ala Gly Cys Cys Ala Gly Ala Cys Ala Gly Cys Ala Gly Cys Thr Cys Cys Cys Cys Thr Ala Cys Cys Cys Gly Cys Ala Cys Ala Gly Cys Cys Cys Ala Cys Cys Gly Ala Ala Ala Gly Cys Ala Ala Cys 1120 Gly 1135 Ala 1150 Ala 1165 Cys 1180 Ala 1195 Ala 1210 Ala 1225 Thr 1240 Gly 1255 Thr 1270 Ala 1285 Thr 1300 Thr 1315 Ala 1330 Ala Gly Ala Ala Ala Ala Ala Gly Gly Thr Gly Thr Gly Gly Gly Ala Thr Thr Gly Gly Cys Ala Gly Ala Cys Gly Cys Ala Ala Gly Ala Gly Gly Cys Cys Thr Ala Gly Thr Thr Thr Gly Gly Thr Cys Thr Cys Ala Thr Ala Gly Ala Thr Cys Cys Cys Ala Cys Ala Ala Gly 1125 Ala 1140 Gly 1155 Ala 1170 Thr 1185 Cys 1200 Ala 1215 Ala 1230 Cys 1245 Gly 1260 Gly 1275 Gly 1290 Cys 1305 Cys 1320 Ala 1335 Cys 1350 Ala Gly Thr Cys Ala Cys Thr Cys Ala Cys Cys Ala Gly Cys Thr Ala Gly Gly Gly Gly Ala Gly Ala Cys Cys Ala Gly Gly Ala Cys Gly Ala Ala Gly Ala Ala Cys Ala Cys Cys Ala Ala Ala Cys Gly Ala Ala Cys Ala Ala Gly Cys Cys Thr Gly Ala Gly Thr Thr 1340 1345 72/99 00 0 00 0 00 Gly Thr Cys Ala Gly Ala Ala Ala Ala Gly Thr Thr 1355 1360 Gly Gly 1370 Ala Ala 1385 Cys Ala 1400 Ala Ala 1415 Ala Ala 1430 Cys Ala 1445 Cys Thr 1460 Ala Cys 1475 Cys Ala 1490 Ala Cys 1505 Thr Cys 1520 Ala Cys 1535 Gly Gly 1550 Ala Gly 1565 Thr Ala Cys Cys Cys Gly Thr Ala Thr Cys Ala Ala Gly Thr Gly Thr Cys Cys Ala Thr Gly Cys Ala Ala Ala Ala Ala Cys Gly Ala Ala Ala Gly Gly Ala Gly Thr Gly Gly Cys Thr Cys Thr Gly Cys Ala Gly Gly Gly Ala Ala Thr Cys Ala Ala Gly Cys 1375 Cys 1390 Thr 1405 Gly 1420 Cys 1435 Ala 1450 Cys 1465 Cys 1480 Thr 1495 Ala 1510 Cys 1525 Ala 1540 Ala 1555 Ala 1570 Thr Gly Cys Cys Thr Thr Gly Thr Cys Ala Ala Ala Gly Thr Ala Thr Ala Thr Cys Cys Gly Cys Thr Cys Thr Cys Thr Cys Cys Gly Ala Cys Cys Cys Ala Thr Cys Ala Cys Thr Ala Ala Gly Gly Gly Ala Thr Cys Ala Cys Ala Ala Gly Ala Thr Cys 1365 Thr 1380 Gly 1395 Ala 1410 Gly 1425 Thr 1440 Cys 1455 Thr 1470 Ala 1485 Gly 1500 Cys 1515 Gly 1530 Cys 1545 Ala 1560 Thr 1575 Gly Ala Ala Cys Cys Cys Ala Thr Thr Thr Ala Cys Ala Ala Ala Gly Ala Ala Gly Thr Gly Thr Cys Gly Gly Ala Thr Ala Ala Cys Gly Cys Thr Ala Gly Cys Ala Ala Ala Cys Ala Cys Cys Thr Gly I Cys Thr Thr Gly Thr Gly Thr. Gly Cys Cys Ala Gly Thr Gly Ala 1580 1585 1590 73/99 00 210> 36 C1211> 530 ;212> PRT 213> Homo sapiens :2 20 00 .221> MISCFEAI :223> human DUB 00 :400> 36 let Giu Asp Asp 1JRE 8.8 Ser Leu Pyr Leu Gly Asp Trp-Gin Phe Asn His )he Ser Lys ,ln Arg Thr Leu Thr Ser Ser Arg Le U 25 Asp Ala Ala Phe Ala Glu Ile Giu Thr Arg Ser Leu Ser Giu Ser Pro Leu Ser ?he Asp so Leu Cys Asp Asp Ala Pro Val Ala Gin Leu Ala Pro Giu Lys Leu Pro Ser'Ser Arg Arg Ala Ala Val Gly 31y Leu Gin Lys Cys Leu Thr Tyr 100 Asp Ser Gin Thr 115 Gly Asn Thr Phe Tyr 90 Val Asn Val Ser Leu Gin Thr Leu Pro Leu Ser 105 Asn Tyr Met Leu Ser Arg Glu. 110 Cys Thr Met Cys His Leu Lys Cys Cys Met Phe 125 Gin Ala 130 His Ile Thr Trp Ala L~u Tyr Arg Pro 135 Gly 140 His Val Ile Gin Ser Gin Val Leu Ala Gly Phe His Gly Giu Gin Giu Asp 160 Ala His Giu Phe Leu Met Phe Thr Val 165 Asp 170 Ala Met Lys Lys Ala Cys 74/99 00 Leu Pro Gly His Lys Gin Leu Asp His 180 185 His Ser Lys ASP Thr Thr Leu 190 Lys Tyr Leu Slie His Gin 195 His Cys His 210 00 zLeu Asp Ile 225 00 Val Lys Pro Ile Phe Gly Ala Tyr 200 Trp Arg Ser Gin Ile 205 Gly Ilie Ser Gin Ala Ala 230 Asp 215 Thr Phe Asp Pro Leu Asp Ile Ala Gin Ser Val Lys Ala Leu Giu Gin Leu 240 Lys Leu Asn Gly Giu Ala Tyr His Cys Gly Leu 255 Cys Leu Gin Ala Lys Val 275 Ala Pro Ala Ser LYS 265 Thr Leu Thr Leu Pro Thr Ser 270 Val Thr Gly Leu Ile Leu Val Leu 280 Lys Arg Phe Ser Asn Lys 290 Leu Ala Lys Asn Gin Tyr Pro Lys Cys Arg Asp Met Gin 300 Val Tyr Val Leu Tyr Pro 305 Tyr Met Ser Gin Gin 310 Asn Thr Gly Pro Leu 315 Ala Val Leu Val His 325 Aia Gly Trp Ser Cys 330 His Asn Gly His Tyr Phe 335 Ser Tyr Val Giu Val Thr 355 Lys 340 Ala Gin Giu Gly Gin 345 Trp Tyr Lys Met 350 Gin Ala Tyr Ala Ser Giy Ilie Thr 360 Ser Val Leu Ser Val Leu 370 Phe Tyr Ile Gin Ser Giu Trp Giu His Ser Glu Ser Ser Arg Gly Arg Giu 390 Pro Arg Ala Leu Ala Giu Asp Thr Asp 400 Ary Pro Ala Thr Gin Gly Giu Leu Lys Arg Asp His Pro Cys Leu Gin 405 410 415 Vai Pro Giu Leu Asp Glu His Leu Val Giu Arg Aia Thr Gin Giu Ser 420 425 430 75/99 00 Thr Leu ;Z Giu Phe 450 Asp His Trp Lys Phe Pro Gi* n Lys Gin Asn 435 440 Thr Lys Pro Asn Val Arg Lys Val1 455 Glu Giy Thr Leu Pro 460 Pro Asn Val Leu v al 465 I1 le His Gin Ser Tyr Lys Cys Gly Lys Asn His His Glu Gin Gin Ser Ser 485 Val Leu Asn Leu Ser 490 Ser Thr Lys Pro Thr Asp 495 Gin Giu Ser Arg Arg Ser 515 Met 500 Asn Thr Gly Thr Leu 505 Ala Ser Leu Gin 51~0 Leu Leu Val Lys Gly Asn Asn His Ser Lys Arg Cys Gin 530 <210> <211> <212> <213> <220> <221> <223> 37 1254 DNA Homo sapiens misc feature human DUBB.11 <400> 37 atggaggacg acatcttctc tcacaactct c agc tcg ct c gggctccaga ataccgcccc aagtgctgca catgtcatcc gcccttgaat actcactcta ggccagatgc caactgagac ccagggagaa atatgggaaa ttgccaacta tgctctgtac agccctcaca ttctcatgtt ct tgggaggt agcctttgct ccgcgtcgac gcttcctctg. tacctgctac catgctgtcc catggaagct ggcattggct cactgtggat gagtggcagt gaaatccagc ttctgcgatg agtagcagga gtgaacgctt cgggagcact cacatcacat gctggcttcc gccatgaaaa tcaaccactt ggact tct Ct atttggccgc gacctgctgc cccagcagtg ctcaaacatg ggcccctcca atagaggcaa aggcatgcct ttcaaaactc ccctgagaag tgtggcaaga ygtgggggct tctgacatac tcatcgtcac cattcctggc gcaggaagct tcccgggcac 120 180 240 300 360 420 480 540 76/99 00 a~ agcagatcc ;Z aagaatgtgc gacctcttg 0 39acattact gagaagagtg 00 >ctcggCgctg M tgcctccagg N' ttagaccact 00 aaacttgaag gggatgaaaa ccgacagatc agatccaaag tcatcctcgt atggaagaga ttctccgatg tcacaggcaa caaaattgcc aatatcctga tctatgtcct tctcttatgt aatgggaaag aagacacaga tacccgagtt ggaaattcct gtacctgcc accatcatc aggagtccat ggaagaacaa gtgccttgac ctatgctgtg caaagttcaa acacagtgag caggcgagca ggacgagcac ccaagagcaa tcccaacgta tgaacagcaa gaacactggc acactgcaag atgcagccat ctggtccacg gaaggccagt agtgtgtcaa acgcaaggag ttgg tggaaa aacaaaacga cttgtgattc agctccctgc acactcgctt agggctctgc acatgtctca ccgggtggag ggtataaaat gaggcaggga agctcaagag gagccactca agcctgagtt atcaatcaaa taaacctctc ctctgcaagg ttgtgtgcca gcagaacaca ttgtcacaac ggatgatgcc accaagagcc agactacccc ggaaagcacc caacgtcaga atacaagtgt ttcgacgaac gaggaccagg gtga 660 720 780 840 900 960 1020 1080 1140 1200 1254 <210> 38 <211> 417 <212> <213> <220> <221> <223> PRT H-omo sapiens MISCFEATURE human DUBS.11 <400> 38 Met Giu Asp Asp Ser 1 5 Leu Tyr Leu Gly Gly 10 Glu Trp Gin Phe Asfl His Phe Ser Lys Gin Arg Thr Val. Asp Phe Leu Thr Ser Ser Arg Pro 25 Lys Ser 40 Asp Ala Ala Phe Ala Glu Ile Glu Thr Arg Ser Leu Pro Giu Cys Asp Asp Leu 55 Gin Leu Ser Thr Ala Ala Val Ala Arg Gin Leu Ala Pro Arg Glu Lys Leu Pro Ser Ser Arg Arg Pro Ala Ala Val Gly Ala 75 77/99 00 'ly .ys Leu Gin Asn Gly Asn Thr Cys Val Asn Ala Ser Gin Gin Leu Thr Ile Pro Pro Leu Asn Tyr Met Leu Ser Arg Giu ilo Cys Thr Met [is Ser Gin 115 Thr Cys His Arg Lys Cys Cys Met Leu 125 ,iu Ala (i 130 00 )ro Ser His Ile Thr Trp Pro 135 Leu His Ile Pro Giy 140 His Val Ile Gin Gin Ala Leu Al a 150 Aia Gly Phe His Arg 155 Gly Lys Gin Giu kla Leu Giu Phe Met Phe Thr Val Ala Met Lys Lys Ala Cys 175 ,eu Pro Gly sp Val Thr 195 Lys Gin Ilie Leu Leu Val Trp Lys Arg Phe Ser 190 Pro Giu Cys Gly Asn Lys Ile Lys Asn Val Gin .eu Asp 210 Met Gin Pro Tyr Met 215 Ser Gin Gin Asn Thr 220 Gly Pro Leu Val Val Leu Tyr Ala Val1 230 Leu Val His Ala G ly 235 Trp Ser Cys His Gly His Tyr Phe Ser 245 Tryr Vai Lys Val Gin 250 Glu Gly Gin Trp,Tyr Lys 255 Met Asp Asp Ser Arg Giy 275 Ala 260 Giu Lys Ser Giu Trp 26 5 Giu Arg His Ser Giu Ser Val 270 Gly Ala Giu Asp Thr Asp Arg 285 Arg Giu Pro Arg Ala Leu 280 Arg Ala 290 Thr Gin Gly Giu Leu 295 Lys Arg Asp Tyr Cys Leu Gin Val Pro 305 Giu Leu Asp Giu Leu Val Giu Arg Ala Thr Gin Giu Ser Thr 315 320 Leu Asp His Trp Leu Ap Hi Trp Phe Leu Gin Giu AsLsThLy Asn Lys Thr Lys Pro Giu 335 78/99 00 Phe Asn Val Arg ;Z 340 tle His Gin Ser 355 Lys Leu. Giu Gly Thr Leu Pro Pro Asn Val Leu. Val 345 350 Lys Tyr Lys Cys Gly 360 Met Lys Asn His 365 His Pro Giu Gin Gin 370 Giu Ser 385 Ser Ser Leu Leu Met Asn Thr Giy 390 Leu Ser Ser Thr Asn 380 Pro Thr Asp Gin Thr Leu Ala Ser Gin Gly Ary Thr Arg 400 Arg Ser Lys Gly Lys Asn 405 Lys His Cys Lys Arg Ala Leu Leu Val. Cys 410 415 <210> <211> <212> <213> <220> <221> <223> 39 1594 DNA Homno sapiens misc-feature human DUB4.4 <400> 39 atggaggagg acatcttctc tcaccactct cagcttgctc gggctccaga acaccgcccc aagggctgca cacgtcatcc gcccatgaat aagcaggtag actcactcta ggctcgatgc catgtgagac ccagggagaa atatgggaaa ttgccaacta tgctctg tac agccctcaca ttctcatgtt atcatccctc ct tgggtggt agcttttgct ccgtgtcgac gcttcCtctg tacctgctac catgctgtcc tatgcaagct ggcattggct cactgtggat taaggacacc gagtggcagt g aaa tccag c ct ctgtgatg agtagcagga gtgaacgctt cgggagcact cacatcacac gctggcttcc gccatgaaaa accctcatcc tcaaccactt ggacttctct atttggttc gacctgctgc ccttgcagtg ctcaaacgtq gggccctcca atagaggcaa aggcatgcct acca a a tat t ttcaaaactc ccctgagaag tgaggcaaga ggtgggggct cctgacatac tcatcgtcac caatcctggc gcaggaagat. tcccgggcac tggaggctac 120 180 240 300 360 420 480 540 600 79/99 00 C1ggagatctc OJtggacatcg tgaagcccg [cgccggcct .agagattct 0 ttgacatgc CI*' ctgtgctgg I ctcaagaag 00 tctgtcctg C]cacagtgag aggcgagta [gacgagcac .caagagcaa =ccacgta :gaacagcaa jaacaatggc icacagcaag aaatcaagtg ccctggatat aagaactcaa ccaagacgtt ccgatgtcac agccatacat t cc atgc tgg gccagtggta agtcaacagg agtgtgtcaa acgcaaggag t tggtggaaa aacaaaacga. cttgtgattc agctcctgc acactcgctt tctccactgc ccaggcagct tggagagaat aactttacac,, aggcaacaag gtctcagcag gtggagttgt taaaatggat cctacgtcct gaggcaggga agctcaagag gagccactca agcctgagtt atcaatcaaa. taaacctctc ccctgcgagg cacggcattt cagagtgtcc gcctatcatt act tctgcca attgccaaga aacacaggac c a ca acgga c gatgccgagg cttttacatc ac ca ag agcc agaccacccc ggaaagcacc caacgtcaga atacaagtgt ttcgacgacc gagggccagg cagacacttt agcaagcttt gtggtgtttg aggtcctcat atgtgcaata ctcttgtcta attacttctc t ca cc gcc tc cagaagagtg cttggcgcag tgactccagg ttagaccact aaagtcgaag gggatgaaga ccgacacatc agatccaaag tgacccttac ggaacagttg tctccagagg ccttgtattg tcctgagtgc tgtcctctat ttatgtcaaa ttagcatcac aatgggaaag aagacacaga cccccgagtt ggaaattcct gtaccctgcc accatcatcc agcagtccat ggaagaacaa. 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1594 agggctctgc ttgtgtgcca gtga :210> :211> 357 :212> PRT <213> Homo sapiens <220> <221> MISCFEATURE <223> human DUB4.4 <400> Met Glu Glu Asp Ser Leu Tyr Leu Gly Gly Glu Trp Gin Phe Asn His 1 5 10 Phe Ser Lys Leu Thr Ser Ser Arg Leu Asp Ala Ala Phe Ala Glu Ile 25 80/99 00 Sl~n A~rg Thr Ser Leu Pro ;Val Asp Leu Cys Asp Asp Giu Lys 40 Ser Pro Leu Ser Cys Giu Thr Arg Val Pro Giu Ala Arg Gin Leu Ala Pro Arg Giu Lys Leu Pro Leu 70 Ser Ser Arg Arg Pro Ala Ala Val Gly Gly Leu Gin Asn Met B5 Gly Asfl Thr Cys Tyr 90 Val Asn Ala Ser Leu Gin Cys Leu Thr His Ser Gin 115 Thr Pro Pro Leu Ala 105. Asn Tyr Met Leu Ser Arg Giu 110 Cys Thr Met Thr Cys His Arg His 120 Lys Gly Cys Met Gin Ala 130 His Ile Thr Arg Leu His Asn Pro His Val Ile Gin Pro 145 Ser Gin Ala Leu Ala Gly Phe His Arg 155 Gly Lys Gin Giu Asp 160 Ala His Glu Phe Met Phe Thr Val Asp 170 Ala Met Lys Lys Ala Cys 175 Leu Pro Gly Ile His Gin 195 Lys Gin Val Asp His 185 Pro Ser Lys Asp Thr Thr Leu 190 Lys Cys Leu Ile Phe Gly Gly Tyr 200 Trp Arg Ser Gin His Cys 210 His Gly Ile Ser Asp 215 Thr Phe Asp Pro Leu Asp Ile Aia Asp Ile Gin Ala Ala 230 Gin Ser Val Gin Gin 235 Ala Leu Giu Gin Val Lys Pro Glu Giu Leu Asn Giy Giu 245 Cys Leu Gin Arg Ala Pro Ala Ser Lys 260 265 Ala Tyr His Cys Gly Val 255 Thr Leu Thr Leu His Thr Ser 270 Ala Lys Val Leu Ile 275 Leu Val Leu Lys Arg Phe Ser Asp Val Thr Gly 280 285, 8 1/99 00 Sn ;Zro ~la Ly s 290 Ile Ala Lys Asn Gin Tyr Pro Giu Cys 300 Leu Asp Met Gin Tyr Met Ser Gin Gin 310 Asn Thr Gly Pro Val Tyr Val Leu Val Leu Val His 325 Ala Gly Trp Ser His Asn Gly His Tyr Phe 335 00 er Tyr Val Lys Ala Gin Giu Gly 340 00 ;l Val Thr Ala Ser 355 Trp Tyr Lys Met Asp Asp Ala 350 210> 211> :212> .213> 41 1197 DNA Homo sapiens :220> :221> misc-feature :223> human DUB4.9 :400> 41 itggaggacg actcactcta cttgggaggt gagtggcagt tcaaccactt ttcaaaactc acatctcctc ggcccgatgc tcaccactct catgtgagac cagcttgctc gggctccaga acaccgcccc aagggctgca cacgtcatcc gcccatgaat aagcaggtgg tggagatCtC ctggacatcg gtgaagcccg ccagggagaa atatgggaaa ttgccaacta tgctctgtac agccctcaca ttctcatgtt atcatcactc aaatcaagtg ccctggatat aagaactcaa agcttttgCt ccgtgtcgac qcttcCtctg tacctgctac catgctgtcc tatgcaagct ggcat tggct cactgtggat taaggacacc tctccactgc ccaggcagct tggagagaat gaaatccagc ctctgtgatt agtagcagga gtgaacgct t cgggagcact cacatcacac gctggcttcc gccatgaaaa accctcatcc cacggcattt cagagtgtCC gc ctatcatt ggacttctct atttggCtcc gacctgctgc ccttgcagtg ctcaaacgtg ggg ccc tcc a atagaggcaa. aggcatgcct accaaatatt cagacacttt agcaagcttt gtggtgtttg ccctgagaag tgtggcaaga ggtgggggct cctgacatac tcatcgtcac caatcctggc gcaggaagat tcccgggcac tggaggctac tgacccttac ggaacagttg tctccagagg 120 180 240 300 360 420 480 540 600 660 720 780 82/99 00 00 00 gcgccggcct aagagattct cttgacatgc gctgtgctgg gctcaagaag tctgtcctga cacagtgaga ccaagacgtt ccgatgtcac agccatacat tccacgctgg gccagtggta ctcaacaggc gtgtgtcaag aactttacac aggcaacaag gtctcagcag gtggagttgt taaaattgat ctacgtcctc aggcagggaa acctctgcca attgccaaga a ac a cagga c cacaacggac gatgccgagg ttttacatcc ccaagagccc aggtcctcat atgtgcaata ctcttgtcta attacttctc tcaccgcctc agaagagtga ttggctctga ccttgtattg tcctgagtgc tgtcctctat ttatgtcaaa tagcatcact atgggaaaga agactaa 840 900 960 1020 1050 1140 1197 <210> <211> <212> <213> <220> <221> <223> 42 398 PRT H-omo sapiens MISCFEATURE human DUB4.9 <400> 42 Met GIU Asp 1 Phe Ser Lys Gin Arg Thr 3S Asp Ser Leu Tyr Leu Gly Gly Giu Trp Gin Phe Asn His Leu Thr Ser Pro Arg Asp Ala Ala Phe Ala Glu Ile Glu Thr Arg Ser Leu Pro Giu Ser Pro Leu Ser Cys Val Asp Leu Cys Asp Tyr Lys Leu Pro Leu 70. Ala Pro Val Ala Arg Gin Leu Ala Pro Arg Glu Ser Ser Arg Arg Ala Ala Val Gly Al a Gly Leu Gin Asn Cys Leu Thr Tyr 100 Gly Asn Thr Cys Tyr Val Asn Ala Ser Leu Gin Ser Arg Giu 110 Thr Pro Pro Leu Asn Tyr Met Leu 83/99 00 SHis Her Gin Thr Cys His Arg Lys Gly Cys Met Leu 125 Cys Thr Met Gin Ala His Ile Thr Arg Ala 135 LeU His Asn Pro Gly 140 His Val Ile Gin Pro 145 Ser Gin Ala Leu Ala Gly Phe His Giy Lys Gin Giu Asp 160 Ala His Glu Phe Met Phe Thr Val Ala Met Lys Lys Ala Cys 175 Leu Pro Gly Ile His Gin 195 His Lys Gin Val Asp His His Ser Lys Asp Thr Thr Leu 190 Lys Cys Leu Ile Phe Gly Gly Tyr 200 Trp Arg Her Gin Ile 205 His Cys 210 His Gly Ile Her Asp Thr 215 Phe Asp Pro Leu Asp Ile Ala Asp Ilie Gin Ala Gin Ser Val Gin Gin 235 Ala Leu Glu Gin VJai Lys Pro Giu Glu 245 Leu Asn Gly Glu Asn 250 Ala Tyr His Cys Gly Val 255 Cys Leu Gin Ala Lys Val 275 Ala Pro Ala Ser Thr Leu Thr Leu His Thr Her 270 Val Thr Gly Leu Ile Leu Val Leu 280 Lys Arg Phe Her Asn Lys 290 Ilie Ala Lys Asn Val1 295 Gin TPyr Pro Giu Leu Asp Met Gin Pro 305 Tyr Met Her Gin Asn Thr Gly Pro Leu Val Tyr Val Leu 315 Ala Val Leu Val Ala G ly Trp Her His Asn Gly His Tyr Phe 335 Ser Tyr Val Giu Val Thr 355 Lys 340 Ala Gin Giu Gly Trp Tyr Lys Ile Asp Asp Ala 350 Gin Ala Tyr Ala Her Her Ile Thr Her Val Leu Thr Gin 365 84/99 00 Val Leu Phe Tyr Ile Gin Lys Ser Glu Trp Giu Arg His Ser Glu Ser 370 375 380 Val Ser Arg Gly Arg Glu Pro Arg Ala Leu Gly Ser Glu Asp 385 390 395 <210> 43 <211> 1706 <212> DNA <213> Homo sapiens <220> <221> misc feature <223> human 8.2 <400> 43 atgcggccag cggtcccagc tacttgggag gcagcttttg acccgcgtcg aagcttcctc aatacctgct tacatgctgt actatgcaag caggtgttgg ttcactgtgg tctaaggaca tgtttccact atccaggcag aatggataaa ttaactttac acaggcaaca atgtctcagc gggtggagtt agagcccgtc cgaaaaacct gtgagtggca Ctgaaatcca acctctgtga tgagtagcag acgtgaacgc cccgggagca ctcacatcac ctgctggctt atgccatgaa ccaccctcat gccacgggat ctcagagtgt atgcctatca acacttctgc aacttgccaa agaacacagg gtcacaacgg atttgaagac tgtgatcctt gttcaaccac gcggacttct tgatttggct gagacctgct ttccctgcag ctctcaaacg atggcccctc ccatagaggc aaaggcattc ccaccaaata ttcagacacc caagcaagct ttgtggtctt caaggtcctc gaatgtgcaa. acctcttgtc acattactta. tcggaagaga gttccgggCg ttttcaaaac ctctctgaga cctgtggcaa gcggtggggg tgcctgacat tgtcatcgtc cacagtcctg gagcaggaag cttcccgggc tttggagggt tttgaccctt ttgtaacagt tgtctccaga atccttgtat tatcctgagt tatgtcctct t Ct tatgt ca tagcgtcttt acatggagga. tcacatcttc agtcatcact gaca9ctcgc ctgggctcca acacaccgcc acaagtgctg gccatgtcat atgcccatga acaagcattt actggagatc acctggacat tggtgaagcc aggcgcctgc tgaagagatt gccttgacat atgctgtgct aactcaagaa ctgcaacctg cgactcactc tcggccagat ctcatctgag tcccagggag gaatatggga ccttgccaac catgctctgt ccagccctca atttctcatg agataatcac t ca cat caa c cgccctggat cgaagaactc ct cc agg a cg ctctgaggtc gcagccatac ggtccacgct ggccattggt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 85199 00 0 taaaatgga toJ:ctatgtcct aggcaggga zcatgaataa -ttaaccaat 00 gtgtaaccat z:ttcagaatc :tcttcactc 00 aagaattccc 3- attgcccct tga tgccgag cttttacatc accaagagct atcttgcagt atcaatgcct ggcctctgga acttcaggtg aggaaaactc tcaggagtga ttgtctcttc gtcactgcct cagaagaatg ctttgcgtga ggagtattta agtgcctacc ttgcttatga gtggtaacag tcactgagac aattggtggc aggact ccggtatcac aatttggaag aggcaagtga tttgtctcaC ccccagagat ctctgaagat ataacacatc aaaggaaaat tccttcCtcc ttctgtcctg acccagttac attgtgtgtg tttgtaatca aagaacttcc aattctcctt agtccctttc cctatggttt ctgtcaagtc agtcaacagg agtgtgtcca aaataaaatg gtgaatgagc actctct tat tcccccaacg tctctctttt actggggagg tcttcctcag 1200 1260 1320 1380 1440 1500 1560 1620 1680 1706 .210> -211> -212> ,213> <220> :2 21 -c223 44 271 PRT Homo sapiens MISCFEATURE human DUB8.2 c400> 44 Met Arg Pro Giu Ser 1 5 Pro Ser Phe Giu Ser Giu Glu Ile Ala Ser Phe Cys Asn Leu Arg Ser Gin Pro Lys 25 Asn Leu Val Ile Leu Val Pro Trp Gin Phe Gly Asp Met Giu Asp Asp Ser Leu Tyr 40 Leu Gly Gly Giu Asn His Giu Ilie Phe Ser Lys Leu Thr Ser Ser Arg Pro Ala Ala Phe Ala Gin Arg Thr Leu Ser Giu Lys Ser Leu Ser Ser Thr Arg Val Asp Leu Cys Asp Asp Leu Ala 90 Pro Val Ala Arg Gin Leu 86/99 00 Ala Pro Arg Gly Ala Gly 115 Glu :100 Lys Leu Pro Leu Ser 105 Ser Arg Arg Pro Ala Ala Val 11.0 Leu Gin Asn Met Asn Thr Cys Tyr Val1 125 Asn Ala Ser Leu Gin 130 Cys Leu Thr Tyr Thr Pro Pro Leu Ala As n 140 Tyr Met Leu Ser Glu His Ser Gin Thr 150 CyS His Arg His Cys Cys Met Leu Thr Met Gin Ala Ile Thr Trp Pro His Ser Pro Gly His Val 175 Ile Gin Pro Glu Asp Ala 195 Ser 180 Gin Val Leu. Ala Gly Phe His Arg 190 Met Lys Lys His Glu Phe Leu Met 200 Phe Thr Val Asp Ala Phe 210 Leu Pro Gly His His Leu Asp Asn His 220 Ser Lys Asp Thr Thr 225 Leu Ile His Gin Phe Gly Gly Tyr Arg Ser His Ile Cys Phe His Cys His 245 Gly Ile Ser Asp Phe Asp Pro Tyr Leu Asp 255 Ile Ala Leu Asp 260 Ile Gin Ala Ala Gin Ser Val Lys Gin Ala Leu. 265 270 <210> <211> 1463 <212> DNA <213> Homno sapiens <220> <221> misc-feature c223> human DIJB8 .9 87/99 00 S<400> Satggaggaag acatcttctc tcaccactct ~tcagcttgctc ggtctccaga 00 acaccgcccc ~Jaagtgctgca Sccatgtcatc 00 tgcccatgaa caagcagcta ctagagatct cctggatatc ggtgaagccc ggcgcctgcc gaagagattc cgttgacatg tgctgttctc actcaagaag tctccttaga cccagttaca attgtggtga taatcagtga acttccagtt ctcctgtccc cctttctctc actcactcta agccagatgc catcggagac ccagggagaa atatgggaaa ttgccaacta tgctctgtat cagccctcac tttctcatat gatcatcact caaatcaagt gccctggaLta gaagaactca gccaagacgt tccgatgtca cagccataca gtcatcaccg gccagtggta St ca a ca gg c gggtgtccgc aataatatgt atgagcttta tctcatgtgt ccaaagtttc cttgggaggt agcttttcct ccgtgtcgac gcttcctccg tacctgccac catgctgtcc tatggaagct aggcattggc t cact gtgga gcaaggacac gtctctactt tccaggcagc. atggagagaa taactttacc caggcaacaa tgtctcagca ggtggagttg taaaatggat ctatgtcctc aggcagagaa catgaataaa acgaatatca aatcatggca gagtggcagt gaaatccagc ctctgtgacg agtagcagga ttgaatgctt tgggagctct cacagcacac tgctgacttc tgccattaga catcctcatc ccacggcatt tcagagtgtc tgcctatcat cacttctgcc act tgccaag gaacacagga tcacaacgga gatgccgagg ttttacatcc ccaagagctc tcttgcagca atgcctagtg tctggattgc tcaaccactt ggacttctct atttggctcc gacctgctgc ccctgcagtg ctcaaatgtg gggcacctcc catagagaca aaggcatgcc c ac ca a atat tcagacacct aagcaagc7tt tgtggtcttt aaggtcctca aatctgcaat cctct t ttc t cattacttct tcactgcctc agaagaatga tttgtgctga gatttatttg cctacccccc tcatgattct ttcaaaactc ccctgagaag tgtgacaaga ggtgggagct cctgacatac t cat cg tccc accgtcctgg agcaggaaga. ttcccgggca ttggagggta tcgaccctta tggaacagtt gtctccagaa tccttgtctt atcctgagtg atgtcctcta cttgtgtcaa tggtatcact atttggaaga agacaattga tctcactttg agagataaga gaagataatt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1492 agaatcactt caggtggtag aaacagataa cacatcagtc tcttttctct tca <210> 46 <211> 248 <212> PRT <213> H-omo sapiens <220> 88/99 00 <221> MISCFEATURE <223> human DUB8.9 <400> 46 Met Glu Asp Asp 1 Ser Leu. Tyr Leu Giy Gly Giu Trp Gin Phe Asn His 5 10 Phe Ser Lys Gin Arg Thr Thr Ser Ser Arg Asp Ala Ala Phe Glu Thr Arg Ser Leu Ser Glu Ser Ser Leu Ser Ser Val Asp s0 Leu Cys Asp Asp Leu Ala Pro Val Ala Gin Leu Ala Pro Glu Lays Leu Pro Leu Ser Ser Arg Arg Ala Ala Val Gly Gly Leu Gin Asn Met Gly Asn Thr Cys Val Asn Ala Ser Leu. Gin Cys Leu Thr His Ser Gin 115 Tyr 100 Thr Pro Pro Leu. Asn Tyr Met Leu Ser Arg Glu 110 Cys Thr Met Thr Cys His Arg His 120 Lys Cys Cys Met Gin Ala 130 His Ile Thr Trp Pro 135 Leu His Ser Pro His Val Ile Gin Ser Gin Val Leu Ala 150 Ala Gly Phe His Gly Giu Gin Giu Asp 160 Ala His Giu Phe Leu Met Phe Thr Val 165 Asp 170 Ala Met Lys Lys Ala Phe 175 Leu Pro Gly Ile His Gin 195 His 180 Lys His Leu Asp His Ser Lys Asp Thr Thr Leu. 190 Ile Phe Gly Gly Trp Arg Ser His Ile Asn Cys Phe His Cy5 210 His Gly Ilie Ser Asp Thr Phe Asp Pro 215 Leu Asp Ilie Ala 89/99 00 00 00 Leu Asp Ile Gin Ala Ala Gin Ser Val Lys Gin Ala Leu Glu Gin Leu 225 230 235 240 Val Lys Pro Glu Glu Leu Asn Gly 245 <210> 47 <211> 1661 <212> DNA <213> Homo sapiens <220> <221> misc feature <223> human DUB 8.10 <400> 47 atggaggacg acatcttctc tcatcactct cagctcgctc gggc tccaga acaccgcccc aagtgctgca. catgtcatcc gcccatgaat aagcatttag tggagatctc ctggacatcg gtgaagcccg gcgcctacct aagagattct cttgacatgc gctgtgctgg ctcaagaagg ctgtcctgag actcactcta ggccagatgc catctgagac ccagggagaa atatgggaaa ttgccaacta tgctctgtac agccttcaca ttctcatgtt ataatcactc acatcaactq ccctggatat aagaactcaa ccaggacgtt ctgatgtcac agccatacat tccacgctgg ccattggtat tcaacaggcc ct tgggaggt agcttttgct ccgcgtcgac gcttcCtctg tacctgctac catgctgtcc tatgcaagct ggtgt tggct cactgtggat taaggacacc tttccactgc ccaggcagct tggataaaat aactttacac aggcaacaaa gtctcagcag gtggagttgt aaaatggatg tatgtcctct gagtggcagt gaaatccagc ctctgtgatg agtagcagga gtgaacgctt cgggagcact cacatcacat gctggcttcc gccatgaaaa accctcatcc catgggattt cagagtgtca gcctatcatt acttctgcca cttgccaaga aacacaggac cacaacggac atgccgaggt tttacatcca tcaaccactt ggacttctct atttggctcc gacctgctgc ccctgcagtg ctcaaacgtg ggcccctcca atagaggcga aagcattcc~t accaaatatt cagacacctt agcaagcttt gtggtctttg aggt cc tcat atgtgcaata. ct Cttgt Cta attacttatc cactgcctcc gaagaatgaa. ttcaaaactc ctctgagaag tgtggcaaga ggtgggggct cctgacatac tcatcgtcac cagtcctggc gcaggaagat tcccgggcac tggagggtac tgacccttac ggaacagttg tctccagaag ccttgtattg tcctgagtgc tgtcctctat ttatgtcaaa ggtatcactt tttggaagac 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 90/99 00 00 00 ccagttacag tgtgtgtgaa tgtaatcagt gaacttccac ttCtcctttc tccctttctC tatggtttaC gtcaagtctc agatgccccc tgtgtccata ataaaatgtc gaatgagctt tctcttatgt ccccaacgtt tctcttttct tggggaggaa ttcctcagga tggttgtgca ggcagggaac atgaataaat taaccaatat gtaaccatgg tcagaatcac c t tcact cag gaattccctc ttgccccttt t acc tggc ct cgagagctct cttgcagtgg caatgcctag cctctggatt ttcaggtggi gaaaactctc aggagtgaaa gtctcttcag gtgaagaaat ttgcgtgaag agtatttatt tgcctacccc 9 ct tatgact ggtaacagat actgagacaa ttggtggctc gactctgctc a gcaagtgaat tgtctcactt ccagagataa ctgaagataa aacacatcag aggaaaatcc cttcctccct atcaggcccg 1200 1260 1320 1380 1440 1500 1560 1620 1661 <210> <211> <212> <213> <220> <221> <223> 48 151 PRT Homo sapiens MISCFEATURE human DtTB8.10 <400> 48 Met Glu Glu 1 Phe Ser Lys Gin Arg Thr Asp Ser Leu Tyr Leu Gly Gly Glu Trp Gin Phe Asn His Leu Thr Ser Ser Gin Asp Ala Ala Phe Glu Thr Arg Ser Leu Pro Glu Lys Ser Pro Leu Ser Val Asp Leu Cys Asp Asp Ala Pro Val Thr Gin Leu Ala Pro Arg G1u Lys Leu Pro Ser Ser Arg Arg Pro Ala Ala Val Gly Gly Leu Gin Asn Met Gly Asn Thr Cys His Leu 90 Asn Ala Ser Leu Gin 91/99 00 0 Cys Leu Thr Tyr 100 SLeu Ser Gin met 115 Glu Ala His Ser 130 Thr Pro Pro Leu Ala Asn 105 Cys His Thr Arg Arg Pro Lys Cys 120 Ala Pro Pro Pro 135 Tyr Met Leu Ser Trp Glu 110 Cys Met Leu Cys Ile Met 125 Ser TrpPro Cys His Pro 140 00 >Ala Leu Thr Gly Ile Gly Cys 145 150 <210> 49 00 g <211> 2001 <212> DN~A <213> Homo sapiens <220> <221> <223> misc-feature promoter sequence for human DUB4.6 <400> 49 gcatgactgg gcacaccgat ctcggcatct ctccctgtgg ggcacaggaa. gggccaaagg ggccctgaag gccctgttcc ctgctaagcc tgtccacttt acaatgcgta caggatatgc ggcacgctat cagggcctca cagacagctt gcccaggtcc gcattgctca agcatctttc gccttctgat tcacagtcct ccagggctgt ttaccgtcta agacagccgg cggcagcatt actggaaatg acggcttatt cctctgtttc cttccgtcag atcgattggg' cggc tgcagg tgcttctggg taagcagtgc ggagcacacc ctcatcccat ttctttacac agacatgttg aagacacacc acaattttgg gaggcaacat ttggcctttt actccctgct ccgggctttt ctcccctcaa aataagaccc gatcattctc tcttttcttc tggcccatga catcctcctt ctagaggcct ggaaaatccc caaattctgt caccaaatgt ctccgatcct cccactgaaa tttaaacgtc ccacggtata aat cggtt at tccagggtct ctgaaaatgg ccccaggaca aaagacaagg aaaatcatcc tggcgccggg tagagccagg ccc tct tact gctaactgca gaacgatcga caagggccag tccgatgttt attttccttg gagcattcaa tgtgtgaagc tggctccttt ctttacatcc gaaagaaacg taatttcatg cctcaattcc atcttcattc tcagggaaca attccaccat tgcgagaatc tattaaaaat ctccctgaga tttgcttttg tccaaattag aactttttat ttcacctcta ggaaacgttg atc6attatc acatacgt .at 92/99 00 ggaaatatta tcacacatgc tgtgagatac gttgttttta ttttcatcaa ttctttaata aacaaacggt taaactgccg ctggcaaaca ccaaaggctt tctaccattt gacttgtctt cgtggaaagg ggaagaaaat cactttcgac acttggaagt cacgaacaca gccattgctt ctattatatg tgtgggctgt tgaattgagt gcggttggag actctctcgg atccttgttC <210> tatagctggg at tcgcacgtcc ga taaatttggg ga tcacagtcta ct catgctttct ta gttctccact gg ttatcgctgg aa acgctgtgct aa ttcttgtctt tc tcatcgcaga aa atcacacaca ca tacctaaaat az tgcctatcat cc gtctgttgaa tt gctgatattt g9 ggggtgactt ac aagggatagc gt caqtcgacat g accttctg aaccgctc .ttgtcatc ttgtgcac .tttggcaa caggtaat ggtctgtt atactata :cgtcgctg Laaacacac cacactca Lggcaactg :tgaggagt :cccagcga ittggctta :agaagggc ag ttc tcaag actatgcagt aattagtctc tgagtat.ctc tctagcttcc ttcactcaga tgattccacg cttcattgac agaggatgat acacacacgc cacggtttcc tgtggccact aatttgattc tgcaagggga tcgcgcacct tgatgcggcc ttttttgttt 9tcatgaccg tcggggattg ttc aaacttc acaagagcat tagagaatca gatct.ctcct tattctcagg ggcagctgcc gcccccccCa tacgtaaaga gtcccaaccc aggtgttCtg cacaccctgt gatgagtggg agagagctcg cgtgttttct tctctctttt catgatttcc agtgcatgtt ttcatgcaaa ataggctcaa ttctcattag tcagaaagcg aaaagtacat. cacacacaca. tttcttccct ggttacactc gaag tc atg c gactCCtCC tgtggtgttC tcatttgaag 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2001 tctttctgc aacctgcggt cccagcagaa aaaccttgtg <211> <212> <2 13> <220> <221> <223> 1901 DNA Homo sapiens misC feature promoter sequence for human DUB4.7 <400> tcctcagcgt cggtttttag gcctggcata agctgtttga aacccaggaa cgtaccccac ccatcatctt tggcctagtt aacacctccc ctccgtgtgt ggtggtttgg agaacctgct ttttcctcat cccactgatC ccaaacccag gacaeccctac agctgctgac~caggattaaa 93/99 00 ;Z 00 cctaatggag cat tcactta actttgggaa catggtgaaa tgtaatccca gttgcagtga agaaaacaaa tgatccaatg tgtcttgtga gttctgagat tgctggaaag attggttggc tccctccctc ggctctgctg agaagagata tttcacgcct tccacaagag ggatagagaa acggatctct gactattctc gatg~ccagct cacgcccccc taggtaaaga gtcccaaccc aggtgttctg cacaccctgt gatgagtggg agagagctcg cccagcagac <210> 51 atttaatgcc catacttgca gccgaggtgg ccccgtctct gctactcagg gccaagatta aaacccaaaa ccttcctttt tatttacaat gtctgctgtg caggtcttgg cagaagccca cctccctccc gctgccaaga agaaattcca gtaatcccag catttcacgc tcaataggct cctttctcat aggtcagaaa gccaaaagta cacacacaca tttcttccct ggttacgctc gaagtcatgt gattccttcc tggggtgttc tcatttgaag aaaccttgtg attaaatcag gagtcggcca gtggatcacg actaaaaata aggctgaggc tgccattgca acttgcagag tctctttctc ctaggagaag tttgcaggta cgctatattt attgtcactc tctccaagat tgggccacca cagggctgat cacttgggag aaagacttgt caacgtggaa tagggaagaa gcgcactttc catacttgga cacacaaaca gccattgctt ctattatat g tgtgggctgt tgaattgagt gcggttggtg actctctcgg atccttgttc aagaaattct ggtgtgttgg aggtcaagaa caaaaattaa aggcgat ttg ctccagcctg tgaatttagg aaatattttg gcaggagaga ccttccctca ataccatg gt tctctctctg atccagtaac gcaaaaaggg aagaaagacc gccaggatgg cttgttctcc ajgttatcgc aatacgctgt gacttcttgt ag tt cat ccc cactcacaca tacctaa aat tgcctatcat gtctgttgaa gctgatattt ggggtgactt aagggatagc cagtcgacat gattctcagg ctcacacctg ttcgagacca ctggtgtagc cttgaacctg qgcaacagag aaaccatgaa agccaggtac gaactaa~jaa* atttccctac acttcccctc tctccctctc tgactgatca aaaattggtt atdggcttcc tcggatttgg actggcaggt tggaaggtct gctaaatact ccttccgtcg agcacaaaca cacacacgca aaggcaactg cctgaggagt ttcccagc ga gattggctta acagaagggc gtccttctgc gactgacatt taatcccagc t cc tggcca a tgtgcgtgcc ggaggtggag cgagactctc gtacacagtt tatcctagac cagagagcat tcactggcca cctatactca gctccctccc gctgggggtg gtgagtgaga aggcgcggtg caatctagct aatttcactc gtttaattcc. atacttcatt ctgagaggat cacacacaca cacqgt ttcc tgaggccact aatttgattc tgccagggga tcgcgcacct tgatgcggcc aacctgcggt 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1901 <211> 2001 94/99 00 S<212> DNA <23.Homo sapiens ~f<220> <221> misc-feature 00 <223> promoter sequence for human DUB4.8 S<400> 51 cagggctccg tagaaccaca gaatcttggg cgcaaccctg ctcaagcacc caaatgtgca tacgaacagg gacagcttat ccaggtccg attgctcatg catctttcta cttctgatgg acagtcctct agggctgttt accgtctaag acagccggaa gcagcattac tggaaatgga ggcttatttt tctgtttcac tccgtcagcc ctttttattt acacatgctg tagctgggat gcacgtccga aatttgggga acagtctact tgctttatta tctccactgS atcgctggaa gtctccgtgt cgattgggct gctgcaggaa cttctgggga agcagtgctc agcacacctg catcccatca ctttacacct acatgttggg gacacaccca aattttggca ggcaacatct ggccttttc tccctgcttt gggcttttct cacctctagg tgagatacgt a cc tt ctgag aaccgctcac *ttgtcatcaa *ttgtgcactg tttggcaatc Icaggtaattt LggtctgtttC gacgtgtgtg cccctcaaaa taagacctc tcattctcct ttttcttcCC gcccatgaaa tcctccttaa agaggccttg aaaatcccta aattctgtcc ccaaatgtgc ccgatcctga cactgaaaca taaacgtctc acggtataat aaacgt tgat tgtttttatt ttctcaagtt tatgcagtgt ttagtctctc iagtatctctt tagcttccac cacttggaca Iattccacgga aaaactacag tcggttatga cagggtcttg gaaaatggtg ccaggacact agacaaggga aatcatccta gcgccggycc gagccaggat ctcttacttc taactgcaat acgatcgatg agggccagta cgatgtttCt tttccttgtt ccattatcac ttcatcaatt ttttgtttC9_ catgaccgtc ggggattgcz caaacttcac aagagcattt Lgagaatcaat ktctctccttt tgtgatgagc gcattcaagc tgtgaagcct gctcctttct ttacatccgg aagaaacggg atttcatggg tcaattccgc cttcattcct agggaacatg tccaccatac cgagaatcca ttaaaaatgg ccctgagaca tgcttttgtc atacgtatgg ctttaataaa tgttttctta tctcttttct LtgatttcccC 5tgcatgtttc -catgcaaagz :aggctcaacc :ctcattagg atgactggca acaccgatgC cggcatctgc ccctgtggag cacaggaagc gccaaaggtc ccctgaagcc cctgttcctt gctaagccag tccactttcg aatgcgtaac ggatatgcac cacgctatcc gggcctcact caaattagaa aaatattatc caaacggtta aactgccgtc ggcaaacata aaaggctttc taccatttga Icttgtcttct j tggaaaggtt 3 aagaaaatac 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500* 95/99* 00 gctgtgctaa cttgtCcttc atcccagcac cacacacaca taaaataagg atactatact cgtcgctgag aaacacacac cactcacacg caactgtgtg tcattgacta aggatgatgg acacacgcgc gtttcctacg gccactgtcc tgattcaggt Aggggacaca gcacctgatg 9 ttctcaggtc cagctgccaa cccccccaca taaagatttc caacccggtt gttctggaag ccctgtgact agtgggtggg agaaagcgca aagtac atac cacacacaca ttccctgcca acactcctat tcatgctgtg9 ccttcctgah gtgttcgcgg ctttcgactt ttggaggttc cgaacacaat ttgctttacc tatatgtgcc ggctgtgtct ttgagtgctg ttggtggggg, 1560 1620 1680 1740 1800 1860 1920 1980 2001 00 tatcatcctg aggagtaa gttgaatacc cagcgatg atatttgatt ggcttatc 00tgacttacag aagggctg <210> 52 <211> 1805 <212> DNA <213> Homo sapiens tt ca gc at <220> <221> <223> misc-feature promoter sequence for human DUB4.9 <400> 52 gcatctttct ccttctgatg cacagtcctc agggctgttt accgtctaay acagccggaa gcagcattac tggaaatgga. ggcttatttt tctgtttcac tccgtcagcc agtcagcgct gagcacacct tcctcccatc ctttacacct acatgttggg gacacaccca aattttggca ggcaacatct ggccttttcc tccctgcttt gggcttttct Cttttcttcg ggcccatgaa atcctcctta agaggccttg aaaatcccta aattctgtcc ccaaatgtgc ccgatcctga cactgaaaca taaacgtctc acggtataat ccc aga ca c aagccaaggg aaatcatcct gcgccgggcc Sagccaggat ctcttacttc taactgcaat acgatcgatg agggccagta cgatgttgct tttcCttgtt ccattatcac tttacatccg aaagaaacgg aatttcctgg tcaattccgc cttcattcct agggaacatg tccaccatac cgagaatcca ttaaaaatgg ccc tg aga ca tgcttttgtc atacgtatg gcacacgaag ggccaaaggt ccctgaagcc cctgttcctt gctaagccag tccactttcg aatgcctaac ggatatgcac cacgctatcc ggacctcact caaattagaa aaatattatc ctttttattt catctctagg aaacgttgat acacatgctg tgagatacgttgtttttatt ttcatcaatt ctttaataaa caaaaggtta 96/99 00 C1tagctgggat gcacgtccga aatttgggga Sacagtctact tgctttatta 00 tctccactgg M ttcgctggaa N' actgtgctaa 00 atcccagcac acacacacaa aataaggcaa catcctgagg gaatitcccag atttgattgg acttacagaa tagcgtcttt acatg accttctgag aaccgctcac tigtcatcaa ttgtgcactg tttggcaatc caggtacttt ggtCtgtttg atactatact cgtcgctgag aaacacacac tcacacggtt ctgtgtgacc agtaatttga cgatgccagg cttatcgcgc gggctgatgc ctgcaacctg ttctcaagtt tatgcagtgt ttagtctctc agtatctctt tagcttccac cactcggaca attccacgga tcattgacta aggatgatgg acacgcgccc tcctaggtaa actgtcccaa ttcaggtgtt gggacacacc acctgatgag ggccagagag cggtcccagc ttttgtttcg catgaccgtc ggggattgca caaacttcag aag agc at tt gagaatcaat tctctccttt ttctcaggtc cagctgccaa ccccacacac agatttcttc cccggttaca ctggaagtca ctgtgactcc tgggtggggt ctcgtcattt agaaaaacct tgttttctta tctcttttct tgatttcccc tgcatgtttc catgcaaaga aggctcaacg ctcattaggg agaaagcgca aagtacatac acacacaaac cctgccatgg ctcctattat tgctgtggga ttcctgaatt gttcgcggtt gaagactctc tgtgatcctt aactgccgtc ggcaaacata aaaggctttc tacaatttga cttgtcttgt tggaaaggtt aagaaaatac ctttcgactt ttggaagttC acaatcacac ctttacctaa atgtgcctat tgtgtctgtt gagtgctgat ggtgggggtg tcggaaggga gttccagtcg 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1805 <210> 53 <211> 2001 <212> DNA <213> Homo sapiens <220> <221> misc-feature <223> promoter sequence for human DUB4.10 <400> 53 agcaagcttt ggaacagttg gtgaagcccg aagaactcaa. gtggtgtttg tctccagagg gcgccggcct ccaagacgt-t aggtcctcat ccttgtattg aagagattct ccgatgtcac atgtgcaata tcctgagtgc cttgacatgc agccatacat tggagagaat gcctatcatt aactttacac acctctgcca aggcaacaag attgccaaga gtctcagcag aacacaggac 120 180 240 9 7/99 00 Ctcttgtcta tcaccgccgc agaagagtga ttggcgcaga 00 gcctccaggc ~±tagaccactg C)aagtcaaagg N0 00ggatgaagaa cgacacatca gatccaaagg ggaagtaccg aactacaccc aatcctacat agtgatggct agtcttccga gtgtgtattt gactcggttt gaaggtgaaa gaaactggaa tttttacact ccacataacg agtccaaacg aataaaggaa gaaatcaatc ccagctgcga ccgacgtggt ctgattagac gaggaaagct ccctgctcaa tgtcctctat ttatgtcaaa tagcatcact atgggaaaga agacacagac ccccgagt tg gaaattcctt taccctgcct ccatcatcct ggagtccatg gaagaacaaa acccacacgt agaagcgcgc aaactaatga acatctcagg acctctggag ctgaatatga cgtattttct tgtggctcat tgcatttgga ggttcctgaa ccggaagcgg gaaaattttc agcaaacaca tcactgggtg aagctgcatc gtttccgtgg ttcatggtcc gcccagggca gcacccaaat gctgtgctgg gctcaagaag tctgtcctga catagtgaga aggcgagcaa gacgagcact caagagcaaa cccgacgtac gaacagcaaa a a cact gg ca cacagcaaga aggggtgcac acgcaaacac ggagcccaag atgagcccgc ggactgtctg cctaccgacg ct tggggtgt gtgggacatc, agagaagaac tggacctcag acagaccgac ccacgggcat ggagtgtgtg tgtttaaaaa tctgaagcac aaatgattgt ctttctcgtc caactcaggg tccacgctga gc cagt ggt a gtcaacaggc gtgtgtcaag cgcaaggaga tggtggaaag acaaaacgaa ttgtgattca gctccctgct cactcgcttc gggctctgct* acacacacgc acacacaccc tttctgt Ctc atatgggaaa agtgtttgtg tgtaggtttg g tt t catt cg cgtggatcat ggtgctcttc gcgccctggg ttgcctgttt gtaagtcatc tattcaactg tggcatttgg agtccctgtc gggaaatggc aggtacagtg ctccgtagaa gtggagttgt taaaatggat ctacgtcctc aggcagggaa gctcaagaga agccactcag gcctgagttc tcaatcaaaa aaacctctct cctgcgaggg tgtgtgccag acacacacag acacaaacac tacaacaggg catcaagttt ttcatgatag cgtgtgaggt tcagttgttg tctcgccacc tttcttccc acttgtgctc cacggtgccc tggaagtaag aaataaattc ggaatttctg ccgcagtgag*. cccttccttt atcaaagttg ccacagaatc cacaacggac gatgccgagg ttttacatcc ccaagagccc gaccacccct gaaagcacct aacgtcagaa t acaagt gt g tcgtcgaccc agggccagga tgatctcagt acacacacat gaacaccgtc acaactggat tggggtcgtg gtgacattca aattgcaggg gtcggcatga ttgaatagtg gggctcgccg ttgctggaac gcttcccatg ctgtattgat agaaagccct ggtcatttgt a cttattgat tctctatttg accagcccca ttgggcgcaa 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2001 <210> 54 98/99 00 00 00 <211> <212> <213> <220> <221> <223> 2002 DNA Homo sapiens misc feature promoter sequence for human DUB4.11 <400> 54 cagcaagctt tgtggtgttt aaggtcctca aatgtgcaat cc tc tcgtc t cattactcct gtcaccgcct cagaagagtg cttggcgtag tgcctccagg ttagaccact agagtcgaag cggatgaaga ccgacagatc agatccaaag tggaagtacc taactacacc caatcctaca tagagatggc gagtcttccg agtgtgtatt ggactcggtt agaaggtgaa tggaacagtt gtctccagag tccttgtatt atcctgagtg atgtcctcta. cttatgtcaa ctagcatcac aatgggaaag aagacacaga cccccgagtt ggaaattcct gtacggtgcc accatcatcc aggagtccat ggaagaacaa gacccacacg cagaagcgcg taaactaatg tacatctcag aacctctgga tatgaatatg tcgtattttc atttggctca ggtgaagccc ggcgccggcc gaagagattc cc ttgacatg tgctgtgctg agc tcaagaa ttctgtcctg acacagtgag caggcgagca ggacgagcac tcaagagcaa tcccgacgta tgaacagcaa gaacactggc acacagcaag taggggtgca cacgcaaaca aggagcccaa gatgagcccg gggactgtc~t acctaccgac tcttggggtg tgtgggacat gaagaactca tccaaqacgt cccgatgtca cagccataca. gtccacgctg ggccagtggt agtcaacagg agtgtgtcaa acgcaaggag ttggtggaaa. aacaaaacga cttgtgattc agctccctgc acactcgctt agggctctgc tacacacaca cacacacacc catatgggaa gagtgtttgt gtgtaggttt itgtttcattc ,ccgtggatca atggagagaa taactttaca caggcaacaa tgtct.cagca. ggtggagttg- ataaaatgga cctacgtcct gaggcaggga agctcaagag gagccactca agcctgagtt atcaatcaaa taaacctctc ccctacgagg ttgtgtgcca cacacacaca cacacaaaca. gtacaacagg aca tcaagtt gttcatgata. gcgtgtgagg gacagttgtt ttctcgccac tgcctatcat caactctgcc aattgccaag gaacacagga tcacaacgga tgatgccgag cttttacatc accaagagcc agaccacccc ggaaagcacc caacgtcaga atacaagtgt ttcgacgacc gaggaccagg gtgatctcag cacacacaca cgaacaccgt gacaac tgga ttggggtcgt ggtgacattc taattgcagg ggtcggcacg cttgaatagt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 ggaaactgga atgcatttgg aagagaagaa cggtgctctt ctttcttccc cgggctcgcc 99/99 00 ;Z 00 gtttttacac cccacataac gagtccaaac taataaagga tgaaatcaat tccagctgcg t ccgacgtgg gctgactaga agaggaaagc accctgctca tagttcctga gccggaagca ggaaaatttt aagcaaacac ctcactgggt aaagctycat tgtttccgtq cttcatggtc tgcccagggc agcacccaaa atggacctca gacagaccga cccacgggca aggagtgtgt gtgtttaaaa ctctgaagca gaaatgattg cc t ttct cgt acaactcagg tg ggcgc cc tgg cttgcctgtt tgtaagtcat gtattcaaca atggcatttg cagtccctgt tgggaaatgg caggtacagt gctccataga gacttgtgct tcacggtgcc ctggaagtaa gaaataaatt gggaatttct cccgcagtga ccccttcctt gatcaaagtt accacagaat cttgctggaa cgcttcccat gctgtattga cagaaAgccc gggtcatttg gacttattta ttctctattt gaccaacccc cttgggagca 1500 1560 1620 1680 1740 1800 1860 1920 1980 2002