WO2007141346A2

WO2007141346A2 - Genes regulating intracellular cholesterol trafficking as targets for treatment of cholesterol-related diseases

Info

Publication number: WO2007141346A2
Application number: PCT/EP2007/055726
Authority: WO
Inventors: Sandipan Chatterjee; Kumlesh K Dev; Rainer R Kuhn; Rajeev Sivasankaran
Original assignee: Novartis Ag
Priority date: 2006-06-09
Filing date: 2007-06-11
Publication date: 2007-12-13
Also published as: GB0611463D0; WO2007141346A9; WO2007141346A3; EP2032599A2

Abstract

The present invention relates to novel genes, which regulate the intracellular cholesterol trafficking and which are involved in the development and/or progression of cholesterol- related diseases, disorders or conditions, such as neurological diseases, for example neurodegenerative conditions, e. g. Niemann-Pick type C disease. The invention also relates to the use of the said genes as novel drug targets for the development of medicaments useful to treat, prevent or ameliorate the said cholesterol-related diseases, disorders or conditions.

Description

GENES REGULATING INTRACELLULAR CHOLESTEROL TRAFFICKING AS TARGETS FOR TREATMENT OF CHOLESTEROL-RELATED DISEASES

Background of the invention

Cholesterol is highly enriched in the brain as compared to other tissues, e. g., in mammals 25 % of the total body cholesterol is found in the brain. In the normal adult brain, cholesterol is found at the highest levels in myelin, although neurons and glial cells also contain cholesterol. Failure in cholesterol dynamics in myelin-forming oligodendrocytes is a primary pathogenic cause in a number of neurological diseases, such as Alzheimer's disease, Down's syndrome, multiple sclerosis, Huntington's disease or Niemann-Pick type C disease. Cellular cholesterol is mostly found in the plasma membrane and is concentrated in detergent resistant micro-domain signaling centers, called lipid rafts. The regulation of cholesterol synthesis, trafficking and metabolism is crucial for normal physiology, where a deregulation causes a wide range of disorders, such as Tangier disease, atherosclerosis or other lipid related disorders.

The present invention relates to genes for novel proteins, which modulate the cholesterol level and/or the cholesterol trafficking inside the cell. The present invention relates also to such proteins, that modulate the cholesterol level and/or the cholesterol trafficking. A cellular luciferase assay, that measures the amount/trafficking of cholesterol/lipids inside the cell, is used according to the present invention. The present invention relates to eleven genes, that activate, and eight genes, that repress, the cholesterol/lipid levels/trafficking significantly. Thus, according to the present invention these genes represent novel targets for the therapeutic intervention in the case of a wide range of cholesterol related diseases, disorders or conditions. Detailed description of the invention

The disruption of the cholesterol metabolism and/or trafficking is a primary cause of, inter alia, the neurodegeneration in sporadic and familial Alzheimer's disease (AD), Niemann-Pick type C disease and Down's syndrome. Cholesterol regulates the phosphorylation level of Tau and, thus, may alter the cytoskeleton organization. The effect of cholesterol on oxidative reactions is suggested to regulate the membrane lipid peroxidation and fluidity. In addition, cholesterol alters the Aβ levels, which leads to changes in the synaptic plasticity. Thus, the neural cholesterol dynamics is, e. g., essential for neurotransmission, synapse function, plasticity and behavior.

Under normal conditions, cholesterol is internalized by cells through low-density lipoprotein receptor (LDL-R) mediated endocytosis. The hydrolysis of cholesterol esters associated with LDL particles to free cholesterol occurs in the late endosomal/lysosomal compartments, and the free cholesterol is then transported to the plasma membrane. Excess cholesterol from the plasma membrane is thought to traffic to the endoplasmatic reticulum (ER). The membranes of the ER harbor proteins, which serve as the cholesterol/lipid 'sensors' of the cell. These proteins are the Sterol Regulatory Element Binding Protein (SREBP), the SREBP-Cleavage Activating Protein (SCAP) and the lnsig proteins. A reduction of the sterol levels in the ER is detected by the SCAP, which then translocates SREBP to the Golgi, where the SREBP undergoes two sequential cleavage events - the first by a luminal protease, SKI-1/S1 P, which is followed by a transmembrane protease S2P, which cleaves SREBP in the transmembrane region, releasing its N-terminal fragment. The N-terminus of SREBP acts as a transcription factor, up-regulating SRE-containing genes, such as LDL-R and HMG-CoA, thus increasing cholesterol entry/synthesis and thereby restoring a normal cholesterol level. As the level of cholesterol recovers, the mechanism of up-regulation is turned off by retention of the SCAP-SREBP complex to the ER by the lnsig proteins.

The production of Aβ is dependent on SREBP signaling and is altered in site 2 processing deficient cells, where SREBP is no longer able to regulate cholesterol synthesis and turnover. Thus, APP processing and Aβ generation are dependent on cholesterol efflux, intracellular trafficking and uptake. Down's syndrome patients show a specific pattern of the SREBP activation and a sterol-independent maturation of SREBP. In Niemann-Pick type C disease, the SREBP mediated signaling is up-regulated as cholesterol does not reach the ER membrane. This causes more cholesterol uptake and synthesis via SRE-mediated up- regulation of gene expression. Due to the influence of the SREBP on various neurodegenerative diseases, the disrupted cholesterol metabolism and trafficking may be a common cascade unifying the cause of neurodegeneration in sporadic and familial Alzheimer's disease (AD), Niemann-Pick type C disease and Down's syndrome. According to the present invention, mammalian cDNA's are tested to identify novel genes, that regulate the cleavage of endogenous SREBP. This molecular based assay allows to identify both positive and negative components of the cholesterol/SREBP trafficking pathway. This information is of interest for the understanding of both the normal cholesterol pathway and cholesterol related diseases, disorders or conditions.

Luciferase constructs. Three copies of the sterol regulatory element (SRE, AAAATCACCCCACTGCAAACTCCTCCCCCTGC) from the low-density lipoprotein receptor gene promoter were subcloned upstream of a pTransLucent luciferase vector (Panomics) to create a pSRE-WT plasmid. As a control, a mutated version of this promoter was synthesized (Medigenomics, Germany) to contain four point mutations in each SRE element based on the mutational analysis conducted in

(AAAAGAACCCCTATGCAAACTCCTCCCCCTGC). AS a normalization control, a humanized Renilla gene driven by the SV-40 promoter (phRL-SV40, Promega) was used.

Plasmids and human cDNA collection. The cDNA used as internal control for the assay, namely full length SREBP-cleavage activating protein (SCAP) (Hua et al, 2006), lnsigi (Yang et al, 2002), dominant positive SCAP (DP-SCAP, Nohturfft et al, 1998)) and dominant negative SCAP (DN-SCAP) (Sakai et al, 1998) have been previously described. For the genome-wide study, approximately 10,000 full-length cDNA clones were purchased from OriGene Technologies (Rockville, MD) and prepared for screening as previously described (lourgenko et al., 2003).

Cell culture and high throughput screening. HEK 293 cells were grown in DMEM (Invitrogen) supplemented with 10% fetal bovine serum (Invitrogen) and containing 1x Penicillin- Streptomycin (Invitrogen) antibiotic. Trypsinized cells were plated in 384-well white opaque bottom plates (Nunc) at density of 2500 cells/well at 25μl per well using a Multidrop 384 (Thermo Labsystems, Vantaa, Finland) and incubated at 37⁰C in 5% CO₂. The transfection mix consisted of 70ng reporter plasmid, 0.7ng Renilla and Fugene 6 (Roche) at a ratio of 3μl Fugene to 1 μg of DNA in 5μl of Optimem (Invitrogen). The cDNA's were screened at a concentration of 120ng/well. Reverse transfection protocol was followed for the screen. The transfection mixture was added to the 384-well plates containing the cDNA clones using a FlexDrop (Perkin Elmer). Genome-wide cDNA study and luciferase assays. A reverse transfection protocol was followed for testing the 10,000 genes for their effect in the SREBP signaling assay. Trypsinized cells were added to 384-well white opaque bottom plates (Nunc), containing the cDNA clone and transfection mix, at density of 2500 cells/well at 25μl per well using a Multidrop 384 (Thermo Labsystems) and incubated at 37⁰C in 5% CO₂. The transfection mix consisted of 17.5ng reporter plasmid/well, 0.7ng Renilla/well and Fugene 6 (Roche) at a ratio of 3μl Fugene to 1 μg of DNA in 5μl of Optimem (Invitrogen). The transfection mixture was added to the 384-well plates containing the cDNA clone using a FlexDrop (Perkin Elmer). The cDNA's were screened at a concentration of 120ng/well. For cholesterol stimulation, 25- hydroxy-cholesterol (Sigma) in 0.01 % ethanol was added to cells at a concentration of 1 μg/ml, and incubated for 24 hours. Firefly and Renilla luciferase activity was measured 40 hours post transfection using the Dual Glow assay system (Promega). Plates were allowed to cool for 10 minutes before 30μl of each assay reagent was added. The plates were shaken for 10 minutes on a multi-plate shaker. Luminescence was determined using an EnVision plate reader (Perkin Elmer) with a 100 msec integration time. For luciferase assays carried out in 96-well plates, all reagents were proportionally increased 4-fold. Cells were lysed and assayed 15 hours post-transfection.

Data Analysis. Results from the assay were analyzed using Spotfire Decisionsite software and Microsoft Excel.

Optimization of the SERBP cleavage assay. The SREBP cleavage assay used has been described (Hua et al., 1996). In brief, the assay is based on the cleavage of endogenous SREBP that activates the expression of a luciferase gene, by binding to a sterol regulatory element promoter present upstream of the luciferase gene. The assay was optimized by a series of steps. First, in order to use an optimal reporter construct three SRE elements were subcloned and tested in a number of Luciferase vectors including, pGL3-Basic and pTransLucent. The pTransLucent displayed a higher Luciferase level and less signal to noise ratio in a 384-well format and was hence chosen in future experiments. In general, we observed a correlation between the amount of reporter vector transfected and luciferase signals. For the screen, the amount of reporter vector used was 17.5ng per 384 well. Second, two mammalian cell lines, HEK293 and HeLa were tested for cell line of choice. HEK293 cell line showed lower assay variability and gave higher luciferase signals as well as fold difference and was hence chosen for the screen. Third, a mutant SRE promoter (Briggs et al., 1993) was generated to prove specificity to our experiments. This promoter is totally inactive in our assay. Fourth, for stimulation with 25-OH cholesterol, a dose response curve for both cholesterol concentrations as well as time of incubation was performed. This result showed that incubating cells with 1 μg/ml 25-OH cholesterol for 24 hours was sufficient to repress the assay as efficiently as using 5μg/ml 25-OH cholesterol and hence the lower concentration was used for further studies.

SCAP, lnsig and Cholesterol regulate SREBP-cleavage. To determine the effects of SCAP and lnsig overexpression on SERBP cleavage under basal conditions we co-transfected them with wildtype SRE promoter and measured changes in luciferase levels. We note an approximate three and a half fold activation or repression of basal levels of luciferase activity in the presence of SCAP or lnsig, respectively. In contrast, we find the mutant SRE promoter to be inactive and not influenced by the over-expression of SCAP or lnsig. Next, we find that SREBP cleavage is susceptible to high cholesterol (1 μg/ml 25-OH cholesterol) levels where cleavage of SREBP significantly reduced. These low luciferase levels can be 'rescued' by the over-expression of positive components of the assay such as wild-type SCAP or a dominant- positive form of SCAP. Under such conditions of low luciferase activity we find no further 'inhibitory' effects of lnsig. There are downstream SREBP cleavage events following the overexpression of SCAP as well as effects of cholesterol on SREBP cleavage.

Identification of Novel Genes Regulating SREBP cleavage. Having determined the signal-to- noise ratio of the SERBP cleavage assay, we made use of the sufficiently large fold difference under basal conditions to identify novel activators and repressors of SREBP cleavage and/or intracellular cholesterol trafficking. To this end, a collection of 10,000 full length human cDNA's were screened using a gene-by-gene unbiased assay. The assay was conducted in duplicate so that the data could be subjected to 2-dimentional normalization; data normalizing with respect to Renilla levels as well as for well-to-well variation. A scatter plot for the primary screen was obtained by plotting the 2D normalized luciferase value for a clone in the first duplicate against that obtained in the second duplicate. The clones lying at the extremities displaying the most activity were subseguently selected and further validated.

A total of 88 activators and 88 repressors were identified from the clone collection based on their ability to activate or inhibit luciferase levels more than 2-fold and were retested for their effects in the SERBP-cleavage assay. Each clone was assayed in triplicate for all the subseguent follow up experiments. The first fist of these experiments was to confirm the behavior of each clone under identical conditions as that used for the original gene-by-gene unbiased assay. The scatter plot of the re-screen shows the points lie along a straight line indicating internal consistency of the employed experimental conditions. Furthermore, we see that the activators show good separation from the repressors, another indication that the primary screen was successful. Activator clones showing no discrimination from the repressors clones were removed from further analysis. Genes at the extremities were chosen for further analysis as they activate or suppress SREBP cleavage significantly.

We next utilized the mutated SRE promoter in front of the Luciferase gene to identify nonspecific activators and repressors of Luciferase. When compared to the internal controls, we see that there are a number of genes that either activate or repress the SRE promoter, as found at the extremities of the scatter plot. These genes were discarded as being false positives. Genes that did not activate the mutant SRE were deemed as candidates genes that regulate SERBP-cleavage. Thus starting from 176 clones this primary analysis left us with 28 activators and 40 repressors that did not activate the mutant SRE promoter and showed good activity with the wild-type SRE promoter.

Over expression of human SREBF1 activates the SRE promoter under high cholesterol conditions. To understand further the mechanism of action of candidate genes, we tested the activators in the presence of excess cholesterol and asked the question whether, like SCAP and DP-SCAP, the isolated candidates can overcome repressed luciferase levels. Under conditions of high cholesterol where the SREBP-cleavage assay is inhibited we see that the majority of the genes are clustered at the bottom corner of the scatter plot. We found that overexpression of the Sterol Regulatory Element Binding Factor 1 (SREBF1 ), the human homologue of SREBP, was the only clone that was able to activate luciferase signals as efficiently as SCAP or DP-SCAP. It is likely that the over expression of SREBF1 can overcome the inhibitory effects of lnsig (under high cholesterol conditions) and results in the generation of an N-terminus of SREBF1 that acts as a transcription factor, up-regulating SRE dependent luciferase activity. The identification of SREBF1 as a positive hit in our gene-by- gene unbiased assay indicates the success of this screen and also suggests that in the human cDNA's we tested, there are no novel genes that are as potent as SREBF1 or SCAP in activating the assay. Hence, we conclude that the activators that we have identified will likely be modulators and not effectors of this assay.

Novel mechanisms regulating Insiq. To further define a mechanism of action of the activators, we examined how the activator genes behaved under the conditions of lnsig over- expression. It is known that overexpression of lnsigi inhibits SREBP cleavage, and the over- expression of SCAP under such conditions can overcome lnsig mediated repression of SREBP cleavage. We hence decided to apply a similar mechanistic test for the activators identified in this screen. As positive controls, we find that over-expression of SCAP overcomes lnsig over-expression as expected, and DP-SCAP which lacks the lnsig interaction domain is not inhibited by lnsig. Under these conditions, over-expression of SREBF1 was also able to overcome lnsig and increase luciferase levels, similar to that seen under high cholesterol conditions. We have now identified eleven novel genes can activate the Insig-repressed luciferase levels to a greater extent than SCAP. These genes include BIN1 , HKR3, KLF11 , HMG3, FLJ25477, MBP, NCAM1 , PLCB1 , PODXL2, RAP2B and SNX8 (Table 1 ).

Table 1 : List of novel SREBP-cleavage activators.

Abbreviation Full Name Function Genebank Refs

No.

BIN1 Bridging integrator c-Myc interacting protein, binds NM_139351 Kajiho et al.,

1 clathrin and plays a role in 2003; Ramjaun synaptic vesicle endocytosis and McPherson,

1998; Sakamuro et al., 1996;

Sarret et al.,

2004

HKR3 GLI-Kruppel family The GLI-Kruppel family of NM_005341 Maris et al., member HKR3 transcription factors are know to 1997; Ruppert et play a role in developmental al., 1988 regulation of gene expression and have also been implicated in the development of some cancers

HMG3 High-mobility group DNA binding proteins that NM 005342 Vaccari et al., box 3 regulate transcription 1998.

FLJ25477 Hypothetical NM 152704 protein

MBP Myelin basic Major component of the myelin XM_117096 Pribyl et al., 1993 protein sheets and is required for proper maintenance of oligodendrocytes and neurons

NCAM 1 Neural cell Cell adhesion, neurite outgrowth XM _041415 Lanier et al., adhesion molecule and proper spatial organization of 1991. 1 the neurons

PLCB1 Phospholipase C, Signal transduction activity by the NM _015192 Caricasole et al., beta 1 production of secondary 2000; Manzoli et messengers diacylglycerol and al., 2005 inositol triphosphates

RAP2B RAP2B, member of RAS family of oncogenes and is NM _002886 Holtta-Vuori et RAS oncogene thus involved in GTPase al., 2002; Narita family mediated signal transduction et al., 2005

SNX8 Sorting nexin 8 Intracellular vesicular transport NM _013321 Worby and

Dixon, 2002

KLF11 Krueppel-like factor Transcription factor NM _003597 {Cook, 1998 #70}

1 1

PODXL2 Podocalyxin-like 2 NM 015720 Sassetti et al., Bridging integrator 1 (BIN1 ) is a c-Myc interacting protein, binds clathrin and plays a role in synaptic vesicle endocytosis. The GLI-Krueppel like protein HKR3 is a Zn-finger protein belonging to the GLI family of transcription factors. The GLI-Kruppel family of transcription factors are know to play a role in developmental regulation of gene expression and have also been implicated in the development of cancers. In addition, some Krueppel like factors (KLF1 1 and KLF13) have been shown to play a role in the modulation of genes via the SREBP promoter. The identification of KLF1 1 in our screen is another positive hit of our assay thus emphasizing that this assay can be used as a tool in the identification of novel SREBP pathway regulators. The high-mobility group family of proteins are DNA binding proteins that regulate transcription. HMGB1 is known to interact with SREBPs. HMG3 hence might represent a novel SREBP interacting DNA binding protein. FLJ25477 is a protein of unknown function. Sequence analysis of this protein does not throw light on its possible function. However, this gene activated the SREBP assay to the largest extent and hence its mechanism of action could be interesting. Myelin basic protein (MBP) is a major component of the myelin sheets and is required for proper maintenance of oligodendrocytes and neurons. Interestingly, neurons from NPC mutant mice also display a demyelinating phenotype. Another neuronal specific gene to come out of this screen is neural cell adhesion molecule 1 (NCAM1 ). NCAM is incolved in cell adhesion, neurite outgrowth and proper spatial organization of the neurons. Phospholipase C, beta 1 (PLCB1 ) is involved in the signal transduction activity by the production of secondary messengers diacylglycerol and inositol triphosphates (IP3). PLCB1 also plays a role in lipid metabolism. RAP2B is a member of the RAS family of oncogenes and is thus involved in GTPase mediated signal transduction. Members of the RAB/RAS family have been shown to play a role in the trafficking of LDL-cholesterol and RAP2B could thus represent a novel component of this machinery. Sorting nexins are proteins that are involved in various stages of intracellular vesicular transport. SNX8 could thus represent a novel component of the trafficking machinery.

Novel genes acting at the level of or downstream of SCAP. The repressors isolated were examined under conditions of SCAP over-expression to identify genes that behave similarly to Insig, a known negative regulator of this pathway. It is known that activation of SREBP cleavage by overexpression of SCAP can be reversed by co-overexpression of Insig. In this screen, we have found eight genes that can repress SCAP mediated activation of SREBP

cleavage as efficiently as Insig. These include BMP1 , BANP, DDX28, LTBR, MASP2, NAGLU, SORCS1 and TRHDE (Table 2).

Table 2: List of novel SREBP-cleavage repressors.

Abbreviation Full Name Function Genebank References

No.

BMP1 Bone morphogenetic Belongs to the Tolloid like family of NM_006128 Gonzalez et protein 1 metal loproteases and is important al., 2005 for bone formation

BANP BTG3 associated Negative regulation of cell cycle NM_079837 Birot et al., nuclear protein 2000

DDX28 DEAD box Mitochondrial and nuclear protein NM_018380 Valgardsdottir polypeptide 28 that can bind DNA and has et al., 2001 helicase activity

LTBR Lymphotoxin beta Can associate with TRAFs and is NM_002342 Nakano et al., receptor thought to mediate apoptosis 1996; Wu et through interaction with TRAFs al., 1999

MASP2 Mannan-binding lectin Serum protease that plays a role NM_139208 Thiel et al., serine peptidase 2 in activation of the complement 1997 system

NAGLU N- Lysosomal enzyme and is involved NM_000263 Weber et al., acetylglucosaminidas in the degradation of heparin 2001 e, alpha sulfate

SORCS1 Sortilin-related VSPIO Type I membrane protein involved NM_052918 Hermey et al., domain containing in intracellular sorting and is 2003; receptor 1 localized to neurons Hermey et al.,

2001

TRHDE Thyrotropin-releasing Type Il membrane protein that NM_013381 Schomburg et hormone degrading specifically inactivates TRH after al., 1999 enzyme its release

Bone morphogenetic protein 1 (BMP1 ) belongs to the Tolloid like family of metalloproteases and is important for bone formation. BTG3 associated nuclear protein (BANP) was found in a yeast two-hybrid system to identify BTG3 interacting proteins. The BTG3 family of proteins have not been well characterized but are thought to play a role in the negative regulation of cell cycle. The DEAD box polypeptide 28 (DDX28) is a mitochondrial and nuclear protein that can bind DNA and has helicase activity. The lymphotoxin beta receptor (LTBR) is a type I membrane protein that can associate with TRAFs and is thought to mediate apoptosis through interaction with TRAFs. Mannan-binding lectin serine peptidase 2 (MASP2) is a serum protease that plays a role in activation of the complement system. N- acetylglucosaminidase, alpha (NAGLU) is a lysosomal enzyme and is involved in the degradation of heparin sulfate. Loss of NAGLU is the primary cause of Sanfilippo syndrome type B, a lysosomal storage disease. This is interesting as Niemann-Pick type-C disease is also a lysosomal storage disease. The sortilin-related VSP10 domain containing receptor 1 (SORCS1 ) is a type I membrane protein involved in intracellular sorting and is localized to neurons. Thyrotropin-releasing hormone degrading enzyme (TRHDE) is a type Il membrane protein and as the name suggests, specifically inactivates TRH after its release.

We have identified a number of genes which show a specific effect in the SREBP-cleavage assay. In addition, the activators were tested for their ability to overcome repressed luciferase levels as a result of either high cholesterol levels or lnsig over-expression, while the repressors were tested for their ability to overcome high luciferase levels as a result of SCAP over-expression. We show that 12 activators can activate the assay significantly stronger than SCAP in the presence of lnsig over-expression and 8 repressors that suppress the assay as efficiently as lnsig, under the conditions of SCAP co-overexpression. These genes comprise of a variety of proteins with different functions and mechanisms of action.

Disrupted cholesterol metabolism and trafficking is a primary cause of neurodegeneration and/or demyelination in sporadic and familial Alzheimer's disease (AD), Down syndrome, Multiple Sclerosis, Huntington's disease and Niemann-Pick type C disease. A deregulation of cholesterol also causes Tangier disease, atherosclerosis and other lipid related disorders, since many of the genes we identified are receptors or enzymes, these proteins that can be easily targeted for regulation and thus represent potential drug targets in cholesterol related disorders.

More particularly the invention relates to the following sequences of genes and proteins and to the use thereof in medicine, e. g., as drug targets for the development of medicaments for, especially neurodegenerative, diseases as described hereinabove.

LOCUS NM_139351 2075 bp mRNA linear PRI 06-NOV-

2005 DEFINITION Homo sapiens bridging integrator 1 (BINl), transcript variant 10, mRNA.

ACCESSION NM_139351

VERSION NM_139351.1 GI:21536416 KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhim;

Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 2075)

AUTHORS Pineda-Lucena, A. , Ho, C. S., Mao, D. Y., Sheng,Y., Laister, R. C . ,

Muhandiram, R. , Lu, Y., Seet,B.T., Katz,S., Szyperski, T . , Penn, L. Z . and Arrowsmith, C .H.

TITLE A structure-based model of the c-Myc/Binl protein interaction shows alternative splicing of Binl and c-Myc phosphorylation are key binding determinants

JOURNAL J. MoI. Biol. 351 (1), 182-194 (2005) PUBMED 15992821 REMARK GeneRIF: tumor-specific isoforms of Binl are precluded from interaction with c-Myc through an intramolecular polyproline-

SH3 domain interaction. Furthermore, c-Myc/Binl interaction can be inhibited by phosphorylation of c-Myc at Ser62.

REFERENCE 2 (bases 1 to 2075) AUTHORS Ko]iraa,C, Hashimoto, A. , Yabuta,I., Hirose,M., Hashimoto, S .,

Kanaho,Y., Sumimoto,H., Ikegami,T. and Sabe,H.

TITLE Regulation of Binl SH3 domain binding by phosphoinositides JOURNAL EMBO J. 23 (22), 4413-4422 (2004) PUBMED 15483625 REMARK GeneRIF: Phosphoinositides regulate BINl SH3 domain binding. REFERENCE 3 (bases 1 to 2075) AUTHORS Beausoleil, S .A. , Jedrychowski, M. , Schwartz, D., Elias, J.E . , Villen,J., Li, J., Conn, M.A., Cantley,L.C. and Gygi,S.P.

TITLE Large-scale characterization of HeLa cell nuclear phosphoproteins

JOURNAL Proc. Natl. Acad. Sci. U.S.A. 101 (33), 12130-12135 (2004)

PUBMED 15302935

REFERENCE 4 (bases 1 to 2075)

AUTHORS Ziegelbauer, J. , Wei, J. and T]ian,R.

TITLE Myc-interacting protein 1 target gene profile: a link to microtubules, extracellular signal-regulated kinase, and cell growth

JOURNAL Proc. Natl. Acad. Sci. U.S.A. 101 (2), 458-463 (2004) PUBMED 14704274 REMARK GeneRIF: role in activating various target genes after induction with the microtubule disrupting agent T113242

REFERENCE 5 (bases 1 to 2075)

AUTHORS Kajiho, H. , Saito,K., Tsujita, K. , Kontani,K., Araki,Y.,

Kurosu, H. and Katada,T.

TITLE RIN3 : a novel Rab5 GEF interacting with amphiphysin II involved in the early endocytic pathway

JOURNAL J. Cell. Sci. 116 (PT 20), 4159-4168 (2003)

PUBMED 12972505

REFERENCE 6 (bases 1 to 2075) AUTHORS Muller,A.J., Baker, J. F., DuHadaway, J. B . , Ge, K., Farmer, G., Donover, P . S . , Meade,R., Reid, C., Grzanna,R., Roach, A. H., Shah, N.,

Soler,A.P. and Prendergast , G . C .

TITLE Targeted disruption of the murine Binl/Amphiphysin II gene does not disable endocytosis but results in embryonic cardiomyopathy with aberrant myofibril formation

JOURNAL MoI. Cell. Biol. 23 (12), 4295-4306 (2003) PUBMED 12773571 REMARK GeneRIF: Studies in mouse indicate that Binl is dispensable for endocytosis but essential for appropriate cardiac development.

REFERENCE 7 (bases 1 to 2075) AUTHORS Leprince, C. , Le Scolan,E., Meunier,B., Fraisier,V., Brandon, N., De

Gunzburg,J. and Camonis, J.

TITLE Sorting nexin 4 and amphiphysin 2, a new partnership between endocytosis and intracellular trafficking

JOURNAL J. Cell. Sci. 116 (PT 10), 1937-1948 (2003) PUBMED 12668730 REMARK GeneRIF: Sorting nexin 4 and amphiphysin 2 have roles in endocytosis and intracellular trafficking

REFERENCE 8 (bases 1 to 2075) AUTHORS DuHadaway, J. B. , Lynch, F. J., Bπsbay,S., Bueso-Ramos, C . , Troncoso,P., McDonnell, T. and Prendergast , G . C .

TITLE Immunohistochemical analysis of Binl /Amphiphysin II in human tissues: diverse sites of nuclear expression and losses in prostate cancer

JOURNAL J. Cell. Biochem. 88 (3), 635-642 (2003) PUBMED 12532338 REMARK GeneRIF: Results document the extent of expression of nuclear Binl isoforms, which exhibit cancer suppression and proapoptotic activity in human cells.

REFERENCE 9 (bases 1 to 2075) AUTHORS Messina, S., Onofπ,F., Bongiorno-Borbone, L . , Giovedi, S . ,

Valtorta,F., Girault, J.A. and Benfenati, F .

TITLE Specific interactions of neuronal focal adhesion kinase isoforms with Src kinases and amphiphysin

JOURNAL J. Neurochem. 84 (2), 253-265 (2003)

PUBMED 12558988

REFERENCE 10 (bases 1 to 2075)

AUTHORS Lee, E., Marcucci, M. , Darnell, L., Pypaert,M., Weisz,0.A., Ochoa,G.C, Farsad,K., Wenk,M.R. and De Camilla., P .

TITLE Amphiphysin 2 (Binl) and T-tubule biogenesis in muscle JOURNAL Science 297 (5584), 1193-1196 (2002) PUBMED 12183633 REMARK GeneRIF: findings support a role of the bilayer-deforming properties of amphiphysin at T-tubules and, more generally, a physiological role of amphiphysin in membrane deformation

REFERENCE 11 (bases 1 to 2075) AUTHORS Kim, K. C, Kim, T. S., Kang,K.H. and Choi, K. H. TITLE Amphiphysin IIb-1, a novel splicing variant of amphiphysin II, regulates p73beta function through protein-protein interactions

JOURNAL Oncogene 20 (46), 6689-6699 (2001)

PUBMED 11709703

REFERENCE 12 (bases 1 to 2075)

AUTHORS Ramjaun, A. R. , Angers, A., Legendre-Guillemin, V. , Tong,X.K. and McPherson, P . S . TITLE Endophilin regulates JNK activation through its interaction with the germinal center kinase-like kinase

JOURNAL J. Biol. Chem. 276 (31), 28913-28919 (2001)

PUBMED 11384986

REFERENCE 13 (bases 1 to 2075)

AUTHORS Bara]on,I., Rumio,C, Donetti,E., Imberti,A., Bπvio,M. and

Castano, P .

TITLE Pattern of expression of c-Myc, Max and Binl in human anagen hair follicles

JOURNAL Br. J. Dermatol. 144 (6), 1193-1203 (2001)

PUBMED 11422041

REFERENCE 14 (bases 1 to 2075)

AUTHORS DuHadaway, J. B. , Sakamuro,D., Ewert,D.L. and Prendergast , G . C .

TITLE Binl mediates apoptosis by c-Myc in transformed primary cells

JOURNAL Cancer Res. 61 (7), 3151-3156 (2001)

PUBMED 11306501

REFERENCE 15 (bases 1 to 2075)

AUTHORS Elliott, K., Ge, K., Du, W. and Prendergast , G . C .

TITLE The c-Myc-interacting adaptor protein Binl activates a caspase-independent cell death program

JOURNAL Oncogene 19 (41), 4669-4684 (2000)

PUBMED 11032017

REFERENCE 16 (bases 1 to 2075)

AUTHORS Onofπ,F., Giovedi,S., Kao,H.T., Valtorta,F., Bongiorno Borbone, L. ,

De Camilla., P . , Greengard,P. and Benfenati,F.

TITLE Specificity of the binding of synapsin I to Src homology 3 domains

JOURNAL J. Biol. Chem. 275 (38), 29857-29867 (2000)

PUBMED 10899172

REFERENCE 17 (bases 1 to 2075)

AUTHORS Lee, C, Kim, S. R., Chung, J. K., Frohman, M.A. , Kilimann, M. W. and

Rhee,S.G.

TITLE Inhibition of phospholipase D by amphiphysins

JOURNAL J. Biol. Chem. 275 (25), 18751-18758 (2000)

PUBMED 10764771

REFERENCE 18 (bases 1 to 2075)

AUTHORS Ramjaun, A. R. , Philie, J. , de Heuvel,E. and McPherson, P . S .

TITLE The N terminus of amphiphysin II mediates dimeπzation and plasma membrane targeting

JOURNAL J. Biol. Chem. 274 (28), 19785-19791 (1999)

PUBMED 10391921

REFERENCE 19 (bases 1 to 2075)

AUTHORS Wixler,V., Laplantine, E . , Geerts,D., Sonnenberg, A. , Petersohn, D » ,

Eckes,B., Paulsson,M. and Aumailley,M.

TITLE Identification of novel interaction partners for the conserved membrane proximal region of alpha-integπn cytoplasmic domains

JOURNAL FEBS Lett. 445 (2-3), 351-355 (1999)

PUBMED 10094488

REFERENCE 20 (bases 1 to 2075)

AUTHORS Ramjaun, A. R. and McPherson, P . S .

TITLE Multiple amphiphysin II splice variants display differential clathrin binding: identification of two distinct clathπn- binding sites

JOURNAL J. Neurochem. 70 (6), 2369-2376 (1998)

PUBMED 9603201

REFERENCE 21 (bases 1 to 2075) AUTHORS Wechsler-Reya, R. J. , Elliott, K. J. and Prendergast , G . C . TITLE A role for the putative tumor suppressor Binl in muscle cell differentiation

JOURNAL MoI. Cell. Biol. 18 (1), 566-575 (1998) PUBMED 9418903 REMARK GeneRIF: Binl plays a crucial role in terminal differentiation of myoblasts; associated with induction of a muscle-specific splice isoform and subcellular relocalization .

REFERENCE 22 (bases 1 to 2075) AUTHORS Wechsler-Reya, R. , Sakamuro,D., Zhang, J., Duhadaway,J. and

Prendergast, G. C .

TITLE Structural analysis of the human BINl gene. Evidence for tissue-specific transcriptional regulation and alternate RNA splicing

JOURNAL J. Biol. Chem. 272 (50), 31453-31458 (1997) PUBMED 9395479 REMARK GeneRIF: Several tissue-specific splice isoforms of the human Binl gene are found only in brain or muscle.

REFERENCE 23 (bases 1 to 2075) AUTHORS Micheva, K. D. , Kay, B. K. and McPherson, P . S . TITLE Synapto^amn forms two separate complexes in the nerve terminal .

Interactions with endophilin and amphiphysin

JOURNAL J. Biol. Chem. 272 (43), 27239-27245 (1997)

PUBMED 9341169

REFERENCE 24 (bases 1 to 2075)

AUTHORS Wigge,P., Kohler,K., Vallis,Y., Doyle, CA. , Owen, D., Hunt, S. P. and

McMahon,H.T.

TITLE Amphiphysin heterodimers : potential role in clathrin-mediated endocytosis

JOURNAL MoI. Biol. Cell 8 (10), 2003-2015 (1997)

PUBMED 9348539

REFERENCE 25 (bases 1 to 2075)

AUTHORS Micheva, K. D. , Ramjaun, A. R. , Kay, B. K. and McPherson, P . S .

TITLE SH3 domain-dependent interactions of endophilin with amphiphysin

JOURNAL FEBS Lett. 414 (2), 308-312 (1997)

PUBMED 9315708

REFERENCE 26 (bases 1 to 2075)

AUTHORS McMahon, H. T. , Wigge,P. and Smith, C.

TITLE Clathrin interacts specifically with amphiphysin and is displaced by dynamin

JOURNAL FEBS Lett. 413 (2), 319-322 (1997)

PUBMED 9280305

REFERENCE 27 (bases 1 to 2075)

AUTHORS Tsutsui,K., Maeda,Y., Tsutsui,K., Seki,S. and Tokunaga,A.

TITLE cDNA cloning of a novel amphiphysin isoform and tissue-specific expression of its multiple splice variants

JOURNAL Biochem. Biophys. Res. Commun. 236 (1), 178-183 (1997)

PUBMED 9223448

REFERENCE 28 (bases 1 to 2075)

AUTHORS Ram]aun, A. R. , Micheva, K. D ., Bouchelet,I. and McPherson, P . S .

TITLE Identification and characterization of a nerve terminal- enriched amphiphysin isoform

JOURNAL J. Biol. Chem. 272 (26), 16700-16706 (1997) PUBMED 9195986 REFERENCE 29 (bases 1 to 2075)

AUTHORS Butler, M. H., David, C, Ochoa,G.C, Freyberg,Z., Darnell, L.,

Grabs, D., Cremona, 0. and De Camilli, P . TITLE Amphiphysin II (SH3P9; BINl), a member of the amphiphysin/Rvs family, is concentrated in the cortical cytomatrix of axon initial segments and nodes of ranvier in brain and around T tubules in skeletal muscle JOURNAL J. Cell Biol. 137 (6), 1355-1367 (1997)

PUBMED 9182667 REFERENCE 30 (bases 1 to 2075)

AUTHORS Sakamuro,D., Elliott , K. J. , Wechsler-Reya, R. and Prendergast, G. C .

TITLE BINl is a novel MYC-interacting protein with features of a tumour suppressor JOURNAL Nat. Genet. 14 (1), 69-77 (1996)

PUBMED 8782822 REMARK GeneRIF: A nucleocytosolic myc-interacting isoform of Binl has properties of a tumor suppressor. REFERENCE 31 (bases 1 to 2075)

AUTHORS Negorev,D., Riethman,H., Wechsler-Reya, R. , Sakamuro,D.,

Prendergast, G. C . and Simon, D.

TITLE The Binl gene localizes to human chromosome 2ql4 by PCR analysis of somatic cell hybrids and fluorescence in situ hybridization JOURNAL Genomics 33 (2), 329-331 (1996)

PUBMED 8725406

COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from AF068915.1 and AL713697.1.

Summary: This gene encodes several isoforms of a nucleocytoplasmic adaptor protein, one of which was initially identified as a

MYC-interacting protein with features of a tumor suppressor.

Isoforms that are expressed in the central nervous system may be involved in synaptic vesicle endocytosis and may interact with dynamm, synapto^amn, endophilin, and clathrin. Isoforms that are expressed in muscle and ubiquitously expressed isoforms localize to the cytoplasm and nucleus and activate a caspase-independent apoptotic process. Studies in mouse suggest that this gene plays an important role in cardiac muscle development. Alternate splicing of the gene results in ten transcript variants encoding different isoforms. Aberrant splice variants expressed in tumor cell lines have also been described.

Transcript Variant: This variant (10) lacks six in-frame exons in the coding region, compared to variant 1. Isoform 10, also called

BINl-10-13, is shorter than isoform 1 and is ubiquitously expressed.

COMPLETENESS: full length. FEATURES Location/Qualifiers source 1..2075 /organism="Homo sapiens"

/mol_type="mRNA"

/db_xref="taxon: 9606"

/chromosome="2"

/map="2ql4" gene 1..2075

/gene="BINl"

/note="synonyms: AMPH2, AMPHL, SH3P9, MGC10367,

DKFZp547F068"

/db_xref="GeneID:274"

/db_xref="HGNC: 1052"

/db_xref="HPRD:HPRD_03150"

/db_xref="MIM: 601248" raise feature 1

/gene="BINl"

/note="5 ' -most transcription initiation site is undetermined" misc_feature 189

/gene="BINl"

/note="alternate transcription initiation site"

CDS 346..1575

/gene="BINl"

/go_component="actin cytoskeleton [pmid 9182667]; cytoplasm; nucleus"

/go_function="protein binding"

/go_process="cell differentiation; cell proliferation

[pmid 8782822]; negative regulation of progression through cell cycle; regulation of endocytosis"

/note="isoform 10 is encoded by transcript variant 10; amphiphysin-like; amphiphysin II; box dependant MYC interacting protein 1"

/codon_start=l

/product= "bπdging integrator 1 i so form 10 "

/protein_id="NP_647601.1"

/db_xref="GI:21536417"

/db_xref="CCDS:CCDS2143.1"

/db_xref="GeneID:274"

/db_xref="HGNC: 1052"

/db_xref="HPRD:HPRD_03150"

/db_xref="MIM: 601248"

/translation="MAEMGSKGVTAGKIASNVQKKLTRAQEKVLQKLGKADETKDEQF

EQCVQNFNKQLTEGTRLQKDLRTYLASVKAMHEASKKLNECLQEVYEPDWPGRDEANK IAENNDLLWMDYHQKLVDQALLTMDTYLGQFPDIKSRIAKRGRKLVDYDSARHHYESL QTAKKKDEAKIAKAEEELIKAQKVFEEMNVDLQEELPSLWNSRVGFYVNTFQSIAGLE ENFHKEMSKLNQNLNDVLVGLEKQHGSNTFTVKAQPSDNAPAKGNKSPSPPDGSPAAT PEIRVNHEPEPAGGATPGATLPKSPSQSSLPAVWETFPATVNGTVEGGSGAGRLDLP

PGFMFKVQAQHDYTATDTDELQLKAGDWLVIPFQNPEEQDEGWLMGVKESDWNQHKE

LEKCRGVFPENFTERVP"

STS 514..651

/gene="BINl"

/standard_name="PMC156129P2"

/db_xref="UmSTS:271364" STS 1540..1699

/gene="BINl" /db_xre f= " Um STS : 150648 "

STS 1768 . . 2012

/gene= " BINl "

/ standard_name= " STS-AA039724 "

/db_xre f= " Um STS : 77577 " polyA_s ite 2069

/gene= " BINl "

/ experiment= " expeπraental evidence , no addit ional details recorded"

ORIGIN

1 cgcgcccctc cctcctcgcg gacctggcgg tgccggcgcc cggagtggcc ctttaaaagg

61 cagcttattg tccggagggg gcgggcgggg ggcgccgacc gcggcctgag gcccggcccc

121 tcccctctcc ctccctctgt ccccgcgtcg ctcgctggct agctcgctgg ctcgctcgcc

181 cgtccggcgc acgctccgcc tccgtcagtt ggctccgctg tcgggtgcgc ggcgtggagc

241 ggcagccggt ctggacgcgc ggccggggct gggggctggg agcgcggcgc gcaagatctc

301 cccgcgcgag agcggcccct gccaccgggc gaggcctgcg ccgcgatggc agagatgggc

361 agtaaagggg tgacggcggg aaagatcgcc agcaacgtgc agaagaagct cacccgcgcg

421 caggagaagg ttctccagaa gctggggaag gcagatgaga ccaaggatga gcagtttgag

481 cagtgcgtcc agaatttcaa caagcagctg acggagggca cccggctgca gaaggatctc

541 cggacctacc tggcctccgt caaagccatg cacgaggctt ccaagaagct gaatgagtgt

601 ctgcaggagg tgtatgagcc cgattggccc ggcagggatg aggcaaacaa gatcgcagag

661 aacaacgacc tgctgtggat ggattaccac cagaagctgg tggaccaggc gctgctgacc

721 atggacacgt acctgggcca gttccccgac atcaagtcac gcattgccaa gcgggggcgc

781 aagctggtgg actacgacag tgcccggcac cactacgagt cccttcaaac tgccaaaaag

841 aaggatgaag ccaaaattgc caaggccgag gaggagctca tcaaagccca gaaggtgttt

901 gaggagatga atgtggatct gcaggaggag ctgccgtccc tgtggaacag ccgcgtaggt

961 ttctacgtca acacgttcca gagcatcgcg ggcctggagg aaaacttcca caaggagatg

1021 agcaagctca accagaacct caatgatgtg ctggtcggcc tggagaagca acacgggagc

1081 aacaccttca cggtcaaggc ccagcccagt gacaacgcgc ctgcaaaagg gaacaagagc

1141 ccttcgcctc cagatggctc ccctgccgcc acccccgaga tcagagtcaa ccacgagcca

1201 gagccggccg gcggggccac gcccggggcc accctcccca agtccccatc tcagagctct

1261 cttcctgctg tcgtggtgga gaccttccca gcaactgtga atggcaccgt ggagggcggc

1321 agtggggccg ggcgcttgga cctgccccca ggtttcatgt tcaaggtaca ggcccagcac

1381 gactacacgg ccactgacac agacgagctg cagctcaagg ctggtgatgt ggtgctggtg

1441 atccccttcc agaaccctga agagcaggat gaaggctggc tcatgggcgt gaaggagagc

1501 gactggaacc agcacaagga gctggagaag tgccgtggcg tcttccccga gaacttcact

1561 gagagggtcc catgacggcg gggcccaggc agcctccggg cgtgtgaaga acacctcctc

1621 ccgaaaaatg tgtggttctt ttttttgttt tgttttcgtt tttcatcttt tgaagagcaa

1681 agggaaatca agaggagacc cccaggcaga ggggcgttct cccaaagatt aggtcgtttt

1741 ccaaagagcc gcgtcccggc aagtccggcg gaattcacca gtgttcctga agctgctgtg

1801 tcctctagtt gagtttctgg cgcccctgcc tgtgcccgca tgtgtgcctg gccgcagggc

1861 ggggctgggg gctgccgagc caccatgctt gcctgaagct tcggccgcgc cacccgggca

1921 agggtcctct tttcctggca gctgctgtgg gtggggccca gacaccagcc tagcctggct

1981 ctgccccgca gacggtctgt gtgctgtttg aaaataaatc ttagtgttca aaacaaaatg

2041 aaacaaaaaa aaaatgataa aaactctcaa aaaaa

//

LOCUS NM_005341 2289 bp mRNA linear PRI 23-SEP-

2005

DEFINITION Homo sapiens GLI-Kruppel family member HKR3 (HKR3), mRNA. ACCESSION NM_005341 VERSION NM_005341.1 GI:4885418 KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Cramata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 2289)

AUTHORS Mans, J.M., Jensen, S.J. , Sulman,E.P., Beltinger, C . P . , Gates, K.,

Allen, C, Biegel, J.A. , Brodeur,G.M. and White, P. S.

TITLE Cloning, chromosomal localization, physical mapping, and genomic characterization of HKR3 JOURNAL Genomics 35 (2), 289-298 (1996)

PUBMED 8661141 REFERENCE 2 (bases 1 to 2289)

AUTHORS Sugawara,M., Scholl,T., Ponath,P.D. and Strominger, J. L .

TITLE A factor that regulates the class II rαa]or histocompatibility complex gene DPA is a member of a subfamily of zinc finger proteins that includes a Drosophila developmental control protein JOURNAL MoI. Cell. Biol. 14 (12), 8438-8450 (1994)

PUBMED 7969177 REFERENCE 3 (bases 1 to 2289)

AUTHORS Ruppert, J. M. , Kinzler, K. W. , Wong, A. J., Bigner,S.H., Kao,F.T.,

Law, M. L., Seuanez, H.N. , O'Brien, S.J. and Vogelstein, B . TITLE The GLI-Kruppel family of human genes JOURNAL MoI. Cell. Biol. 8 (8), 3104-3113 (1988)

PUBMED 2850480

COMMENT PROVISIONAL REFSEQ: This record has not yet been subject to final

NCBI review. The reference sequence was derived from U45325.1. FEATURES Location/Qualifiers source 1..2289

/organism="Homo sapiens" /mol_type="mRNA" /db_xref="taxon: 9606" /chromosome=" 1 " /map="lp36.3" gene 1..2289

/gene="HKR3" /note="synonym: pp9964" /db_xref="GeneID:3104" /db_xref="HGNC:4930" /db_xref="HPRD:HPRD_01316" /db_xref="MIM: 165270" CDS 156..2222

/gene="HKR3" /go_component="nucleus"

/go_function="metal ion binding; protein binding; transcription factor activity [pmid 8661141]; zinc ion binding"

/go_process="regulation of transcription, DNA- dependent; transcription" /codon_start=l /product="GLI-Kruppel family member HKR3" /protein_id="NP_005332.1" /db_xref="GI: 4885419" /db_xref="CCDS:CCDS84.1" /db_xref="GeneID:3104" /db_xref="HGNC:4930" /db_xref="HPRD:HPRD_01316" /db_xref="MIM: 165270"

/translation="MDGSFVQHSVRVLQELNKQREKGQYCDATLDVGGLVFKAHWSVL ACCSHFFQSLYGDGSGGSWLPAGFAEIFGLLLDFFYTGHLALTSGNRDQVLLAAREL RVPEAVELCQSFKPKTSVGQAAGGQSGLGPPASQNVNSHVKEPAGLEEEEVSRTLGLV PRDQEPRGSHSPQRPQLHSPAQSEGPSSLCGKLKQALKPCPLEDKKPEDCKVPPRPLE AEGAQLQGGSNEWEVWQVEDDGDGDYMSEPEAVLTRRKSNVIRKPCAAEPALSAGSL AAEPAENRKGTAVPVECPTCHKKFLSKYYLKVHNRKHTGEKPFECPKCGKCYFRKENL LEHEARNCMNRSEQVFTCSVCQETFRRRMELRVHMVSHTGEMPYKCSSCSQQFMQKKD LQSHMIKLHGAPKPHACPTCAKCFLSRTELQLHEAFKHRGEKLFVCEECGHRASSRNG LQMHIKAKHRNERPHVCEFCSHAFTQKANLNMHLRTHTGEKPFQCHLCGKTFRTQASL DKHNRTHTGERPFSCEFCEQRFTEKGPLLRHVASRHQEGRPHFCQICGKTFKAVEQLR VHVRRHKGVRKFECTECGYKFTRQAHLRRHMEIHDRVENYNPRQRKLRNLI IEDEKMV

WALQPPAELEVGSAEVIVESLAQGGLASQLPGQRLCAEESFTGPGVLEPSLI ITAAV

PEDCDT"

STS 1958..2093

/gene="HKR3"

/standard_name="RH78576"

/db_xref="UmSTS:2663^ 1"

ORIGIN

1 tacgcatagc cgggcactag gttcgtgggc tgtggaggcg acggagcagg gggccagtgg

61 ggccagctca gggaggacct gcctgggagc tttctcttgc ataccctcgc ttaggctggc

121 cggggtgtca cttctgcctc cctgccctcc agaccatgga cggctccttc gtccagcaca

181 gtgtgagggt tctgcaggag ctcaacaagc agcgggagaa gggccagtac tgcgacgcca

241 ctctggacgt ggggggcctg gtgtttaagg cacactggag tgtccttgcc tgctgcagtc

301 actttttcca gagcctctac ggggatggct cagggggcag tgtcgtcctc cctgctggct

361 tcgctgagat ctttggcctc ttgttggact ttttctacac tggtcacctc gctctcacct

421 cagggaaccg ggatcaggtg ctcctggcag ccagggagtt gcgagtgcca gaggccgtag

481 agctgtgcca gagcttcaag cccaaaactt cagtgggaca ggcagcaggt ggccagagtg

541 ggctggggcc ccctgcctcc cagaatgtga acagccacgt caaggagccg gcaggcttgg

601 aagaagagga agtttcgagg actctgggtc tagtccccag ggatcaggag cccagaggca

661 gtcatagtcc tcagaggccc cagctccatt ccccagctca gagtgagggc ccctcctccc

721 tctgtgggaa actgaagcag gccttgaagc cttgtcccct tgaggacaag aaacccgagg

781 actgcaaagt gcccccaagg cccttagagg ctgaaggtgc ccagctgcag ggcggcagta

841 atgagtggga agtggtggtt caagtggagg atgatgggga tggcgattac atgtctgagc

901 ctgaggctgt gctgaccagg aggaagtcaa atgtaatccg aaagccctgt gcagctgagc

961 cagccctgag cgcgggctcc ctagcagctg agcctgctga gaacagaaaa ggtacagcgg

1021 tgccggtcga atgccccaca tgtcataaaa agttcctcag caaatattat ctaaaagtcc

1081 acaacaggaa acatactggg gagaaaccct ttgagtgtcc caaatgtggg aagtgttact

1141 ttcggaagga gaacctcctg gagcatgaag cccggaattg catgaaccgc tcggaacagg

1201 tcttcacgtg ctctgtgtgc caggagacat tccgccgaag gatggagctg cgggtgcaca

1261 tggtgtctca cacaggggag atgccctaca agtgttcctc ctgctcccag cagttcatgc

1321 agaagaagga cttgcagagc cacatgatca aacttcatgg agcccccaag ccccatgcat

1381 gccccacctg tgccaagtgc ttcctgtctc ggacagagct gcagctgcat gaagctttca

1441 agcaccgtgg tgagaagctg tttgtgtgtg aggagtgtgg gcaccgggcc tcgagccgga 1501 atggcctgca gatgcacatc aaggccaagc acaggaatga gaggccacac gtatgtgagt 1561 tctgcagcca cgccttcacc caaaaggcca atctcaacat gcacctgcgc acacacacgg 1621 gtgagaagcc cttccagtgc cacctctgtg gcaagacctt ccgaacccaa gccagcctgg 1681 acaagcacaa ccgcacccac accggggaaa ggcccttcag ttgcgagttc tgtgaacagc 1741 gcttcactga gaaggggccc ctcctgaggc acgtggccag ccgccatcag gagggccggc 1801 cccacttctg ccagatatgc ggcaagacct tcaaagccgt ggagcaactg cgtgtgcacg 1861 tcagacggca caagggggtg aggaagtttg agtgcaccga gtgtggctac aagtttaccc 1921 gacaggccca cctgcggagg cacatggaga tccacgaccg ggtagagaac tacaacccgc 1981 ggcagcgcaa gctccgcaac ctgatcatcg aggacgagaa gatggtggtg gtggcgctgc 2041 agccgcctgc agagctggag gtgggctcgg cggaggtcat tgtggagtcc ctggcccagg 2101 gcggcctggc ctcccagctc cccggccaga gactgtgtgc agaggagagc ttcaccggcc 2161 caggtgtcct ggagccctcc ctcatcatca cagctgctgt ccccgaggac tgtgacacat 2221 agcccattct ggccaccaga gcccacttgg ccccacccct caataaaccg tgtggctttg 2281 gactctcgt

LOCUS NM 005342 3556 bp mRNA linear PRI 24-SEP-

2005

DEFINITION Horao sapiens high-mobility group box 3 (HMGB3), mRNA.

ACCESSION NM_005342

VERSION NM_005342.2 GI:71143136

KEYWORDS

SOURCE Homo sapiens (human)

ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata;

EuteleostomiL;;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhim; Catarrhini; Hominidae; Homo.

REFERENCE 1 (bases 1 to 3556)

AUTHORS Vaccaπ,T., Beltrame,M., Ferrari, S. and Bianchi,M.E.

TITLE Hmg4, a new member of the Hmgl/2 gene family

JOURNAL Genomics 49 (2), 247-252 (1998)

PUBMED 9598312

REFERENCE 2 (bases 1 to 3556) AUTHORS Wilke,K., Wiemann,S., Gaul, R., Gong, W. and Poustka,A. TITLE Isolation of human and mouse HMG2a cDNAs : evidence for an HMG2a-specific 3' untranslated region

JOURNAL Gene 198 (1-2), 269-274 (1997)

PUBMED 9370291

REFERENCE 3 (bases 1 to 3556)

AUTHORS Davis, D. L. and Burch,J.B.

TITLE Isolation of a chicken HMG2 cDNA clone and evidence for an HMG2-specific 3 ' -untranslated region

JOURNAL Gene 113 (2), 251-256 (1992) PUBMED 1572546

REFERENCE 4 (bases 1 to 3556) AUTHORS Shirakawa, H. , Tsuda,K. and Yoshida,M. TITLE Primary structure of non-histone chromosomal protein HMG2 revealed by the nucleotide sequence

JOURNAL Biochemistry 29 (18), 4419-4423 (1990) PUBMED 2350545 COMMENT VALIDATED REFSEQ: This record has undergone preliminary review of the sequence, but has not yet been subject to final review. The reference sequence was derived from DN996967.1, Y10043.1, BC037210.1 and AF003626.2.

On JuI 26, 2005 this sequence version replaced gi:4885420. COMPLETENESS: complete on the 3' end.

FEATURES Location/Qualifiers source 1..3556

/organism="Homo sapiens"

/mol_type="mRNA"

/db_xref="taxon:9606"

/chromosome="X"

/map="Xq28" gene 1..3556

/gene="HMGB3"

/note="synonyms: HMG4, HMG2A, MGC90319"

/db_xref="GeneID:3149"

/db_xref="HGNC:5004"

/db_xref="HPRD:HPRD_02181"

/db_xref="MIM:300193"

CDS 93..695

/gene="HMGB3"

/go_component="chromatin; nucleus"

/go_function="DNA bending activity [pmid 9598312]; DNA binding" /go_process="development [pmid 9598312]; regulation of transcription, DNA-dependent "

/note="high-mobility group (nonhistone chromosomal) protein 4; non-histone chromosomal protein"

/codon_start=l

/product="high-mobility group box 3"

/protein_id="NP_005333.2 "

/db_xref="GI: 71143137"

/db_xref="GeneID:3149"

/db_xref="HGNC:5004"

/db_xref="HPRD:HPRD_02181"

/db_xref="MIM:300193"

/translation="MAKGDPKKPKGKMSAYAFFVQTCREEHKKKNPEVPVNFAEFSKK CSERWKTMSGKEKSKFDEMAKADKVRYDREMKDYGPAKGGKKKKDPNAPKRPPSGFFL

FCSEFRPKIKSTNPGISIGDVAKKLGEMWNNLNDSEKQPYITKAAKLKEKYEKDVADY

KSKGKFDGAKGPAKVARKKVEEEDEEEEEEEEEEEEEEDE" STS 807..1656

/gene="HMGB3"

/standard_name="HMGB3 6575"

/db_xref="UmSTS:463983" STS 1296..1485

/gene="HMGB3" /standard_name="RH45008" /db_xref="UmSTS : 5357 " variation 1348

/gene="HMGB3"

/note="deleted in clone: Qc-12Cll , deleted in clone: LL0XNC01-220B3" /replace=" " STS 2356..2490

/gene="HMGB3"

/standard_name=" SHGC-58788" /db_xref="UmSTS: 94334" STS 3178..3300

/gene="HMGB3" /standard_name="RH98216" /db_xref="UmSTS: 85515" STS 3250..3521

/gene="HMGB3"

/standard_name="SHGC-132841" /db_xref="UmSTS:170921" STS 3315..3548

/gene="HMGB3"

/ standard_name=" SHGC-53292 " /db_xref="UmSTS : 73608 " ORIGIN

1 ggctctcgtg gaggcagcta gcgcgaggct ggggagcgct gagccgcgcg tcgtgccctg 61 cgctgcccag actagcgaac aatacagtca ggatggctaa aggtgacccc aagaaaccaa 121 agggcaagat gtccgcttat gccttctttg tgcagacatg cagagaagaa cataagaaga 181 aaaacccaga ggtccctgtc aattttgcgg aattttccaa gaagtgctct gagaggtgga 241 agacgatgtc cgggaaagag aaatctaaat ttgatgaaat ggcaaaggca gataaagtgc 301 gctatgatcg ggaaatgaag gattatggac cagctaaggg aggcaagaag aagaaggatc 361 ctaatgctcc caaaaggcca ccgtctggat tcttcctgtt ctgttcagaa ttccgcccca 421 agatcaaatc cacaaacccc ggcatctcta ttggagacgt ggcaaaaaag ctgggtgaga 481 tgtggaataa tttaaatgac agtgaaaagc agccttacat cactaaggcg gcaaagctga 541 aggagaagta tgagaaggat gttgctgact ataagtcgaa aggaaagttt gatggtgcaa 601 agggtcctgc taaagttgcc cggaaaaagg tggaagagga agatgaagaa gaggaggagg 661 aagaagagga ggaggaggag gaggaggatg aataaagaaa ctgtttatct gtctccttgt 721 gaatacttag agtaggggag cgccgtaatt gacacatctc ttatttgaga agtgtctgtt 781 gccctcatta ggtttaatta caaaatttga tcacgatcat attgtagtct ctcaaagtgc 841 tctagaaatt gtcagtggtt tacatgaagt ggccatgggt gtctggagca ccctgaaact 901 gtatcaaagt tgtacatatt tccaaacatt tttaaaatga aaaggcactc tcgtgttctc 961 ctcactctgt gcactttgct gttggtgtga caaggcattt aaagatgttt ctggcatttt 1021 ctttttattt gtaaggtggt ggtaactatg gttattggct agaaatcctg agttttcaac 1081 tgtatatatc tatagtttgt aaaaagaaca aaacaaccga gacaaaccct tgatgctcct 1141 tgctcggcgt tgaggctgtg gggaagatgc cttttgggag aggctgtagc tcagggcgtg 1201 cactgtgagg ctggacctgt tgactctgca gggggcatcc atttagcttc aggttgtctt 1261 gtttctgtat atagtgacat agcattctgc tgccatctta gctgtggaca aaggggggtc 1321 agctggcatg agaatatttt ttttttttaa gtgcggtagt ttttaaactg tttgttttta 1381 aacaaactat agaactcttc attgtcagca aagcaaagag tcactgcatc aatgaaagtt 1441 caagaacctc ctgtacttaa acacgattcg caacgttctg ttattttttt tgtatgttta 1501 gaatgctgaa atgtttttga agttaaataa acagtattac atttttaaaa ctcttctcta 1561 ttataacagt caatttctga ctcacagcag tgaacaaacc cccactccat tgtatttgga 1621 gactggcctc cctataaatg tggtagcttc ttttattact cagtggccag ctcacttagg 1681 gctgagatga aggagagggc tacttgaagc tactgtgtga ttttgtttgt gtctgagtgg 1741 cattcagatg aagtctggag gagttaggag aacgacatag gcaaggttca gcagccttcc 1801 aaggtatagg aaggtgggtg attaggactg aggctatcta ggtttaactt ttgtcccacc 1861 tccaccccct attttgtggg gccaaatgca ttgctaaaca gcaatttcag agtgtatggt 1921 gtgtcaaaaa ttaaggcctt attgtttttc tctttcaccc ctaccccccg tgctcctggc 1981 acatatcaca ttatttgtgg tgcccaacat ttggggtctt gagcctgctg ctggtctcct 2041 ggatgccagt gagggtatgt gggatggggt ggtggggtag gggacggtat cctttttttg 2101 ctcctacttg gaaacaccaa acaccccaag gaagatgata ggctccatct tgggccacct 2161 gagctatagg gcaggctaat ggaatcaacc atttctgagc actaaatgta tcatgaaaag 2221 ttgaatggcc tgctcataag tttagctcat tcactggaaa tgtagattga tgttcaatgt 2281 taaactggaa ggagcttggt ttgtgtgtca gtggttatat tagtgggtag tgtaacattt 2341 tatccaggtt ggggtgaggg gagatggcca cagtagcaag tggtgacact aaataccatt 2401 ttgaaggctg atgtgtatat acatcattac tgtccgtagc aatgaaggat acagtactgt 2461 gttgtgggtg agtgttgcta ttgcccagca ttaatatttg ggtgtgtatg tttgaggcta 2521 tgaaacacgc aggagtgttt ttgtgctatt aattttaaga gaaagcagct ttttcttaaa 2581 attcactgtt gagaaacttg catgtctgga ggcggtgtcc tctccgccct gtcgggtcct 2641 ggatgagtac gagttatggt cacggtcaca gcctgatctc ttatgtgttc atagccattc 2701 gctctcccat cagaactgtt tgtcctgaat gtgttcctct agttctagaa aatgaccact 2761 aatttaaaaa actcggttgt gaggtttgcc cagaggcact tgttccagaa tttcccctcc 2821 tgcttcagcc atgtccttgt cacttggcat tctaagctaa agctttagct tcccaattcg 2881 tgatgtgcta ggccaagatt cgggagctgt tgccagcctc gtcaaatatg gaagagaaac 2941 aacctgcggt caaaagggag tgatttgtta agtggtgcgc gtctatctca taactagatg 3001 taccaaccag ggaagggcca aggatggaaa ggggtaactt ttgtgcttcc aaagtagcta 3061 agcagaagtg ggggagcagt ttagccagat gatctttgat taggcaaaca ttgagtttta 3121 aagaggctgt caagttgagg ccacttggtc cattagctgg ggcagcaaga tcactactca 3181 acgttttcac actgtggcaa gattgctctt ctagtggaat aatgccctag tttctctgag 3241 atgatgtaag tggcatgatg ttacctaagg cttaggctta gcttgatttc tgggcccact 3301 gtctgtgttc ttaagatgcc aacctgttgc tttttttttt tttttccccc atttaaaagg 3361 atagtaccta ctccctctaa ccacctcacc ccattcttga atgacatttt atccttcgga 3421 aagaacaagg ctgtgatgta gtgactattg tctgtgtctc ctgtgtgtgt ctgttcttgt 3481 cacaaatgta tttggggacg ttggatgcat tcattttctg taataaagtt tcttaatcac 3541 tcttcccaaa aagtaa

LOCUS NM_152704 3198 bp mRNA linear PRI 23-APR-

2005

DEFINITION Homo sapiens hypothetical protein FLJ25477 (FLJ25477), transcript variant 1, mRNA.

ACCESSION NM_152704

VERSION NM_152704.2 GI:40288202

KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata;

Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

REFERENCE 1 (bases 1 to 3198)

AUTHORS Ota, T., Suzuki, Y., Nishikawa, T . , Otsuki,T., Sugiyama,T.,

Iπe,R. ,

Wakamatsu, A. , Hayashi,K., Sato, H., Nagai,K., Kimura,K.,

Makita,H.,

Sekine,M., Obayashi,M., Nishi,T., Shibahara, T . , Tanaka,T., Ishn,S., Yamamoto,J., Saito,K., Kawai,Y., Isono,Y.,

Nakamura, Y . ,

Nagahaπ,K., Murakami, K., Yasuda,T., Iwayanagi, T . ,

Wagatsuma, M. ,

Shiratoπ, A. , Sudo,H., Hosoiπ,T., Kaku,Y., Kodaira,H.,

Kondo, H. ,

Sugawara,M., Takahashi, M. , Kanda,K., Yokoi,T., Furuya,T., Kikkawa,E., Omura,Y., Abe, K., Kamihara,K., Katsuta,N., Sato, K., Tanikawa,M., Yamazaki,M., Ninomiya,K., Ishibashi, T . ,

Yamashita, H . ,

Murakawa,K., Fu]imoπ,K., Tanai,H., Kimata,M., Watanabe,M., Hiraoka,S., Chiba,Y., Ishida,S., Ono,Y., Takiguchi, S . ,

Watanabe, S . ,

Yosida,M., Hotuta,T., Kusano, J., Kanehoπ,K., Takahashi-

Fu]Ii, A. ,

Hara,H., Tanase,T.O., Nomura, Y., Togiya,S., Komai,F., Hara,R., Takeuchi,K., Aπta,M., Imose,N., Musashino, K. , Yuuki,H.,

Oshima, A. ,

Sasaki, N., Aotsuka,S., Yoshikawa, Y . , Matsunawa, H . , Ichihara,T., Shiohata,N., Sano,S., Moπya,S., Momiyama,H., Satoh,N.,

Takami, S . ,

Terashima, Y. , Suzuki, 0., Nakagawa,S., Senoh,A., Mizoguchi, H . , Goto, Y., Shimizu,F., Wakebe,H., Hishigaki, H . , Watanabe, T., Sugiyama,A., Takemoto,M., Kawakami,B., Yamazaki,M.,

Watanabe, K. ,

Kumagai,A., Itakura,S., Fukuzumi,Y., Fujimori, Y., Komiyama,M., Tashiro,H., Tanigami,A., Fu]iwara,T., Ono,T., Yamada,K.,

Fu]ii,Y.,

Ozaki,K., Hirao,M., Ohmoπ,Y., Kawabata,A., Hikiji, T . ,

Kobatake, N. ,

Inagaki,H., Ikema,Y., Okamoto,S., Okitani,R., Kawakami,T., Noguchi,S., Itoh,T., Shigeta,K., Senba,T., Matsumura, K. , Naka]ima,Y., Mizuno,T., Moπnaga,M., Sasaki, M., Togashi,T., Oyama,M., Hata,H., Watanabe, M., Komatsu,T., Mizushima-

Sugano, J. ,

Satoh,T., Shirai,Y., Takahashi, Y ., Nakagawa,K., Okumura,K., Nagase,T., Nomura, N., Kikuchi,H., Masuho,Y., Yamashita, R. , Nakai,K., Yada,T., Nakamura, Y., 0hara,0., Isogai,T. and

Sugano, S .

TITLE Complete sequencing and characterization of 21,243 full-length human cDNAs JOURNAL Nat. Genet. 36 (1), 40-45 (2004) PUBMED 14702039

COMMENT VALIDATED REFSEQ: This record has undergone preliminary review of the sequence, but has not yet been subject to final review. The reference sequence was derived from BC041392.1, AK098343.1, BM680074.1 and AL832627.1.

On Dec 22, 2003 this sequence version replaced gi : 22749404. FEATURES Location/Qualifiers source 1..3198

/organism="Homo sapiens" /mol_type="mRNA" /db_xref="taxon: 9606" /chromosome="13" /map="13ql2.13" gene 1..3198

/gene="FLJ25477" /db_xref="GeneID:219287" /db_xref="HPRD:HPRD_08067" CDS 101..2116

/gene="FLJ25477"

/note="isoform 1 is encoded by transcript variant 1"

/codon_start=l

/product="hypothetical protein LOC219287 isoform 1"

/protein_id="NP_689917.2"

/db_xref="GI:40288203"

/db_xref="GeneID:219287"

/db_xref="HPRD:HPRD_08067"

/translat1On=¹¹METSRSRGGGGAVSERGGAGASVGVCRRKAEAGAGTGTLAADMD

LHCDCAAETPAAEPPSGKINKAAFKLFKKRKSGGTMPSIFGVKNKGDGKSSGPTGLVR SRTHDGLAEVLVLESGRKEEPRGGGDSGGGGGGRPNPGPPRAAGPGGGSLASSSVAKS HSFFSLLKKNGRSENGKGEPVDASKAGGKQKRGLRGLFSGMRWHRKDKRAKAEAAEGR APGGGLILPGSLTASLECVKEETPRAAREPEEPSQDAPRDPAGEPAGGEEVPAPADRA PARSCREAEGLAHPGDTGARGEDAAGHRRAEPGPGEVRTAEDASRTGAVPVKTVPLVD SEGGSGRAPAAPDPASVDPPSDPSADRICLMFSDVTSLKSFDSLTGCGDIIADQEEEA GPSCDKHVPGPGKPALSKKNPGWAYQGGGEEMASPDEVDDTYLQEFWDMLSQTEEQG PEPQEGAAKVAAALETKWPETPKDTRCVEAAKDASSVKRRRLNRIPIEPHPKEEPKH PEKEQQEGVPNSDEGYWDSTTPGPEEDSSSSGKKAGIPRDSYSGDALYDLYADPDGSP

ATLPGGKDNEETSSLSRLKPVSPGTITCPLRTPGSLLKDSKIPISIKHLTNLPSSHPV

VHQQPSRSEMPRTKIPVSKVLVRRVSNRGLAGTTIRATACHDSAKKL"

STS 2424..2544

/gene="FLJ25477"

/ standard_name=" STS-H92893 "

/db_xref="UmSTS: 16086" STS 2854..3157

/gene="FLJ25477"

/standard_name="G60154"

/db_xref="UmSTS : 137409 " STS 2886 . . 3159

/gene="FLJ25477"

/db_xref="UmSTS : 153179 " STS 2928 . . 3093 /gene= " FLJ25477 " / standard_name= " G43527 " /db_xre f= " Um STS : 94 984 "

STS 2 994 . . 3127 /gene= " FLJ25477 " / standard_name= " RH15722 ' /db_xre f= " Um STS : 7721 "

ORIGIN

1 cggcggcggc gagcgcggct caggttgatt tagaatacgg gtgacagtgg cctggcgcga

61 gcccactgct gacgaaagcg gcttatcccg cgcggtttcc atggagacga gccggagccg

121 cggcggcggc ggggctgtca gcgagcgcgg cggagctggc gcgtccgtgg gggtctgcag

181 gaggaaggcg gaggccgggg ccgggaccgg gaccctcgcg gcagacatgg acttgcattg

241 tgactgtgcc gccgaaacgc cggccgccga gccgccgtcg gggaagatta ataaagctgc

301 cttcaaatta ttcaagaaga ggaaatcggg tggcaccatg cccagcattt ttggggtcaa

361 aaacaaaggg gacgggaaaa gctcgggtcc gacggggctg gtgaggagca ggacccacga

421 cggacttgcc gaggtgctgg tgctggagag cggcaggaag gaggagccgc gcggcggggg

481 cgacagcggc gggggcggcg gggggcggcc gaacccgggg ccccccagag ccgcagggcc

541 cggcgggggc tccctcgcca gcagctcggt ggccaagtcg cacagcttct tctcgctgct

601 gaagaagaac gggcgctcgg aaaacggcaa gggagagcct gtggacgcga gcaaggccgg

661 cggcaaacaa aagcgggggc tgcgggggct gttcagcggc atgcgctggc acaggaaaga

721 caagcgggcc aaggcggagg ccgcggaggg gcgcgcgccc gggggcggct tgatcctacc

781 cggctcgctc accgccagcc tggagtgcgt caaggaggag acgcccagag ccgcgcgcga

841 gccggaggag cccagccagg acgccccgcg agacccagca ggtgagcccg cagggggaga

901 ggaggtgccc gcccccgccg accgcgcccc agcgcggagc tgccgagagg cagagggcct

961 cgcgcacccc ggcgacaccg gcgcccgggg agaggacgcc gcggggcatc ggcgcgccga

1021 gccggggccc ggggaggtcc gcacggcaga ggacgcttcc aggacggggg ccgttcccgt

1081 aaagacggtc ccccttgtcg actccgaagg cggcagcggc cgggcgcccg ccgccccaga

1141 ccctgcctct gtcgatccac cctcagaccc gtcggcagat cgtatttgtt tgatgttttc

1201 tgacgtgact tcactgaaaa gctttgactc tcttacaggc tgtggagata ttattgcaga

1261 ccaagaggaa gaggcaggtc ccagctgtga caagcatgtc cccgggccag gcaagccggc

1321 tctgtctaaa aagaaccccg gcgtggtggc ctaccaagga ggcggggaag agatggccag

1381 cccggacgag gtggacgaca cctatctaca ggagttctgg gacatgctct cccagaccga

1441 ggagcaggga cccgagcccc aggagggcgc ggctaaggtg gcagctgcgc tggaaaccaa

1501 ggtggtgccc gagaccccca aagacaccag gtgtgtggaa gcggccaagg acgcgtcctc

1561 ggtcaagcgc aggaggctca accggattcc catcgagccc catcctaagg aggagcccaa

1621 gcacccggag aaggagcagc aggaaggcgt ccccaacagc gacgagggct actgggactc

1681 caccacgcca ggcccagagg aagacagctc gagcagcggg aagaaggcgg gcatcccccg

1741 ggatagctac agcggggacg cgctctatga tctctatgct gacccggacg gaagtccagc

1801 aacccttcct ggagggaagg acaacgagga gacgtcctcc ctgtcccggt taaagcccgt

1861 atctccaggc accatcacct gtccactgcg aacaccaggc agcttgctga aggactctaa

1921 gatccctatt agcatcaagc acctgaccaa ccttccatct agccatcccg tggtgcacca

1981 gcaaccctcc aggagtgaga tgcccagaac aaaaatcccg gtttccaaag tgctggtccg

2041 cagagtcagc aaccggggct tggctgggac caccatcaga gcaacggcct gccacgacag

2101 tgccaaaaag ttgtgaggtc ttccaggcca aggtggatgg gccccatgcc aaggaataca

2161 acttttccct ggaaaccact aaagtaagtt ttgcttttcc taaagaaagt cttttaggac

2221 accacccgtc ccccgccctg ctccagagcg tggaccgagg aggtctttgt gccctgagca

2281 gggaccggat aacaccagaa agagggatgc tacacggggg tttctcctct caagataagt

2341 ccctgagaat tattttcaag cacttttttc ttttttacct ttaagttttt cttccttttg

2401 ctttaatata ctgaacactt ggaagtcacc tttacttgcc tttgcagaaa acagaactta

2461 gccaaaccta agtaagagtc atgcctggat attgggataa gccagtgtct agaggcctga

2521 aggaaccgct gaagaaccag aggagatctc ctcttccaag acacgtttcc ttccttccct

2581 tctttcctct ttcctttcca gttaaaaaaa aacaaaaaca aaaacaaaac cctttgctgt

2641 atcactgtgt ggaaaatacc tccaaagctg aaagagccag gtatttacct gatgagcaga

2701 ggggaccact gattggcaga aaacttccct acgttcagtt gttagatatg caaattgata

2761 aggatctaac actaggaaaa taaaggcgag ttttggtttg gttggtttca gtcatttgtt

2821 tggggagata taaaaggctc aggagagcag gcttttgctt ttgcttttgt ttgtttcttc

2881 ccccacccag tgcagaaatc aggatcaggg aaagatttta ttaaatgcca atagatacag

2941 tatttaagca tttataaact gaaacctttt catgtgaaga taatgcatat tttaccgttt

3001 atccagctgt taacattttg taatcagtca attcaataga attattctgg ataattctat

3061 atctagaata taaaatctgg tcttatagct agacatgatg atggtcccca aaccattgat

3121 gttctgttat gtactgtaat gggaagcgat tctgattttg ttttatatgg gttctctggt

3181 tctcaaaaaa aaaaaaaa //

LOCUS XM_117096 1414 bp mRNA linear PRI 01-AUG-

2002

DEFINITION Homo sapiens myelin basic protein (MBP) , mRNA. ACCESSION XM_117096

VERSION XM_117096.2 GI:22060068 KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Primates; Catarrhim; Homimdae; Homo. REFERENCE 1 (bases 1 to 1414)

AUTHORS NCBI Annotation Project.

TITLE Direct Submission

JOURNAL Submitted (31-JUL-2002 ) National Center for Biotechnology

Information, NIH, Bethesda, MD 20894, USA

COMMENT MODEL REFSEQ: This record is predicted by automated computational analysis. This record is derived from an annotated genomic sequence

(NT_024997) using gene prediction method: BLAST, supported by EST evidence .

Also see:

Documentation of NCBI ' s Annotation Process

On Aug 1, 2002 this sequence version replaced gi : 20557210.

FEATURES Location/Qualifiers source 1..1414

/organism="Homo sapiens" /mol_type="mRNA" /db_xref="taxon:9606" /chromosome=" 18" gene 1..1414 /gene="MBP"

/db_xref="GeneID:4155" /db_xref="MIM: 159430"

CDS 172..510 /gene="MBP" /codon_start=l /product="similar to Myelin basic protein (MBP)

(Myelin Al protein) (Myelin membrane encephalitogenic protein) "

/protein_id="XP_117096.2"

/db_xref="GI: 22060069"

/db_xref="GeneID:4155"

/db_xref="MIM: 159430"

/translat1On=¹¹MGNHAGKRELNAEKASTNSETNRGESEKKRNLGELSRTTSEDNE

VFGEADANQNNGTSSQDTAVTDSKRTADPKNAWQDAHPADPGSRPHLIRLFSRDAPGE

GGQHLQRQAL" ORIGIN

1 tcctttcgcg tccacctgag cccccccgtt ttggaaggtg gagtggggct tgggaaaagg 61 ttcaagcgtc tttggggacc cccgtgcgac tctggctgga aacaggcgag ctctggttcc 121 ttgttccgtt ttccaattgc aacaaccctc tgaagagcca atccattcag gatgggaaac 181 cacgcaggca aacgagaatt aaatgccgag aaggccagta cgaatagtga aactaacaga 241 ggagaatctg aaaaaaagag aaacctgggt gaactttcac ggacaacctc agaggacaac 301 gaagtgttcg gagaggcaga tgcgaaccag aacaatggga cctcctctca ggacacagcg 361 gtgactgact ccaagcgcac agcggacccg aagaatgcct ggcaggatgc ccacccagct 421 gacccaggga gccgccccca cttgatccgc ctcttttccc gagatgcccc nggggaggga 481 ggacaacacc ttcaaagaca ggccctctga gtccgacgag ctccagacca tccaagaaga 541 cagtgcagcc acctccgaga gcctggatgt gatggcgtca cagaagagac cctcccagag

601 gcacggatcc aagtacctgg ccacagcaag taccatggac catgccaggc atggcttcct

661 cccaaggcac agagacacgg gcatccttga ctccatcggg cgcttctttg gcggtgacag

721 gggtgcgccc aagcggggct ctggcaaggt gagctctgag gagtagagga gttttagttt

781 aaatggaaaa agcaaaggag aaatcagtag gtgaactcag ccattagagg aagaactggc

841 acgtagcctc ttgctgtcta aggtctcgtt ccgtgctgga gaatgcatat gagcccaaga

901 gtgtgggcct gagtggctgc ttaggacgtt ttcgtttaac tcaccccctc ttttcctcac

961 aagggatggt ggccggggtg tggctcagga atgtaaggac atgctgaatt ctggatctct

1021 aagggtgcct ggacatgggc gttgcagaaa gagagccaca ttctcagggt ctctggtggt

1081 gtgtgcttgc ggacttgatg actgatgttg cctctgcagc ccacacgctg gggttcaaca

1141 ctgggttatg ctcgtttttt cctggagtca gtgctgctag cttcatgttg ctctgcgaca

1201 atcataggat tgaggtcgag gaagactttt gaacaaactc ctcaatttaa atccgccttg

1261 agcaaacgtt ctctgtggtc tgagaagtgg aaggggggag ggataaatga gtgtctatga

1321 atcaaagctt tattatcttg tgattccatt aatttgcata cagagtctta gaagtttctt

1381 tattcaaaag caaatgtgga taaaaatgta ttac

LOCUS XM_041415 2826 bp mRNA linear PRI 13-MAY-

2002

DEFINITION Homo sapiens neural cell adhesion molecule 1 (NCAMl), mRNA. ACCESSION XM_041415

VERSION XM_041415.1 GI:14770522 KEYWORDS

SOURCE Homo sapiens ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Primates; Catarrhim; Homimdae; Homo. REFERENCE 1 (bases 1 to 2826)

AUTHORS NCBI Annotation Project.

TITLE Direct Submission

JOURNAL Submitted ( 09-MAY-2002 ) National Center for Biotechnology

Information, NIH, Bethesda, MD 20894, USA

(NT_009151) using gene prediction method: BLAST, supported by mRNA evidence .

Also see:

Documentation of NCBI ' s Annotation Process

FEATURES Location/Qualifiers source 1..2826

/orgamsm="Homo sapiens "

/mol_type="mRNA"

/db_xref="taxon : 9606 "

/chromosome=" 11 " gene 1..2826

/gene="NCAMl"

/note="synonyms: CD56, NCAM"

/db_xref="GeneID:4684"

/db_xref="MIM: 116930" CDS 532..2724

/gene="NCAMl"

/codon_start=l

/product="neural cell adhesion molecule 1"

/protein_id="XP_041415.1"

/db_xref="GI : 14770523"

/db_xref="GeneID:4684"

/db_xref="MIM: 116930"

/translation="MFKNAPTPQEFREGEDAVIVCDWSSLPPT11WKHKGRDVILKK DVRFIVLSNNYLQIRGIKKTDEGTYRCEGRILARGEINFKDIQVIVNVPPTIQARQNI VNATANLGQSVTLVCDAEGFPEPTMSWTKDGEQIEQEEDDEKYIFSDDSSQLTIKKVD KNDEAEYICIAENKAGEQDATIHLKVFAKPKITYVENQTAMELEEQVTLTCEASGDPI PSITWRTSTRNISSEEKTLDGHMWRSHARVSSLTLKSIQYTDAGEYICTASNTIGQD SQSMYLEVQYAPKLQGPVAVYTWEGNQVNITCEVFAYPSATISWFRDGQLLPSSNYSN IKIYNTPSASYLEVTPDSENDFGNYNCTAVNRIGQESLEFILVQADTPSSPSIDQVEP YSSTAQVQFDEPEATGGVPILKYKAEWRAVGEEVWHSKWYDAKEASMEGIVTIVGLKP ETTYAVRLAALNGKGLGEISAASEFKTQPVPGEPSAPKLEGQMGEDGNSIKVNLIKQD DGGSPIRHYLVRYRALSSEWKPEIRLPSGSDHVMLKSLDWNAEYEVYWAENQQGKSK AAHFVFRTSAQPTAIPANGSPTSGLSTGAIVGILIVIFVLLLVWDITCYFLNKCGLF

MCIAVNLCGKAGPGAKGKDMEEGKAAFSKDESKEPIVEVRTEEERTPNHDGGKHTEPN

ETTPLTEPEKGPVEAKPECQETETKPAPAEVKTVPNDATQTKENESKA" misc_feature 547..747

/gene="NCAMl"

/note="IG; Region: Immunoglobulin"

/db_xref="CDD:smart00409" misc_feature 565..753

/gene="NCAMl"

/note="IGc2; Region: Immunoglobulin C-2 Type"

/db_xref="CDD:smart00408" misc_feature 571..747

/gene="NCAMl"

/note="ig; Region: Immunoglobulin domain"

/db_xref="CDD:pfam00047" misc_feature 841..1092

/gene="NCAMl"

/note="IG; Region: Immunoglobulin"

/db_xref="CDD:smart00409" misc_feature 859..1059

/gene="NCAMl"

/note="IGc2; Region: Immunoglobulin C-2 Type"

/db_xref="CDD:smart00408" misc_feature 859..1044

/gene="NCAMl"

/note="ig; Region: Immunoglobulin domain"

/db_xref="CDD:pfam00047" misc_feature 865..1056

/gene="NCAMl"

/note="IGcl; Region: Immunoglobulin C-Type"

/db_xref="CDD: smart00407" misc_feature 1144..1386

/gene="NCAMl"

/note="IG; Region: Immunoglobulin"

/db_xref="CDD:smart00409" misc_feature 1144..1353

/gene="NCAMl"

/note="IGc2; Region: Immunoglobulin C-2 Type"

/db_xref="CDD:smart00408" misc_feature 1144..1338

/gene="NCAMl"

/note="ig; Region: Immunoglobulin domain"

/db_xref="CDD:pfam00047" misc_feature 1408..1644

/gene="NCAMl"

/note="IG; Region: Immunoglobulin"

/db_xref="CDD:smart00409" misc_feature 1429..1635

/gene="NCAMl"

/note="IGc2; Region: Immunoglobulin C-2 Type"

/db_xref="CDD:smart00408" misc_feature 1432..1620

/gene="NCAMl"

/note="ig; Region: Immunoglobulin domain"

/db_xref="CDD:pfam00047" misc_feature 1675..1941 /gene="NCAMl"

/note="fn3; Region: Fibronectin type III domain"

/db_xref="CDD:pfam00041" rai se feature 1675..1926

/gene="NCAMl"

/note="FN3; Region: Fibronectin type 3 domain"

/db_xref="CDD:smart00060" misc_feature 1972..2220

/gene="NCAMl"

/note="FN3; Region: Fibronectin type 3 domain"

/db_xref="CDD:smart00060" rai se feature 1981..2226

/gene="NCAMl"

/note="fn3; Region: Fibronectin type III domain"

/db_xref="CDD:pfam00041"

ORIGIN

1 gcgcgtgaac gcagctcggc tgccgctggc aggaaacaat tctgcaaaaa taatcatact

61 cagcctggca attgtctgcc cctaggtctg tcgctcagcc gccgtccaca ctcgctgcag

121 gggggggggc acagaattta ccgcggcaag acatccctcc cagccagcag attacaatgc

181 tgccaaacta aggatttcat ttggactttg tttttcctgg gaactgcagt ttctctgcag

241 gtggatattg ttcccagcca gggggagatc agcgttggag agtccaaatt cttcttatgc

301 caagtggcag gagatgccaa agataaagac atctcctggt tctcccccaa tggagaaaag

361 ctcaccccaa accagcagcg gatctcagtg gtgtggaatg atgattcctc ctccaccctc

421 accatctata acgccaacat cgacgacgcc ggcatttaca agtgtgtggt tacaggcgag

481 gatggcagtg agtcagaggc caccgtcaac gtgaagatct ttcagaagct catgttcaag

541 aatgcgccaa ccccacagga gttccgggag ggggaagatg ccgtgattgt gtgtgatgtg

601 gtcagctccc tcccaccaac catcatctgg aaacacaaag gccgagatgt catcctgaaa

661 aaagatgtcc gattcatagt cctgtccaac aactacctgc agatccgggg catcaagaaa

721 acagatgagg gcacttatcg ctgtgagggc agaatcctgg cacgggggga gatcaacttc

781 aaggacattc aggtcattgt gaatgtgcca cctaccatcc aggccaggca gaatattgtg

841 aatgccaccg ccaacctcgg ccagtccgtc accctggtgt gcgatgccga aggcttccca

901 gagcccacca tgagctggac aaaggatggg gaacagatag agcaagagga agacgatgag

961 aagtacatct tcagcgacga tagttcccag ctgaccatca aaaaggtgga taagaacgac

1021 gaggctgagt acatctgcat tgctgagaac aaggctggcg agcaggatgc gaccatccac

1081 ctcaaagtct ttgcaaaacc caaaatcaca tatgtagaga accagactgc catggaatta

1141 gaggagcagg tcactcttac ctgtgaagcc tccggagacc ccattccctc catcacctgg

1201 aggacttcta cccggaacat cagcagcgaa gaaaagactc tggatgggca catggtggtg

1261 cgtagccatg cccgtgtgtc gtcgctgacc ctgaagagca tccagtacac tgatgccgga

1321 gagtacatct gcaccgccag caacaccatc ggccaggact cccagtccat gtaccttgaa

1381 gtgcaatatg ccccaaagct acagggccct gtggctgtgt acacttggga ggggaaccag

1441 gtgaacatca cctgcgaggt atttgcctat cccagtgcca cgatctcatg gtttcgggat

1501 ggccagctgc tgccaagctc caattacagc aatatcaaga tctacaacac cccctctgcc

1561 agctatctgg aggtgacccc agactctgag aatgattttg ggaactacaa ctgtactgca

1621 gtgaaccgca ttgggcagga gtccttggaa ttcatccttg ttcaagcaga caccccctct

1681 tcaccatcca tcgaccaggt ggagccatac tccagcacag cccaggtgca gtttgatgaa

1741 ccagaggcca caggtggggt gcccatcctc aaatacaaag ctgagtggag agcagttggt

1801 gaagaagtat ggcattccaa gtggtatgat gccaaggaag ccagcatgga gggcatcgtc

1861 accatcgtgg gcctgaagcc cgaaacaacg tacgccgtaa ggctggcggc gctcaatggc

1921 aaagggctgg gtgagatcag cgcggcctcc gagttcaaga cgcagccagt cccaggggaa

1981 cccagtgcac ctaagctcga agggcagatg ggagaggatg gaaactctat taaagtgaac

2041 ctgatcaagc aggatgacgg cggctccccc atcagacact atctggtcag gtaccgagcg

2101 ctctcctccg agtggaaacc agagatcagg ctcccgtctg gcagtgacca cgtcatgctg

2161 aagtccctgg actggaatgc tgagtatgag gtctacgtgg tggctgagaa ccagcaagga

2221 aaatccaagg cggctcattt tgtgttcagg acctcggccc agcccacagc catcccagcc

2281 aacggcagcc ccacctcagg cctgagcacc ggggccatcg tgggcatcct catcgtcatc

2341 ttcgtcctgc tcctggtggt tgtggacatc acctgctact tcctgaacaa gtgtggcctg

2401 ttcatgtgca ttgcggtcaa cctgtgtgga aaagccgggc ccggggccaa gggcaaggac

2461 atggaggagg gcaaggccgc cttctcgaaa gatgagtcca aggagcccat cgtggaggtt

2521 cgaacggagg aggagaggac cccaaaccat gatggaggga aacacacaga gcccaacgag

2581 accacgccac tgacggagcc cgagaagggc cccgtagaag caaagccaga gtgccaggag

2641 acagaaacga agccagcgcc agccgaagtc aagacggtcc ccaatgacgc cacacagaca

2701 aaggagaacg agagcaaagc atgatgggtg aagagaaccg agcaaagatc aaaataaaaa 2761 gtgacacagc agcttcacca gagcatttcc aacaccacag acacacacac gcacgcacac 2821 acacaa

LOCUS NM_015192 6705 bp mRNA linear PRI 08-JAN-

2006

DEFINITION Homo sapiens phospholipase C, beta 1 (phosphoinositide- specific)

(PLCBl), transcript variant 1, mRNA. ACCESSION NM_015192

VERSION NM_015192.2 GI:33356545 KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhim;

Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 6705)

AUTHORS Martelli, A.M. , Fiume,R., Faenza,I., Tabellini, G . , Evangelista, C . ,

Bortul,R., Folio, M. Y., FaIa, F. and Cocco,L. TITLE Nuclear phosphoinositide specific phospholipase C (PI-PLC) -beta

1: a central intermediary in nuclear lipid-dependent signal transduction

JOURNAL Histol. Histopathol. 20 (4), 1251-1260 (2005) PUBMED 16136505 REMARK Review article

GeneRIF: This review summarizes current knowledge about nuclear

PI-PLC-beta 1, its localization, activity changes during cell cycle phases, and possible involvement in the progression of myelodisplastic syndrome to acute myeloid leukemia.

REFERENCE 2 (bases 1 to 6705) AUTHORS Lo Vasco,V.R., Calabrese, G . , Manzoli,L., Palka,G., Spadano,A., Morizio, E. , Guanciali-Franchi, P . , Fantasia, D. and Cocco,L.

TITLE Inositide-specific phospholipase c betal gene deletion in the progression of myelodysplastic syndrome to acute myeloid leukemia JOURNAL Leukemia 18 (6), 1122-1126 (2004) PUBMED 15085153 REMARK GeneRIF: The myelodysplastic syndrome patients, bearing the deletion, rapidly evolved to acute myeloid leukemia.

REFERENCE 3 (bases 1 to 6705) AUTHORS McCullar, J. S . , Larsen,S.A., Millimaki, R.A. and Filtz,T.M. TITLE Calmodulin is a phospholipase C-beta interacting protein JOURNAL J. Biol. Chem. 278 (36), 33708-33713 (2003) PUBMED 12821674 REMARK GeneRIF: PLC beta 3 and PLC beta 1 bind to calmodulin

REFERENCE 4 (bases 1 to 6705) AUTHORS Bennasser, Y . , Badou,A., Tkaczuk,J. and Bahraoui,E. TITLE Signaling pathways triggered by HIV-I Tat in human monocytes to induce TNF-alpha

JOURNAL Virology 303 (1), 174-180 (2002)

PUBMED 12482669

REFERENCE 5 (bases 1 to 6705)

AUTHORS Rochdi,M.D., Watier,V., La Madeleine, C ., Nakata,H., Kozasa,T. and

Parent, J. L.

TITLE Regulation of GTP-binding protein alpha q (Galpha q) signaling by the e z πn-radixin-moes in-binding phosphoprotein-50 ( EBP 50 )

JOURNAL J. Biol. Chem. 277 (43), 40751-40759 (2002)

PUBMED 12193606

REFERENCE 6 (bases 1 to 6705) AUTHORS Peruzzi,D., Aluigi,M., Manzoli, L. , Billi, A.M. , Di Giorgio, F . P .,

Morleo,M., Martelli, A.M. and Cocco,L.

TITLE Molecular characterization of the human PLC betal gene JOURNAL Biochim. Biophys. Acta 1584 (1), 46-54 (2002) PUBMED 12213492 REMARK GeneRIF: detailed analysis of the human PLC betal gene showing the existence of alternative splicing; complete determination of the exon/intron structure of the gene spanning 250 kb of DNA

REFERENCE 7 (bases 1 to 6705) AUTHORS Popova,J.S., Greene, A. K., Wang, J. and Rasenick, M. M. TITLE Phosphatidylinositol 4 , 5-bisphosphate modifies tubulin participation in phospholipase Cbetal signaling

JOURNAL J. Neurosci. 22 (5), 1668-1678 (2002)

PUBMED 11880496

REFERENCE 8 (bases 1 to 6705)

AUTHORS Singer, A. U., Waldo, G. L., Harden, T. K. and Sondek,J.

TITLE A unique fold of phospholipase C-beta mediates dimeπzation and interaction with G alpha q

JOURNAL Nat. Struct. Biol. 9 (1), 32-36 (2002) PUBMED 11753430

REFERENCE 9 (bases 1 to 6705) AUTHORS Xu, A., Wang, Y., Xu, L. Y. and Gilmour,R.S. TITLE Protein kinase C alpha -mediated negative feedback regulation is responsible for the termination of insulin-like growth factor I-induced activation of nuclear phospholipase C betal in Swiss

3T3 cells

JOURNAL J. Biol. Chem. 276 (18), 14980-14986 (2001)

PUBMED 11278470

REFERENCE 10 (bases 1 to 6705)

AUTHORS Xu, A., Suh,P.G., Marmy-Conus,N. , Pearson, R. B ., Seok,O.Y.,

Cocco, L. and Gilmour,R.S.

TITLE Phosphorylation of nuclear phospholipase C betal by extracellular signal-regulated kinase mediates the mitogenic action of insulin-like growth factor I JOURNAL MoI. Cell. Biol. 21 (9), 2981-2990 (2001)

PUBMED 11287604 REFERENCE 11 (bases 1 to 6705)

AUTHORS Dowal,L., Elliott, J., Popov, S., Wilkie,T.M. and Scarlata,S. TITLE Determination of the contact energies between a regulator of G protein signaling and G protein subunits and phospholipase C beta 1

JOURNAL Biochemistry 40 (2), 414-421 (2001)

PUBMED 11148035 REFERENCE 12 (bases 1 to 6705)

AUTHORS Caricasole, A. , SaIa, C, Roncarati, R. , Formenti,E. and Terstappen, G. C .

TITLE Cloning and characterization of the human phosphoinositide- specific phospholipase C-beta 1 (PLC beta 1)

JOURNAL Biochim. Biophys. Acta 1517 (1), 63-72 (2000)

PUBMED 11118617

REFERENCE 13 (bases 1 to 6705)

AUTHORS Tang, Y., Tang, J., Chen, Z., Trost,C, Flockerzi, V. , Li, M., Ramesh, V. and Zhu,M.X. TITLE Association of mammalian trp4 and phospholipase C isozymes with

PDZ domain-containing protein, NHERF

JOURNAL J. Biol. Chem. 275 (48), 37559-37564 (2000)

PUBMED 10980202

REFERENCE 14 (bases 1 to 6705)

AUTHORS Mayne,M., Holden,C.P., Nath,A. and Geiger,J.D.

TITLE Release of calcium from inositol 1 , 4 , 5-trisphosphate receptor-regulated stores by HIV-I Tat regulates TNF-alpha production in human macrophages

JOURNAL J. Immunol. 164 (12), 6538-6542 (2000)

PUBMED 10843712

REFERENCE 15 (bases 1 to 6705)

AUTHORS Peruzzi,D., Calabrese, G . , Faenza,I., Manzoli,L., Matteucci, A. , Gianfrancesco, F . , Billi, A.M. , Stuppia, L. , Palka,G. and Cocco,L.

TITLE Identification and chromosomal localisation by fluorescence in situ hybridisation of human gene of phosphoinositide-specific phospholipase C beta(l)

JOURNAL Biochim. Biophys. Acta 1484 (2-3), 175-182 (2000)

PUBMED 10760467

REFERENCE 16 (bases 1 to 6705)

AUTHORS Haughey,N. J. , Holden,C.P., Nath,A. and Geiger,J.D.

TITLE Involvement of inositol 1 , 4 , 5-trisphosphate-regulated stores of intracellular calcium in calcium dysregulation and neuron cell death caused by HIV-I protein tat

JOURNAL J. Neurochem. 73 (4), 1363-1374 (1999)

PUBMED 10501179

REFERENCE 17 (bases 1 to 6705)

AUTHORS Snow, B. E., Hall, R.A., Krumins, A.M. , Brothers, G .M. , Bouchard, D., Brothers, C .A. , Chung, S., Mangion,J., Gilman, A.G. ,

Lefkowitz, R .J. and Siderovski, D .P .

TITLE GTPase activating specificity of RGS12 and binding specificity of an alternatively spliced PDZ (PSD-95/Dlg/ZO-l ) domain

JOURNAL J. Biol. Chem. 273 (28), 17749-17755 (1998)

PUBMED 9651375

REFERENCE 18 (bases 1 to 6705)

AUTHORS Mayne,M., Bratanich, A. C . , Chen, P., Rana,F., Nath,A. and Power, C.

TITLE HIV-I tat molecular diversity and induction of TNF-alpha: implications for HIV-induced neurological disease

JOURNAL Neuroimmunomodulation 5 (3-4), 184-192 (1998)

PUBMED 9730685

REFERENCE 19 (bases 1 to 6705)

AUTHORS Chen, P., Mayne,M., Power, C. and Nath,A.

TITLE The Tat protein of HIV-I induces tumor necrosis factor-alpha production. Implications for HIV-1-associated neurological diseases JOURNAL J. Biol. Chem. 272 (36), 22385-22388 (1997) PUBMED 9278385

REFERENCE 20 (bases 1 to 6705) AUTHORS Hwang, S. C, Park, K. H., Ha, M. J., Noh,I.S., Park, T. B. and

Lee, Y. H. TITLE Distribution of phospholipase C isozymes in normal human lung tissue and their immunohistochemical localization

JOURNAL J. Korean Med. Sci. 11 (4), 305-313 (1996)

PUBMED 8878798

REFERENCE 21 (bases 1 to 6705)

AUTHORS Zauli,G., Previati,M., Caramelli, E . , Bassim,A., Falcieπ, E . , Gibellini, D . , Bertolaso, L . , Bosco,D., Robuffo,I. and

Capitani, S . TITLE Exogenous human immunodeficiency virus type-1 Tat protein selectively stimulates a phosphatidylinositol-specific phospholipase C nuclear pathway in the Jurkat T cell line

JOURNAL Eur. J. Immunol. 25 (9), 2695-2700 (1995) PUBMED 7589147 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from AJ278313.1 and AB011153.3. On JuI 31, 2003 this sequence version replaced gi : 12083580.

Summary: The protein encoded by this gene catalyzes the formation of inositol 1, 4, 5-trisphosphate and diacylglycerol from phosphatidylinositol 4 , 5-bisphosphate . This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals. This gene is activated by two G-protein alpha subumts, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene.

Transcript Variant: This variant (1) encodes the longer isoform (a) . COMPLETENESS: complete on the 3' end.

FEATURES Location/Qualifiers source 1..6705

/organism="Homo sapiens"

/mol_type="mRNA"

/db_xref="taxon: 9606"

/chromosome="20 "

/map="20pl2" gene 1..6705

/gene="PLCBl"

/note="synonyms: PLC-I, PI-PLC, PLC-154"

/db_xref="GeneID: 23236"

/db_xref="HGNC: 15917"

/db_xref="HPRD:HPRD_06177"

/db_xref="MIM: 607120"

CDS 4..3654

/gene="PLCBl"

/EC_number=" 3.1.4.11"

/go_component="cytoplasm [pmid 11118617]; nucleus

[pmid

10760467] "

/go_function="calcium ion binding; hydrolase activity; phosphoinositide phospholipase C activity [pmid

11118617] signal transducer activity"

/go_process="intracellular signaling cascade; lipid catabolism; lipid metabolism; regulation of progression through cell cycle [pmid 10760467]"

/note="isoform a is encoded by transcript variant 1; PLC-beta-1; l-phosphatidylinositol-4 , 5-bisphosphate phosphodiesterase beta 1; tπphosphoinositide phosphodiesterase; phosphoinositidase C; monophosphatidylinositol phosphodiesterase; l-phosphatidyl-D-myo-inositol-4, 5-bisphosphate; inositoltrisphosphohydrolase" /codon_start=l

/product="phosphoinositide-specific phospholipase C beta 1 isoform a"

/protein_id="NP_056007.1" /db_xref="GI: 12083581" /db_xref="CCDS:CCDS13102.1" /db_xref="GeneID: 23236" /db_xref="HGNC: 15917" /db_xref="HPRD:HPRD_06177" /db_xref="MIM: 607120"

/translat1On=¹¹MAGAQPGVHALQLKPVCVSDSLKKGTKFVKWDDDSTIVTPIILR TDPQGFFFYWTDQNKETELLDLSLVKDARCGRHAKAPKDPKLRELLDVGNIGRLEQRM

ITWYGPDLVNISHLNLVAFQEEVAKEWTNEVFSLATNLLAQNMSRDAFLEKAYTKLK LQVTPEGRIPLKNIYRLFSADRKRVETALEACSLPSSRNDSIPQEDFTPEVYRVFLNN LCPRPEIDNIFSEFGAKSKPYLTVDQMMDFINLKQRDPRLNEILYPPLKQEQVQVLIE KYEPNNSLARKGQISVDGFMRYLSGEENGWSPEKLDLNEDMSQPLSHYFINSSHNTY LTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAEEEPVITHGFTMTTEISFKEVI EAIAECAFKTSPFPILLSFENHVDSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGV PLPSPMDLMYKILVKNKKKSHKSSEGSGKKKLSEQASNTYSDSSSMFEPSSPGAGEAD TESDDDDDDDDCKKSSMDEGTAGSEAMATEEMSNLVNYIQPVKFESFEISKKRNKSFE MSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVAL NFQTMDLAMQINMGMYEYNGKSGYRLKPEFMRRPDKHFDPFTEGIVDGIVANTLSVKI ISGQFLSDKKVGTYVEVDMFGLPVDTRRKAFKTKTSQGNAVNPVWEEEPIVFKKWLP TLACLRIAVYEEGGKFIGHRILPVQAIRPGYHYICLRNERNQPLTLPAVFVYIEVKDY VPDTYADVIEALSNPIRYVNLMEQRAKQLAALTLEDEEEVKKEADPGETPSEAPSEAR TTPAENGVNHTTTLTPKPPSQALHSQPAPGSVKAPAKTEDLIQSVLTEVEAQTIEELK QQKSFVKLQKKHYKEMKDLVKRHHKKTTDLIKEHTTKYNEIQNDYLRRRAALEKSAKK DSKKKSEPSSPDHGSSTIEQDLAALDAEMTQKLIDLKDKQQQQLLNLRQEQYYSEKYQ KREHIKLLIQKLTDVAEECQNNQLKKLKEICEKEKKELKKKMDKKRQEKITEAKSKDK SQMEEEKTEMIRSYIQEWQYIKRLEEAQSKRQEKLVEKHKEIRQQILDEKPKLQVEL

EQEYQDKFKRLPLEILEFVQEAMKGKISEDSNHGSAPLSLSSDPGKVNHKTPSSEELG

GDIPGKEFDTPL"

STS 3455..3652

/gene="PLCBl"

/standard_name="AO 07B46 "

/db_xref="UmSTS : 3741 " STS 3530..3631

/gene="PLCBl"

/standard_name="D20S580E" /db_xref="UmSTS : 7842 "

STS 3644 . . 3795 /gene="PLCBl " / standard_name="D20 S594E ' /db_xref="UmSTS : 37163 " STS 5001 . . 5148 /gene="PLCBl " / standard_name="A006R17 " /db_xref="UmSTS : 39851 " STS 6399 . . 6496 /gene="PLCBl " / standard_name="RH78853 " /db_xref="UmSTS : 46819 " polyA_signal 6685 . . 6690 /gene="PLCBl " polyA_site 6705 /gene="PLCBl "

ORIGIN

1 cagatggccg gggctcaacc cggagtgcac gccttgcaac tcaagcccgt gtgcgtgtcc

61 gacagcctca agaagggcac caaattcgtc aagtgggatg atgactcaac tattgttact

121 ccaattattt tgaggactga ccctcaggga tttttctttt actggacaga tcaaaacaag

181 gagacagagc tactggatct cagccttgtc aaagatgcca gatgtgggag acacgccaaa

241 gctcccaagg accccaaatt acgtgaactt ttggatgtgg ggaacatcgg gcgcctggag

301 cagcgcatga tcacagtggt gtatgggcct gacctcgtga acatctccca tttgaatctc

361 gtggctttcc aagaagaagt ggccaaggaa tggacaaatg aggttttcag tttggcaaca

421 aacctgctgg cccaaaacat gtccagggat gcatttctgg aaaaagccta tactaaactt

481 aagctgcaag tcactccaga agggcgtatt cctctcaaaa acatatatcg cttgttttca

541 gcagatcgga agcgagttga aactgcttta gaggcttgta gtcttccatc ttcaaggaat

601 gattcaatac ctcaagaaga tttcactcca gaagtgtaca gagttttcct caacaacctt

661 tgccctcgac ctgaaattga taacatcttt tcagaatttg gtgcaaaaag caaaccatat

721 cttaccgttg atcagatgat ggattttatc aaccttaagc agcgagatcc tcggcttaat

781 gaaatacttt atccacctct aaaacaagag caagtccaag tattgattga gaagtatgaa

841 cccaacaaca gcctcgccag aaaaggacaa atatcagtgg atgggttcat gcgctatctg

901 agtggagaag aaaacggagt cgtttcacct gagaaactgg atttgaatga agacatgtct

961 cagccccttt ctcactattt cattaattcc tcgcacaaca cctacctcac agctggccaa

1021 ctggctggaa actcctctgt tgagatgtat cgccaagtgc tcctgtctgg ttgtcgctgt

1081 gtggagctgg actgctggaa gggacggact gcagaagagg aacctgtcat cacccatggc

1141 ttcaccatga caactgaaat atctttcaag gaagtgatag aagcaattgc ggagtgtgca

1201 tttaagactt caccttttcc aattctcctt tcgtttgaga accatgtgga ttccccaaag

1261 cagcaagcca agatggcgga gtactgccga ctgatctttg gggatgccct tctcatggag

1321 cccctggaaa aatatccact ggaatctgga gttcctcttc caagccctat ggatttaatg

1381 tataaaattt tggtgaaaaa taagaagaaa tcacacaagt catcagaagg aagcggcaaa

1441 aagaagctct cagaacaagc ctccaacacc tacagtgact cctccagcat gttcgagccc

1501 tcatccccag gagccggaga agctgatacg gaaagtgacg acgacgatga tgatgatgac

1561 tgtaaaaaat cttcaatgga tgaggggact gctggaagtg aggctatggc cacagaagaa

1621 atgtctaatc tggtgaacta tattcagcca gtcaagtttg agtcatttga aatttcaaaa

1681 aaaagaaata aaagttttga aatgtcttcc ttcgtggaaa ccaaaggact tgaacaactc

1741 accaagtctc cagtggaatt tgtagaatat aacaaaatgc agcttagcag gatatatcca

1801 aaaggaacac gtgtggattc atccaactat atgcctcagc tcttctggaa tgcaggttgt

1861 cagatggtgg cacttaattt ccagacaatg gacctggcta tgcaaataaa tatggggatg

1921 tatgaataca acgggaagag tggctacaga ttgaagccag agttcatgag gaggcctgac

1981 aagcattttg atccatttac tgaaggcatc gtagatggga tagtggcaaa cactttgtct

2041 gttaagatta tttcaggtca gtttctttct gataagaaag ttgggactta cgtggaagta

2101 gatatgtttg gtttgcctgt ggatacaagg aggaaggcat ttaagaccaa aacatcccaa

2161 ggaaatgctg tgaatcctgt ctgggaagaa gaacctattg tgttcaaaaa ggtggttctt

2221 cctactctgg cctgtttgag aatagcagtt tatgaagaag gaggtaaatt cattggccac

2281 cgtatcttgc cagtgcaagc cattcggcca ggctatcact atatctgtct aaggaatgaa

2341 aggaaccagc ctctgacgct gcctgctgtc tttgtctaca tagaagtgaa agactatgtg

2401 ccagacacat atgcagatgt catcgaagct ttatcaaacc caatccgata tgtgaacctg

2461 atggaacaga gagctaagca attggctgct ttgacactgg aagatgaaga agaagtaaag

2521 aaagaggctg atcctggaga aacaccatca gaggctccaa gtgaagcgag aacgactcca

2581 gcagaaaatg gggtgaatca cactacaacc ctgacaccca agccaccctc ccaggctctc 2641 cacagccagc cagctccagg ttctgtaaag gcacctgcca aaacagaaga tcttattcag 2701 agtgtcttaa cagaagtgga agcacagacc atcgaagaac taaagcaaca gaaatcgttt 2761 gtgaaacttc aaaagaaaca ctacaaagaa atgaaagacc tggttaagag acaccacaag 2821 aaaaccactg accttatcaa agaacacact accaagtata atgaaattca gaatgactac 2881 ttgagaagga gagccgcttt ggaaaagtcc gccaaaaagg acagtaagaa aaaatcggaa 2941 cccagcagcc ctgatcatgg ttcatcaacg attgagcaag acctcgctgc tctggatgct 3001 gaaatgaccc aaaagttaat agacttgaag gacaaacaac agcagcagct gcttaatctt 3061 cggcaagaac agtattatag tgaaaaatac cagaagcgag aacatattaa actgcttatt 3121 caaaagttga cggatgtcgc agaagagtgt cagaacaatc agttaaagaa gctcaaagaa 3181 atctgtgaga aagaaaagaa agaattaaag aagaaaatgg ataaaaagag gcaggagaag 3241 ataacagaag ctaaatccaa agacaaaagt cagatggaag aggagaagac agagatgatc 3301 cggtcatata tccaggaagt ggtgcagtat atcaagaggc tagaagaagc gcaaagtaaa 3361 cggcaagaaa aactcgtaga gaaacacaag gaaatacgtc agcagatcct ggatgaaaag 3421 cccaagctgc aggtggagct ggagcaagaa taccaagaca aattcaaaag actgcccctc 3481 gagattttgg aattcgtgca ggaagccatg aaaggaaaga tcagtgaaga cagcaatcac 3541 ggttctgccc ctctctccct gtcctcagac cctggaaaag tgaaccacaa gactccctcc 3601 agtgaggagc tgggaggaga catcccagga aaagaatttg atactcctct gtgaatgctc 3661 ctgccaggcc ttcagaaatt gcatggccac tccagcgtca tcggactctc tcttattaca 3721 aagatcactg cccaggacca tcttcccgag aagcatccct tagcctaaaa tccacaccaa 3781 agggagagtt ccagaggaat ccatgaagaa ttcccatgcc caggctccat gtgtcatgtg 3841 gaaacctcca caggtctgct agtgaagaat gcatgtatgt gagatttttg ttttctttcc 3901 aatagcaaat tcaaagcaag caacttgcag gctccatgga acttttaatg aaggacagtg 3961 tcttctttga agaaaatcaa gctcgtgttt ttattcgaag ctctggtgta aaatatttca 4021 aagtcataga aatagtttga gaaatgcata gcattattta acactattga acagccgact 4081 ttgagcattg tttcttctaa ctgcccctca actaccatta tcttcaagtc aacatgcata 4141 ttacattttc atcctttgct ttgcaagcac tggtggcttg cagtttgcta atttatttat 4201 catagagtca tcaatgtatt tgttgctgac atggttttat tagatactgt agtgattcaa 4261 ataagttttc tatttgaaaa aaaaaatcac ttgattgtat ccttgcccag tgaagccatc 4321 ctaagactta gcaatatgga ttgtacattt ggctgcatga gcaagtcggc cgcacacttc 4381 cagacagtgt gctgtttgaa ttgactattt gcactcaaag tctgggtatt cattggttat 4441 tggcctgaaa tgatcaaata actacaaatg atctgttgaa taaaaatagt tgagctgata 4501 tatgttaagc agatattcaa tcagaatgaa caggttccgg tggttatttt gccgtttgac 4561 attttttatg gttcatttat ttttaatata gagaggaaga ttgaatattt atctagagaa 4621 tacaaagacc cacatgtaaa tgataggtat tatctccatg tatatatgta cccacttagt 4681 catgtaagtg catatacaca tacacacaca tgagtgtaga catgtgttta ttaattgaca 4741 atgacccaaa tctcttccac aagacttaaa accaaattca gggacaaatg gatagagaag 4801 aaaagggtca aacatcgaga ttacatggat gttaaattat atggagacgc taagaaataa 4861 ttgatggagc cattgatgca aaccgaagta gatttagaac ttatatgaat ttgatttata 4921 ttttgcaaga tcaaaaatta gatgttaagt atcagatttt aagcttgttt taatggtcaa 4981 aaaattagga cagaaataat atggacattt attagtatct tccataattt ttaagtctga 5041 cacatttcta ttttattcta acataaaaaa acttccatta tatatttact aagtatattt 5101 aattcactta actctgtctt tataagttcc tattttagat ggaataagag aaacaaatta 5161 tatcaaggta aaactgatca aaagcataat tgaaagttct gaaaaaagaa aaataataat 5221 atgtagaaaa atgtaactta gagagtaaca catgaacatt gaagttaaaa cccagaagcc 5281 agatgctcac agttttattt tactttaaaa taaacctgtc tgactgtagc tttgtgaaat 5341 atcttaaaac gcaaaaacca attgtgtcct gaaaattgtt tcaagaattt aatattttta 5401 tgaaaattat tttatttaac tttaagcaat aactagagat tacaattaaa ttttaatcaa 5461 aatgaaggct tagttcaaac ataaggaaac agtgtttgat taaaaaaaac acatctagta 5521 agacgtaagg ggaaaatcac atcctctttg gagatgatta tattttgatc tgaagggttt 5581 ggggtgttca ttagacactt aataaaactt aacttccaat gaaaaagaaa tcttttgtaa 5641 atcattctac ttttgcactt tgaaagaaag gcgttaatca taaagaagca agaatggtca 5701 aaatcgaatg ctgcattttt ataaacaaaa ttacagactg tctgaaattg aagaagaatg 5761 aactaataat agcattcata accaaacaca atgatgatta ttgcagaaca ttgtatcaca 5821 ttttagtcca gagatagaat aaagttgaat aaccttgact tacacaaaac tgttttggta 5881 gttggatttc attatcttag tgaatttagt cattttacaa tatgtttgta tttggccatt 5941 tactgtaatc acatttttat atctgtacaa tgacactttt tgcagttgtg gggtagtgtg 6001 taacactgtc catcttgcat cattgaaact actacaatga tactatcatt taataatatt 6061 aatattactt gaaatagact aagataaaga aaaggggtct gtatgatgtg cagttttgtg 6121 cctttatgta tttgccttgt tctttgtcga atgtgtgaaa ttccgtactg tggtttttcc 6181 tataatagaa agtagagctg tgtattaaat tagactgtgt ctctctgata cctttacact 6241 actgagaata gcatggtttt ggccatgtaa accaattttc aaagttctaa tgacatagcc 6301 atgtgttttt ggttttttat atttcatttt aaaatttgag tatcaccata cattaattaa 6361 tactcctgta gtagataagc tgtcattaag taattcccaa aaaaagggcc atttgcttgc

6421 attactttga atttaatgtt gcgcttgtgc actgtgttaa tattgtttgt gatggattgg

6481 acgttgtgac tcttgccttt taagaagaaa aaaaagatag gacaaagtat ttgaagctct

6541 taaaatgtac atattttggt tcttctatct caaattattt aaaatgcata attcacattt

6601 ttgtaataat tctatgcaat tttgtggcat gatgtttctt ccacttgtaa ttttatgtgc

6661 tttcatcaca aatccaaagg aaagaataaa aatttcttaa cacaa

LOCUS NM_002886 6237 bp mRNA linear PRI 16-0CT-

2005

DEFINITION Homo sapiens RAP2B, member of RAS oncogene family (RAP2B) , mRNA.

ACCESSION NM_002886

VERSION NM_002886.2 GI:38201689 KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;

Catarrhim; Homimdae; Homo.

REFERENCE 1 (bases 1 to 6237) AUTHORS Greco, F., Sinigaglia, F . , Balduini,C. and Torti,M. TITLE Activation of the small GTPase Rap2B in agonist-stimulated human platelets

JOURNAL J. Thromb. Haemost. 2 (12), 2223-2230 (2004) PUBMED 15613030

REMARK GeneRIF: the small GTPase Rap2B is involved in platelet activation REFERENCE 2 (bases 1 to 6237)

AUTHORS Evellin,S., Nolte,J., Tysack,K., vom Dorp, F., Thiel,M., Weernink, P .A. , Jakobs,K.H., Webb, E. J., Lomasney, J. W. and Schmidt, M.

TITLE Stimulation of phospholipase C-epsilon by the M3 muscarinic acetylcholine receptor mediated by cyclic AMP and the GTPase Rap2B

JOURNAL J. Biol. Chem. 277 (19), 16805-16813 (2002) PUBMED 11877431

REMARK GeneRIF: Stimulation of phospholipase C-epsilon by the M3 muscarinic acetylcholine receptor mediated by cyclic AMP and the

GTPase Rap2B

REFERENCE 3 (bases 1 to 6237) AUTHORS Nancy, V., Callebaut , I . , El Mar]ou,A. and de Gunzburg,J. TITLE The delta subunit of retinal rod cGMP phosphodiesterase regulates the membrane association of Ras and Rap GTPases

JOURNAL J. Biol. Chem. 277 (17), 15076-15084 (2002)

PUBMED 11786539

REFERENCE 4 (bases 1 to 6237)

AUTHORS Nancy, V., Wolthuis, R. M. , de Tand,M.F., Janoueix-Lerosey, I . ,

Bos, J. L. and de Gunzburg,J.

TITLE Identification and characterization of potential effector molecules of the Ras-related GTPase Rap2

JOURNAL J. Biol. Chem. 274 (13), 8737-8745 (1999)

PUBMED 10085114

REFERENCE 5 (bases 1 to 6237)

AUTHORS Torti,M., Ramaschi,G., Sinigaglia, F ., Lapetina, E . G . and Balduim, C .

TITLE Association of the low molecular weight GTP-binding protein rap2B with the cytoskeleton during platelet aggregation

JOURNAL Proc. Natl. Acad. Sci. U.S.A. 90 (16), 7553-7557 (1993)

PUBMED 8356055

REFERENCE 6 (bases 1 to 6237)

AUTHORS Mollinedo, F . , Perez-Sala, D . , Ga^ate,C, Jimenez, B., Rodriguez, P . and Lacal,J.C. TITLE Localization of rapl and rap2 proteins in the gelatinase- containing granules of human neutrophils

JOURNAL FEBS Lett. 326 (1-3), 209-214 (1993)

PUBMED 8391995

REFERENCE 7 (bases 1 to 6237)

AUTHORS Farrell, F .X. , Yamamoto,K. and Lapetina, E . G .

TITLE Prenyl group identification of rap2 proteins: a ras superfamily member other than ras that is farnesylated

JOURNAL Biochem. J. 289 (PT 2), 349-355 (1993)

PUBMED 8424780

REFERENCE 8 (bases 1 to 6237)

AUTHORS Ohmstede,C.A. , Farrell, F . X ., Reep,B.R., Clemetson, K. J. and

Lapetina, E.G.

TITLE RAP2B: a RAS-related GTP-binding protein from platelets

JOURNAL Proc. Natl. Acad. Sci. U.S.A. 87 (17), 6527-6531 (1990)

PUBMED 2118648

REFERENCE 9 (bases 1 to 6237)

AUTHORS Farrell, F. X. , Ohmstede, C .A. , Reep,B.R. and Lapetina, E . G .

TITLE cDNA sequence of a new ras-related gene (rap2b) isolated from human platelets with sequence homology to rap2

JOURNAL Nucleic Acids Res. 18 (14), 4281 (1990)

PUBMED 2115998

REFERENCE 10 (bases 1 to 6237)

AUTHORS Pizon,V., Chardin,P., Lerosey,I., 01ofsson,B. and Tavitian,A.

TITLE Human cDNAs rapl and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the 'effector' region

JOURNAL Oncogene 3 (2), 201-204 (1988) PUBMED 3045729 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from BC012362.1, AC117394.10,

AL713766.1 and BF965860.1.

On Nov 7, 2003 this sequence version replaced gi:4506416.

Summary: This intronless gene belongs to a family of RAS- related genes. The proteins encoded by these genes share approximately 50% amino acid identity with the classical RAS proteins and have numerous structural features in common. The most striking difference between the RAP and RAS proteins resides in their

61st amino acid: glutamine in RAS is replaced by threonine in RAP proteins. Evidence suggests that this protein may be polyisoprenylated and palmitoylated. COMPLETENESS: complete on the 3' end.

FEATURES Location/Qualifiers source 1..6237

/organism="Homo sapiens"

/mol_type="mRNA"

/db_xref="taxon: 9606"

/chromosome="3"

/map="3q25.2" gene 1..6237

/gene="RAP2B"

/note="synonym: MGC20484"

/db_xref="GeneID:5912"

/db_xref="HGNC: 9862"

/db_xref="HPRD:HPRD_01548" /db_xref="MIM: 179541" CDS 455..1006

/gene="RAP2B"

/go_function="GTP binding; nucleotide binding"

/go_process="protein transport; small GTPase mediated signal transduction"

/note="Ras-related protein RAP-2B; small GTP binding protein; Ras family small GTP binding protein RAP2B"

/codon_start=l

/product="RAP2B, member of RAS oncogene family"

/protein_id="NP_002877.2"

/db_xref="GI: 38201690"

/db_xref="CCDS:CCDS3170.1"

/db_xref="GeneID:5912"

/db_xref="HGNC: 9862"

/db_xref="HPRD:HPRD_01548"

/db_xref="MIM: 179541"

/translat1On=¹¹MREYKVWLGSGGVGKSALTVQFVTGSFIEKYDPTIEDFYRKEI EVDSSPSVLEILDTAGTEQFASMRDLYIKNGQGFILVYSLVNQQSFQDIKPMRDQIIR

VKRYERVPMILVGNKVDLEGEREVSYGEGKALAEEWSCPFMETSAKNKASVDELFAEI

VRQMNYAAQPNGDEGCCSACVIL" STS 535..734

/gene="RAP2B"

/standard_name="flO5fO9.xl"

/db_xref="UmSTS:201903" STS 1498..1753

/gene="RAP2B"

/standard_name=" SHGC-77466"

/db_xref="UmSTS:34924" STS 1505..1752

/gene="RAP2B"

/standard_name="RH79703"

/db_xref="UmSTS: 84632" polyA_site 2483

/gene="RAP2B"

/experiment=" expeπmental evidence , no additional details recorded"

STS 3666..3853

/gene="RAP2B"

/standard_name="SHGC-77468'

/db_xref="UmSTS: 83232" polyA_signal 6217..6222

/gene="RAP2B" polyA_site 6237

/gene="RAP2B"

ORIGIN

1 gagagagcgc gatgggccgc ggcggtgggc gcacgttccg cggggactca tgccacgcgc

61 gtcccggccc gacgcgcaat tagcagccac ctccgcagcc cgccgccacc gcctccctgc

121 cctcccgggc tgccgcagct aggagctcca gccgtcgcct cgcgcaggct gcgggcattg

181 tcctctcggt tcgccgcccg ggctgctgct gccgccgcgg actgctgcgg ggcccggacc

241 cgcaccccag ggatacgctg ccgccgccgc cggccggccc ggcgcccggc ctccgttcgg

301 tggtttccgc cctgcgttct ctgggttgct ctctcctggg tttttcctgc gtagctgagg

361 aaggggaaga gaagtccagc cgccaagccc agccttcccc ggcgcgcagc cccgacgggg

421 ccgcggcagg cgcggcgaga gcgctgacgg agccatgaga gagtacaaag tggtggtgct

481 gggctcgggc ggcgtgggca agtccgcgct caccgtgcag ttcgtgacgg gctccttcat

541 cgagaagtac gacccgacca tcgaagactt ttaccgcaag gagattgagg tggactcgtc

601 gccgtcggtg ctggagatcc tggatacggc gggcaccgag cagttcgcgt ccatgcggga

661 cctgtacatc aagaacggcc agggcttcat cctggtctac agcctcgtca accagcagag 721 cttccaggac atcaagccca tgcgggacca gatcatccgc gtgaagcggt acgagcgcgt 781 gcccatgatc ctggtgggca acaaggtgga cctggagggt gagcgcgagg tctcgtacgg 841 ggagggcaag gccctggctg aggagtggag ctgccccttc atggagacgt cggccaaaaa 901 caaagcctcg gtagacgagc tatttgccga gatcgtgcgg cagatgaact acgcggcgca 961 gcccaacggc gatgagggct gctgctcggc ctgcgtgatc ctctgaggcg gccaccgcgc 1021 gccggccgcg ctctgcgcac aaaagccaaa cgcatccgac tctctaaatg tgatttattt 1081 cttgctttga gattggagac cactttgcat tggccagggt gtcttgggag cccggctggc 1141 ctccgcggcc ggcgtcccct gcctccaccc tgtgcccgag ggggtgtccg gtcctgccca 1201 tccgatactc tggtggaaat gtggctcttt gcagcatgta cgtttctccc tgattttggt 1261 tgatgcatat ttccccgttt aagtagccgt tagggcgcag tatcggcagc ttgacaccca 1321 ccaagcaaaa gtttcagcct ggaaaaaaaa tgggggggaa gggtggatga aaaggaggga 1381 gagaaggtgg aaatggtttt tttttttttt tttctatttt ctttcttttt tttttttttt 1441 ttttttggtc aacagccgtt tttctagttc caagttttaa atacatggaa ggaagtccgg 1501 gagaaccata tgaaggagca ggaggagagg aagaaacttt ttttccttct tttccaggag 1561 tagctggaaa ttaagatcgg gttccttttc tgccagcttg gaagggcaac cccatgactg 1621 attgcgattc tgaggatgtc tatgcaaagt tggattcttg ttacagtgta tccaatctga 1681 agtattgcac atctgaactg ggactgttaa cactgatgcc aatacagtgt ggggtgccag 1741 aaagtgtctg ctgatatttg tggaaaaaaa atctattttg tttacctact gtatcaaagg 1801 ggagtctggg ggagaatggt agtatttttt ttttttatca gctgtgaaaa aaatgttaca 1861 gatctgcaca ttttcgtgtg tactatggtg tgtgtgtgta tgtgtgtggt gtgtgtgtgt 1921 tttaagttta gccttttgtt tttgtttttt ggttggcagt aaccgatttt aatgactagc 1981 ttttaaaaat acagtacaaa gactttgtaa atgtgattca gggcccccag cacccctgtg 2041 tctgcagagt gccttcaaaa ctcagctgtt ccagccggtg ccaacctgtg aacttcccac 2101 catatcccag aatctgctat tccccaaacc acttcccagt ttcctttcag taatctttct 2161 gaaggagcca ggacaatagg gcctgttgtt tagtgaattt ctttattatt ttcagccttt 2221 aaaatgtaat ttccatctct tgcaatgaat ttgtttccct tttttttgct tcattttgtt 2281 taaattttca ggtatttagc tcccctttca tattattttt aaatttttta attacctgtt 2341 gtagggtgtt cctccagaag caaagagcaa aattttactg ttgtgatgta ccaattctaa 2401 ctaattgtaa tttttaattt catgcgttta atcattgtct cttcatttta agacttttaa 2461 tacaaatgtc atttttaaag aaacaaaccc aaaactattg tttgtgtttc tgtgtttcat 2521 attcagtgat ttaatacagt atcatggctg aggtggatgg ggcaggtgca tgatactctt 2581 cagagctatt tgtgaaattt taaagacaga agtgtctcag tgacaagttg gatgacacta 2641 ctcccaactt tttaaatttg gagaaaacca tcaaggtcga ggaagccctg ggtatggcca 2701 ttaccatctg attagaagat gaacaggtat tttgaatctg atctgacatg gaacagttta 2761 cctcattgta ggtagggaac aagagaaccc atctattaaa attgccttag atctgggaaa 2821 gtaaccatcc ttctggcaaa gtaggatggc acttttaagt ttttcttcct tttttccctc 2881 tgtttatatt gcacatcaag tcaaaaacat gtttgggaaa gatggttttc aattctgaag 2941 ttatacctag tgatgttttt tgcagtacat ttgaatggat tgtagacact gcctcaaccc 3001 ttttgaggtt ttgatttgga aatagattta aaagaaaaca ggctaagata atatccttgt 3061 tctcatttac accctgcagt ttggaccaca tttgacctca taagtttttc cttttaacag 3121 taggaggcag tgtgagcttt ttatttttta tttttcttaa ggtggtctta gtaatataac 3181 atgttcatac atatcaagag agtacttggt ataccttagg tctatgaagt gtagctgaaa 3241 tctgaagagt cttgacaaag ggatttacac ccttgacaaa accaaaagaa attaacaggc 3301 cacaggtttc tttaaagctg tgttaacata tcttgcctta aaatgtgtgt gtgtgttttt 3361 gctttgcttt tttttttttg cccaagaggc atctcagtac tccagcaatg gaggaagaat 3421 agagaatttt gcctggcaat ggtcctactg ccattttttt tttcccactc tgatctcact 3481 taagtttgat atcaaacaca attgggaggc aatagtatca atatcctaaa tgtagaaatt 3541 aaaagatact gtataatttt atgcctttgc aaagattcgt tcttgtattt gaataaattc 3601 agttgctaaa gtagatccaa agtgttaaaa atgctgaagt catgtcaagt actgtctgga 3661 gggttttttt aagaaaaggc atttggcatt taactgtctc ttgttttatt tttaagtttt 3721 tggaaacctt ttgacataaa atgctgccaa gtatctaaga aatgtatata ctgacagaag 3781 atatttgaaa gtggaaaatt ggaaatgaaa tatgttgctg ggtgcgttaa tcacctccgc 3841 ccaggattta gtcacttgca ggacctcttt atagtctagg atggcagagc agaagatttt 3901 aatatgcttt tattaagtga tgtaaaataa atgctttttg gattatcaat gaaagcaatt 3961 ttatgtgtgc ctgaagcaag aaaatagcgt ttttggtttt atctcatatt ttcttggcaa 4021 aattgagaga aattaggaac actgctattt ttttcttaaa aatgttttta agaatatgtt 4081 cgtttctttg actattaaga accccttgtg gtattagtgt gtgaagagat aagggcattt 4141 gtttcaatga aaaagttagt gttaaaggaa gtgagtcagg gagggcggag tttgttgtaa 4201 ggcaatcacc tgtcaaaaca gaaattgggt gggaaaggag tctttatctt ggggagcaaa 4261 agctgacttt taaacttgac ccctgctgtt tttaaacagc ttttcctttt ggtctctgac 4321 agtcaatcca ggttttatgt tatttcaaaa gggttatttt tgtcctcctt ttttaatagc 4381 ttcaggaaag ttaaaggtat catcttaggt ctaacactct agtctttgag agttacggtt 4441 ctttcgtaga acaatttcca tgttgttaac tgttgtagac ttaattgaat cacattttgg 4501 gaccagatgt atttggggat agaattcttt aaatgtatgg gacttcatgc ttcctgatta 4561 tgtaatattt cctgtggttg ggaatcctag aatgcctgat ctattttatc tgttcaggta 4621 gttttgttat tgtaccctct tttgggtcat attctagtat ttctcacagg gggtatgaga 4681 aacagaaagc tatatgtagc agctggtctt gagaagtaga agcatcttaa ctgtcataag 4741 agcatagatt ttttgttttt cacaacagct ggaataagtt cctgcattat aagtataaag 4801 ggaaccgaga tttaatttgg agatcatcac tgttaaaacg ataccagaca tttgtcacag 4861 tgtcttattt ggggaaagtt tgctaatata cattttgtct gtgaaaatat agtaaatttt 4921 aaaatactaa tataatgtgg tattcttgat tacagtattt tatgcagact attaggaatg 4981 attcagtgca tttaactgaa cacagagcta gttctaggtg agtgagatct ttatctatta 5041 actggatttt gaaggtttga gaaggctatg gggatcatct ggttgaaagg ttctcaaact 5101 tgaccatata tcaaaatcac ctggagctta aaacatgtac tgctgggacc ctcctccagt 5161 ttcttaccca gtgggtctcg ggtagggtct caattttcat ttctaacaag tttccaagtg 5221 attgtgttat tgctgttcca gggaccacac tttgaaaacc agtgatctag actgaactcc 5281 aaatgagtac tatactgaca gccacctaga tattgagaga cacagacttc agactcatgt 5341 cacacatttt ggagtgctgt ctactacagt tagagaataa tctctattga aatctaagct 5401 aaagaggaca tataccattt atactaagac taactgttgt gtgtgaaata gaataaacat 5461 tgcaggtagt ttttgatcat tttcacatta ttacaggaac attttgacta tggttttcaa 5521 tgttaattca gaagttgact ttaaatgaaa atgtggttag aatagaggca aagcctaagt 5581 gatcagaatc aacattcccc ttctccccaa cctaggggaa aaaaaatttg aaaagtatgt 5641 cttcaataaa aggggacact ttatttgtct tctcttcaac attaaaaaac aaagatttta 5701 agttttcatg gcaagggttc taaaaatcat tgtgccagag aatttaaatc ttcatatcat 5761 ggtaagcaca tgcgtatgtc tgtgactcag tttcttagcc agacttccag gtgttagtta 5821 attccttctc atttagttct actgtaatcc attctgggaa aatgcatacc acaaaactgt 5881 gtatcttgca gcttctttcg ttatgcatct taattccctc agaaggtccc agaactttat 5941 gttaaagatc tgggttttta aagacaattt gggggccttc taaagaaaca atagtagatc 6001 taattacaag tagtggattg cttacttcaa atttctcttt tacaatttag aaagtttagt 6061 accagtttat agactgaggg agtagtagct actatttaga tgctgagaat aatattatca 6121 tgcttgggtg gggaagaaag gcccttactc aaatctccat tttcattttt aatgcttcct 6181 ggacttcagt tattttcttg cttttgcctc aagaataata aatatttttg gttaaaa

LOCUS NM_013321 1522 bp mRNA linear PRI 02-MAR-

2006

DEFINITION Homo sapiens sorting nexin 8 (SNX8), mRNA. ACCESSION NM_013321

VERSION NM_013321.1 GI:23943857 KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhim; Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 1522)

AUTHORS Scherer, S .W. , Cheung, J., MacDonald, J. R. , Osborne, L . R. ,

Nakabayashi, K. , Herbrick, J. A. , Carson, A. R., Parker-Katiraee, L . , Skaug,J., Kha^a,R., Zhang, J., Hudek,A.K., Li, M., Haddad,M., Duggan,G.E., Fernandez, B .A. , Kanematsu, E . , Gentles, S., Chπstopoulos, C . C . , Choufam,S., Kwasmcka, D . , Zheng, X. H., Lai, Z . ,

Nusskern,D., Zhang, Q., Gu, Z., Lu, F., Zeesman,S., Nowaczyk, M. J. , Teshima, I . , Chitayat,D., Shuman,C., Weksberg,R., Zackai,E.H., Grebe, T. A., Cox, S. R., Kirkpatπck, S . J. , Rahman, N., Friedman, J. M. ,

Heng,H.H., Pelicci, P . G . , Lo-Coco,F., Bellom,E., Shaffer, L . G ., Pober,B., Morton, C. C, Gusella, J. F . , Bruns,G.A., Korf,B.R., Quade,B.J., Ligon, A.H. , Ferguson, H., Higgins, A. W. , Leach, N. T., Herrick, S . R. , Lemyre,E., Farra,C.G., Kim, H. G., Summers, A.M. , Gπpp,K.W., Roberts, W., Szatmaπ,P., Winsor,E.J., Grzeschik, K. H. ,

Teebi,A., Minassian, B. A. , Kere,J., Armengol,L., Pujana, M. A. , Estivill,X., Wilson, M. D., Koop,B.F., Tosi,S., Moore, G. E., Boπght, A. P . , Zlotorynski, E . , Kerem,B., Kroisel, P .M. , Petek,E., Oscier,D.G., Mould, S.J. , Dohner,H., Dohner,K., Rommens, J. M. , Vincent, J. B. , Venter, J. C, Li, P. W., Mural, R. J., Adams, M. D. and Tsui, L. C.

TITLE Human chromosome 7: DNA sequence and biology JOURNAL Science 300 (5620), 767-772 (2003)

PUBMED 12690205 REFERENCE 2 (bases 1 to 1522)

AUTHORS Worby,C.A. and Dixon,J.E.

TITLE Sorting out the cellular functions of sorting nexins

JOURNAL Nat. Rev. MoI. Cell Biol. 3 (12), 919-931 (2002)

PUBMED 12461558 REMARK Review article REFERENCE 3 (bases 1 to 1522)

AUTHORS Teasdale, R. D. , Loci, D., Houghton,F., Karlsson,L. and Gleeson,P.A.

TITLE A large family of endosome-localized proteins related to sorting nexin 1 JOURNAL Biochem. J. 358 (PT 1), 7-16 (2001)

PUBMED 11485546

COMMENT PROVISIONAL REFSEQ: This record has not yet been subject to final

NCBI review. The reference sequence was derived from BC021565.1 and

AF121858.1.

FEATURES Location/Qualifiers source 1..1522

/organism="Homo sapiens" /mol_type="mRNA" /db_xref="taxon: 9606" / chromosome= " 7 "

/map= " 7p22 . 2 " gene 1 . . 1522

/gene= " SNX8 "

/db_xre f= " Gene ID : 2 9886 "

/db_xre f= " HGNC : 14 972 "

/db_xre f= " HPRD : HPRD_11592 "

CDS 44 . . 1441

/gene= " SNX8 "

/go_f unct ion= "phosphoinos it ide binding ; protein binding "

/go_proces s= " int racel lular s ignal ing cascade ; protein t ransport "

/codon_start=l

/product="sorting nexin 8"

/protein_id="NP_037453.1"

/db_xref="GI: 23943858"

/db_xref="CCDS:CCDS5331.1"

/db_xref="GeneID:29886"

/db_xref="HGNC:14972"

/db_xref="HPRD:HPRD_11592"

/translation="MTGRAMDPLPAAAVGAAAEAEADEEADPPASDLPTPQAIEPQAI

VQQVPAPSRMQMPQGNPLLLSHTLQELLARDTVQVELIPEKKGLFLKHVEYEVSSQRF KSSVYRRYNDFWFQEMLLHKFPYRMVPALPPKRMLGADREFIEARRRALKRFVNLVA RHPLFSEDWLKLFLSFSGSDVQNKLKESAQCVGDEFLNCKLATRAKDFLPADIQAQF AISRELIRNIYNSFHKLRDRAERIASRAIDNAADLLIFGKELSAIGSDTTPLPSWAAL NSSTWGSLKQALKGLSVEFALLADKAAQQGKQEENDWEKLNLFLDLLQSYKDLCERH EKGVLHKHQRALHKYSLMKRQMMSATAQNREPESVEQLESRIVEQENAIQTMELRNYF

SLYCLHQETQLIHVYLPLTSHILRAFVNSQIQGHKEMSKVWNDLRPKLSCLFAGPHST

LTPPCSPPEDGLCPH"

ORIGIN

1 gccgggtggc gcgggaggaa gtcacgtggg agcgcgggct cacatgactg gccgcgcgat

61 ggacccgctg cccgcggctg cagtcggggc ggcagctgag gcggaggctg acgaggaggc

121 ggatcccccg gcgtcagatc tgccgacacc ccaggccatc gagccccagg ccatcgtgca

181 gcaggtccca gcccccagtc gaatgcagat gccgcagggg aacccgctgc tgctgtccca

241 caccctgcag gagctgctgg ccagggacac cgtgcaggtg gagctcattc cggagaagaa

301 gggcctcttc ctgaagcatg tggagtatga ggtttccagc cagcgcttca agtcctcggt

361 atacagacgg tacaatgact tcgtggtctt ccaggagatg ctcctgcaca agttccccta

421 ccgtatggtg cctgccctgc cacccaagag aatgctggga gctgacaggg agttcatcga

481 ggccaggagg agagccctga agcgcttcgt caacctggtg gcgcgacacc ccctgttctc

541 cgaggatgtg gtcctcaagc tcttcctgtc cttcagcggc tcggatgtgc agaacaagtt

601 aaaggagtca gcacagtgcg tcggggacga attcctgaac tgtaagctgg ctaccagggc

661 caaggacttc ctcccagctg acatccaggc tcagtttgcc atcagccggg agctgatccg

721 gaacatctac aatagctttc acaagcttcg cgacagggcc gagcggatcg cgtcgcgggc

781 catcgacaat gcggcagatc ttctcatatt cgggaaggag ctaagtgcaa tagggtctga

841 cacgaccccg ctgccctcct gggccgctct gaatagcagc acgtgggggt ccctgaagca

901 ggctctgaaa ggcctgtctg tggaattcgc gctgctcgcc gacaaggctg cacaacaggg

961 taagcaggaa gagaacgacg tggtggagaa gctgaacctc ttcttggatc tgctgcagtc

1021 ctataaggac ctgtgcgagc ggcatgagaa gggcgtgttg cacaagcacc agcgggccct

1081 gcacaagtac agcctgatga agaggcagat gatgagcgcc accgcgcaga accgcgagcc

1141 ggagtccgtg gagcagctgg agtcccgcat cgtggagcag gagaacgcga ttcagacgat

1201 ggagctgcgg aactacttct ccctgtactg cctgcaccag gagacgcagc tcatccacgt

1261 ctacctgccc ctcacctccc acatcctccg cgccttcgtc aactctcaga tccaagggca

1321 caaggagatg agcaaggtgt ggaacgacct gaggcccaag ctcagctgcc tctttgcggg 1381 accacacagc accctgaccc caccgtgctc cccgccggag gacggcctgt gtcctcacta 1441 gcgcctgagg ctgaggtggt gctccctgcg gccgcactaa aacctctttc caaaaaaaaa 1501 aaaaaaaaaa aaaaaaaaaa aa

LOCUS NM 003597 4051 bp mRNA linear PRI 04-MAR-

2006

DEFINITION Homo sapiens Kruppel-like factor 11 (KLFIl), mRNA.

ACCESSION NM_003597 XM_938887

VERSION NM_003597.4 GI:40548370

KEYWORDS

SOURCE Homo sapiens (human)

ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata;

EuteleostomiL;;

REFERENCE 1 (bases 1 to 4051) AUTHORS Neve, B., Fernandez-Zapico, M. E . , Ashkenazi-Katalan, V. , Dina,C, Hamid,Y.H., JoIy, E., Vaillant,E., Benmezroua, Y . , Durand,E., Bakaher,N., Delannoy,V., Vaxillaire, M. , Cook, T., Dallinga-Thie, G. M. , Jansen,H., Charles, M.A. , Clement, K.,

Galan,P. ,

Hercberg,S., Helbecque, N . , Charpentier, G . , Prentki,M., Hansen, T . ,

Pedersen,O., Urrutia,R., Melloul,D. and Froguel,P.

TITLE Role of transcription factor KLFIl and its diabetes-associated gene variants in pancreatic beta cell function

JOURNAL Proc. Natl. Acad. Sci. U.S.A. 102 (13), 4807-4812 (2005) PUBMED 15774581 REMARK GeneRIF: KLFIl plays a role in the regulation of pancreatic beta cell physiology, and its variants may contribute to the development of diabetes.

REFERENCE 2 (bases 1 to 4051) AUTHORS Cao,S., Fernandez-Zapico, M. E . , Jin, D., Pun, V., Cook, T.A.,

Lerman,L.O., Zhu,X.Y., Urrutia,R. and Shah, V.

TITLE KLFll-mediated repression antagonizes Spl/sterol-responsive element-binding protein-induced transcriptional activation of caveolin-1 in response to cholesterol signaling

JOURNAL J. Biol. Chem. 280 (3), 1901-1910 (2005) PUBMED 15531587 REMARK GeneRIF: in the presence of cholesterol, KLFIl acts as a dominant repressor of the caveolin-1 gene

REFERENCE 3 (bases 1 to 4051) AUTHORS Ellenπeder, V. , Buck, A., Harth,A., Jungert,K., Buchholz,M.,

Adler,G., Urrutia,R. and Gress,T.M.

TITLE KLFIl mediates a critical mechanism in TGF-beta signaling that is inactivated by Erk-MAPK in pancreatic cancer cells

JOURNAL Gastroenterology 127 (2), 607-620 (2004) PUBMED 15300592 REMARK GeneRIF: novel mechanism in TGF-beta-regulated gene expression:

KLFIl potentiates Smad-signaling activity in normal epithelial cells through termination of the negative feedback loop imposed by

Smad7.

REFERENCE 4 (bases 1 to 4051) AUTHORS Ou, X. M., Chen, K. and Shih,J.C. TITLE Dual functions of transcription factors, transforming growth factor-beta-inducible early gene (TIEG) 2 and Sp3, are mediated by

CACCC element and SpI sites of human monoamine oxidase (MAO) B gene JOURNAL J. Biol. Chem. 279 (20), 21021-21028 (2004) PUBMED 15024015 REMARK GeneRIF: TIEG2 is an activator of Monoamine oxidase B gene expression .

REFERENCE 5 (bases 1 to 4051) AUTHORS Ellenπeder, V. , Zhang, J. S., Kaczynski, J. and Urrutia,R. TITLE Signaling disrupts mSin3A binding to the Madl-like Sin3- interacting domain of TIEG2, an Spl-like repressor

JOURNAL EMBO J. 21 (10), 2451-2460 (2002)

PUBMED 12006497

REFERENCE 6 (bases 1 to 4051)

AUTHORS Jia,L., Young, M. F., Powell, J., Yang, L., Ho, N. C, Hotchkiss, R. ,

Robey,P.G. and Francomano, C .A.

TITLE Gene expression profile of human bone marrow stromal cells: high-throughput expressed sequence tag sequencing analysis

JOURNAL Genomics 79 (1), 7-17 (2002)

PUBMED 11827452

REFERENCE 7 (bases 1 to 4051)

AUTHORS Zhang, J. S., Moncrieffe, M. C . , Kaczynski, J. , Ellenπeder, V. ,

Prendergast, F .G. and Urrutia,R.

TITLE A conserved alpha-helical motif mediates the interaction of

Spl-like transcriptional repressors with the corepressor mSin3A

JOURNAL MoI. Cell. Biol. 21 (15), 5041-5049 (2001)

PUBMED 11438660

REFERENCE 8 (bases 1 to 4051)

AUTHORS Scohy,S., Gabant,P., Van Reeth,T., Hertveldt , V. , Dreze,P.L., Van

Vooren,P., Riviere, M., Szpirer,J. and Szpirer,C.

TITLE Identification of KLF13 and KLF14 (SP6) , novel members of the SP/XKLF transcription factor family

JOURNAL Genomics 70 (1), 93-101 (2000)

PUBMED 11087666

REFERENCE 9 (bases 1 to 4051)

AUTHORS Asano,H., Li, X. S. and Stamatoyannopoulos, G .

TITLE FKLF, a novel Kruppel-like factor that activates human embryonic and fetal beta-like globin genes

JOURNAL MoI. Cell. Biol. 19 (5), 3571-3579 (1999)

PUBMED 10207080

REFERENCE 10 (bases 1 to 4051)

AUTHORS Cook, T., Gebelein,B., Mesa, K., Mladek,A. and Urrutia,R.

TITLE Molecular cloning and characterization of TIEG2 reveals a new subfamily of transforming growth factor-beta-inducible Spl-like zinc finger-encoding genes involved in the regulation of cell growth

JOURNAL J. Biol. Chem. 273 (40), 25929-25936 (1998) PUBMED 9748269 COMMENT VALIDATED REFSEQ: This record has undergone preliminary review of the sequence, but has not yet been subject to final review. The reference sequence was derived from CB990375.1, AF272830.1, AI183650.1, BQ881155.1, AK002186.1, BM548792.1 and AI755210.1. On or before Mar 4, 2006 this sequence version replaced gi:88954805, gi : 40255017.

FEATURES Location/Qualifiers source 1..4051

/orgamsm="Homo sapiens "

/mol_type="mRNA"

/db_xref="taxon : 9606 "

/chromosome="2 "

/map="2p25" gene 1..4051

/gene="KLFll"

/note="synonyms: FKLF, FKLFl, TIEG2"

/db_xref="GeneID: 8462"

/db_xref="HGNC: 11811"

/db_xref="HPRD:HPRD_04488"

/db_xref="MIM: 603301"

CDS 163..1701

/gene="KLFll"

/go_component="nucleus [pmid 9748269]"

/go_function="metal ion binding; transcription factor activity [pmid 9748269]; zinc ion binding"

/go_process="negative regulation of cell proliferation

[pmid 9748269]; negative regulation of transcription f rom

RNA polymerase II promoter [pmid 9748269]; regulation o f transcription, DNA-dependent ; transcription; t ranscript ion from RNA polymerase II promoter [pmid 9748269]"

/note="TGFB inducible early growth response 2"

/codon_start=l

/product="Kruppel-like factor 11"

/protein_id="NP_003588.1"

/db_xref="GI: 4507503"

/db_xref="CCDS: CCDSl 668.1"

/db_xref="GeneID: 8462"

/db_xref="HGNC: 11811"

/db_xref="HPRD:HPRD_04488"

/db_xref="MIM: 603301"

/translation="MHTPDFAGPDDARAVDIMDICESILERKRHDSERSTCSILEQTD MEAVEALVCMSSWGQRSQKGDLLRIRPLTPVSDSGDVTTTVHMDAATPELPKDFHSLS TLCITPPQSPDLVEPSTRTPVSPQVTDSKACTATDVLQSSAWARALSGGAERGLLGL EPVPSSPCRAKGTSVIRHTGESPAACFPTIQTPDCRLSDSREGEEQLLGHFETLQDTH LTDSLLSTNLVSCQPCLHKSGGLLLTDKGQQAGWPGAVQTCSPKNYENDLPRKTTPLI SVSVPAPPVLCQMIPVTGQSSMLPAFLKPPPQLSVGTVRPILAQAAPAPQPVFVGPAV PQGAVMLVLPQGALPPPAPCAANVMAAGNTKLLPLAPAPVFITSSQNCVPQVDFSRRR NYVCSFPGCRKTYFKSSHLKAHLRTHTGEKPFNCSWDGCDKKFARSDELSRHRRTHTG

EKKFVCPVCDRRFMRSDHLTKHARRHMTTKKIPGWQAEVGKLNRIASAESPGSPLVSM

PASA"

STS 318..450

/gene="KLFll" /standard_name="RH78629" /db_xref="UmSTS:80550"

STS 3747..4003

/gene="KLFll" /standard_name="A005P43" /db_xref="UmSTS: 22254"

STS 3747..4003

/gene="KLFll" /standard_name="G20404" /db_xref="UmSTS: 22253"

STS 3757..3868 /gene="KLFll" /standard_name="RH11597" /db_xref="UmSTS: 10463"

STS 3891..3998 /gene="KLFll"

/standard_name="SHGC-36737' /db_xref="UmSTS: 11113"

ORIGIN

1 gagggccgcg ccggggcaga gccgcgcggg cgggcgaggc gcgtgccggc cgcaggagct

61 ccgggttgcc gccgccgccg ccgcccgcag cccacgtgcg gccgctgctg cgcccgagct

121 cacgccccgc ggccgctttg ttgctcccgg ccggcctgca cgatgcacac gccggacttc

181 gcaggcccag acgacgcgcg cgcagttgac atcatggaca tatgtgagtc catcctggag

241 aggaagcggc atgacagcga aaggtctact tgcagcatct tggagcagac agacatggaa

301 gctgtcgagg ctcttgtttg tatgagctcc tggggtcaaa gatcccagaa aggtgacctg

361 ttgcggataa gacccctcac gcctgtctct gactctgggg atgtcaccac cactgtgcat

421 atggatgcag ccacacctga actaccaaaa gacttccatt ctttatcgac tctgtgcata

481 actcctcctc agagccctga tctcgtggag ccatcgacaa ggacacctgt ttctccccaa

541 gtaacagatt ccaaagcatg tacagccacg gatgttctcc agtcctctgc cgtagtggcc

601 agagctctga gcgggggcgc ggagaggggc ttgctgggtt tggagccagt gcccagctct

661 ccctgcaggg ccaaggggac tagcgtgatc cgacacactg gggagagccc tgctgcctgc

721 tttcccacca tccagactcc agattgccgg ctttctgaca gcagagaagg agaagagcag

781 cttctgggac actttgaaac tttgcaggac acacacctca cggacagttt actcagcact

841 aacttggtgt cctgtcagcc ctgcttgcac aagtctggtg gcctgctgct cactgacaaa

901 ggccagcagg cagggtggcc tggtgcagtt cagacttgct caccaaagaa ttatgaaaat

961 gacctgccca ggaaaaccac ccctctgatt tctgtctctg tccctgctcc ccctgtcctt

1021 tgccagatga tccctgtgac tggacaaagt agcatgttac cagctttttt gaagccccct

1081 ccccagttgt ctgtggggac tgtgagaccc atcctagctc aggctgctcc agcgcctcaa

1141 cctgtgttcg tgggacctgc tgtgcctcag ggagctgtga tgttggtcct gccccaggga

1201 gccctccctc cgcctgcccc ctgtgcagcc aatgtcatgg ctgccgggaa taccaagttg

1261 ttgccccttg cccctgctcc agtgttcatc acctctagcc aaaactgtgt ccctcaggta

1321 gacttttccc gaaggaggaa ctatgtttgc agcttcccag gttgccggaa gacctacttc

1381 aaaagttccc accttaaggc ccatcttcgc actcacacag gggagaagcc tttcaactgc

1441 agctgggatg gctgtgataa aaagtttgct cgttcggatg agctgtcacg ccaccgcaga

1501 actcacacag gggagaagaa gtttgtgtgc ccggtgtgtg accgacgttt catgcgcagt

1561 gaccacctga cgaagcatgc ccggcgccac atgacgacca agaagatccc aggctggcag

1621 gcagaggttg gcaagctgaa cagaatcgcc tctgcagaga gcccggggag cccactggtg

1681 agcatgccag cctctgcctg aaaggtccat taggacatca ctcatgggat ttttaaaaag

1741 cctctttcca ggaatggaac tgatggattc ctctcccact gcctcaccca aaaaaaacgg

1801 tcttggcggc ctaggggaag atcggggagc tggttttgat gaaagtatgt taacttttct

1861 tttccacttg ggaccctgtt cagtatcttt tgtagtttca gaagtttttt tgttttggtt

1921 ttttttttaa agaaatggta gaaaatttga taatctgaat caccagcatt caaacaaata

1981 tttcggcaat aaagtttaca aaatctggat ttttacaacc ttttctattg atgttttgta

2041 gaaataagac agggtactaa tttttatact ggtttttaga aaaatattta tattgttggt

2101 gctcaaatca ccaatttcta gctagatcat tttgcagcct tcttttcagt gtttaataac

2161 aaagtttttc ctaatggccc ttcttttagt aaactggaca tgttattcca ctacaaaaac

2221 cacaagttat ctggcctttt agatcttttt ggaatcggac ctggttgagt aaggacctct

2281 taaaagggaa aaataaattt tgccgtcagc ttcttcataa cgttttcaag gaaattctag

2341 gcaatcattc ctgtcaccaa agaactaaaa ttttggttga ctggaactag tgagctgtgt

2401 ccatggtgtg tcatgaagga tgtaccccag agagtaacat gagccactgg gcagatccca

2461 gggaccagta cttgctgcag gatctagtct gtaatagtct tggccatggc tctgctgaaa

2521 gcaagccatt cagtttcttg tttgtaccta aaacaccaaa aaagaaacac tcaaatccag

2581 ctgctttgtc aattgtcagt tctgactcct tttgctgtgg ccttatccgt actatattgt

2641 gggtagagta acttctcaga aaaaaaggaa atgtctgtat tggttggatg aaactccacc

2701 agagcacagc ttagctgggg cgagatgcat gtgaaggcag gcagtgccaa gattccgctt

2761 cctttgtttg ccaaatacta gaaacacaag gaaatgcaag ttacgctaaa tggcagtaat

2821 actacccaac tgcctttctg ttcattttgt ttgaaggaaa ttgttttgac caaacagaaa

2881 attacttgga atggtgtgtt ttacagtcta cctagaaaat agatggacaa tatttttcaa

2941 ctgtatgagc acgtagataa ccgagagaat gtggccacct gtgttcaaga agccactgat

3001 actggttttt gttaaacatt ggaagttcag gcaatggaat aaatgtagga acatacagaa

3061 tgttgcacta atttggtagc ctgggaattt tttttattgt gcagtatgta tttaaatttt

3121 gtctatgtta attaccagca tttaccttta tttaaatgat ggtaaggtgg aatattgaat

3181 aaaattaggt tttgtgtttt gttctttgta gtctgataaa atctccacct ggtcattcat 3241 tgtgtgtgac ttgatacctg ttaacttgcc ccttagtatc agctgttact tgacacaaat 3301 gtgtgtgtta ttcagaggtt ttcagtctgg acactccata ggtgagtgtc gtgtcttcgt 3361 gagacagcac agttgtctca tgttgtgcat agttcatgtt tcctcaccac ccagtccttt 3421 ctcctgctca tcaaaatcag catacacatt tttgactgta cacactataa atggcatcaa 3481 atttggatat ttttcttaat tatgacatgc aaagtaatgt gagtcctgcc agtattctgg 3541 tggataaggt cttttgagta tttggttgct tgtcacaaca ttctccaagc agtgatattt 3601 ctaaagagga gatacatgtt gaaaacggtt ttaatttaca cttccatttc ctgattacat 3661 ttggaaatac tttgtgtaaa ccatccccct tccacctcca tttgtctgtt gaaagatttt 3721 aagttggaaa cagttcctgt ctgaaaactc ttctgagaac cacaaacctt gtgtatggat 3781 tcggcatgga gccctcagct ggcggctctg ggtgctgacg gccgctggag aggtgggctc 3841 ccctcgtgca ctttattgcc tgggcagttt tgcttgatct tttgtgactt tgagcctttt 3901 aagtagtttg aatgataaga cttaaaatgt ttcataatta tgttttatgt aacagacttt 3961 gacattattt aaacgagcat gtgtaatgta acttttctct ttgaatcata taaaacttga 4021 ttttacattg aaaaaaaaaa aaaaaaaaaa

LOCUS NM_015720 2269 bp mRNA linear PRI 02-MAR-

2006

DEFINITION Homo sapiens podocalyxin-like 2 (PODXL2), mRNA. ACCESSION NM_015720 VERSION NM_015720.1 GI:7657464 KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhim;

Catarrhini; Hominidae; Homo.

REFERENCE 1 (bases 1 to 2269)

AUTHORS Clark, H. F., Gurney, A. L . , Abaya,E., Baker, K., Baldwin, D.,

Brush, J. ,

Chen, J., Chow, B., Chui,C, Crowley,C, Currell,B., Deuel,B., Dowd,P., Eaton, D., Foster, J., Gπmaldi,C, Gu, Q., Hass,P.E., Heldens,S., Huang, A., Kim, H. S., Klimowski, L . , Jin, Y.,

Johnson, S .

Lee, J., Lewis, L., Liao,D., Mark, M., Robbie, E., Sanchez, C, Schoenfeld, J. , Seshagiπ, S . , Simmons, L., Singh, J., Smith, V., Stinson, J. , Vagts,A., Vandlen,R., Watanabe,C, Wieand,D.,

Woods, K. ,

Xie,M.H., Yansura,D., Yi, S., Yu, G., Yuan, J., Zhang, M., Zhang, Z . ,

Goddard,A., Wood, W. I., Godowski,P. and Gray, A.

TITLE The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins : a bioinformatics assessment

JOURNAL Genome Res. 13 (10), 2265-2270 (2003)

PUBMED 12975309

REFERENCE 2 (bases 1 to 2269)

AUTHORS Fieger,C.B., Sassetti, C .M. and Rosen, S. D.

TITLE Endoglycan, a member of the CD34 family, functions as an L- selectin ligand through modification with tyrosine sulfation and sialyl

Lewis x

JOURNAL J. Biol. Chem. 278 (30), 27390-27398 (2003) PUBMED 12889478 REMARK GeneRIF: endoglycan functions as an L-selectin ligand through modification with tyrosine sulfation and sialyl Lewis x

REFERENCE 3 (bases 1 to 2269) AUTHORS Sassetti, C, Van Zante,A. and Rosen, S. D. TITLE Identification of endoglycan, a member of the CD34/podocalyxin family of sialomucins

JOURNAL J. Biol. Chem. 275 (12), 9001-9010 (2000) PUBMED 10722749 COMMENT PROVISIONAL REFSEQ: This record has not yet been subject to final

NCBI review. The reference sequence was derived from

AF219137.1. FEATURES Location/Qualifiers source 1..2269

/orgamsm="Homo sapiens "

/mol_type=" mRNA "

/db_xref="taxon : 9606 "

/chromosome="3"

/map="3q21.3" gene 1..2269

/gene="PODXL2"

/note="synonym: PODLX2" /db_xref="GeneID: 50512" /db_xref="HGNC: 17936" /db_xref="HPRD:HPRD_15154" CDS 21..1838

/gene="PODXL2"

/go_component=" integral to plasma membrane [pmid 10722749]; membrane"

/go_function="glycosaminoglycan binding [pmid 10722749]"

/go_process="cell adhesion" /codon_start=l /product="endoglycan" /protein_id="NP_056535.1" /db_xref="GI: 7657465" /db_xref="CCDS:CCDS3044.1" /db_xref="GeneID: 50512" /db_xref="HGNC: 17936" /db_xref="HPRD:HPRD_15154"

/translation="MGRLLRAARLPPLLSPLLLLLVGGAFLGACVAGSDEPGPEGLTS

TSLLDLLLPTGLEPLDSEEPSETMGLGAGLGAPGSGFPSEENEESRILQPPQYFWEEE EELNDSSLDLGPTADYVFPDLTEKAGSIEDTSQAQELPNLPSPLPKMNLVEPPWHMPP REEEEEEEEEEEREKEEVEKQEEEEEEELLPVNGSQEEAKPQVRDFSLTSSSQTPGAT KSRHEDSGDQASSGVEVESSMGPSLLLPSVTPTTVTPGDQDSTSQEAEATVLPAAGLG VEFEAPQEASEEATAGAAGLSGQHEEVPALPSFPQTTAPSGAEHPDEDPLGSRTSASS PLAPGDMELTPSSATLGQEDLNQQLLEGQAAEAQSRIPWDSTQVICKDWSNLAGKNYI ILNMTENIDCEVFRQHRGPQLLALVEEVLPRHGSGHHGAWHISLSKPSEKEQHLLMTL VGEQGWPTQDVLSMLGDIRRSLEEIGIQNYSTTSSCQARASQVRSDYGTLFWLWI

GAICIIIIALGLLYNCWQRRLPKLKHVSHGEELRFVENGCHDNPTLDVASDSQSEMQE

KHPSLNGGGALNGPGSWGALMGGKRDPEDSDVFEEDTHL"

STS 375..564

/gene="P0DXL2" /standard_name=" SHGC-77281" /db_xref="UmSTS: 59943" ORIGIN

1 ccagttccgg cacgaggacc atgggccggc tgctgcgggc cgcccggctg ccgccgctgc 61 tttcgccgct gctgcttctg ctggttgggg gagcgttcct gggtgcctgt gtggctgggt 121 ctgatgagcc tggcccagag ggcctcacct ccacctccct gctagacctc ctgctgccca 181 ctggcttgga gccactggac tcagaggagc ctagtgagac catgggcctg ggagctgggc 241 tgggagcccc tggctcaggc ttccccagcg aagagaatga agagtctcgg attctgcagc 301 caccacagta cttctgggaa gaggaggaag agctgaatga ctcaagtctg gacctgggac 361 ccactgcaga ttatgttttt cctgacttaa ctgagaaggc aggttccatt gaagacacta 421 gccaggctca agagctgcca aacctcccct ctcccttgcc caagatgaat ctggttgagc 481 ctccctggca tatgcctccc agagaggagg aagaagagga agaggaagag gaggagaggg 541 agaaggaaga ggtagagaaa caagaggagg aggaagagga ggagctgctc cctgtgaatg 601 gatcccaaga agaagccaag cctcaggtcc gtgacttttc tctcaccagc agcagccaga 661 ccccaggggc caccaaaagc aggcatgaag actccgggga ccaggcctca tcaggtgtgg 721 aggtggagag cagcatgggg cccagcttgc tgctgccttc agtcacccca actacagtga 781 ctccggggga ccaggactcc accagccaag aggcagaggc cacagtgctg ccagctgcag 841 ggcttggggt agagttcgag gctcctcagg aagcaagcga ggaagccact gcaggagcag 901 ctggtttgtc tggccagcac gaggaggtgc cggccttgcc ttcattccct caaaccacag 961 ctcccagtgg ggccgagcac ccagatgaag atccccttgg ctctagaacc tcagcctctt 1021 ccccactggc ccctggagac atggaactga caccttcctc tgctaccttg ggacaagaag 1081 atctcaacca gcagctccta gaagggcagg cagctgaagc tcaatccagg ataccctggg 1141 attctacgca ggtgatctgc aaggactgga gcaatctggc tgggaaaaac tacatcattc 1201 tgaacatgac agagaacata gactgtgagg tgttccggca gcaccggggg ccacagctcc 1261 tggccctggt ggaagaggtg ctgccccgcc atggcagtgg ccaccatggg gcctggcaca 1321 tctctctgag caagcccagc gagaaggagc agcaccttct catgacactg gtgggcgagc 1381 agggggtggt gcccactcaa gatgtccttt ccatgctggg tgacatccgc aggagcctgg 1441 aggagattgg catccagaac tattccacaa ccagcagctg ccaggcgcgg gccagccagg 1501 tgcgcagcga ctacggcacg ctcttcgtgg tgctggtggt cattggggcc atctgcatca 1561 tcatcattgc gcttggcctg ctctacaact gctggcagcg ccggctgccc aagctcaagc 1621 acgtgtcgca cggcgaggag ctgcgcttcg tggagaacgg ctgccacgac aaccccacgc 1681 tggacgtggc cagcgacagc cagtcggaga tgcaggagaa gcaccccagc ctgaacggcg 1741 gcggggccct caacggcccg gggagctggg gggcgctcat ggggggcaag cgggaccccg 1801 aggactcgga cgtgttcgag gaggacacgc acctgtgagc gcagcgaggc gcaggccgag 1861 tgggccgcca ggaccaagcg aggtggaccc cgaaacggac ggcccggagc ccgcaccagc 1921 cccgcgccta cccggccgcc cccgcgcctg gccctcggcg cgggctcctt cccgcttccc 1981 ccgacttcac acggcggctt cggaccaact ccctcactcc cgcccgaggg gcaggcctca 2041 aagcccgcct tggccccgct ttcccgcccc tgaaccccgg ccccgcgggc ggcgggcgcg 2101 cttcctgcgc cccgggactc aattaaaccc gcccggagac cacgcgggcc cagcgaaaaa 2161 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2221 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa

LOCUS NM 006128 2853 bp mRNA linear PRI 19-MAR-

2006

DEFINITION Homo sapiens bone morphogenetic protein 1 (BMPl), transcript variant BMP1-2, mRNA.

ACCESSION NM_006128 VERSION NM_006128.1 GI:5902807 KEYWORDS SOURCE Homo sapiens (human)

ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata;

EuteleostomiL;;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhim; Homimdae; Homo.

REFERENCE 1 (bases 1 to 2853) AUTHORS Petropoulou, V. , Garπgue-Antar, L . and Kadler,K.E. TITLE Identification of the minimal domain structure of bone morphogenetic protein-1 (BMP-I) for chordinase activity: chordinase activity is not enhanced by procollagen C-proteinase enhancer-1

(PCPE-I)

JOURNAL J. Biol. Chem. 280 (24), 22616-22623 (2005)

PUBMED 15817489

REMARK GeneRIF: chordinase activity of BMPl is not enhanced by PCPE-I

REFERENCE 2 (bases 1 to 2853)

AUTHORS Gonzalez, E. M. , Reed, C. C, Bix,G., Fu, J., Zhang, Y.,

Gopalakπshnan, B . , Greenspan, D . S . and Iozzo,R.V.

TITLE BMP-1/Tolloid-like metalloproteases process endorepellin, the angiostatic C-terminal fragment of perlecan

JOURNAL J. Biol. Chem. 280 (8), 7080-7087 (2005) PUBMED 15591058 REMARK GeneRIF: cleaves LG3 from recombinant endorepellin at the physiologically relevant site and cleaves LG3 from endogenous perlecan in cultured mouse and human cells

REFERENCE 3 (bases 1 to 2853) AUTHORS Gallant, CL. , Olson, M. E. and Hart, D.A. TITLE Molecular, histologic, and gross phenotype of skin wound healing in red Duroc pigs reveals an abnormal healing phenotype of hypercontracted, hyperpigmented scarring

JOURNAL Wound Repair Regen 12 (3), 305-319 (2004) PUBMED 15225209 REMARK GeneRIF: Dermal wound healing in red Duroc pigs show unique mRNA expression of HSP47, BMP-I, TIMP1-3 and hypercontracted, hyperpigmented scars .

REFERENCE 4 (bases 1 to 2853) AUTHORS Leighton,M. and Kadler,K.E. TITLE Paired basic/Fuπn-like proprotein convertase cleavage of Pro-

BMP-I in the trans-Golgi network

JOURNAL J. Biol. Chem. 278 (20), 18478-18484 (2003) PUBMED 12637569

REMARK GeneRIF: Pro-BMP-1 is cleaved in the trans-Golgi network REFERENCE 5 (bases 1 to 2853)

AUTHORS Hartigan , N . , Garπgue-Antar, L . and Kadler, K . E .

TITLE Bone morphogenetic protein-1 (BMP-I) . Identification of the minimal domain structure for procollagen C-proteinase activity

JOURNAL J. Biol. Chem. 278 (20), 18045-18049 (2003) PUBMED 12637537 REMARK GeneRIF: the minimal domain structure for PCP activity is considerably shorter than expected and comprises the metalloproteinase domain and the CUBl and CUB2 domains of BMP-I

REFERENCE 6 (bases 1 to 2853) AUTHORS Garπgue-Antar, L . , Hartigan,N. and Kadler,K.E. TITLE Post-translational modification of bone morphogenetic protein-1 is required for secretion and stability of the protein

JOURNAL J. Biol. Chem. 277 (45), 43327-43334 (2002) PUBMED 12218058 REMARK GeneRIF: Post-translational modification is required for secretion and stability of the protein.

REFERENCE 7 (bases 1 to 2853) AUTHORS Rattenholl, A. , Pappano, W.N . , Koch, M., Keene,D.R., Kadler,K.E.,

Sasaki, T., Timpl,R., Burgeson, R. E . , Greenspan, D . S . and

Bruckner-Tuderman, L.

TITLE Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen

JOURNAL J. Biol. Chem. 277 (29), 26372-26378 (2002) PUBMED 11986329 REMARK GeneRIF: bone morphogenetic protein-1 (BMP-I), which exhibits procollagen C-proteinase activity, cleaves the C-terminal propeptide from human procollagen VII

REFERENCE 8 (bases 1 to 2853) AUTHORS Unsold, C., Pappano, W.N ., Imamura,Y., Steiglitz, B .M. and

Greenspan, D . S .

TITLE Biosynthetic processing of the pro-alpha 1 (V) 2pro-alpha 2 (V) collagen heterotrimer by bone morphogenetic protein-1 and fuπn-like proprotein convertases

JOURNAL J. Biol. Chem. 277 (7), 5596-5602 (2002)

PUBMED 11741999

REFERENCE 9 (bases 1 to 2853)

AUTHORS Garπgue-Antar, L . , Barker, C. and Kadler,K.E.

TITLE Identification of amino acid residues in bone morphogenetic protein-1 important for procollagen C-proteinase activity

JOURNAL J. Biol. Chem. 276 (28), 26237-26242 (2001)

PUBMED 11283002

REFERENCE 10 (bases 1 to 2853)

AUTHORS Scott, I.C., Blitz, I. L., Pappano, W.N. , Maas,S.A., Cho,K.W. and

Greenspan, D . S .

TITLE Homologues of Twisted gastrulation are extracellular cofactors in antagonism of BMP signalling

JOURNAL Nature 410 (6827), 475-478 (2001)

PUBMED 11260715

REFERENCE 11 (bases 1 to 2853)

AUTHORS Amano,S., Scott, I. C, Takahara,K., Koch, M., Champliaud, M. F . , Gerecke, D .R. , Keene,D.R., Hudson, D. L., Nishiyama, T . , Lee, S., Greenspan, D . S . and Burgeson, R. E .

TITLE Bone morphogenetic protein 1 is an extracellular processing enzyme of the laminin 5 gamma 2 chain

JOURNAL J. Biol. Chem. 275 (30), 22728-22735 (2000)

PUBMED 10806203

REFERENCE 12 (bases 1 to 2853)

AUTHORS Janitz,M., Heiser,V., Bottcher,U., Landt,O. and Lauster,R.

TITLE Three alternatively spliced variants of the gene coding for the human bone morphogenetic protein-1

JOURNAL J. MoI. Med. 76 (2), 141-146 (1998)

PUBMED 9500680

REFERENCE 13 (bases 1 to 2853)

AUTHORS Li, S. W., Sieron,A.L., Fertala,A., Ho]ima, Y., Arnold, W.V. and Prockop, D.J. TITLE The C-proteinase that processes procollagens to fibrillar collagens is identical to the protein previously identified as bone morphogenic protein-1

JOURNAL Proc. Natl. Acad. Sci. U.S.A. 93 (10), 5127-5130 (1996)

PUBMED 8643539

REFERENCE 14 (bases 1 to 2853 )

AUTHORS Kessler, E . , Takahara, K . , Bimaminov, L . , Brusel , M . and

Greenspan , D . S .

TITLE Bone morphogenetic protein-1 : the type I procollagen C- proteinase

JOURNAL Science 271 (5247), 360-362 (1996)

PUBMED 8553073

REFERENCE 15 (bases 1 to 2853)

AUTHORS Takahara,K., Lee, S., Wood, S. and Greenspan, D . S .

TITLE Structural organization and genetic localization of the human bone morphogenetic protein 1/mammalian tolloid gene

JOURNAL Genomics 29 (1), 9-15 (1995)

PUBMED 8530106

REFERENCE 16 (bases 1 to 2853)

AUTHORS Takahara,K., Lyons, G. E. and Greenspan, D . S .

TITLE Bone morphogenetic protein-1 and a mammalian tolloid homologue (mTld) are encoded by alternatively spliced transcripts which are differentially expressed in some tissues

JOURNAL J. Biol. Chem. 269 (51), 32572-32578 (1994)

PUBMED 7798260

REFERENCE 17 (bases 1 to 2853)

AUTHORS Yoshiura,K., Tamura,T., Hong, H. S., Ohta,T., Soejima, H. , Kishino, T . ,

Jinno,Y. and Nnkawa,N.

TITLE Mapping of the bone morphogenetic protein 1 gene (BMPl) to 8p21: removal of BMPl from candidacy for the bone disorder in Langer-Giedion syndrome JOURNAL Cytogenet. Cell Genet. 64 (3-4), 208-209 (1993)

PUBMED 8404039 REFERENCE 18 (bases 1 to 2853)

AUTHORS Tabas,J.A., Zasloff,M., Wasmuth, J. J. , Emanuel, B . S . , Altherr,M.R. ,

McPherson, J. D . , Wozney,J.M. and Kaplan, F. S.

TITLE Bone morphogenetic protein: chromosomal localization of human genes for BMPl, BMP2A, and BMP3 JOURNAL Genomics 9 (2), 283-289 (1991)

PUBMED 2004778 REFERENCE 19 (bases 1 to 2853)

AUTHORS Wozney,J.M., Rosen, V., Celeste, A. J. , Mitsock, L .M. , Whitters,M. J.,

Kπz,R.W., Hewick,R.M. and Wang, E.A.

TITLE Novel regulators of bone formation: molecular clones and activities

JOURNAL Science 242 (4885), 1528-1534 (1988) PUBMED 3201241 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from M22488.1 and L35278.1.

Summary: The BMPl locus encodes a protein that is capable of inducing formation of cartilage in vivo. Although other bone morphogenetic proteins are members of the TGF-beta superfamily, BMPl encodes a protein that is not closely related to other known growth factors. BMPl protein and procollagen C proteinase (PCP), a secreted metalloprotease requiring calcium and needed for cartilage and bone formation, are identical. PCP or BMPl protein cleaves the

C-terminal propeptides of procollagen I, II, and III and its activity is increased by the procollagen C-endopeptidase enhancer protein. The BMPl gene is expressed as alternatively spliced variants that share an N-terminal protease domain but differ in their C-terminal region.

Transcript Variant: This is splice variant BMP1-2. It contains sequence insertion from exon 20 which encodes a histidine rich region of protein isoform 2 and results in a different COOH-terminus.

FEATURES Location/Qualifiers source 1..2853

/orgamsm="Homo sapiens "

/mol_type="mRNA"

/db_xref="taxon : 9606 "

/chromosome=" 8 "

/map="8p21" gene 1..2853

/gene="BMPl"

/note="synonyms: PCP, TLD, PCOLC, FLJ44432"

/db_xref="GeneID: 649"

/db_xref="HGNC:1067"

/db_xref="HPRD:HPRD_00209"

/db_xref="MIM: 112264"

CDS 30..2501

/gene="BMPl"

/EC_number=" 3.4.24.19"

/go_component="extracellular space"

/go_function="astacin activity; calcium ion binding; cytokine activity; growth factor activity; metallopeptidase activity [pmid 7798260]; procollagen

C-endopeptidase activity; zinc ion binding"

/go_process="cartilage condensation [pmid 3201241]; cell differentiation; ossification; proteolysis"

/note="splice variant BMP1-2; splice variant BMP-1/His isoform 2, precursor is encoded by transcript variant

BMP1-2; procollagen C-endopeptidase"

/codon_start=l

/product="bone morphogenetic protein 1 isoform 2, precursor"

/protein_id="NP_006119.1"

/db_xref="GI: 5902808"

/db_xref="CCDS:CCDS6027.1"

/db_xref="GeneID: 649"

/db_xref="HGNC:1067"

/db_xref="HPRD:HPRD_00209"

/db_xref="MIM: 112264"

/translation="MPGVARLPLLLGLLLLPRPGRPLDLADYTYDLAEEDDSEPLNYK DPCKAAAFLGDIALDEEDLRAFQVQQAVDLRRHTARKSSIKAAVPGNTSTPSCQSTNG QPQRGACGRWRGRSRSRRAATSRPERVWPDGVIPFVIGGNFTGSQRAVFRQAMRHWEK HTCVTFLERTDEDSYIVFTYRPCGCCSYVGRRGGGPQAISIGKNCDKFGIWHELGHV VGFWHEHTRPDRDRHVSIVRENIQPGQEYNFLKMEPQEVESLGETYDFDSIMHYARNT FSRGIFLDTIVPKYEVNGVKPPIGQRTRLSKGDIAQARKLYKCPACGETLQDSTGNFS SPEYPNGYSAHMHCVWRISVTPGEKI ILNFTSLDLYRSRLCWYDYVEVRDGFWRKAPL RGRFCGSKLPEPIVSTDSRLWVEFRSSSNWVGKGFFAVYEAICGGDVKKDYGHIQSPN YPDDYRPSKVCIWRIQVSEGFHVGLTFQSFEIERHDSCAYDYLEVRDGHSESSTLIGR YCGYEKPDDIKSTSSRLWLKFVSDGSINKAGFAVNFFKEVDECSRPNRGGCEQRCLNT LGSYKCSCDPGYELAPDKRRCEAACGGFLTKLNGSITSPGWPKEYPPNKNCIWQLVAP TQYRISLQFDFFETEGNDVCKYDFVEVRSGLTADSKLHGKFCGSEKPEVITSQYNNMR VEFKSDNTVSKKGFKAHFFSVLEGAGDRHSHLSGLELLLCPHALVDTVPAPPSALHGD

THAHTHTHVHTHCPIAQETCRGPPLGASRLSPQGPGHLTLAPQEGSYLDFWDTHRGDP

KPRRRRKSLKTFSLTPATFRGIWAL" sig_peptide 30..95

/gene="BMPl" mat_peptide 390..2498 /gene="BMPl"

/product="bone morphogenetic protein 1" misc_feature 390..992 /gene="BMPl"

/note="Region : metalloprotease domain" misc_feature 993..1331 /gene="BMPl"

/note="Region: CUB I domain" misc_feature 1332..1667 /gene="BMPl"

/note="Region: CUB II domain" misc_feature 1668..1793 /gene="BMPl"

/note="Region : EGF-like, calcium-binding domain" misc_feature 1800..2138 /gene="BMPl"

/note="Region: CUB III domain" misc_feature 2241..2285 /gene="BMPl"

/note= " Region : hi st idine-πch region " misc feature 96 . . 24 98 /gene= " BMP l " /note= " encodes bone morphogenet ic protein 1 proprotein" misc_feature 2137..2502

/gene="BMPl"

/note="alternatively spliced exon 20 sequence; Region: exon 20"

STS 2620..2839

/gene="BMPl"

/standard_name="SGC35299"

/db_xref="UmSTS: 65042"

STS 2677..2800

/gene="BMPl" / standard_name="RH78932 ' /db_xref="UmSTS : 9345 "

ORIGIN

1 gccgcttccc tcgccgccgc cccgccagca tgcccggcgt ggcccgcctg ccgctgctgc

61 tcgggctgct gctgctcccg cgtcccggcc ggccgctgga cttggccgac tacacctatg

121 acctggcgga ggaggacgac tcggagcccc tcaactacaa agacccctgc aaggcggctg

181 cctttcttgg ggacattgcc ctggacgaag aggacctgag ggccttccag gtacagcagg

241 ctgtggatct cagacggcac acagctcgta agtcctccat caaagctgca gttccaggaa

301 acacttctac ccccagctgc cagagcacca acgggcagcc tcagagggga gcctgtggga

361 gatggagagg tagatcccgt agccggcggg cggcgacgtc ccgaccagag cgtgtgtggc

421 ccgatggggt catccccttt gtcattgggg gaaacttcac tggtagccag agggcagtct

481 tccggcaggc catgaggcac tgggagaagc acacctgtgt caccttcctg gagcgcactg

541 acgaggacag ctatattgtg ttcacctatc gaccttgcgg gtgctgctcc tacgtgggtc

601 gccgcggcgg gggcccccag gccatctcca tcggcaagaa ctgtgacaag ttcggcattg

661 tggtccacga gctgggccac gtcgtcggct tctggcacga acacactcgg ccagaccggg

721 accgccacgt ttccatcgtt cgtgagaaca tccagccagg gcaggagtat aacttcctga

781 agatggagcc tcaggaggtg gagtccctgg gggagaccta tgacttcgac agcatcatgc

841 attacgctcg gaacacattc tccaggggca tcttcctgga taccattgtc cccaagtatg

901 aggtgaacgg ggtgaaacct cccattggcc aaaggacacg gctcagcaag ggggacattg

961 cccaagcccg caagctttac aagtgcccag cctgtggaga gaccctgcaa gacagcacag

1021 gcaacttctc ctcccctgaa taccccaatg gctactctgc tcacatgcac tgcgtgtggc

1081 gcatctctgt cacacccggg gagaagatca tcctgaactt cacgtccctg gacctgtacc

1141 gcagccgcct gtgctggtac gactatgtgg aggtccgaga tggcttctgg aggaaggcgc

1201 ccctccgagg ccgcttctgc gggtccaaac tccctgagcc tatcgtctcc actgacagcc

1261 gcctctgggt tgaattccgc agcagcagca attgggttgg aaagggcttc tttgcagtct

1321 acgaagccat ctgcgggggt gatgtgaaaa aggactatgg ccacattcaa tcgcccaact

1381 acccagacga ttaccggccc agcaaagtct gcatctggcg gatccaggtg tctgagggct

1441 tccacgtggg cctcacattc cagtcctttg agattgagcg ccacgacagc tgtgcctacg

1501 actatctgga ggtgcgcgac gggcacagtg agagcagcac cctcatcggg cgctactgtg

1561 gctatgagaa gcctgatgac atcaagagca cgtccagccg cctctggctc aagttcgtct

1621 ctgacgggtc cattaacaaa gcgggctttg ccgtcaactt tttcaaagag gtggacgagt

1681 gctctcggcc caaccgcggg ggctgtgagc agcggtgcct caacaccctg ggcagctaca

1741 agtgcagctg tgaccccggg tacgagctgg ccccagacaa gcgccgctgt gaggctgctt

1801 gtggcggatt cctcaccaag ctcaacggct ccatcaccag cccgggctgg cccaaggagt

1861 acccccccaa caagaactgc atctggcagc tggtggcccc cacccagtac cgcatctccc

1921 tgcagtttga cttctttgag acagagggca atgatgtgtg caagtacgac ttcgtggagg

1981 tgcgcagtgg actcacagct gactccaagc tgcatggcaa gttctgtggt tctgagaagc

2041 ccgaggtcat cacctcccag tacaacaaca tgcgcgtgga gttcaagtcc gacaacaccg

2101 tgtccaaaaa gggcttcaag gcccacttct tctcagtctt ggagggggca ggggaccgac

2161 actcacatct atcaggcctg gagttactgc tctgccccca tgccctggtc gacactgtgc

2221 ccgccccacc ctcagccctg cacggagaca cacacgccca cacgcacaca catgtgcaca

2281 cacattgccc catcgcacaa gaaacctgca gaggaccccc actgggggca tcgaggctca

2341 gccctcaggg cccggggcat ctgactctgg ccccccagga ggggagctat ttggactttt

2401 gggacaccca ccgaggagac cctaagccaa gaaggagaag aaagagcctg aagaccttca

2461 gtctgacccc tgccaccttc cggggcattt gggcactgta ggaaaagagg ccagctctgc

2521 agccccctcg gggacgcccc caccagctca aattccgagt gcagaaaaga aaccggaccc

2581 cccagtgagg cctgccaggc ctcccggacc ccttgttact caggaacctc accttggacg

2641 gaatgggatg ggggcttcgg tgcccaccaa ccccccacct ccactctgcc attccggccc

2701 acctccctct ggccggacag aactggtgct ctcttctccc cactgtgccc gtccgcggac

2761 cggggaccct tccccgtgcc ctaccccctc ccattttgat ggtgtctgtg acatttcctg

2821 ttgtgaagta aaagagggac ccctgcgtcc tgc

// LOCUS NM_079837 2127 bp mRNA linear PRI 04-MAR-

2006

DEFINITION Homo sapiens BTG3 associated nuclear protein (BANP) , transcript variant 2, mRNA.

ACCESSION NM_079837 XM_938904 VERSION NM_079837.1 GI:17986267 KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhim; Homimdae; Homo. REFERENCE 1 (bases 1 to 2127)

AUTHORS Rampalli, S. , Pavithra,L., Bhatt,A., Kundu,T.K. and Chattopadhyay, S .

TITLE Tumor suppressor SMARl mediates cyclin Dl repression by recruitment of the SIN3/histone deacetylase 1 complex JOURNAL MoI. Cell. Biol. 25 (19), 8415-8429 (2005)

PUBMED 16166625 REMARK GeneRIF: SMARl regulates cyclin Dl by modification of chromatin through the SIN3/histone deacetylase 1 complex REFERENCE 2 (bases 1 to 2127)

AUTHORS Kaul-Ghanekar, R. , Manumdar, S . , Jalota,A., Gulati,N., Dubey,N., Saha,B. and Chattopadhyay, S .

TITLE Abnormal V(D)J recombination of T cell receptor beta locus in SMARl transgenic mice

JOURNAL J. Biol. Chem. 280 (10), 9450-9459 (2005) PUBMED 15623522 REMARK GeneRIF: SMARl plays an important role in the regulation of T cell development as well as V(D)J recombination

REFERENCE 3 (bases 1 to 2127) AUTHORS Chattopadhyay, S ., Kaul,R., Charest,A., Housman,D. and Chen, J. TITLE SMARl, a novel, alternatively spliced gene product, binds the Scaffold/Matrix-associated region at the T cell receptor beta locus

JOURNAL Genomics 68 (1), 93-96 (2000)

PUBMED 10950932

REFERENCE 4 (bases 1 to 2127)

AUTHORS Birot,A., Duret,L., Bartholin, L ., Santalucia, B . , Tigaud, I . ,

Magaud,J. and Rouault,J.

TITLE Identification and molecular analysis of BANP JOURNAL Gene 253 (2), 189-196 (2000) PUBMED 10940556

COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff.

The reference sequence was derived from BC009424.1 and AK001039.1. On Mar 4, 2006 this sequence version replaced gi : 89041071.

Summary: BTG3 is a protein that interacts with CAFl, a component of the general transcription multisubumt complex. It is thought that BTG3 is involved in negative control of the cell cycle. The protein encoded by this gene binds BTG3. Studies with mouse homolog suggest that this protein may also interact with a specific nuclear matrix/scaffold-associated region (MAR) . Transcript variants encoding different isoforms have been described for this gene.

Transcript Variant: This variant (2) lacks 9 nt in one of the coding exons as compared to transcript variant 1. However, it maintains the same reading frame, and encodes an isoform (b) which is 3 aa shorter than isoform a. COMPLETENESS: full length. FEATURES Location/Qualifiers source 1..2127

/organism="Homo sapiens"

/mol_type="mRNA"

/db_xref="taxon: 9606"

/chromosome="16"

/map="16q24" gene 1..2127

/gene="BANP"

/note="synonyms: SMARl, SMARBPl, FLJ10177, FLJ20538,

DKFZp761H172"

/db_xref="GeneID:54971"

/db_xref="HGNC: 13450"

/db_xref="HPRD:HPRD_16538" CDS 153..1553

/gene="BANP"

/go_component="nucleus"

/note="isoform b is encoded by transcript variant 2 ; BANP homolog; SMARl homolog"

/codon_start=l

/product="BTG3 associated nuclear protein isoform b"

/protein_id="NP_524576.1"

/db_xref="GI: 17986268"

/db_xref="CCDS: CCDSl 0966.1"

/db_xref="GeneID:54971"

/db_xref="HGNC: 13450"

/db_xref="HPRD:HPRD_16538"

/translation="MMSEHDLADWQIAVEDLSPDHPWLENHWTDEDEPALKRQRL EINCQDPSIKSFLYSINQTICLRLDSIEAKLQALEATCKSLEEKLDLVTNKQHSPIQV PMVAGSPLGATQTCNKVRCAVPGRRQNTIWKVPGQEDSHHEDGESGSEASDSVSSCG QAGSQSIGSNVTLITLNSEEDYPNGTWLGDENNPEMRVRCAI IPSDMLHISTNCRTAE KMALTLLDYLFHREVQAVSNLSGQGKHGKKQLDPLTIYGIRCHLFYKFGITESDWYRI KQSIDSKCRTAWRRKQRGQSLAVKSFSRRTPNSSSYCPSEPMMSTPPPASELPQPQPQ PQALHYALANAQQVQIHQIGEDGQVQVGHLHIAQVPQGEQVQITQDSEGNLQIHHVGQ

DGQVLQGAQLIAVASSDPAAAGVDGSPLQGSDIQVQYVQLAPVSDHTAGAQTAEALQP

TLQPEMQLEHGAIQIQ" misc_feature 1235^Λ1236

/gene="BANP"

/note="Region : location of alternate exon sequence" STS 1931..2088

/gene="BANP"

/standard_name="STS-T49824"

/db_xref="UmSTS:26838" STS 1971..2088

/gene="BANP" /standard_name="STS-T49824"

/db_xref="UmSTS:26838" polyA_signal 2108..2113

/gene="BANP" polyA_site 2127

/gene="BANP"

/experiment="experimental evidence, no additional details recorded"

ORIGIN

1 gcagagcggc ggcttctctc gcgaggacgg acgccattat cgcatctccc cgacaaacac

61 cacgagaatt ccgcagccca cacggtgacc aaaagccagc cccactgtga gttgaactct

121 ttcgtgttga ccggccactc tccgtgctct ggatgatgtc ggaacacgac ctggccgatg

181 tggttcagat tgcagtggaa gacctgagcc ctgaccaccc agttgttttg gagaatcatg

241 tagtgacaga tgaagacgaa cctgctttga aacgccagcg actagaaatc aattgccagg

301 atccatctat aaagtcattc ctgtattcca tcaaccagac aatctgcttg cggttggata

361 gcattgaagc caaattgcaa gccctggagg ctacttgtaa atccttagaa gaaaagctgg

421 atctggtcac gaacaagcag cacagcccca tccaggtccc catggtggcc ggctcccctc

481 tcggggcaac ccagacgtgc aacaaagtgc gatgcgctgt gcctgggcgt cggcagaaca

541 ccattgtggt gaaggtgccg ggccaagaag acagccacca cgaggacggg gagagcggct

601 cggaggccag cgactctgtg tccagctgtg ggcaggcggg cagtcagagc atcgggagca

661 acgtcacgct catcaccctg aactcggaag aggactaccc caatggcacc tggctgggcg

721 acgagaacaa ccccgagatg cgggtacgct gcgccatcat cccctccgac atgctgcaca

781 tcagcaccaa ctgccgcacg gccgagaaga tggcgctaac gctgctggac tacctcttcc

841 accgcgaggt gcaggctgtg tccaacctct cggggcaggg caagcacggg aagaagcagc

901 tggacccgct caccatctac ggcatccggt gtcacctttt ctataaattt ggcatcacag

961 aatccgactg gtaccgaatc aagcagagca tcgactccaa gtgccgcacg gcgtggcggc

1021 gcaagcagcg gggccagagc ctggcggtca agagcttctc gcggagaacg cccaactcgt

1081 cctcctactg cccttcagag ccgatgatga gcaccccacc tcctgccagc gagctcccgc

1141 agccacagcc gcagccgcag gccctgcact acgcgctggc caacgcacag caggtgcaga

1201 tccaccagat cggagaagac ggacaggtgc aagtaggaca cctccacatc gcccaggtgc

1261 cgcaggggga gcaagtccag atcacgcagg acagcgaggg caacctccag atccatcacg

1321 tggggcagga cggtcaggtg ctgcagggtg cacagctgat cgccgtggcc tcctcggacc

1381 ccgcggcggc gggcgtggat gggtcgccac tccagggcag cgacatccag gttcagtacg

1441 tgcagctggc gccagtgagt gaccacacgg ccggggcaca gacggccgaa gccctgcagc

1501 ccacgctaca gccggagatg cagctcgagc acggggccat ccagattcag tgagcggtgc

1561 ccatggcacc aggagcccct cgccggctcc gcctacggcc cggcccccac gcgccctgct

1621 ctcacggcct cggcacaggc agcggctgca cgtgttctgc tgaagtgcgt ctgaaggccg

1681 ctgcctccgc ggggaacagc atcctatgaa ctgaaagagc agccgccgcc gcccccagcc

1741 ggagacccct ttcgtttgag tcctgctgtt ggtgtcggag cacgagggga ggcacggtgc

1801 ggagagcgtc gcatatgcgc gggaaatcaa gaactatgat atttttctgt ttaaacagct

1861 ttttttaatt tgctatggtg tttataacaa aaaagaaaat ttgaaaaaaa aaatcccagg

1921 ggagtagcag gagccctttg ctgtgtgctc tgtccagtgt catgagacgg gagccctttg

1981 ctgtgtgctc tgtccagtgt catgaggcag gtgtttgcaa agccagctct cggttccgat

2041 ggggtattgc tgacctactt ttctagggga aatgctctta aacactgtaa ttatgcattt

2101 ctaatgaaat aaaatgtatt tatgacc

//

LOCUS NM 018380 2786 bp mRNA linear PRI 17-0CT-

2005

DEFINITION Homo sapiens DEAD (Asp-Glu-Ala-Asp) box polypeptide 28 (DDX28) , nuclear gene encoding mitochondrial protein, mRNA.

ACCESSION NM_018380 VERSION NM 018380.2 GI:20336295 KEYWORDS SOURCE Homo sapiens (human)

ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;

Catarrhim; Homimdae; Homo. REFERENCE 1 (bases 1 to 2786)

AUTHORS Valgardsdottir,R. and Prydz,H.

TITLE Transport signals and transcription-dependent nuclear localization of the putative DEAD-box helicase MDDX28

JOURNAL J. Biol. Chem. 278 (23), 21146-21154 (2003) PUBMED 12663657 REMARK GeneRIF: Three domains in the N-terminal half of the protein and its RNA binding ability were essential for nucleolar localizationi as well as transcription-inhibition-dependent localization to nuclear subcompartments and two were the nuclear localization signal

REFERENCE 2 (bases 1 to 2786) AUTHORS Valgardsdottir, R. , Brede,G., Eide,L.G., Frengen,E. and Prydz,H. TITLE Cloning and characterization of MDDX28, a putative dead-box helicase with mitochondrial and nuclear localization

JOURNAL J. Biol. Chem. 276 (34), 32056-32063 (2001)

PUBMED 11350955

REFERENCE 3 (bases 1 to 2786)

AUTHORS Loftus,B.J., Kim, U. J., Sneddon, V. P Kalush,F., Brandon, R., Fuhrmann, J., Mason, T., Crosby, M. L. Barnstead, M. , Cronin,L., Deslattes Mays, A., Cao,Y., Xu, R. X. Kang,H.L., Mitchell, S., Eichler, E. E. , Harris, P. C, Venter, J. C. and Adams, M. D.

TITLE Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q

JOURNAL Genomics 60 (3), 295-308 (1999) PUBMED 10493829 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from AF329821.1.

On Apr 28, 2002 this sequence version replaced gi:8922975.

Summary: DEAD box proteins, characterized by the conserved motif

Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly, Based on their distribution patterns, some members of the DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene is intronless. It encodes an RNA-dependent ATPase. The encoded protein is localized in the mitochondria and the nucleus, and can be transported between the mitochondria and the nucleus. COMPLETENESS: complete on the 3' end. FEATURES Location/Qualifiers source 1..2786

/orgamsm="Homo sapiens "

/mol_type=" mRN A "

/db_xref="taxon : 9606 "

/chromosome="16"

/map="16q22.1" gene 1..2786

/gene="DDX28"

/note="synonyms: MDDX28, FLJ11282"

/db_xref="GeneID:55794"

/db_xref="HGNC: 17330"

/db_xref="HPRD:HPRD_06357"

/db_xref="MIM: 607618" CDS 855..2477

/gene="DDX28"

/go_component="nucleus"

/go_function="ATP binding; ATP-dependent helicase activity; hydrolase activity; nucleic acid binding"

/note="mitochondπal DEAD-box polypeptide 28 ; DEAD/H

(Asp-Glu-Ala-Asp/His) box polypeptide 28"

/codon_start=l

/product="DEAD (Asp-Glu-Ala-Asp) box polypeptide 28"

/protein_id="NP_060850.1"

/db_xref="GI: 8922976"

/db_xref="CCDS: CCDSl 0858.1"

/db_xref="GeneID : 55794 "

/db_xref="HGNC: 17330"

/db_xref="HPRD:HPRD_06357"

/db_xref="MIM: 607618"

/translation="MALARPVRLFSLVTRLLLAPRRGLTVRSPDEPLPWRIPVALQR

QLEQRQSRRRNLPRPVLVRPGPLLVSARRPELNQPARLTLGRWERAPLASQGWKSRRA RRDHFSIERAQQEAPAVRKLSSKGSFADLGLEPRVLHALQEAAPEWQPTTVQSSTIP SLLRGRHWCAAETGSGKTLSYLLPLLQRLLGQPSLDSLPIPAPRGLVLVPSRELAQQ VRAVAQPLGRSLGLLVRDLEGGHGMRRIRLQLSRQPSADVLVATPGALWKALKSRLIS LEQLSFLVLDEADTLLDESFLELVDYILEKSHIAEGPADLEDPFNPKAQLVLVGATFP EGVGQLLNKVASPDAVTTITSSKLHCIMPHVKQTFLRLKGADKVAELVHILKHRDRAE RTGPSGTVLVFCNSSSTVNWLGYILDDHKIQHLRLQGQMPALMRVGIFQSFQKSSRDI

LLCTDIASRGLDSTGVELWNYDFPPTLQDYIHRAGRVGRVGSEVPGTVISFVTHPWD

VSLVQKIELAARRRRSLPGLASSVKEPLPQAT" misc_feature 861..908

/gene="DDX28"

/note="Region : mitochondrial targeting signal" misc_feature 1392..1427

/gene="DDX28"

/note="Region : nuclear export signal" misc_feature 2412..2423

/gene="DDX28"

/note="Region : nuclear localization signal" STS 1222..1346 /gene="DDX28"

/standard_name=" SHGC-57903"

/db_xref="UmSTS:49297"

STS 2572..2665

/gene="DDX28"

/standard_name="Bdy91fO3"

/db_xref="UmSTS:71954" polyA_signal 2730..2735

/gene="DDX28" polyA_site 2750

/gene="DDX28"

/experiment=" expeπmental evidence , no additional details recorded" polyA_site 2781

/gene="DDX28"

/experiment=" expeπmental evidence , no additional details recorded"

ORIGIN

1 gaattcaggt aaaatattct gcctgaccag ggctacatga taagccacgt acttgatcac

61 tttgtagggt cgcagcaccc ttcttactac tattttaggt aattcaggtt tctgacgggg

121 aagccagtgg agctgagcgg gctgcaagag gggtgggttc tggatgagaa gttgggacgc

181 gtgacgaggg agtagagagt gaaccttggc ttaaaaggaa ggaaaataac tgtgaagaaa

241 agatgaccca acttgaaata aaacctgaag accttatctc ccacttgaga gagagaagaa

301 gctgaaagcc atcagcttgc actctgggct cacagacaga gagggtgagg ggttgagccc

361 agatctatga cttcagaccc ctgtctcggc ccctaggcct gatcattcat tcaaactctc

421 aataaacacg gattaccaga ccctgcgcag ggaacacatc tgggaaaaca gctgcaacct

481 cggataccag cacgggacaa gctatctcag ggcaatgagg aacaactaaa gagaatccca

541 ggaaccaggt aaccaatcgc cagaagccct ccgccctcat ggtccattgg gtcaaggccc

601 cactgccgcc tcgtatcgcc agcctccagt cctgcctcca cgacgcgccc ttccccaagg

661 ctggccgggt ctggatgtcg ccatccccta ttcggagcta cagacctcgc agctgaactc

721 ttaaaaagaa cctcgcttct tcctcacggt gctccagctc cacacaccgt actgagcctc

781 gccagccacc gtacgcgagg tcgcggcgcg tccgtgacgt cactgatgtg cgcttctccc

841 gcactaaggg aaacatggct ctagcgcggc cggtgcggct cttttccctc gtgactcggt

901 tgctcctggc gccgcgacgg ggcctcacgg tccgcagtcc cgacgaaccc ctgccggtgg

961 tgcgcatccc agtggctcta cagcggcagt tggaacagcg gcagagcagg cggcggaacc

1021 tcccgaggcc ggtgctggtt cgacccggac cgctgctggt ttcggcgcgg cggccggagt

1081 tgaaccagcc ggcgcgcctc acactgggcc gttgggagcg cgcgccgcta gcctctcaag

1141 gctggaagag tcgacgcgcg cgtcgggacc acttctccat cgagcgcgcg caacaggagg

1201 cgccagcggt gcgaaagctc tcgtctaagg gcagctttgc tgacctgggc ctggagcccc

1261 gtgtgctgca cgcactacag gaggctgcgc ctgaagtcgt tcagcccaca accgtgcagt

1321 ctagcaccat cccctcacta cttcgcggcc gccatgtcgt ttgcgccgca gaaaccggca

1381 gtggcaagac tctcagctac ctcctgccgc tgcttcaacg gctcttgggc cagccaagcc

1441 tggactccct tcctatcccc gcgccccgag gcctggtcct tgttccttcc cgagaattgg

1501 cccaacaggt gcgggctgtg gcccaaccct tgggccgctc cttgggcctg ctggtgcggg

1561 acctggaggg aggccacggc atgcgtagga tcaggctgca gctgtccaga cagccttcag

1621 cagatgtgct tgtggccact ccaggggctc tgtggaaggc cctgaaaagt cgactgatca

1681 gtctggagca actctccttc ttggtgttgg atgaggcaga cacactgctg gatgaaagct

1741 tcctggaact ggtggactac atcttagaga agagccacat agcagaaggc ccagctgact

1801 tggaagaccc cttcaatccc aaagctcagt tagtgctggt aggagccaca tttcccgaag

1861 gtgtaggcca gttgctgaat aaagtcgcca gcccagatgc tgtcaccacc atcaccagct

1921 ccaagctcca ctgtatcatg cctcatgtga aacagacatt tctgagactg aagggagcag

1981 ataaggtggc cgagctggtg cacatcctca agcatcgtga cagagcagaa aggactggtc

2041 cctcaggaac tgttctggtg ttctgtaata gctccagcac tgtgaactgg ctgggatata

2101 ttctggatga ccacaaaatc caacacctaa ggttgcaggg gcaaatgcca gccttgatga

2161 gggtaggaat cttccagtcc ttccagaaga gctcccgaga catacttctc tgcacagaca

2221 tagcctctcg gggcctggac agcactggtg tggagctggt tgtcaattat gatttccccc

2281 caacgctgca agattacatc cacagagcag ggagagtggg ccgtgtgggg agcgaggtgc

2341 caggcaccgt catcagtttt gtgacccatc cctgggatgt gagcctggtt cagaagattg

2401 agctggcggc tcgccgaagg agaagtcttc caggactagc atcctcggtg aaagagcctt

2461 tgccccaagc aacctgattt tgacaaatct gattaaaatg tgatgctaga acagggatct 2521 ttcccagtat cttgagtggg tgaccacact tgtcagtggg aggctctggg ctgccctgtc

2581 ggctccttga gggcgggatg aactgctttg tgacttggaa aggtacgctg ctggccagca

2641 ttggagaaga agctgctgag catggctttc tgtagtcttt agcaagacac aagtggattt

2701 tgactttgta tcatgtcatg atttctaaca ataaatgatg tttttatgtg cctcccctaa

2761 gaataattag caccggggcg gaattc

LOCUS NM_002342 2136 bp mRNA linear PRI 29-JAN-

2006

DEFINITION Homo sapiens lymphotoxin beta receptor (TNFR superfamily, member 3)

(LTBR) , mRNA. ACCESSION NM_002342 VERSION NM_002342.1 GI:4505038 KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhim; Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 2136)

AUTHORS Anders, R.A., Subudhi, S . K. , Wang, J., Pfeffer,K. and Fu, Y. X. TITLE Contribution of the lymphotoxin beta receptor to liver regeneration

JOURNAL J. Immunol. 175 (2), 1295-1300 (2005) PUBMED 16002734 REMARK GeneRIF: Signaling through the lymphotoxin beta receptor (LTbetaR) expressed on mature hepatocytes induces massive hepatomegaly; LTbetaR and its ligands define a new pathway in supporting liver regeneration

REFERENCE 2 (bases 1 to 2136) AUTHORS Chang, Y. H., Hsieh, S . L. , Chao,Y., Chou,Y.C. and Lin, W. W. TITLE Proinflammatory effects of LIGHT through HVEM and LTbetaR interactions in cultured human umbilical vein endothelial cells

JOURNAL J. Biomed. Sci. 12 (2), 363-375 (2005) PUBMED 15917993 REMARK GeneRIF: both LTbetaR and HVEM can discπminatively mediate the expression of different genes in cultured human umbilical vein endothelial cells, including LIGHT, a proinflammatory cytokine

REFERENCE 3 (bases 1 to 2136) AUTHORS Li, C, Norπs,P.S., Ni, C. Z., Havert,M.L., Chiong,E.M., Tran, B. R. ,

Cabezas,E., Reed, J. C, Satterthwait, A. C . , Ware, CF. and

Ely, K. R. TITLE Structurally distinct recognition motifs in lymphotoxin-beta receptor and CD40 for tumor necrosis factor receptor-associated factor (TRAF) -mediated signaling

JOURNAL J. Biol. Chem. 278 (50), 50523-50529 (2003) PUBMED 14517219 REMARK GeneRIF: LTbetaR, CD40 and TANK interact with TRAF3 at sites that promote molecular interactions driving specific signaling

REFERENCE 4 (bases 1 to 2136) AUTHORS Matsuda,A., Suzuki, Y., Honda, G., Muramatsu, S . , Matsuzaki, O . , Nagano, Y., Doi,T., Shimotohno, K. , Harada,T., Nishida,E.,

Hayashi, H. and Sugano, S .

TITLE Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways

JOURNAL Oncogene 22 (21), 3307-3318 (2003)

PUBMED 12761501

REFERENCE 5 (bases 1 to 2136)

AUTHORS Chen, M. C, Hwang, M. J., Chou,Y.C, Chen, W. H., Cheng, G., Nakano, H . ,

Luh,T.Y., Mai, S. C. and Hsieh, S . L . TITLE The role of apoptosis signal-regulating kinase 1 in lymphotoxin-beta receptor-mediated cell death

JOURNAL J. Biol. Chem. 278 (18), 16073-16081 (2003) PUBMED 12566458 REMARK GeneRIF: ASKl is one of the factors involved in the caspase-independent pathway of LTbetaR-induced cell death.

REFERENCE 6 (bases 1 to 2136) AUTHORS Kuai,J., Nickbarg,E., Wooters,J., Qiu,Y., Wang, J. and Lin, L. L. TITLE Endogenous association of TRAF2, TRAF3, cIAPl, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis JOURNAL J. Biol. Chem. 278 (16), 14363-14369 (2003) PUBMED 12571250 REMARK GeneRIF: TRAF2, TRAF3, cIAPl, Smac, and lymphotoxin beta receptor associate and are involved in apoptosis

REFERENCE 7 (bases 1 to 2136) AUTHORS Jiang, X., Takahashi, N . , Matsui,N., Tetsuka,T. and Okamoto,T. TITLE The NF-kappa B activation in lymphotoxin beta receptor signaling depends on the phosphorylation of p65 at serine 536

JOURNAL J. Biol. Chem. 278 (2), 919-926 (2003) PUBMED 12419817 REMARK GeneRIF: The NF-kappa B activation in lymphotoxin beta receptor signaling depends on the phosphorylation of p65 at serine 536.

REFERENCE 8 (bases 1 to 2136) AUTHORS Bush, T. S., St Coeur,M., Resendes, K. K. and Rosmarin, A. G . TITLE GA-binding protein (GABP) and SpI are required, along with retinoid receptors, to mediate retinoic acid responsiveness of CD18

(beta 2 leukocyte lntegπn) : a novel mechanism of transcriptional regulation in myeloid cells

JOURNAL Blood 101 (1), 311-317 (2003) PUBMED 12485937 REMARK GeneRIF: GA-binding protein (GABP) and SpI and retinoid receptors are required to mediate retinoic acid responsiveness of CD18 transcriptional activation in myeloid cells.

REFERENCE 9 (bases 1 to 2136) AUTHORS Matsui,H., Hikichi,Y., Tsu]i,I., Yamada,T. and Shintani,Y. TITLE LIGHT, a member of the tumor necrosis factor ligand superfamily, prevents tumor necrosis factor-alpha-mediated human primary hepatocyte apoptosis, but not Fas-mediated apoptosis

JOURNAL J. Biol. Chem. 277 (51), 50054-50061 (2002)

PUBMED 12393901

REFERENCE 10 (bases 1 to 2136)

AUTHORS Gill, R. M., Ni, J. and Hunt, J. S.

TITLE Differential expression of LIGHT and its receptors in human placental villi and amniochorion membranes

JOURNAL Am. J. Pathol. 161 (6), 2011-2017 (2002) PUBMED 12466117 REMARK GeneRIF: Data show that mRNA encoding LIGHT and its receptors [HVEM, LTbetaR, and TR6 (DcR3) ] are present in placentas and cytotrophoblast cells at term.

REFERENCE 11 (bases 1 to 2136) AUTHORS Chang, Y. H., Hsieh, S . L. , Chen, M. C. and Lin, W. W. TITLE Lymphotoxin beta receptor induces interleukin 8 gene expression via

NF-kappaB and AP-I activation

JOURNAL Exp. Cell Res. 278 (2), 166-174 (2002) PUBMED 12169272 REMARK GeneRIF: Lymphotoxin beta receptor induces interleukin 8 gene expression via NF-kappaB and AP-I activation. (AP-I)

GeneRIF: Lymphotoxin beta receptor induces interleukin 8 gene expression via NF-kappaB and AP-I activation.

REFERENCE 12 (bases 1 to 2136) AUTHORS Langeggen, H. , Berge,K.E., Johnson, E. and Hetland,G. TITLE Human umbilical vein endothelial cells express complement receptor

1 (CD35) and complement receptor 4 (CDllc/CDlδ) in vitro

JOURNAL Inflammation 26 (3), 103-110 (2002) PUBMED 12083416 REMARK GeneRIF: The presence of CRl (CD35) and CR4 (CDlc/CDlδ) on HUVEC indicates that endothelial cells (EC) have the potential to bind C3b and iC3b, respectively, which both mediate biological effects in the course of complement activation.

REFERENCE 13 (bases 1 to 2136) AUTHORS Rooney,I.A., Butrovich, K. D . , Glass, A.A., Borboroglu, S . ,

Benedict, CA. , Whitbeck, J. C . , Cohen, G. H., Eisenberg, R. J. and

Ware, CF.

TITLE The lymphotoxin-beta receptor is necessary and sufficient for

LIGHT-mediated apoptosis of tumor cells

JOURNAL J. Biol. Chem. 275 (19), 14307-14315 (2000)

PUBMED 10799510

REFERENCE 14 (bases 1 to 2136)

AUTHORS Yu, K. Y., Kwon,B., Ni, J., Zhai,Y., Ebner,R. and Kwon,B.S.

TITLE A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis

JOURNAL J. Biol. Chem. 274 (20), 13733-13736 (1999)

PUBMED 10318773

REFERENCE 15 (bases 1 to 2136)

AUTHORS Wu, M. Y., Wang, P. Y., Han, S. H. and Hsieh,S.L.

TITLE The cytoplasmic domain of the lymphotoxin-beta receptor mediates cell death in HeLa cells

JOURNAL J. Biol. Chem. 274 (17), 11868-11873 (1999)

PUBMED 10207006

REFERENCE 16 (bases 1 to 2136)

AUTHORS Boussaud,V., Soler,P., Moreau, J., Goodwin, R. G. and Hance,A.J.

TITLE Expression of three members of the TNF-R family of receptors (4-1BB, lymphotoxin-beta receptor, and Fas) in human lung

JOURNAL Eur. Respir. J. 12 (4), 926-931 (1998)

PUBMED 9817170

REFERENCE 17 (bases 1 to 2136)

AUTHORS Murphy, M., Walter, B.N. , Pike-Nobile, L . , Fanger,N.A., Guyre, P.M.,

Browning, J. L ., Ware, C. F. and Epstein, L. B.

TITLE Expression of the lymphotoxin beta receptor on follicular stromal cells in human lymphoid tissues

JOURNAL Cell Death Differ. 5 (6), 497-505 (1998)

PUBMED 10200501

REFERENCE 18 (bases 1 to 2136)

AUTHORS Kra^ewska, M. , Kra^ewski, S . , Zapata,J.M., Van Arsdale,T.,

Gascoyne, R. D . , Berern,K., McFadden,D., Shabaik,A., Hugh, J.,

Reynolds, A., Clevenger, C .V. and Reed, J. C

TITLE TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues JOURNAL Am. J. Pathol. 152 (6), 1549-1561 (1998) PUBMED 9626059 REFERENCE 19 (bases 1 to 2136)

AUTHORS Wu, M. Y., Hsu, T. L., Lin, W. W., Campbell, R. D . and Hsieh,S.L.

TITLE Serine/threonine kinase activity associated with the cytoplasmic domain of the lymphotoxin-beta receptor in HepG2 cells

JOURNAL J. Biol. Chem. 272 (27), 17154-17159 (1997)

PUBMED 9202035

REFERENCE 20 (bases 1 to 2136)

AUTHORS VanArsdale, T. L. , VanArsdale, S . L . , Force, W. R., Walter, B.N. , Mosialos,G., Kieff,E., Reed, J. C. and Ware, C. F.

TITLE Lymphotoxin-beta receptor signaling complex: role of tumor necrosis factor receptor-associated factor 3 recruitment in cell death and activation of nuclear factor kappaB

JOURNAL Proc. Natl. Acad. Sci. U.S.A. 94 (6), 2460-2465 (1997)

PUBMED 9122217

REFERENCE 21 (bases 1 to 2136)

AUTHORS Matsumoto,M. , Hsieh,T.Y., Zhu,N., VanArsdale, T ., Hwang, S. B., Jeng,K.S., Gorbalenya, A. E . , Lo, S. Y., Ou, J. H., Ware, CF. and Lai, M. M.

TITLE Hepatitis C virus core protein interacts with the cytoplasmic tail of lymphotoxin-beta receptor

JOURNAL J. Virol. 71 (2), 1301-1309 (1997)

PUBMED 8995654

REFERENCE 22 (bases 1 to 2136)

AUTHORS Wang, X., Bornslaeger, E .A. , Haub,0., Tomihara-Newberger, C . ,

Lonberg,N., Dinulos, M. B . , Disteche, C .M. , Copeland,N.,

Gilbert, D. J. ,

Jenkins, N.A. and Lacy, E. TITLE A candidate gene for the amnionless gastrulation stage mouse mutation encodes a TRAF-related protein

JOURNAL Dev. Biol. 177 (1), 274-290 (1996)

PUBMED 8660894

REFERENCE 23 (bases 1 to 2136)

AUTHORS Nakano,H., Oshima,H., Chung, W., Williams-Abbott , L ., Ware, CF.,

Yagita,H. and Okumura,K.

TITLE TRAF5, an activator of NF-kappaB and putative signal transducer for the lymphotoxin-beta receptor

JOURNAL J. Biol. Chem. 271 (25), 14661-14664 (1996)

PUBMED 8663299

REFERENCE 24 (bases 1 to 2136)

AUTHORS Baens,M., Aerssens, J., van Zand, K., Van den Berghe,H. and

Marynen, P .

TITLE Isolation and regional assignment of human chromosome 12p cDNAs JOURNAL Genomics 29 (1), 44-52 (1995) PUBMED 8530100

REFERENCE 25 (bases 1 to 2136) AUTHORS Crowe, P. D., VanArsdale, T . L ., Walter, B.N. , Ware, CF.,

Hession, C . ,

Ehrenfels, B. , Browning, J. L ., Din, W. S., Goodwin, R. G. and

Smith, CA. TITLE A lymphotoxin-beta-specific receptor JOURNAL Science 264 (5159), 707-710 (1994) PUBMED 8171323

REFERENCE 26 (bases 1 to 2136) AUTHORS Baens,M., Chaffanet , M. , Cassiman, J. J. , van den Berghe,H. and

Marynen, P .

TITLE Construction and evaluation of a hncDNA library of human 12p transcribed sequences derived from a somatic cell hybrid

JOURNAL Genomics 16 (1), 214-218 (1993)

PUBMED 8486360

REFERENCE 27 (bases 1 to 2136)

AUTHORS Browning, J. L. , Ngam-ek,A., Lawton,P., DeMaπnis, J. , Tizard,R.,

Chow, E. P., Hession,C, 0 ' Brine-Greco, B ., Foley, S. F. and

Ware, CF. TITLE Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface

JOURNAL Cell 72 (6) , 847-856 (1993) PUBMED 7916655 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from L04270.1.

Summary: The protein encoded by this gene is a member of the tumor necrosis factor (TNF) family of receptors. It is expressed on the surface of most cell types, including cells of epithelial and myeloid lineages, but not on T and B lymphocytes. The protein specifically binds the lymphotoxin membrane form (a complex of lymphotoxin-alpha and lymphtoxin-beta) . The encoded protein and its ligand play a role in the development and organization of lymphoid tissue and tranformed cells. Activation of the encoded protein can trigger apoptosis.

FEATURES Location/Qualifiers source 1..2136

/organism="Homo sapiens"

/mol_type="mRNA"

/db_xref="taxon: 9606"

/chromosome=" 12 "

/map="12pl3" gene 1..2136

/gene="LTBR"

/note="synonyms: CD18, TNFCR, D12S370, TNFR-RP,

TNFRSF3,

TNFR2-RP, LT-BETA-R, TNF-R-III"

/db_xref="GeneID:4055"

/db_xref="HGNC:6718"

/db_xref="HPRD : HPRD_02988 "

/db_xref="MIM: 600979"

CDS 169..1476

/gene="LTBR"

/go_component="integral to membrane; membrane"

/go_function="protein binding [pmid 12393901]; transmembrane receptor activity"

/go_process="apoptosis; immune response; positive regulation of I-kappaB kinase/NF-kappaB cascade [pmid

12761501]; signal transduction [pmid 8171323]"

/note="tumor necrosis factor C receptor; lymphotoxin B receptor; tumor necrosis factor receptor superfamily, member 3; TNFR superfamily, member 3"

/codon_start=l

/product="lymphotoxin beta receptor"

/protein_id="NP_002333.1"

/db_xref="GI: 4505039"

/db_xref="CCDS:CCDS8544.1"

/db_xref="GeneID:4055" /db_xref="HGNC:6718" /db_xref="HPRD : HPRD_02988 " /db_xref="MIM: 600979"

/translat1On=¹¹MLLPWATSAPGLAWGPLVLGLFGLLAASQPQAVPPYASENQTCR

DQEKEYYEPQHRICCSRCPPGTYVSAKCSRIRDTVCATCAENSYNEHWNYLTICQLCR PCDPVMGLEEIAPCTSKRKTQCRCQPGMFCAAWALECTHCELLSDCPPGTEAELKDEV GKGNNHCVPCKAGHFQNTSSPSARCQPHTRCENQGLVEAAPGTAQSDTTCKNPLEPLP PEMSGTMLMLAVLLPLAFFLLLATVFSCIWKSHPSLCRKLGSLLKRRPQGEGPNPVAG SWEPPKAHPYFPDLVQPLLPISGDVSPVSTGLPAAPVLEAGVPQQQSPLDLTREPQLE

PGEQSQVAHGTNGIHVTGGSMTITGNIYIYNGPVLGGPPGPGDLPATPEPPYPIPEEG

DPGPPGLSTPHQEDGKAWHLAETEHCGATPSNRGPRNQFITHD"

STS 1888..2019

/gene="LTBR"

/standard_name="D12S1911" /db_xref="UmSTS: 14505"

ORIGIN

1 gccctggagg cccggcctgg ccgctcccgg ccctggggtg cacatcggcc ctgagtcccg

61 tcccaggctc tgggctcggg cagccgccgc caccgctgcc caggacgtcg ggcctcctgc

121 cttcctccca ggcccccacg ttgctggccg cctggccgag tggccgccat gctcctgcct

181 tgggccacct ctgcccccgg cctggcctgg gggcctctgg tgctgggcct cttcgggctc

241 ctggcagcat cgcagcccca ggcggtgcct ccatatgcgt cggagaacca gacctgcagg

301 gaccaggaaa aggaatacta tgagccccag caccgcatct gctgctcccg ctgcccgcca

361 ggcacctatg tctcagctaa atgtagccgc atccgggaca cagtttgtgc cacatgtgcc

421 gagaattcct acaacgagca ctggaactac ctgaccatct gccagctgtg ccgcccctgt

481 gacccagtga tgggcctcga ggagattgcc ccctgcacaa gcaaacggaa gacccagtgc

541 cgctgccagc cgggaatgtt ctgtgctgcc tgggccctcg agtgtacaca ctgcgagcta

601 ctttctgact gcccgcctgg cactgaagcc gagctcaaag atgaagttgg gaagggtaac

661 aaccactgcg tcccctgcaa ggcagggcac ttccagaata cctcctcccc cagcgcccgc

721 tgccagcccc acaccaggtg tgagaaccaa ggtctggtgg aggcagctcc aggcactgcc

781 cagtccgaca caacctgcaa aaatccatta gagccactgc ccccagagat gtcaggaacc

841 atgctgatgc tggccgttct gctgccactg gccttctttc tgctccttgc caccgtcttc

901 tcctgcatct ggaagagcca cccttctctc tgcaggaaac tgggatcgct gctcaagagg

961 cgtccgcagg gagagggacc caatcctgta gctggaagct gggagcctcc gaaggcccat

1021 ccatacttcc ctgacttggt acagccactg ctacccattt ctggagatgt ttccccagta

1081 tccactgggc tccccgcagc cccagttttg gaggcagggg tgccgcaaca gcagagtcct

1141 ctggacctga ccagggagcc gcagttggaa cccggggagc agagccaggt ggcccacggt

1201 accaatggca ttcatgtcac cggcgggtct atgactatca ctggcaacat ctacatctac

1261 aatggaccag tactgggggg accaccgggt cctggagacc tcccagctac ccccgaacct

1321 ccatacccca ttcccgaaga gggggaccct ggccctcccg ggctctctac accccaccag

1381 gaagatggca aggcttggca cctagcggag acagagcact gtggtgccac accctctaac

1441 aggggcccaa ggaaccaatt tatcacccat gactgacgga gtctgagaaa aggcagaaga

1501 aggggggcac aagggcactt tctcccttga ggctgccctg cccacgtggg attcacaggg

1561 gcctgagtag ggcccgggga agcagagccc taagggatta aggctcagac acctctgaga

1621 gcaggtgggc actggctggg tacggtgccc tccacaggac tctccctact gcctgagcaa

1681 acctgaggcc tcccggcaga cccacccacc ccctggggct gctcagcctc aggcacggac

1741 agggcacatg ataccaactg ctgcccacta cggcacgccg caccggagca cggcaccgag

1801 ggagccgcca cacggtcacc tgcaaggacg tcacgggccc ctctaaagga ttcgtggtgc

1861 tcatccccaa gcttcagaga ccctttgggg ttccacactt cacgtggact gaggtagacc

1921 ctgcatgaag atgaaattat agggaggacg ctccttccct cccctcctag aggagaggaa

1981 agggagtcat taacaactag ggggttgggt aggattccta ggtatgggga agagttttgg

2041 aaggggagga aaatggcaag tgtatttata ttgtaaccac atgcaaataa aaagaatggg

2101 acctaaactc gtgccgctcg tgccgaattc ctgcag

// LOCUS NM_139208 738 bp mRNA linear PRI 28-MAY-

2006

DEFINITION Homo sapiens mannan-binding lectin serine peptidase 2 (MASP2), transcript variant 2, mRNA. ACCESSION NM_139208

VERSION NM_139208.1 GI:21264360 KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;

Catarrhim; Homimdae; Homo.

REFERENCE 1 (bases 1 to 738) AUTHORS Verma,A., Matta,A., Shukla,N.K., Deo, S.V., Gupta, S. D. and

Ralhan, R. TITLE Clinical significance of mannose-binding lectin-associated serine protease-2 expression in esophageal squamous cell carcinoma

JOURNAL Int. J. Cancer 118 (12), 2930-2935 (2006) PUBMED 16395704 REMARK GeneRIF: MASP-2 expression in ESCCs was associated with late clinical stage (p = 0.009, O. R. = 3.430) and nodal metastasis

⁽P =

0.001, O. R. = 4.520) .

REFERENCE 2 (bases 1 to 738) AUTHORS Seyfarth,J., Garred,P. and Madsen,H.O. TITLE Extra-hepatic transcription of the human mannose-binding lectin gene (mbl2) and the MBL-associated serine protease 1-3 genes

JOURNAL MoI. Immunol. 43 (7), 962-971 (2006) PUBMED 16112196 REMARK GeneRIF: The mRNA distribution of maspl and masp2 were found very similar to that of mbl2, while masp3 mRNA seemed ubiquitous present at quite high levels when compared to liver

REFERENCE 3 (bases 1 to 738) AUTHORS Gal, P., Harmat,V., Kocsis,A., Bian,T., Barna,L., Ambrus,G., Vegh,B., Balczer,J., Sim, R. B., Naray-Szabo, G . and Zavodszky,P.

TITLE A true autoactivating enzyme. Structural insight into mannose-binding lectin-associated serine protease-2 activations

JOURNAL J. Biol. Chem. 280 (39), 33435-33444 (2005) PUBMED 16040602 REMARK GeneRIF: Structural insights are presented into MASP2 autoactivation .

REFERENCE 4 (bases 1 to 738) AUTHORS Ytting,H., Christensen, I . J. , Thiel,S., Jensenius, J. C . and

Nielsen, H.J.

TITLE Serum mannan-binding lectin-associated serine protease 2 levels colorectal cancer: relation to recurrence and mortality

JOURNAL Clin. Cancer Res. 11 (4), 1441-1446 (2005) PUBMED 15746044 REMARK GeneRIF: MASP-2 concentration in serum proved to be an independent prognostic marker with high MASP-2 levels predicting recurrence and poor survival .

REFERENCE 5 (bases 1 to 738) AUTHORS Gregory, L.A. , Thielens, N .M. , Matsushita, M. , Sorensen,R.,

Arlaud, G . J . , Fontecilla-Camps , J . C . and Gaboπaud, C .

TITLE The X-ray structure of human mannan-binding lectin-associated protein 19 (MApI 9) and its interaction site with mannan-binding lectin and L-ficolin

JOURNAL J. Biol. Chem. 279 (28), 29391-29397 (2004) PUBMED 15117939 REMARK GeneRIF: Results describe the x-ray structure of human mannan-binding lectin-associated protein 19 (MApI 9), and identify the residues involved in the interaction of MApl9 with mannan-binding lectin and L-ficolin. REFERENCE 6 (bases 1 to 738)

AUTHORS Stengaard-Pedersen,K. , Thiel,S., Gadjeva,M., Moller- Kπstensen, M. ,

Sorensen,R., Jensen, L. T., Sjoholm, A.G. , Fugger,L. and Jensenius, J. C . TITLE Inherited deficiency of mannan-binding lectin-associated serine protease 2 JOURNAL N. Engl. J. Med. 349 (6), 554-560 (2003)

PUBMED 12904520 REFERENCE 7 (bases 1 to 738)

AUTHORS Cseh,S., Vera, L., Matsushita, M. , Fujita,T., Arlaud,G.J. and

Thielens,N.M. TITLE Characterization of the interaction between L-ficolin/p35 and mannan-binding lectin-associated serine proteases-1 and -2 JOURNAL J. Immunol. 169 (10), 5735-5743 (2002)

PUBMED 12421953

REMARK GeneRIF: The interaction of recombinant MASP2, its N-terminal complement modules, and MBL-associated protein 19 with L-ficolin/p35 has been characterized by surface plasmon resonance spectroscopy.

REFERENCE 8 (bases 1 to 738) AUTHORS Matsushita, M. , Kuraya,M., Hamasaki, N. , Tsu]iraura, M. , Shiraki, H. and

Fu]ita, T.

TITLE Activation of the lectin complement pathway by H-ficolin (Hakata antigen) JOURNAL J. Immunol. 168 (7), 3502-3506 (2002)

PUBMED 11907111 REFERENCE 9 (bases 1 to 738)

AUTHORS Stover, C, Endo,Y., Takahashi, M. , Lynch, N. J., Constantinescu, C . ,

Vorup-Jensen, T. , Thiel,S., Fπedl,H., Hankeln,T., Hall, R., Gregory, S., Fu]ita,T. and Schwaeble,W. TITLE The human gene for mannan-binding lectin-associated serine protease-2 (MASP-2), the effector component of the lectin route of complement activation, is part of a tightly linked gene cluster on chromosome lp36.2-3

JOURNAL Genes Immun. 2 (3), 119-127 (2001)

PUBMED 11426320

REFERENCE 10 (bases 1 to 738)

AUTHORS Matsushita, M. , Thiel,S., Jensenius, J. C ., Terai,I. and Fu]ita,T.

TITLE Proteolytic activities of two types of mannose-binding lectin-associated serine protease

JOURNAL J. Immunol. 165 (5), 2637-2642 (2000)

PUBMED 10946292

REFERENCE 11 (bases 1 to 738)

AUTHORS Thiel,S., Petersen, S .V. , Vorup-Jensen, T . , Matsushita, M. , Fu]ita, T. ,

Stover, CM., Schwaeble, W. J. and Jensenius, J. C . TITLE Interaction of CIq and mannan-binding lectin (MBL) with CIr, CIs,

MBL-associated serine proteases 1 and 2, and the MBL-associated protein MApI 9

JOURNAL J. Immunol. 165 (2), 878-887 (2000)

PUBMED 10878362

REFERENCE 12 (bases 1 to 738)

AUTHORS Matsushita, M. , Endo,Y. and Fujita,T.

TITLE Cutting edge: complement-activating complex of ficolin and mannose-binding lectin-associated serine protease

JOURNAL J. Immunol. 164 (5), 2281-2284 (2000)

PUBMED 10679061

REFERENCE 13 (bases 1 to 738)

AUTHORS Takahashi,M. , Endo,Y., Fu]ita,T. and Matsushita, M.

TITLE A truncated form of mannose-binding lectin-associated serine protease (MASP) -2 expressed by alternative polyadenylation is a component of the lectin complement pathway

JOURNAL Int. Immunol. 11 (5), 859-863 (1999)

PUBMED 10330290

REFERENCE 14 (bases 1 to 738)

AUTHORS Stover, CM., Thiel,S., Thelen,M., Lynch, N. J., Vorup-Jensen, T .,

Jensenius, J. C . and Schwaeble, W. J.

TITLE Two constituents of the initiation complex of the mannan- binding lectin activation pathway of complement are encoded by a single structural gene

JOURNAL J. Immunol. 162 (6), 3481-3490 (1999)

PUBMED 10092804

REFERENCE 15 (bases 1 to 738)

AUTHORS Stover, CM., Schwaeble, W. J. , Lynch, N. J., Thiel,S. and Speicher, M .R.

TITLE Assignment of the gene encoding mannan-binding lectin- associated serine protease 2 (MASP2) to human chromosome Ip36.3—>p36.2 by in situ hybridization and somatic cell hybrid analysis JOURNAL Cytogenet. Cell Genet. 84 (3-4), 148-149 (1999)

PUBMED 10393416 REFERENCE 16 (bases 1 to 738)

AUTHORS Vorup-Jensen, T. , Jensenius, J. C . and Thiel,S.

TITLE MASP-2, the C3 convertase generating protease of the MBLectin complement activating pathway JOURNAL Immunobiology 199 (2), 348-357 (1998)

PUBMED 9777418 REMARK Review article REFERENCE 17 (bases 1 to 738)

AUTHORS Thiel,S., Vorup-Jensen, T ., Stover, CM., Schwaeble, W. , Laursen, S .B. ,

Poulsen,K., Willis, A. C, Eggleton,P., Hansen, S., Holmskov,U.,

Reid, K. B. and Jensenius, J. C .

TITLE A second serine protease associated with mannan-binding lectin that activates complement

JOURNAL Nature 386 (6624), 506-510 (1997) PUBMED 9087411

REFERENCE 18 (bases 1 to 738) AUTHORS Sato, T., Endo,Y., Matsushita, M. and Fu]ita,T. TITLE Molecular characterization of a novel serine protease involved in activation of the complement system by mannose-binding protein

JOURNAL Int. Immunol. 6 (4), 665-669 (1994) PUBMED 8018603 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from Y18281.1.

Summary: The Ra-reactive factor (RARF) is a complement- dependent bactericidal factor that binds to the Ra and R2 polysaccharides expressed by certain enterobacteπa. Alternate splicing of this gene results in two transcript variants encoding two RARF components that are involved in the mannan-binding lectin pathway of complement activation. The longer isoform is cleaved into two chains which form a heterodimer linked by a disulfide bond. The encoded proteins are members of the trypsin family of peptidases .

Transcript Variant: This variant (2), also called MApl9, differs in the 3' UTR and 3' coding region compared to variant 1, resulting in a frameshift and upstream stop codon. Isoform 2 has a unique C-terminus and lacks the serine protease catalytic domain, compared to isoform 1.

COMPLETENESS: complete on the 3' end. FEATURES Location/Qualifiers source 1..738

/ orgam sm= " Homo sapiens "

/mol_type= "mRNA"

/db_xre f= " taxon : 9606 "

/chromosome=" 1 "

/map="lp36.3-p36.2" gene 1..738

/gene="MASP2"

/note="synonyms: sMAP, MAP19, MASP-2"

/db_xref="GeneID: 10747"

/db_xref="HGNC: 6902"

/db_xref="HPRD:HPRD_05484"

/db_xref="MIM: 605102" CDS 22..579

/gene="MASP2"

/go_component="extracellular region"

/go_funct ion= " calcium ion binding ; seπne-type endopeptidase activity [pmid 9087411]"

/go_process="antimicrobial humoral response (sensu

Vertebrata) [pmid 9087411]; complement activation, classical pathway; innate immune response; proteolysis"

/note="isoform 2 precursor is encoded by transcript variant 2; mannan-binding lectin serine protease 2;

MBL-associated plasma protein of 19 kD; small

MBL-associated protein; MBL-associated serine protease 2"

/codon_start=l

/product="mannan-binding lectin serine protease 2 isoform

2 precursor"

/protein_id="NP_631947.1"

/db_xref="GI:21264361"

/db_xref="CCDS:CCDS124.1"

/db_xref="GeneID: 10747" /db_xref="HGNC: 6902" /db_xref="HPRD:HPRD_05484" /db_xref="MIM: 605102"

/translation="MRLLTLLGLLCGSVATPLGPKWPEPVFGRLASPGFPGEYANDQE RRWTLTAPPGYRLRLYFTHFDLELSHLCEYDFVKLSSGAKVLATLCGQESTDTERAPG

KDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYAAEDIDECQVAPGEAPTCDHHCHNHL

GGFYCSCRAGYVLHRNKRTCSEQSL" sig_peptide 22..66

/gene="MASP2" mat_peptide 67..576

/gene="MASP2"

/product="mannan-binding lectin serine protease 2, isoform

2" polyA_signal 701..706

/gene="MASP2" polyA_site 721

/gene="MASP2" ORIGIN

1 ggccagctgg acgggcacac catgaggctg ctgaccctcc tgggccttct gtgtggctcg 61 gtggccaccc ccttgggccc gaagtggcct gaacctgtgt tcgggcgcct ggcatccccc 121 ggctttccag gggagtatgc caatgaccag gagcggcgct ggaccctgac tgcacccccc 181 ggctaccgcc tgcgcctcta cttcacccac ttcgacctgg agctctccca cctctgcgag 241 tacgacttcg tcaagctgag ctcgggggcc aaggtgctgg ccacgctgtg cgggcaggag 301 agcacagaca cggagcgggc ccctggcaag gacactttct actcgctggg ctccagcctg 361 gacattacct tccgctccga ctactccaac gagaagccgt tcacggggtt cgaggccttc 421 tatgcagccg aggacattga cgagtgccag gtggccccgg gagaggcgcc cacctgcgac 481 caccactgcc acaaccacct gggcggtttc tactgctcct gccgcgcagg ctacgtcctg 541 caccgtaaca agcgcacctg ctcagagcag agcctctagc ctcccctgga gctccggcct 601 gcccagcagg tcagaagcca gagccagcct gctggcctca gctccgggtt gggctgagat 661 ggctgtgccc caactcccat tcacccacca tggacccaat aataaacctg gccccacccc 721 aaaaaaaaaa aaaaaaaa //

LOCUS NM_000263 2798 bp mRNA linear PRI 26-FEB-

2006

DEFINITION Homo sapiens N-acetylglucosaminidase, alpha- (Sanfilippo disease

IIIB) (NAGLU) , mRNA. ACCESSION NM_000263

VERSION NM_000263.3 GI:66346697 KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhim; Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 2798)

AUTHORS Emre,S., Terzioglu, M. , Tokatli,A., Coskun,T., Ozalp,I., Weber, B. and Hopwood,J.J.

TITLE Sanfilippo syndrome in Turkey: Identification of novel mutations in subtypes A and B JOURNAL Hum. Mutat . 19 (2), 184-185 (2002)

PUBMED 11793481 REMARK GeneRIF: Sanfilippo syndrome (subtypes A and B) in Turkey: identification of novel mutations in SGSH and NAGLU REFERENCE 2 (bases 1 to 2798)

AUTHORS Yogalingam, G. and Hopwood, J. J.

TITLE Molecular genetics of mucopolysaccharidosis type IIIA and IIIB:

Diagnostic, clinical, and biological implications JOURNAL Hum. Mutat. 18 (4), 264-281 (2001)

PUBMED 11668611 REMARK Review article

GeneRIF: Molecular genetics of mucopolysaccharidosis type IIIA and

IIIB: Diagnostic, clinical, and biological implications REFERENCE 3 (bases 1 to 2798)

AUTHORS Weber, B., Hopwood, J.J. and Yogalingam, G .

TITLE Expression and characterization of human recombinant and alpha-N-acetylglucosaminidase JOURNAL Protein Expr. Puπf. 21 (2), 251-259 (2001)

PUBMED 11237686 REFERENCE 4 (bases 1 to 2798)

AUTHORS Zhao, K. W. and Neufeld,E.F.

TITLE Purification and characterization of recombinant human alpha-N-acetylglucosaminidase secreted by Chinese hamster ovary cells JOURNAL Protein Expr. Puπf. 19 (1), 202-211 (2000)

PUBMED 10833408 REFERENCE 5 (bases 1 to 2798)

AUTHORS Bunge,S., Knigge,A., Steglich,C, Kleiner, W. J. , van Diggelen, O. P . ,

Beck, M. and Gal, A.

TITLE Mucopolysaccharidosis type IIIB (Sanfilippo B) : identification of

18 novel alpha-N-acetylglucosaminidase gene mutations JOURNAL J. Med. Genet. 36 (1), 28-31 (1999)

PUBMED 9950362 REFERENCE 6 (bases 1 to 2798)

AUTHORS Schmidtchen, A. , Greenberg, D . , Zhao, H. G., Li, H. H., Huang, Y.,

Tieu,P., Zhao, H. Z., Cheng, S., Zhao, Z., Whitley, C . B . , Di Natale,P. and Neufeld,E.F. TITLE NAGLU mutations underlying Sanfilippo syndrome type B JOURNAL Am. J. Hum. Genet. 62 (1), 64-69 (1998) PUBMED 9443878

REFERENCE 7 (bases 1 to 2798) AUTHORS Zhao, Z., Yazdam,A., Shen,Y., Sun, Z., Bailey, J., Caskey,C.T. and

Lee, CC.

TITLE Molecular dissection of a cosmid from a gene-rich region in 17q21 and characterization of a candidate gene for alpha-N-acetylglucosaminidase with two cDNA isoforms

JOURNAL Mamm. Genome 7 (9), 686-690 (1996) PUBMED 8703123

REFERENCE 8 (bases 1 to 2798)

AUTHORS Zhao, H. G., Li, H. H., Bach, G., Schmidtchen, A. and Neufeld,E.F.

TITLE The molecular basis of Sanfilippo syndrome type B

JOURNAL Proc. Natl. Acad. Sci. U.S.A. 93 (12), 6101-6105 (1996)

PUBMED 8650226

REFERENCE 9 (bases 1 to 2798) AUTHORS Weber, B., Blanch, L., Clements, P . R. , Scott, H. S. and Hopwood,J.J. TITLE Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis III B)

JOURNAL Hum. MoI. Genet. 5 (6), 771-777 (1996)

PUBMED 8776591

REFERENCE 10 (bases 1 to 2798)

AUTHORS Sasaki, T., Sukegawa,K., Masue,M., Fukuda,S., Tomatsu,S. and Om, T.

TITLE Purification and partial characterization of alpha-N-acetylglucosaminidase from human liver JOURNAL J. Biochem. 110 (5), 842-846 (1991)

PUBMED 1783617 REFERENCE 11 (bases 1 to 2798)

AUTHORS Vance, J. M., Pericak-Vance, M.A. , Elston, R.C . , Conneally, P .M. ,

Namboodiπ, K. K. , Wappner,R.S. and Yu, P. L.

TITLE Evidence of genetic variation for alpha-N-acetyl-D- glucosaminidase in black and white populations: a new polymorphism

JOURNAL Am. J. Med. Genet. 7 (2), 131-140 (1980) PUBMED 6781343 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from BF435029.1, U40846.1,

AI299657.1 and BQ012843.1.

On May 19, 2005 this sequence version replaced gi : 40548380.

Summary: This gene encodes an enzyme that degrades heparan sulfate by hydrolysis of terminal N-acetyl-D-glucosamine residues in N-acetyl-alpha-D-glucosaminides . Defects in this gene are the cause of mucopolysaccharidosis type IIIB (MPS-IIIB) , also known as Sanfilippo syndrome B. This disease is characterized by the lysosomal accumulation and urinary excretion of heparan sulfate .

COMPLETENESS: complete on the 3' end. FEATURES Location/Qualifiers source 1..2798

/orgamsm="Homo sapiens " /mol_type="mRNA" /db_xref="taxon : 9606 " /chromosome=" 17 " /map=" 17q21 " gene 1..2798

/gene="NAGLU"

/note="synonyms: NAG, MPS3B, UFHSD, MPS IHB"

/db_xref="GeneID:4669"

/db_xref="HGNC:7632"

/db_xref="HPRD:HPRD_02017"

/db_xref="MIM: 609701"

CDS 341..2572

/gene="NAGLU"

/EC_number="3.2.1.50"

/go_component="lysosome [pmid 8650226]"

/go_function="alpha-N-acetylglucosaminidase activity

[pmid

8650226]; hydrolase activity, acting on glycosyl bonds" /go_process="carbohydrate metabolism; glycosaminoglycan metabolism; nervous system development [pmid 8650226]"

/note="N-acetyl-alpha-glucosaminidase"

/codon_start=l

/product="alpha-N-acetylglucosaminidase precursor"

/protein_id="NP_000254.2"

/db_xref="GI : 66346698"

/db_xref="CCDS: CCDSl 1427.1"

/db_xref="GeneID:4669"

/db_xref="HGNC:7632"

/db_xref="HPRD:HPRD_02017"

/db_xref="MIM: 609701"

/trans1ation="MEAVAVAAAVGVLLLAGAGGAAGDEAREAAAVRALVARLLGPGP

AADFSVSVERALAAKPGLDTYSLGGGGAARVRVRGSTGVAAAAGLHRYLRDFCGCHVA WSGSQLRLPRPLPAVPGELTEATPNRYRYYQNVCTQSYSFVWWDWARWEREIDWMALN GINLALAWSGQEAIWQRVYLALGLTQAEINEFFTGPAFLAWGRMGNLHTWDGPLPPSW HIKQLYLQHRVLDQMRSFGMTPVLPAFAGHVPEAVTRVFPQVNVTKMGSWGHFNCSYS CSFLLAPEDPIFPIIGSLFLRELIKEFGTDHIYGADTFNEMQPPSSEPSYLAAATTAV YEAMTAVDTEAVWLLQGWLFQHQPQFWGPAQIRAVLGAVPRGRLLVLDLFAESQPVYT RTASFQGQPFIWCMLHNFGGNHGLFGALEAVNGGPEAARLFPNSTMVGTGMAPEGISQ NEWYSLMAELGWRKDPVPDLAAWVTSFAARRYGVSHPDAGAAWRLLLRSVYNCSGEA CRGHNRSPLVRRPSLQMNTSIWYNRSDVFEAWRLLLTSAPSLATSPAFRYDLLDLTRQ AVQELVSLYYEEARSAYLSKELASLLRAGGVLAYELLPALDEVLASDSRFLLGSWLEQ ARAAAVSEAEADFYEQNSRYQLTLWGPEGNILDYANKQLAGLVANYYTPRWRLFLEAL VDSVAQGIPFQQHQFDKNVFQLEQAFVLSKQRYPSQPRGDTVDLAKKIFLKYYPRWVA

GSW" sig_peptide 341..409

/gene="NAGLU" mat_peptide 410..2569

/gene="NAGLU"

/product=" alpha-N-acetylglucosamimdase " STS 2349 . . 2481

/gene="NAGLU" /standard_name="RH18065"

/db_xref=" UmSTS: 9904' polyA_signal 2755..2760

/gene="NAGLU" polyA_site 2783

/gene="NAGLU"

ORIGIN

1 agtagggaag tagctatggc agtgcctgat acaaaataaa ctccaaatgt gtatttatta

61 gatggttgga tggaagttat ttgcgtgtga aagcgcgttt tacccgaagg cgctctgtga

121 gggccagcgg gtccccttcg gccctggagc cggggtcaca cgctccccac cgcgtgcggt

181 cacgagacgc ccccaaggga gtatcctggt acccggaagc cgcgactcct ggccctgagc

241 ccgggcttag ccttcgggtc cacgtggccg gaggccggca gctgattgga cgcgggccgc

301 cccaccccct ggccgtcgcg ggacccgcag gactgagacc atggaggcgg tggcggtggc

361 cgcggcggtg ggggtccttc tcctggccgg ggccgggggc gcggcaggcg acgaggcccg

421 ggaggcggcg gccgtgcggg cgctcgtggc ccggctgctg gggccaggcc ccgcggccga

481 cttctccgtg tcggtggagc gcgctctggc tgccaagccg ggcttggaca cctacagcct

541 gggcggcggc ggcgcggcgc gcgtgcgggt gcgcggctcc acgggcgtgg cggccgccgc

601 ggggctgcac cgctacctgc gcgacttctg tggctgccac gtggcctggt ccggctctca

661 gctgcgcctg ccgcggccac tgccagccgt gccgggggag ctgaccgagg ccacgcccaa

721 caggtaccgc tattaccaga atgtgtgcac gcaaagctac tctttcgtgt ggtgggactg

781 ggcccgctgg gagcgagaga tagactggat ggcgctgaat ggcatcaacc tggcactggc

841 ctggagcggc caggaggcca tctggcagcg ggtgtacctg gccttgggcc tgacccaggc

901 agagatcaat gagttcttta ctggtcctgc cttcctggcc tgggggcgaa tgggcaacct

961 gcacacctgg gatggccccc tgcccccctc ctggcacatc aagcagcttt acctgcagca

1021 ccgggtcctg gaccagatgc gctccttcgg catgacccca gtgctgcctg cattcgcggg

1081 gcatgttccc gaggctgtca ccagggtgtt ccctcaggtc aatgtcacga agatgggcag

1141 ttggggccac tttaactgtt cctactcctg ctccttcctt ctggctccgg aagaccccat

1201 attccccatc atcgggagcc tcttcctgcg agagctgatc aaagagtttg gcacagacca

1261 catctatggg gccgacactt tcaatgagat gcagccacct tcctcagagc cctcctacct

1321 tgccgcagcc accactgccg tctatgaggc catgactgca gtggatactg aggctgtgtg

1381 gctgctccaa ggctggctct tccagcacca gccgcagttc tgggggcccg cccagatcag

1441 ggctgtgctg ggagctgtgc cccgtggccg cctcctggtt ctggacctgt ttgctgagag

1501 ccagcctgtg tatacccgca ctgcctcctt ccagggccag cccttcatct ggtgcatgct

1561 gcacaacttt gggggaaacc atggtctttt tggagcccta gaggctgtga acggaggccc

1621 agaagctgcc cgcctcttcc ccaactccac catggtaggc acgggcatgg cccccgaggg

1681 catcagccag aacgaagtgg tctattccct catggctgag ctgggctggc gaaaggaccc

1741 agtgccagat ttggcagcct gggtgaccag ctttgccgcc cggcggtatg gggtctccca

1801 cccggacgca ggggcagcgt ggaggctact gctccggagt gtgtacaact gctccgggga

1861 ggcctgcagg ggccacaatc gtagcccgct ggtcaggcgg ccgtccctac agatgaatac

1921 cagcatctgg tacaaccgat ctgatgtgtt tgaggcctgg cggctgctgc tcacatctgc

1981 tccctccctg gccaccagcc ccgccttccg ctacgacctg ctggacctca ctcggcaggc

2041 agtgcaggag ctggtcagct tgtactatga ggaggcaaga agcgcctacc tgagcaagga

2101 gctggcctcc ctgttgaggg ctggaggcgt cctggcctat gagctgctgc cggcactgga

2161 cgaggtgctg gctagtgaca gccgcttctt gctgggcagc tggctagagc aggcccgagc

2221 agcggcagtc agtgaggccg aggccgattt ctacgagcag aacagccgct accagctgac

2281 cttgtggggg ccagaaggca acatcctgga ctatgccaac aagcagctgg cggggttggt

2341 ggccaactac tacacccctc gctggcggct tttcctggag gcgctggttg acagtgtggc

2401 ccagggcatc cctttccaac agcaccagtt tgacaaaaat gtcttccaac tggagcaggc

2461 cttcgttctc agcaagcaga ggtaccccag ccagccgcga ggagacactg tggacctggc

2521 caagaagatc ttcctcaaat attacccccg ctgggtggcc ggctcttggt gatagattcg

2581 ccaccactgg gccttgtttt ccgctaattc cagggcagat tccagggccc agagctggac

2641 agacatcaca ggataaccca ggcctgggag gaggccccac ggcctgctgg tggggtctga

2701 cctgggggga ttggagggaa atgacctgcc ctccaccacc acccaaagtg tgggattaaa

2761 gtactgtttt ctttccactt aaaaaaaaaa aaaaaaaa

/ / LOCUS NM_052918 7272 bp mRNA linear PRI 19-MAR-

2006

DEFINITION Homo sapiens sortilin-related VPSlO domain containing receptor

1

(SORCSl), transcript variant 1, mRNA. ACCESSION NM_052918

VERSION NM_052918.3 GI:61743972 KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhim;

Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 7272)

AUTHORS Hermey,G., Keat,S.J., Madsen,P., Jacobsen,C, Petersen, C .M. and

Gliemann, J.

TITLE Characterization of sorCSl, an alternatively spliced receptor with completely different cytoplasmic domains that mediate different trafficking in cells

JOURNAL J. Biol. Chem. 278 (9), 7390-7396 (2003) PUBMED 12482870 REMARK GeneRIF: human sorCSl has three isoforms, sorCSla-c, with completely different cytoplasmic tails and differential expression in tissues

REFERENCE 2 (bases 1 to 7272) AUTHORS Hampe,W., Rezgaoui,M., Hermans-Borgmeyer, I . and Schaller, H . C . TITLE The genes for the human VPSlO domain-containing receptors are large and contain many small exons

JOURNAL Hum. Genet. 108 (6), 529-536 (2001) PUBMED 11499680 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from AF284756.1, BE019093.1,

AY099452.1, AK125464.1 and AL133395.21.

On Mar 24, 2005 this sequence version replaced gi : 18379341.

Summary: This gene encodes one family member of vacuolar protein sorting 10 (VPSlO) domain-containing receptor proteins. The VPSlO domain name comes from the yeast carboxypeptidase Y sorting receptor VpslO protein. Members of this gene family are large with many exons but the CDS lengths are usually less than 3700 nt . Very large introns typically separate the exons encoding the VPSlO domain; the remaining exons are separated by much smaller-sized introns. These genes are strongly expressed in the central nervous system. Two of the five family members (sortilin and sortilin-related receptor) are synthesized as preproproteins; it is not yet known if this encoded protein is also a preproprotein . Alternatively spliced transcript variants encoding different isoforms have been identified.

Transcript Variant: This variant (1) represents the longer transcript, but encodes the shorter isoform (a) . COMPLETENESS: complete on the 3' end.

FEATURES Location/Qualifiers source 1..7272

/ orgam sm= " Homo sapiens " /mol_type= "mRNA" /db_xre f= " taxon : 9606 " / chromosome= " 10 " /map= " 10q23-q25 " gene 1 . . 7272

/gene= " SORCS l "

/note="synonyms: FLJ41758, FLJ43475, FLJ44957" /db_xref="GeneID: 114815" /db_xref="HGNC: 16697" /db_xref="HPRD : HPRD_12098 " /db_xref="MIM: 606283"

CDS 9..3515

/gene="SORCSl"

/go_component=" integral to membrane; membrane [pmid 12482870]"

/go_function="neuropeptide receptor activity [pmid 11499680]; protein binding [pmid 12482870] [pmid 12482870]; protein transporter activity" /go_process="intracellular protein transport; neuropept ide signaling pathway [pmid 11499680]"

/note="isoform a is encoded by transcript variant 1;

VPSlO domain receptor SorCS; VPSlO domain receptor protein SORCS

1; SORCS receptor 1"

/codon_start=l

/product="SORCS receptor 1 isoform a"

/protein_id="NP_443150.3"

/db_xref="GI : 61743973"

/db_xref="CCDS:CCDS7559.1"

/db_xref="GeneID: 114815"

/db_xref="HGNC: 16697"

/db_xref="HPRD : HPRD_12098 "

/db_xref="MIM: 606283"

/translation="MGKVGAGGGSQARLSALLAGAGLLILCAPGVCGGGSCCPSPHPS

SAPRSASTPRGFSHQGRPGRAPATPLPLWRPLFSVAPGDRALSLERARGTGASMAVA ARSGRRRRSGADQEKAERGEGASRSPRGVLRDGGQQEPGTRERDPDKATRFRMEELRL TSTTFALTGDSAHNQAMVHWSGHNSSVILILTKLYDYNLGSITESSLWRSTDYGTTYE KLNDKVGLKTILSYLYVCPTNKRKIMLLTDPEIESSLLISSDEGATYQKYRLNFYIQS LLFHPKQEDWILAYSQDQKLYSSAEFGRRWQLIQEGWPNRFYWSVMGSNKEPDLVHL EARTVDGHSHYLTCRMQNCTEANRNQPFPGYIDPDSLIVQDHYVFVQLTSGGRPHYYV SYRRNAFAQMKLPKYALPKDMHVISTDENQVFAAVQEWNQNDTYNLYISDTRGVYFTL ALENVQSSRGPEGNIMIDLYEVAGIKGMFLANKKIDNQVKTFITYNKGRDWRLLQAPD TDLRGDPVHCLLPYCSLHLHLKVSENPYTSGIIASKDTAPSIIVASGNIGSELSDTDI SMFVSSDAGNTWRQIFEEEHSVLYLDQGGVLVAMKHTSLPIRHLWLSFDEGRSWSKYS FTSIPLFVDGVLGEPGEETLIMTVFGHFSHRSEWQLVKVDYKSIFDRRCAEEDYRPWQ LHSQGEACIMGAKRIYKKRKSERKCMQGKYAGAMESEPCVCTEADFDCDYGYERHSNG QCLPAFWFNPSSLSKDCSLGQSYLNSTGYRKWSNNCTDGVREQYTAKPQKCPGKAPR GLRIVTADGKLTAEQGHNVTLMVQLEEGDVQRTLIQVDFGDGIAVSYVNLSSMEDGIK HVYQNVGIFRVTVQVDNSLGSDSAVLYLHVTCPLEHVHLSLPFVTTKNKEVNATAVLW PSQVGTLTYVWWYGNNTEPLITLEGSISFRFTSEGMNTITVQVSAGNAILQDTKTIAV YEEFRSLRLSFSPNLDDYNPDIPEWRRDIGRVIKKSLVEATGVPGQHILVAVLPGLPT TAELFVLPYQDPAGENKRSTDDLEQISELLIHTLNQNSVHFELKPGVRVLVHAAHLTA

APLVDLTPTHSGSAMLMLLSWFVGLAVFVIYKFKRRVALPSPPSPSTQPGDSSLRLQ

RARHATPPSTPKRGSAGAQYAI "

STS 4654..4843

/gene="SORCSl"

/db_xref="UmSTS: 151392"

STS 4678..4841

/gene="SORCSl"

/standard_name="AO 08Rl5 "

/db_xref="UmSTS:40984"

STS 6402..7232

/gene="SORCSl"

/standard_name=" SORCS1 5283"

/db_xref="UmSTS : 464557 "

STS 6752..6854

/gene="SORCSl"

/standard_name="D10S1331E"

/db_xref="UmSTS : 60809 " polyA_signal 7008..7013

/gene="SORCSl" polyA_site 7030

/gene="SORCSl"

/expeπment="experimental evidence, no additional details recorded" polyA_signal 7247..7252 /gene="SORCSl" polyA_site 7272 /gene="SORCSl"

ORIGIN

1 ctcccgcgat gggaaaagtt ggcgccggcg gcggctccca agcccggctg agcgcgctcc

61 tcgccggcgc ggggctcttg atcctctgcg ccccgggcgt ctgcggcggc ggctcctgct

121 gcccctcgcc gcaccccagc tccgctccac gctcggcctc gacccctagg ggcttttccc

181 accaggggcg gccaggcagg gctcctgcca cgcccctgcc cctcgtagtg cgtcccctgt

241 tctcagtggc ccccggggac cgagcgctat ccctggagcg ggctcggggc actggggcat

301 ccatggcggt tgctgcacgc tccggccgga ggagacggag cggagcggat caggagaagg

361 cagaacgggg agagggcgcg agtcggagcc cccggggagt gctaagagat ggagggcagc

421 aggagcctgg gactcgggag cgggacccgg acaaagccac ccgcttccgg atggaggagc

481 tgagactgac cagcaccacg tttgcgctga cgggagactc agcacacaac caagccatgg

541 tccactggtc tggccacaac agcagcgtga ttctcatttt gacaaagctc tatgactata

601 acctggggag catcacagag agctcgcttt ggaggtcaac cgattatgga acaacctatg

661 agaagctgaa tgataaagtt ggtttgaaaa ccattttgag ctatctctat gtgtgtccta

721 ccaacaagcg taagataatg ttactcacag acccggagat tgagagcagt ttattgatca

781 gctcagatga aggggcaact tatcaaaagt accggctgaa cttctacatt caaagcttgc

841 tttttcaccc caaacaagaa gactggattc tggcatacag tcaagaccaa aagttataca

901 gctctgctga atttgggaga agatggcagc ttatccaaga aggggttgta ccaaacaggt 961 tctactggtc tgtgatgggg tcaaataaag aaccagacct tgtgcatctt gaggccagaa 1021 ctgtggatgg tcattcacat tatctaactt gccgaatgca gaactgtaca gaggccaaca 1081 ggaatcagcc ttttccaggc tacattgacc cagactcttt gattgttcag gatcattatg 1141 tgtttgttca gctgacatca ggagggcggc cacattacta cgtgtcctac cgaaggaatg 1201 catttgccca aatgaagctt ccgaaatatg ctttgcccaa ggacatgcat gttatcagca 1261 ccgatgagaa tcaggtgttc gcagcggtcc aagaatggaa ccagaatgac acgtacaacc 1321 tctacatctc agacacacgt ggtgtctact tcaccctggc cttggagaat gtccagagca 1381 gcagaggccc tgagggcaac atcatgatcg acctctatga ggtagcaggg ataaagggaa 1441 tgttcttggc taacaagaag attgacaacc aagtgaagac tttcatcaca tataacaaag 1501 gcagagactg gcgtttgctg caggcgccgg acacggatct aaggggggac cccgtgcact 1561 gcttgctgcc ctattgctca ctacaccttc acctgaaggt ctctgagaat ccctacacat 1621 cagggatcat tgccagcaaa gacacagctc caagcatcat agtggcatca ggtaatatag 1681 gttctgaatt gtcagacact gacatcagca tgtttgtctc ttcagatgca gggaacacct 1741 ggagacagat ctttgaagaa gagcacagtg ttttgtacct ggatcaaggt ggagtcctgg 1801 ttgctatgaa acacacatct ctcccaattc gacatctttg gttgagtttt gatgaaggga 1861 gatcttggag caaatacagt ttcacatcta ttccactttt tgtggatggg gttctgggtg 1921 agcctggaga agagactctc atcatgacag tgtttggaca cttcagccac cgctctgaat 1981 ggcagctggt caaagtagat tacaagtcca tttttgatag acggtgtgcc gaagaggact 2041 acagaccttg gcagctgcac agccaggggg aagcatgtat catgggagca aaaaggatat 2101 ataagaagcg aaaatcagag cggaagtgta tgcaaggaaa atatgcagga gctatggaat 2161 ctgaaccctg tgtctgcact gaggctgatt ttgattgcga ctatggttat gagcgacaca 2221 gcaatggcca gtgcctgccg gcattttggt tcaatccatc ctctctgtca aaggattgca 2281 gcttgggaca gagttacctc aatagtactg ggtacaggaa ggtggtttcc aataattgca 2341 ctgatggcgt aagggaacag tacactgcca aaccgcagaa gtgcccaggg aaagccccgc 2401 gggggctgcg gatagtcacg gctgatggaa agctgacagc ggaacaagga cacaacgtca 2461 ctctcatggt gcaattagaa gagggtgatg ttcagcggac actcatccaa gtggactttg 2521 gcgatggtat cgcggtgtct tacgtcaatc tcagctccat ggaagatggg atcaaacacg 2581 tctatcagaa cgtgggcatt ttccgtgtga ccgtgcaggt ggacaacagt ctgggttctg 2641 acagcgccgt cctgtactta catgtaactt gtcccttgga gcacgtgcac ctgtctcttc 2701 cctttgtcac cacaaagaac aaagaggtca atgcgacggc agtgctgtgg cccagccaag 2761 tgggcaccct cacttacgtg tggtggtacg gaaacaacac ggagcctttg atcaccttgg 2821 agggaagcat atccttcaga tttacttcag aaggaatgaa taccatcaca gtgcaggtct 2881 cagctgggaa tgccatccta caagacacaa agaccatcgc agtatatgag gaattccggt 2941 ctcttcgctt gtccttttct ccaaacctgg atgactacaa cccggacatc cctgagtgga 3001 ggagggacat cggtcgagtc atcaaaaaat ccctggtgga agccacaggg gttccaggcc 3061 agcacatcct ggtggcggtg ctccctggct tacccaccac tgctgaactc tttgtcctac 3121 cctatcagga tccagctgga gaaaacaaaa ggtcaactga tgacctggag cagatatcag 3181 aattgctgat ccacacgctc aaccaaaact cagtacactt cgagctgaag ccaggagtcc 3241 gagtccttgt ccatgctgct cacttaacag cggcccccct ggtggacctc actccaaccc 3301 acagtggatc tgccatgctg atgctgctct cagtggtgtt tgtggggctg gcagtgttcg 3361 tcatctacaa gtttaaaagg agagtagctt taccctcccc tccctcccct tctactcaac 3421 ctggtgactc atctctccga ttgcaaagag caagacacgc cactccgcct tcaacgccaa 3481 agcggggatc tgctggggca cagtatgcaa tttaaggaaa acccccaaag gctacaggcg 3541 acctgctgat caggaaagaa tttcgctctt gtcaagtaca tcatccttca tgaccactaa 3601 ctttgtgttt tttttctttc ctttgttgtt ctgtttccta ttttgccagg aagtatttcc 3661 atagttgctg agaatcaaag cacaaaagaa atccctacct atgtaaatgt ttgaatggag 3721 gacgccagta aaaaaacaaa aacaaaaaca aaacaaaaca taaaatataa acaatcaaaa 3781 tccaaacaaa caaacaaaca ctcactgcat cgggactttt taattcttca gacacagaca 3841 acaagggttt ttagctttaa gcctgtgcat gtggacaata ctctgagaac atgtctggag 3901 gggcagtgta caggtgctct attttaatgg aaaacactcc cctctccctc tttcttcttc 3961 tctctctttt ttctgatcgg tcgtgtttgt agaaaattca taacatatat aggccaagga 4021 aatctgcatg tatttttgga aatattcttg gctctagatt tatcagctat tttagcatta 4081 aaggctgatg ggtggattag ctaccccagc tcctttcata agacacaaag acgtgcacag 4141 gagtttgaaa ccctgagctg tttctctgtt ccactttcca tactgtcatt tcccttctaa 4201 gttagctttg gtagctctgt tggtcagcag tggccacaag gctgctttct gcactctctg 4261 tggccacagg aacaaagatg cgagttgaag atccctttgt gccggtagaa taaggaagga 4321 agggaggcag ggaggcaaag catgtcagaa acggaccttg gtttcctgtt cacctctttc 4381 caccatgatt gcctcccctt gcagctttcc ctactcctgc cccaactgca gtaggaaatg 4441 gaatcccatt agttacccat tgtcctgtct tcacatttgt ttgtcatcca tgtgtgacca 4501 tgatctgttg atatctttga atctcttccc tccaaacccc aagtaagttg tccttcaact 4561 gttctcagtt tttcttccca aacatattgc tagattctgg acattaaccc tgacgtttcc 4621 taaatactgg cctggcctgt gccgcccctg cccccactac tcacaagttt ctgagccctt 4681 tgtcagtttt gtacattccc aagcatgcca gcttctgtgc ccatggacct tgctgcatcc 4741 tgcacagcag ggttcagttt catgtatctt tgtcttttcc tctagaacct gcctttttca 4801 aatatccctg ccttttccca cctggaaaca tatactgtat gcgaaagagt tgatatatgc 4861 aaagtaattc aaacctggcc atgtactttg gaaaagaaag catagagatg aattgtggtg 4921 ttctcacacc ttaacgaaaa tctcgtgcga tctgattcca gaagattctt gtgagaaatg 4981 ttttgaatgt gtgacaattt cgcagggcaa tttcctcctg tgacggttgc tgttacctgg 5041 tatttccact ctcacagtag aatagaaatg tttgtgaaat aaaactgatt ttaactggaa 5101 ggagaaacag gttaatggac tttgtgttta agagtgtcaa acagtctgag agaataaatg 5161 ggggtcttgt cttacattag ggtgagagtt tgattattta ggatgatccc agtgatttca 5221 tgtgtgctct ctgacctctg agtatcatag tatcattaaa gtaaagattt aagtctgtat 5281 aaaggaggag agttactgat tggcaaaaaa gattggcaca aagcatgaag aaaccccatt 5341 tttcccaggg taatcatgaa agaaggctca gagaaagagg gaaacaaaag cctgttcagc 5401 agaggcccct ttagtattat ggactgggca aagcccacta taaactatag gagaaagaag 5461 ttctgataaa cctcttagta tgctcagcct ccttctttgc tatgtcccta agccaacagg 5521 gtataacaca ggccctggtg ataatgaggg tgtcctaaag atcctgatgt ccatgacttc 5581 atgtagttca ggcacagaaa gaatagcaaa gctgctgtca gaagtttgtc aggcagagat 5641 gtttatggtt gaggataccc catatgaatc tgggaaatgg gctaggcctg aggcagtcac 5701 ctatttgtag aactcaattg atccccaacc tgccaggctt cctatctcat aggaaacatc 5761 ctcattgatc ctcttcagtt ggagtctccc aaatttaatg tggaagacaa agtgttggaa 5821 aatcaaaaga ggctcactca aaccagcaca gggagtcctc agagttgcag ttcaattcat 5881 tttaattaga aaagtatgaa agaggtataa cactcttatt ctagcacagt gccttgccta 5941 gagtagtagt atgaaaacta tttgttgaag aaataaatga atggaaagac atagggaaga 6001 atgggctgta aatcctaatt aaaaatagag gtcgacatga gatacctggc attttgggaa 6061 gtgaccaaag atggccagct agagattcag catctccagg atcctcatgt gcctctcctc 6121 aaagctccct cccatctgta ggagattagt gaggcaaggt gctgctcaga gaggaggacc 6181 tcattgttct taggaccttg gccagttgtt ctcaaagtgt ggtacctgga tcagcagtat 6241 cactatcact tgggctagtt agagatccag attctggatc cataccccat acctactgaa 6301 ttagaaactc taggggatga atagtggtgt tctctgttgc taagtgacag tgggcccagc 6361 cacctatttt aacaagccct cccagtgatt gtgatacata ctaaagtttg agaaccattg 6421 tactaggcca ttccagctga atctcaaaca gaaggcagta atgagagcct acaaatggga 6481 gggacctaag tgcctaccta ctcgctaatc gcaggtgcaa acacacaagg agtttggtgg 6541 gcttaaggtc agaggagtgt gtagggaggg atgtatgtgg aaggtaagat tcagggcaag 6601 ctaaaaatcc gatactgcaa cgttttccaa aatcccagaa ggcaaactgt gcatgttcta 6661 ccctgaacca cccaagcaac actttctacc ttgccttatt tttaattgga ttcactgtcc 6721 aaaatgcaga ggtttgcttt gctttttttt cagaagttcc aaacagcaac tttgagagca 6781 gtggggtgct tggcagctgt tctgtgtttt ccaggaatcc aactgagcat tgaaatctct 6841 catttgccga cttattttta taggaagcca attaaaaaaa aaaaaagttt tcttatagta 6901 ttggaactac ttctaatttt aaaatgactt ttttgatgta ttttttgtta aatactatgt 6961 agtgtaatgt ataattgctc ttgtttattg cttttacaat catatttatt aaacagataa 7021 tgtctctaaa gtctttgcct caggtatttt tttttttaat cctaaaccct tggtgttcat 7081 tctaaatata gaagtgttgc atgtatagga tttcataaag gctaattgca taagaaagag 7141 taaacaccac aggcttgagg tttttggctg ttttttacta acaaggcaga atgtatgtac 7201 tacctgaatt ctacctgcat ttcaattaac tatacaatgt ctgtttatta aattactttg 7261 atttaaaaat ta

LOCUS NM_013381 5666 bp mRNA linear PRI 23-SEP-

2005

DEFINITION Homo sapiens thyrotropin-releasing hormone degrading enzyme

(TRHDE) , mRNA. ACCESSION NM_013381 VERSION NM_013381.1 GI:7019560 KEYWORDS

SOURCE Homo sapiens (human) ORGANISM Homo sapiens

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;

Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;

Catarrhim; Homimdae; Homo.

REFERENCE 1 (bases 1 to 5666)

AUTHORS Clark, H. F., Gurney, A. L . , Abaya,E., Baker, K., Baldwin, D.,

Brush, J. ,

Johnson, S .

Woods, K. ,

Xie,M.H., Yansura,D., Yi, S., Yu, G., Yuan, J., Zhang, M.,

Zhang, Z . ,

Goddard,A., Wood, W. I., Godowski,P. and Gray, A.

TITLE The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins : a bioinformatics assessment JOURNAL Genome Res. 13 (10), 2265-2270 (2003)

PUBMED 12975309 REFERENCE 2 (bases 1 to 5666)

AUTHORS Schomburg, L. , Turwitt, S . , Prescher,G., Lohmann,D., Horsthemke, B. and Bauer, K.

TITLE Human TRH-degrading ectoenzyme cDNA cloning, functional expression, genomic structure and chromosomal assignment

JOURNAL Eur. J. Biochem. 265 (1), 415-422 (1999) PUBMED 10491199 COMMENT PROVISIONAL REFSEQ: This record has not yet been subject to final

NCBI review. The reference sequence was derived from

AF126372.1.

Summary: Thyrotropin-releasing hormone (TRH; MIM 275120) acts as a stimulator of hormone secretion from adenohypophyseal cells, and its signals are inactivated by TRH-degrading ectoenzyme. [supplied by OMIM] .

FEATURES Location/Qualifiers source 1..5666

/organism="Homo sapiens" /mol_type="mRNA" /db_xref="taxon: 9606" /chromosome=" 12 " /map="12ql5-q21" gene 1..5666 /gene="TRHDE"

/note="synonyms: PAP-II, PGPEP2, TRH-DE"

/db_xref="GeneID:29953"

/db_xref="HGNC:30748"

/db_xref="HPRD:HPRD_09506"

/db_xref="MIM: 606950"

CDS 97..3171

/gene="TRHDE"

/EC_number=" 3.4.19.6"

/go_component=" integral to plasma membrane [pmid

10491199]"

/go_function="aminopeptidase activity [pmid 10491199]; membrane alanyl aminopeptidase activity; metal ion binding; pyroglutamyl-peptidase II activity; zinc ion binding"

/go_process="cell-cell signaling [pmid 10491199]; proteolysis; signal transduction [pmid 10491199]; sterol depletion response, sterol regulatory element binding-protein cleavage" /note="pyroglutamyl-peptidase II; thyrotropin- releasing hormone degrading ectoenzyme"

/codon_start=l

/product="thyrotropin-releasing hormone degrading enzyme

/protein_id="NP_037513.1" /db_xref="GI: 7019561" /db_xref="CCDS: CCDS 9004.1" /db_xref="GeneID:29953" /db_xref="HGNC:30748" /db_xref="HPRD:HPRD_09506" /db_xref="MIM: 606950"

/translation="MGEDDAALRAGSRGLSDPWADSVGVRPRTTERHIAVHKRLVLAF

AVSLVALLAVTMLAVLLSLRFDECGASATPGADGGPSGFPERGGNGSLPGSARRNHHA GGDSWQPEAGGVASPGTTSAQPPSEEEREPWEPWTQLRLSGHLKPLHYNLMLTAFMEN FTFSGEVNVEIACRNATRYWLHASRVAVEKVQLAEDRAFGAVPVAGFFLYPQTQVLV WLNRTLDAQRNYNLKIIYNALIENELLGFFRSSYVLHGERRFLGVTQFSPTHARKAF PCFDEPIYKATFKISIKHQATYLSLSNMPVETSVFEEDGWVTDHFSQTPLMSTYYLAW AICNFTYRETTTKSGVWRLYARPDAIRRGSGDYALHITKRLIEFYEDYFKVPYSLPK LDLLAVPKHPYAAMENWGLSIFVEQRILLDPSVSSISYLLDVTMVIVHEICHQWFGDL VTPVWWEDVWLKEGFAHYFEFVGTDYLYPGWNMEKQRFLTDVLHEVMLLDGLASSHPV SQEVLQATDIDRVFDWIAYKKGAALIRMLANFMGHSVFQRGLQDYLTIHKYGNAARND LWNTLSEALKRNGKYVNIQEVMDQWTLQMGYPVITILGNTTAENRIIITQQHFIYDIS AKTKALKLQNNSYLWQIPLTIWGNRSHVSSEAIIWVSNKSEHHRITYLDKGSWLLGN INQTGYFRVNYDLRNWRLLIDQLIRNHEVLSVSNRAGLIDDAFSLARAGYLPQNIPLE IIRYLSEEKDFLPWHAASRALYPLDKLLDRMENYNIFNEYILKQVATTYIKLGWPKNN FNGSLVQASYQHEELRREVIMLACSFGNKHCHQQASTLISDWISSNRNRIPLNVRDIV YCTGVSLLDEDVWEFIWMKFHSTTAVSEKKILLEALTCSDDRNLLNRLLNLSLNSEW

LDQDAIDVIIHVARNPHGRDLAWKFFRDKWKILNTRYGEALFMNSKLISGVTEFLNTE

GELKELKNFMKNYDGVAAASFSRAVETVEANVRWKMLYQDELFQWLGKALRH"

STS 3965..4093

/gene="TRHDE" /standard_name="WI-I3400" /db_xref="UmSTS: 76068"

ORIGIN

1 aagaaaaaga agaagaaaaa gaggaagaag aagaaggagg aggaggagga ggaggaggag

61 ggggccgaga agagcagctc acccttcgca gccgcgatgg gggaagacga cgccgcgctt

121 cgggctggca gcagggggct ctccgacccg tgggcagact cagtgggagt gcgaccccgc

181 accacggagc gccacatcgc cgtacacaag cggcttgtgc tggccttcgc tgtgtccctc

241 gtggcattgc tcgcggtcac aatgctcgct gtgctgctca gcctgcgctt cgacgagtgc

301 ggggcgagtg ccacgccagg cgccgacggt ggcccctcag gctttccgga gcgcggcggc

361 aacgggagcc tccctggatc ggcccggcgc aaccaccacg caggcgggga ctcctggcag

421 cccgaggcgg gtggggtggc cagtccgggg accacgtcgg cccagccgcc gtcggaggag

481 gagcgggagc cgtgggagcc gtggacgcag ctgcgcctgt cgggccacct gaagccgctg

541 cactacaatc tgatgctcac cgccttcatg gagaacttca ccttctccgg ggaggtcaac

601 gtggagatcg cgtgccggaa cgccacccgc tacgtagtgc tgcacgcttc ccgagtggcg

661 gtggagaaag tgcagctggc cgaggaccgg gcgttcgggg ctgtccctgt agccggtttt

721 ttcctctacc cgcaaaccca ggtcttagtg gtggtgctga ataggacact ggacgcgcag

781 aggaattaca atctgaagat tatctacaac gcgctcatcg agaatgagct cctgggcttc

841 ttccgcagct cctatgtgct ccacggggag agaagattcc ttggtgttac tcagttttcg

901 cctacacatg ccagaaaggc atttccttgt tttgatgagc caatctacaa ggctactttc

961 aaaatcagca tcaagcatca agcaacctat ttatctttat ctaatatgcc agtggaaact

1021 tccgtgtttg aggaagatgg atgggttacg gatcactttt cacagacccc tctcatgtcc

1081 acatattatt tagcctgggc aatttgcaac ttcacataca gagaaactac caccaagagt

1141 ggggttgtag tacgattata tgcaagacct gatgctatca gaagaggatc cggggactat

1201 gctctccata taacaaagag attaatagaa ttttatgaag actactttaa agtgccctat

1261 tccttgccaa aactagatct tttagctgtg cctaagcatc cgtatgctgc tatggagaac

1321 tggggactaa gtatttttgt ggaacaaaga atactgctgg atcccagtgt ttcatctatt

1381 tcttatttgc tggatgtcac catggtcatt gttcatgaga tatgtcacca gtggtttggt

1441 gaccttgtga cgcctgtgtg gtgggaagac gtgtggctga aggaagggtt tgctcactac

1501 tttgaatttg ttggtacaga ctacctctat cctggctgga acatggaaaa gcagaggttt

1561 ctgaccgatg ttctgcatga agtgatgctg ctggacggtt tggccagttc ccatccagta

1621 tcacaggaag tgctgcaggc aacagatatt gacagggtgt ttgactggat cgcatataaa

1681 aagggtgctg ctttaataag aatgctggct aattttatgg gccattcagt tttccagagg

1741 ggtttgcaag attatttaac cattcataag tatggtaatg cagccagaaa tgatctctgg

1801 aatacattat cggaggcttt aaaaagaaat gggaaatatg taaatataca agaagtaatg

1861 gatcagtgga cactccagat gggttatcct gttatcacca tcttgggaaa cacaacagca

1921 gaaaatagaa taataattac ccaacagcat tttatctatg atatcagtgc taaaactaaa

1981 gcacttaaac ttcagaataa cagttacctg tggcagattc cattaactat tgtggtagga

2041 aatagaagcc atgtgtcttc agaagcaatt atttgggtgt ctaacaaatc agagcaccac

2101 agaataactt atttggacaa aggaagctgg ctgctgggga acatcaatca aactggctat

2161 tttagagtca actatgacct aaggaactgg agattattaa ttgatcaatt aatccggaat

2221 catgaggttc tttctgtcag taaccgagcg ggcttgatcg atgatgcctt cagcctagcc

2281 agggctggct atttgcctca gaatattcct ctggagatta tcagatacct gtctgaggag

2341 aaggattttc ttccttggca tgctgccagc cgagctcttt atcctctaga taaattactg

2401 gaccgcatgg aaaactacaa cattttcaat gaatatattt taaagcaagt tgcaacaaca

2461 tatatcaagc ttgggtggcc gaaaaataat tttaatggat ctcttgttca agcatcctac

2521 caacatgaag aactacgtag agaagttata atgctggcct gcagttttgg caacaagcac

2581 tgtcaccaac aggcatcaac acttatttca gattggattt ccagcaacag gaacagaata

2641 ccactaaatg ttagagacat cgtatactgt acaggagtgt cactactgga tgaggatgtc

2701 tgggaattca tatggatgaa attccattcc accacagcag tttctgagaa gaaaatatta

2761 ttggaagcct taacttgcag tgatgacagg aatttattaa acaggcttct aaatctgtca

2821 ctgaattctg aggtggtgct ggatcaagat gcaattgatg tcataatcca tgtagctcga

2881 aatccacatg gtcgagacct tgcctggaag tttttcaggg ataaatggaa gatattaaat

2941 accaggtatg gagaagcatt gtttatgaat tccaaactca tcagtggtgt cacagaattt 3001 cttaatactg aaggtgaact caaagagctc aagaacttca tgaaaaacta tgatggggta 3061 gctgctgctt ctttctcacg agctgtggaa actgtcgaag ccaatgtgcg ctggaaaatg 3121 ctttaccaag acgagctttt ccaatggtta ggaaaagctc taagacacta atatatgtat 3181 cttataaaca aacaattcaa ctcagaagtt tatgagaaga cacgcttttt gtggaatgag 3241 gaaaatgtac tacctagaaa atggccagat tttcagtgtt aacatgtggg aggaattttt 3301 tttttagttt ttattttttg gttttggggg atatttttta tttgtttcat tcattctgtt 3361 ctgtttctct actgggtgtt cctctctaaa gaaactcttg caagtgaaac tagccatgat 3421 tgcttcagct gtacattcct tgctgtacag gaccaaatat gatagtgatg catgttgatg 3481 ttacagtcaa tttggaaaaa catattcaga atatctgtgc atggatatat tgtcctgcct 3541 gtgttccagc atgcttattt caaacgtcca gtgttgtgtg tgaatatgtg ttacacctag 3601 gatgggcatt atgcaaaagc acaaagatta tatatgacaa tcagtattgc aatgaaagaa 3661 aaactaaaaa cagaaatgat attctcaatt ttgggcaatg tgagaggtaa aatagccctt 3721 gacatgatga acatcactta tttcagcact tggattgtct ggcaatgatt actgtgttgc 3781 taactcattt tctttgagtt aaagctgtgt atacatttta aaaggcatat agatagtgta 3841 tgcatatgta tatgtacata gggaagcccc atatgtatat agtatgttgt acactgcaca 3901 tgtacaaaga atgtcttcag atcaaagaaa atttatctct ttttataaac ttaaggacag 3961 ttgcaaaagg cttcaaggaa tttatctcaa cattattctt tctatgtcct aactaaattt 4021 ctcaactgtt atgaattttt catctacttc ttgaacagtg gtctattctg ctacatgaag 4081 atgaatacaa acaaaatttt tgtataaact actattccag ttctcctgtg tcagtcttgc 4141 ctatagattt tgccatcgtt ttctgtcaaa gttccttttg catgaaacaa ttatgcaaac 4201 ttataattat tagtgctgaa aaagagttta ttttccatct tgtttgtttt cctaccttat 4261 gctgagtagt ccagagagtt aaaaaaattc tctgcatgtt ggtcttttaa gtctgttttg 4321 ctctaatcct ccattaagcg agcatacctc aagtgggtct attagcattt aatgaccttt 4381 tatgccagtt gtgccatccc ttaagatgaa aagttccttt tcttgtgtta atgtacaaag 4441 cttttctttt ggcactgaca actgtgttct acctgggaat tttgaatagc cattttcatg 4501 gctgtgtgtt gtgtaacaca aatgttttta aatggtattc tcacccagta ggccagctct 4561 ccaaacgttg cttagatgct tcaaaattag catattttaa gtttaccagt ataaaatacc 4621 aatgcaacta ctctacatag ccaaatgttt gtaaatcacg tcttattttc ctgaggtttt 4681 tcactccacc aaatcttaca aatcattgaa agaaatatat tctaacagta cgcactgaat 4741 agtgaaaata attagacatt ttaagaacca gagccataga attattttaa attagtagaa 4801 aagaggagct atttccgaat ctatagaata aagtaccacc taaaactgaa ttttatcata 4861 taagcaagta atacctatta gtcataccta aatttttcag cacttcattc aattaaaata 4921 catgaatttt aaatatttta catgatgtga ataggcatga taatactttt agtataaaat 4981 ctaaactttt tccatttatc agaaatgata aaatccagtt accacatatt cacgtttata 5041 aaatccttaa ttaaatgagt aacttctaaa atataacaat actaaatatc acactgtgat 5101 ggaggtccca aatatgtggt ctatcaccac tgaattcatg taatagataa gaaaaaaatt 5161 agaggtggat gtcttgtttt gtgtcatgaa ttactaaaat ctcttagtag ttgtggtata 5221 tttttgagta aaattaccat ttccagattt gagtttgaag ggcttttata gttgtatttt 5281 cctcctcact gttaataatc ataatccttt ttcagtattt tagtggcctt gaacaactgg 5341 tttatctaca atctcaaatc ctaagtgtat aattatgtgc aatgttcaat acctcatata 5401 atacttgctc aacagtatag tggtaccaat ggcattaaga tggtgttttt gttctacata 5461 tttttcaata atttattctt tctaatgttg aaattatatc aggctttacc ggttttttta 5521 gttgtttaaa taagtaatat tttcaaaaga ataaaataac caatgatatc tcttggaata 5581 atctgtaaaa cgtagttata aaattctatt ttctacttaa aaaaaaaaaa aaaaaaaaaa 5641 aaaaaaaaaa aaaaaaaaaa aaaaaa

//

Figure 1

Description of pSRE-WT:

Three copies of a wild type SRE element from the promoter of the LDL-R gene was cloned upstream of a luciferase gene as shown below. The parent vector used was pTransLucent from Panomics Inc., USA.

Claims

1. A gene having one of the sequences disclosed in the description hereinbefore.

2. A protein having one of the sequences disclosed in the description hereinbefore.