KR20160049874A - Composition or method for preventing or treating hair loss, and screening method for a material preventing, treating, or alleviating of hair loss - Google Patents

Abstract

Provided are a pharmaceutical composition for preventing or treating hair loss, a cosmetic composition for preventing or ameliorating hair loss, a method for preventing or treating hair loss, and a method for screening a material for preventing, treating, or ameliorating hair loss. Accordingly, hair loss can be effectively prevented, treated, or ameliorated, and a material effective to prevent, treat, or ameliorate hair loss can be efficiently selected. The pharmaceutical composition for preventing or treating hair loss comprises one or more material selected from the group comprising an activating agent increasing the amount of a keratin 17 (Krt17) transcript or a protein coded by the same; an activating agent increasing the amount of a collagen type 1 alpha 1 (Col1a1) transcript or a protein coded by the same; an inhibitor reducing the amount of a fibrillin 1 (FBn1) transcript or a protein coded by the same; and an inhibitor reducing the amount of a decorin (Dcn) transcript or a protein coded by the same.

Description

The present invention relates to a pharmaceutical composition for prevention or treatment of hair loss, a method for preventing or treating hair loss, and a screening method for preventing, treating, or improving hair loss, alleviating of hair loss}

A pharmaceutical composition for preventing or treating hair loss, a method for preventing or treating hair loss, and a method for screening a hair loss preventive or therapeutic substance.

The changes that occur as aging progresses are very diverse. The greatest change is the change of the appearance, the hair loss and the increase of the swelling, various efforts are under way to cure it. Especially, in the case of hair loss, the frequency of occurrence in young people is remarkably increasing recently, and the cost of treatment for it is also increasing remarkably. As a method of treating hair loss, methods of improving hair loss through autotransplantation (hair transplantation) or administering a pharmaceutical adjuvant by hormone control have been used. In the case of hair transplantation, there is a problem in that the operation cost is very high and pain is often generated at the operation site after the operation. There is a problem that hair loss remedy that suppresses male hormone has to be taken for life, recurred immediately after discontinuing treatment, and can cause side effects of male sexual function. Therefore, it is urgent to develop a new method of treating hair loss.

Expression of most toll-like receptors in aged immune cells was reduced, while Toll-like receptor-5 (TLR5) was well expressed and maintained in function. Immunization with recombinant proteins fused with plasmids and pathogen antigens of Vibrio spp. Activating TLR5 showed activation of immunity and improvement of hair loss in aged rats.

Therefore, it is required to develop a substance having the effect of preventing or treating hair loss by confirming the factors of the skin tissue induced by the mucosal immunostimulation.

A pharmaceutical composition for preventing or treating hair loss is provided.

Thereby providing a cosmetic composition for preventing or alleviating hair loss.

Thereby providing a method of preventing or treating hair loss.

Provides a method of preventing or improving hair loss.

A method for screening a substance for prevention, treatment, or amelioration of hair loss.

According to one aspect, an activator that increases the amount of keratin 17 (Krt17) transcript or the protein encoded thereby; An activator that increases the amount of collagen type 1 alpha 1 transcript (Col1a1) or the protein encoded thereby; An inhibitor that decreases the amount of fibrilrin 1 (Fbnl) transcript or the amount of protein encoded thereby; And at least one substance selected from the group consisting of an agent for decreasing the amount of protein encoded by the decolin (Dcn), or an agent for preventing or treating hair loss.

The keratin is a protein that forms the basis of epithelial structure such as hair, nails, and skin. The keratin 17 (Krt17) is a Type I cytokeratin and is a protein present in the nail bed, hair follicle, sebaceous gland, and other skin appendages. The Krt17 protein is encoded by the KRT17 gene in humans. The amino acid sequences of Krt17 in humans and rats are shown in GenBank Accession No. < RTI ID = 0.0 > No. < / RTI > NP_000413 (SEQ ID NO: 7) and NP_034793 (SEQ ID NO: 9). Nucleic acid sequences encoding Krt17 in humans and rats are shown in GenBank Accession No. < RTI ID = 0.0 > No. < / RTI > NM_000422 (SEQ ID NO: 8) and NM_010663 (SEQ ID NO: 10).

The collagen is a protein existing in bone, skin, cartilage, organ membrane, hair and the like of an animal. The collagen type 1 alpha 1 (Col1a1) is a major component of type 1 collagen, a microfibrillar collagen found in most binding sites including cartilage. Col1a1 is encoded by the COL1A1 gene in humans. The amino acid sequences of Col1a1 in human and rat are GenBank Accession No. NP_000079 (SEQ ID NO: 11) and NP_031768 (SEQ ID NO: 13). Nucleic acid sequences encoding Col1a1 in humans and mice are shown in GenBank Accession No. < RTI ID = 0.0 > No. < / RTI > NM_000088 (SEQ ID NO: 12) and NM_007742 (SEQ ID NO: 14).

The fibrillin is a glycoprotein essential for the formation of elastin fibers present in the connective tissue. The fibrillin 1 (Fbn1) is a major component of the microfibril forming aqueducts surrounding amorphous elastin. Fbn1 is encoded by the FBN1 gene in humans. The amino acid sequences of Fbn1 in humans and rats are shown in GenBank Accession No. < RTI ID = 0.0 > No. < / RTI & NP_000129 (SEQ ID NO: 15) and NP_032019 (SEQ ID NO: 17). Nucleic acid sequences encoding Fbn1 in humans and rats are described in GenBank Accession No. < RTI ID = 0.0 > No. < / RTI > NM_000138 (SEQ ID NO: 16) and NM_007993 (SEQ ID NO: 18).

The decorin (Dcn) is a component of connective tissue and binds to type 1 collagen fibrils and plays a role in the matrix assembly. Dcn affects fibrillogenesis. Dcn is encoded by the DCN gene in humans. The amino acid sequences of Dcn in humans and rats are shown in GenBank Accession No. < RTI ID = 0.0 > No. < / RTI > NP_001911 (SEQ ID NO: 19) and NP_001177380 (SEQ ID NO: 21). Nucleic acid sequences encoding Dcn in humans and rats are described in GenBank Accession No. < RTI ID = 0.0 > No. < / RTI > NM_001920 (SEQ ID NO: 20) and NM_001190451 (SEQ ID NO: 22).

The term " transcription "refers to the process of generating RNA having a nucleic acid sequence complementary to DNA, and the term" transcript "refers to RNA produced by transcription. The transcript may be messenger RNA (mRNA) and also includes complementary DNA (cDNA) obtained by reverse transcription of mRNA.

The term " protein "refers to the linkage of amino acids, and the protein is produced by translation of transcripts.

The amount of the transcript or the protein encoded thereby is also referred to as the expression level.

The active agent may be a transcription activator or a protein active agonist. The transcriptional activator may be a substance that induces the initiation of transcription or inhibits the degradation of the transcription product. The transcriptional activator may be, for example, a transcription factor, a natural extract, a chemical, or a combination thereof. The protein activating agent may be a substance that increases the activity of the protein. The protein active agent may be a natural extract, a chemical, or a combination thereof. Natural extracts include substances obtained from natural products by separation, purification, fractionation, filtration, or a combination thereof. The chemical substance includes a compound, a natural substance, a synthetic substance, and the like.

The inhibitor may be a transcription repressor or a protein active antagonist. The transcription inhibitor may be a substance that inhibits the initiation of transcription or induces degradation of the transcription product. Transcriptional inhibitors include, for example, antisense oligonucleotides, small interference RNAs (siRNA), small hairpin RNAs or short hairpin RNAs, microRNAs (miRNAs), natural extracts, chemicals , Or a combination thereof. The antisense oligonucleotide refers to DNA or RNA or a derivative thereof containing a nucleic acid sequence complementary to the sequence of a specific mRNA, and can bind to a complementary sequence in the mRNA to inhibit translation of the mRNA into a protein. siRNA refers to a nucleic acid that inhibits the expression of a target gene by mediating RNA interference or gene silencing. shRNA refers to RNA that makes a solid hairpin turn and can be used to silence gene expression through RNA interference. miRNAs can bind to the 3'-UTR (untranslation region) of mRNA as a single stranded RNA molecule of 21 to 25 nucleotides to control eukaryotic gene expression. The protein active antagonist refers to a substance that decreases the activity of a protein. The protein active antagonist may be a natural extract, a chemical, or a combination thereof.

The term "hair loss or alopecia" refers to a state in which hair is normally absent from the area where hair should be present, and generally refers to the loss of hair from the scalp. Alopecia Areata, Androgenetic Alopecia, Telogen Effluvium, Traumatic, Trichotillomania, Pressure (Alopecia Areata), Clostridial < RTI ID = 0.0 & Alopecia), or non-rigid, alopecia syphiltiac, Alopecia seborrhecia, symptomatic, non-scarring, scarring or congenital alopecia.

The pharmaceutical composition may further comprise a recombinant fusion protein comprising plaslan or a fragment thereof and a protein or fragment thereof of Streptococcus pneumoniae. The recombinant fusion protein may be a protein having the amino acid sequence of SEQ ID NO: 1 or a protein encoded by the nucleic acid sequence of SEQ ID NO: 2. The plasmin can be the FlaB protein of Vibrio vulnificus. The plasmin may be a protein comprising the amino acid sequence of SEQ ID NO: 3, or a protein comprising the polypeptide encoded by the nucleic acid sequence of SEQ ID NO: 4. The plasmin can be a toll-like receptor (TLR-5) agonist associated with congenital immunity. The plasmin can be used as an immunomodulator or a vaccine regulator to enhance the immune response. The protein of the Streptococcus pneumoniae may be a surface protein PspA (pneumococcal surface protein A) of Streptococcus pneumoniae. The PspA may be a protein comprising the amino acid sequence of SEQ ID NO: 5, or a protein comprising the polypeptide encoded by the nucleic acid sequence of SEQ ID NO: 6.

The term "prophylactic " refers to any act that inhibits disease or delays onset by administration of the composition. The term "treatment" refers to any action that improves or alleviates a symptom of a disease by administration of the composition.

The pharmaceutical composition may further comprise a pharmaceutically acceptable excipient and may be formulated into a unit dosage form suitable for intravenous administration of a patient according to conventional methods in the pharmaceutical field. For example, the formulation may be a formulation for local administration. Formulations for topical administration include all forms of the formulation delivered through the skin of the patient and may be in the form of tablets, capsules, powders, ointments, solutions, gels, pastes, have. Preparations for topical administration may be, for example, a combination with a pharmaceutically acceptable carrier or medium, such as sterile water, physiological saline, vegetable oil, emulsifying agents, suspending agents, surfactants, stabilizers, vehicles, vehicles, preservatives, And then mixed in a form of a pharmaceutically acceptable unit dosage form.

The pharmaceutical composition may be a pharmaceutical composition for local, oral, or parenteral administration. The pharmaceutical composition for local administration can be administered by application.

The pharmaceutical composition may be administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" means an amount sufficient to treat a disease, and the effective dose level will depend upon a variety of factors including the severity of the disease, age, weight, health, sex, And the rate of excretion, the duration of the treatment, factors including drugs used in combination with or co-used with the compositions of the present invention employed, and other factors well known in the medical arts. The dosage of the pharmaceutical composition is, for example, in the range of 0.001 mg / kg to 100 mg / kg on an adult basis.

According to another aspect, an activator that increases the amount of Krt17 transcript or the protein encoded thereby; An activator that increases the amount of the Colla1 transcript or the protein encoded thereby; An inhibitor that reduces the amount of Fbn1 transcript or the amount of protein encoded thereby; And at least one substance selected from the group consisting of an agent that reduces the amount of the protein encoded by the Dcn or an agent that inhibits or reduces hair loss.

The above Krt17, Col1a1, Fbn1, Dcn, transcript, protein, activator, inhibitor, hair loss, and prevention are as described above.

The term " alleviation " refers to any action that improves or alters the condition by administration of the composition.

The cosmetic composition may be at least one selected from the group consisting of hair tonic, hair cream, hair lotion, hair shampoo, hair rinse, hair conditioner, hair spray, hair aerosol, pomade, powder, gel, hair pack, hair treatment, eyebrow hair, Shampoos for pets, rinses for pets, etc., sols gel, emulsion, oil, wax, aerosol, etc., and can be used for the production or processing of scalp or hair instruments such as wigs or hats. The cosmetic composition may be in the form of a lipid, an organic solvent, a solubilizing agent, a thickener, and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, Cosmetics such as emulsifying agents, fillers, sequestering and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or any other ingredient commonly used in cosmetics Or adjuvants conventionally used in the field of dermatology. And, the above ingredients can be introduced in amounts commonly used in the field of dermatology.

The cosmetic composition may further comprise a recombinant fusion protein comprising plasmagin or a fragment thereof and a protein or fragment thereof of Streptococcus pneumoniae. The recombinant fusion protein is as described above.

According to another aspect, there is provided a kit comprising an active agent that increases the amount of Krt17 transcript or protein encoded thereby; An activator that increases the amount of the Colla1 transcript or the protein encoded thereby; An inhibitor that reduces the amount of Fbn1 transcript or the amount of protein encoded thereby; And at least one substance selected from the group consisting of an inhibitor that reduces the amount of protein encoded by the Dcn or an agent of Dcn. do.

The above Krt17, Col1a1, Fbn1, Dcn, transcript, protein, activator, inhibitor, hair loss, and prevention are as described above.

The subject may be a mammal, including a human, mouse, cow, pig, horse, sheep, dog, and cat.

The administration may be local administration, oral administration, or parenteral administration. Local administration may be local administration by application. The dosage may vary depending on factors such as the severity of the disease, the age, body weight, health, sex, sensitivity of the patient to the drug, time of administration, route of administration and rate of excretion, duration of treatment, Factors involved and other factors well known in the medical arts. For example, in the case of local administration, it may be 0.001 mg / kg body weight to 100 mg / kg body weight, and may be administered once or several times in divided doses.

The method may further comprise the step of administering to the subject a recombinant fusion protein comprising plasgel or a fragment thereof and a protein or fragment thereof of Streptococcus pneumoniae. The recombinant fusion protein is as described above.

According to another aspect, there is provided a kit comprising: an active agent that increases the amount of Krt17 transcript or protein encoded thereby; An activator that increases the amount of the Colla1 transcript or the protein encoded thereby; An inhibitor that reduces the amount of Fbn1 transcript or the amount of protein encoded thereby; And at least one substance selected from the group consisting of prodrugs of Dcn or an inhibitor which decreases the amount of the protein encoded thereby, the method comprising the step of administering a cosmetic composition for preventing or ameliorating alopecia of hair loss prevention or improvement A method of preventing or improving hair loss is provided.

The above Krt17, Col1a1, Fbn1, Dcn, transcript, protein, activator, inhibitor, hair loss, prevention, improvement, cosmetic composition and administration are as described above.

The method may further comprise the step of administering to the subject a recombinant fusion protein comprising plasgel or a fragment thereof and a protein or fragment thereof of Streptococcus pneumoniae. The recombinant fusion protein is as described above.

According to yet another aspect, there is provided a method of identifying a cell, comprising incubating a test substance with cells expressing Krt17, Col1a1, Fbn1, Dcn, or a combination thereof; Measuring the amount of the transcript of Krt17, Col1a1, Fbn1, Dcn, or a combination thereof, or the protein encoded thereby; And a step of selecting the test substance which is higher or lower than the control group in the amount of the measured transcript or protein is screened for the prevention, treatment or amelioration of hair loss.

The Krt17, Col1a1, Fbn1, Dcn, transcript, protein, hair loss, prevention, treatment and improvement are as described above.

The method comprises incubating a test substance with cells expressing Krt17, Col1a1, Fbn1, Dcn, or a combination thereof.

The cell may be a hair follicle cell or a fibroblast cell. The fibroblasts may be isolated from the skin tissue.

The term "test substance" refers to an unknown substance used in screening to test whether it increases or decreases the amount of target transcript or target protein. The test substance may be a transcription factor, an antisense oligonucleotide, an siRNA, an shRNA, a miRNA, a natural extract, a chemical substance, or a combination thereof.

The incubation can be performed in vitro. The incubation can be performed at room temperature (about 25 캜).

The method may further comprise washing the test substance after incubation.

The method comprises measuring the amount of a transcript, or a protein encoded thereby, of Krt17, Col1a1, Fbn1, Dcn, or a combination thereof.

The amount of transcript can be measured, for example, by reverse transcription-polymerase chain reaction (RT-PCR). The amount of protein can be measured, for example, by immunoblotting or enzyme-linked immunosorbent assay (ELISA).

The method includes the step of selecting a test substance that has a higher or lower amount of the measured transcript or protein than the control.

The control group may be a cell that does not incubate the test substance.

Said method comprising the steps of: determining as a substance for prevention, treatment, or amelioration of hair loss when the amount of Krt17 transcript or Krt17 protein is increased as compared with the control; Determining a substance for prevention, treatment, or amelioration of hair loss when the amount of Col1a1 transcript or the amount of Col1a1 protein is increased as compared with the control; Treating or improving hair loss when the amount of Fbn1 transcript or Fbn1 protein is decreased as compared with the control; Determining a substance to prevent, treat, or ameliorate hair loss if the amount of Dcn transcript or Dcn protein is decreased as compared with the control; Or a combination thereof.

A pharmaceutical composition for preventing or treating hair loss according to one embodiment, a cosmetic composition for preventing or improving hair loss, a method for preventing or treating hair loss, and a method for preventing or improving hair loss can be used for effectively preventing, treating or improving hair loss According to the method for screening a substance for prevention, treatment, or improvement of hair loss according to one embodiment, it is possible to efficiently select a substance effective for prevention, treatment, or improvement of hair loss.

1A is a schematic diagram showing an aging mouse immunological test plan according to one embodiment, and FIG. 1B is a schematic diagram showing an animal model and an experimental method for recovering an aging function.
Fig. 2 is a photograph of the protein obtained from the dorsal skin tissue of the immunized mouse by electrophoresis.
Fig. 3 is a Venn Diagram showing the protein identified in the mass spectrometry.
Fig. 4 shows the results of immunoblot analysis of the proteins of the dorsal skin of the first group (young mice), the second group (aged mice immunized with PBS) and the third group (aged mice immunized with FlaB / PspA recombinant protein) (Y-mice, young mice, O-PBS, aged mice immunized with PBS, O-FlaB / PspA, aging mice immunized with FlaB / PspA recombinant protein).
Figure 5 shows the results of immunohistochemical staining of the dorsal skin sections of Group 1 (young mice), Group 2 (aged mice immunized with PBS) and Group 3 (aged mice immunized with FlaB / PspA recombinant protein) (Y-mice, young mice, O-PBS, aged mice immunized with PBS, O-FlaB / PspA, aged rats immunized with FlaB / PspA recombinant protein) (400 magnification , Red dotted circle, pore area).

Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example  1. Identification of hair loss-related polypeptides

1.1. Induction of immune mucous membrane stimulation in aging mice

Functional restoration by new mucosal immunostimulation An aging animal model was obtained by the following method. Purified FlaB / PspA Recombinant fusion protein was used to induce mucosal immunostimulation in the aged rats (C57BL / 6J, female, over 21 months) intranasal administration continuously for 2 weeks. The FlaB / PspA recombinant fusion protein is a fusion protein of the surface protein A (PspA) -C terminal of the N-terminal-plasin (FlaB) -Pneumococcal strain and obtained from the professor's laboratory of the clinical vaccine development project team of Chonnam National University. The amino acid sequence of the FlaB / PspA recombinant fusion protein and the nucleic acid sequence encoding the FlaB / PspA recombinant fusion protein are represented by SEQ ID NOS: 1 and 2, respectively, and the amino acid sequence of the FlaB protein and the nucleic acid sequence encoding the FlaB protein are represented by SEQ ID NOS: 3 and 4, The sequences and the nucleic acid sequences encoding them are shown in SEQ ID NOS: 5 and 6, respectively.

All immunizations were performed at SPF (Specific Pathogen Free) facility.

Immune test groups are as follows.

Group 1 (control, Y-mice): As a control, mucosal immunostimulation was performed by administering phosphate-buffered saline (PBS) (16 쨉 l / mouse) to the nasal cavity of young rats (8-10 weeks old) at 8-week intervals every 2 weeks.

Group 2 (O-PBS): PBS (16 쨉 l / mouse) was administered to the aged mouse nares 8 times at intervals of 2 weeks.

Group 3 (O-FlaB / PspA): FlaB / PspA (6.5 [mu] g / 16 [mu] l / mouse) recombinant fusion protein was administered to the aged rat nares 8 times at intervals of 2 weeks.

The rats of group 2 treated with PBS in aged rats showed poor hair condition and increased hair loss and swelling. On the other hand, group 3 rats treated with FlaB / PspA recombinant protein in the aged rats significantly improved hair loss and swelling phenomena as compared with the second group. When stimulating continuous mucosal immunity with FlaB / PspA, the number of hair follicles was found to be maintained as much as in young mice. Therefore, it was confirmed that the FlaB / PspA recombinant protein had an effect of improving hair loss by continuous mucosal immunostimulation.

1.2. Identification of proteins expressed in skin tissue

Three different skin tissues per group of dorsal skin tissues of the first to third groups of Example 1.1 were obtained in order to identify the protein associated with the improvement of hair loss by continuous mucosal immunostimulation of FlaB / PspA recombinant protein.

RIPA buffer (Sigma-Aldrich) was added from the obtained skin tissues and the skin tissue was pulverized. Methanol / chloroform was added to the pulverized protein lysate, and a precipitated protein sample was obtained. The obtained protein samples were quantified, and 10 μg of each sample was electrophoresed and stained with Coomassie Blue. The results are shown in Fig.

Protein expression was observed in the protein samples in each group. The protein digestion was performed by the In Gel digestion experiment as described below. Specifically, a protein sample of each group and a 30% (w / v) acrylamine / Bis solution (Bio-Rad Laboratories Inc.) were mixed at a ratio of 1: 1. To the mixture was added 10% (w / v) Ammonium persulfate (APS) (Sigma-Aldrich) and N, N, N ', N'- TEMED (teramethylethylenediamine) (Sigma-Aldrich) ). The hard gel was then sliced and the pieces transferred to a 96-well plate. 200 [mu] l of 40% acetonitrile (HPLC grade) (Burdick & Jackson) was added to each well and the gel was washed by shaking at 60 [deg.] C at 800 rpm for 5 minutes. 200 [mu] l of 100% acetonitrile (HPLC grade) was again added to each well and the gel was dehydrated by shaking at 60 [deg.] C at a speed of 800 rpm for 5 minutes. Then, 100 μl of 25 mM DTT (Dithiothreitol) (Sigma-Aldrich) dissolved in 50 mM ammonium hydrogencarbonate aqueous solution (Sigma-Aldrich) was added to each well and the mixture was shaken at 56 ° C. at a speed of 800 rpm for 20 minutes Disulfide bond of the peptide was degraded. 100 μl of 25 mM iodoacetamide (Sigma-Aldrich) solution dissolved in 100 mM ammonium hydrogencarbonate aqueous solution was added and the solution was dissolved in a dark condition at room temperature (about 25 ° C) at 800 rpm for 30 minutes to dissolve The peptides were alkylated to avoid recombination. 100 μl of HPLC grade water (Burdick & Jackson) was added to each well and the gel was washed by shaking for 1 minute at room temperature (about 25 ° C) at 800 rpm in the dark. 100 [mu] l of 40% (v / v) acetonitrile (Burdick & Jackson) was added to each well and the gel was washed by shaking for 15 minutes at a rate of 800 rpm at room temperature. 100 [mu] l of 100% (v / v) acetonitrile (Burdick & Jackson) was added to each well and the gel was dehydrated by shaking for 5 minutes at a speed of 800 rpm at room temperature. 100 μl of Trypsin GOLD (Mass Spectrometry Grade) (Promega) was dissolved in 100 μl of 50 mM acetic acid (Sigma-Aldrich), and then 40 mM hydrocarbons dissolved in 10% (v / v) acetonitrile (Burdick & Jackson) Ammonium solution and 100 μl of Trypsin GOLD in 50 μl of acetic acid was mixed at a ratio of 49: 1. 50 μl of the solution was added to each well, followed by incubation at 37 ° C. for 12 to 16 hours The peptide was cut by incubation.

100 μl of 50% (v / v) acetonitrile (Burdick & Jackson) diluted with 0.1% (v / v) formic acid (Sigma-Aldrich) was added to each well to extract proteins in the gel, For 5 minutes. The extracted protein was transferred to each well of a Protein LoBind Tube (Eppendorf), and then 99.9% (v / v) acetonitrile (Burdick & Jackson) diluted with 0.1% (v / v) formic acid (Sigma-Aldrich) And the protein is extracted by shaking for 20 minutes at a rate of 800 rpm at room temperature. Again the solution was transferred to a Protein LoBind Tube and completely dried at 60 ° C under vacuum for about 2 to about 3 hours using a Concentrator Plus (Eppendorf). 70 μl of 0.1% (v / v) formic acid (Sigma-Aldrich) was added to the dried protein, mixed by vortexing, and sonicated twice for about 5-10 minutes to obtain a peptide sample.

The resulting peptide samples were loaded onto a nano high performance liquid chromatography (nano HPLC) instrument, EASY-nLC II autosampler (Thermo Scientific) for mass spectrometry.

EASY-Column (Thermo Scientific) (inner diameter 100 ㎛, length 2 ㎝) and reversed-phase analytical Easy-Column (Thermo Scientific) (inner diameter 75 ㎛, length 10 ㎝, particle size 3 ㎛) . A nano-bore stainless steel emitter (Thermo Scientific, Bremen, Germany) (inner diameter 30 μm) was installed for electrospray ionization. HPLC was performed at a voltage of 2.6 V while maintaining a flow rate of 300 nl (nano liter) per minute. Tune files of the LTQ Orbitrap Velos mass spectrometer (Thermo Scientific), a mass spectrometer, were activated and analyzed. At the time of analysis, the ratio of acetonitrile was increased in the order of 13%, 30%, 60%, and 90%, and analyzed while separating the sample from the column for 90 minutes. When performing a tandem mass analysis (tandom ms / ms analysis), the first total mass analysis has a resolution of 60,000, and the second mass analysis for amino acid sequence analysis is based on collision energy induced dissociation (CID) Were used.

Result analysis was performed using the Sorcerer v3.5 database search engine. IPI.mouse.v3.87 The FASTA database was used, and after the SEQUEST investigation, it was reexamined as X! Tandem and the peptide mass error tolerance was set at 25 ppm. Carbamidomethylation (+ 57.021 Da) of cysteine (C), which is a modification site in the preparation of the sample, is a static modification, and ubiquitination [GlyGly / + 114.043 Da (lysine; K)], acetylation (Acetyl / + 42.011 Da (Lysine), phosphorylation (Phospho / + 79.966 Da, S, threonine, T, tyrosine Y), Oxidation / + 15.995 Da ), Demineralization (Deamidated / + 0.984 Da, asparagine, N, glutamine, Q) were analyzed with Differential Modification. The final result was generated as a '.sf3' , Inc.) The analysis results were confirmed through the 'Quantify' menu.

499 proteins were identified by mass spectrometry. The distribution of the identified proteins in the first to third groups was confirmed, and the results are shown in Fig.

As shown in FIG. 3, the skin of the first group (young mice), the second group (aged mice immunized with PBS), and the third group (aged mice immunized with FlaB / PspA recombinant protein) 442 proteins expressed in all tissues were identified.

1.3. Screening of Differentially Expressed Proteins

The skin tissues of the first group (young mice), the second group (aged mice immunized with PBS), and the third group (aged mice immunized with mucosal immunostimulation with FlaB / PspA recombinant protein) identified in Example 1.2 Of the 442 proteins expressed in all, we identified polypeptides with increased or decreased expression in the skin of the third group (aged rats following continuous mucosal immunostimulation with FlaB / PspA recombinant protein).

Differential expression analysis was performed using the Scaffold 4 viewer software based on the Exclusive spectrum count obtained from the mass spectrometry of Example 1.2. The amount of the polypeptide expressed in the skin tissue of the first group (young rats) was converted into '1', and the second group (an aged rat immunized with mucosal immunity stimulated with PBS) and the third group (FlaB / PspA Fold change "by comparing the amounts of the polypeptides expressed in the skin tissues of the mice (aged mice immunized with mucosal proteins with recombinant proteins). A polypeptide having a value of a multiple of variation of 1.5 or more was determined to have an increased expression and a polypeptide having a value of a multiple of variation of 0.5 or less was determined to have decreased expression. As a result, in the third group (an aged rat immunized with FlaB / PspA recombinant protein) than the second group (aged rat immunized with PBS), high protein was identified as 50 species, In group 3, 54 proteins were found to be lower than in group 2.

In order to increase the reliability, protein expression patterns and functional analyzes were performed on 50 expression - increasing proteins and 54 expression - reducing proteins. Protein expression trends and functional analyzes were performed using STRING v9.1 software (www.string-db.org) and analyzed sequentially with respect to category 3 classification (biological processes, molecular functions, and cellular components) . Proteins labeled in subcategories selected with a P value of 0.05 or less were selected and analyzed for increased and decreased expression of the proteins. Seventeen expression-increasing proteins and fifteen expression-decreasing proteins were selected by further selection among the proteins identified in all five categories of each category. Thereafter, four candidate proteins and genes encoding the four candidate proteins were selected through a review of the texts, and the results are shown in Table 1 below.

As shown in Table 1, Krt17 (keratin 17) and Col1a1 (collagen type 1 alpha 1) were selected in the expression increasing protein group and Fbn1 (fibrillin 1) and Dcn (decorin) were selected in the expression decreasing protein group.

Krt17 plays an important role in hair regrowth and is closely related to the growth of hair follicles. The amino acid sequences of Krt17 in humans and rats are shown in GenBank Accession No. < RTI ID = 0.0 > No. < / RTI > NP_000413 (SEQ ID NO: 7) and NP_034793 (SEQ ID NO: 9), and the nucleic acid sequences encoding Krt17 in humans and rats are GenBank Accession No. NM_000422 (SEQ ID NO: 8) and NM_010663 (SEQ ID NO: 10).

Col1a1 is one of the collagen involved in hair follicle formation. The amino acid sequences of Col1a1 in humans and rats are shown in GenBank Accession No. < RTI ID = 0.0 > No. < / RTI > NP_000079 (SEQ ID NO: 11) and NP_031768 (SEQ ID NO: 13), and the nucleic acid sequences encoding Col1a1 in humans and rats are GenBank Accession No. NM_000088 (SEQ ID NO: 12) and NM_007742 (SEQ ID NO: 14).

Fbn1 is a structural gene of microtubule, which is closely related to elastin and is important for structural support. The amino acid sequences of Fbn1 in humans and rats are shown in GenBank Accession No. < RTI ID = 0.0 > No. < / RTI & NP_000129 (SEQ ID NO: 15) and NP_032019 (SEQ ID NO: 17), and the nucleic acid sequences encoding human and mouse Fbn1 are shown in GenBank Accession No. NM_000138 (SEQ ID NO: 16) and NM_007993 (SEQ ID NO: 18).

Dcn (decorin) is one of the genes that determine hair follicle formation and lifespan. The amino acid sequences of Dcn in humans and rats are shown in GenBank Accession No. < RTI ID = 0.0 > No. < / RTI & NP_001911 (SEQ ID NO: 19) and NP_001177380 (SEQ ID NO: 21), and the nucleic acid sequences encoding Dcn in humans and rats are GenBank Accession No. NM_001920 (SEQ ID NO: 20) and NM_001190451 (SEQ ID NO: 22).

1.4. Identification of differential expression of selected genes

Proteins were extracted from the skin tissues of the first to third groups of Example 1.1 against the genes selected in Example 1.3, and differential expression of Krt17, Col1a1, Fbn1, and Dcn was confirmed by immunoblotting.

As described in Example 1.1, there are three different groups per group in group 1 (young mice), group 2 (aged mice immunized with PBS), and group 3 (aged mice immunized with FlaB / PspA recombinant protein) (Sigma-Aldrich), 150 mM NaCl (Sigma-Aldrich), 1 mM ethylenediamine tetraacetic acid (EDTA) (Sigma-Aldrich), and 1% (w / v) sodium dodecyl sulfate (SDS) (Sigma-Aldrich)), and protein samples were prepared.

The prepared protein samples were subjected to electrophoresis and incubated with anti-Crt17 antibody (Santa Cruz Biotechnology Inc.), anti-Col1a1 antibody (Santa Cruz Biotechnology Inc.), anti-Fbn1 antibody (Santa Cruz Biotechnology Inc.) Santa Cruz Biotechnology Inc.) was used to perform immunoblotting. (Krt17 and Col1a1) and expression-decreasing protein groups (Dcn and Fbn1) (see Table 1 of Example 1.3) in a multiple of the amount of polypeptide expression obtained by mass spectrometry The results are shown in Fig. 4 (Y-mice, young mice, O-PBS, aged mice immunized with PBS, O-FlaB / PspA, aged mice immunized with FlaB / PspA recombinant protein, Tissue 1, 2; skin tissue 2, 3; skin tissue 3).

As shown in Fig. 4, the expression of Krt17 protein was markedly decreased in the second group (aged mice immunized with mucosal immunity stimulated with PBS) compared to the first group (young mice). On the other hand, the expression of Krt17 protein was significantly increased in the third group (aged rats immunized with FlaB / PspA recombinant protein) as compared to the second group (aged rats immunized with PBS). The amount of Krt17 expression in the third group was similar to that in the first group. Expression of Col1a1 protein was decreased in the second group compared to the first group. In addition, the expression of Col1a1 protein was decreased in the third group as compared to the second group. The expression level of Col1a1 protein in the third group was significantly lower than that of the first group. Expression of Dcn protein was not different between the first and third groups. Expression of Fbn protein was significantly decreased in the second group compared to the first group. On the other hand, the expression of Fbn1 protein was significantly increased in the third group as compared to the second group. The amount of Fbn1 expression in the third group was similar to that in the first group. However, the Fbn1 gene is a gene selected from the expression-decreasing protein group in the third group (aged rats immunized with FlaB / PspA recombinant protein). The results of immunoblotting and mass spectrometry showed different results. Therefore, it was confirmed that the Krt17 gene is related to the alopecia improvement effect of mucosal immunostimulation of FlaB / PspA.

1.5. Immunohistochemical staining in skin tissues such as rats Keratin  17

The gene (Krt17) showing the hair loss improving effect according to the mucosal immunostimulation of FlaB / PspA in Example 1.4 was analyzed by immunohistochemistry (IHC) staining method in the skin tissues of the first to third groups of Example 1.1, Were observed.

Skin tissues were obtained in Group 1 (young mice), Group 2 (aged mice immunized with PBS), and Group 3 (aged rats immunized with FlaB / PspA recombinant protein) as described in Example 1.1 After fixation in formalin, a paraffin-block was made. Then, paraffin blocks were cut using a microtome (Leica) to prepare tissue section slides, and the expression patterns of proteins were compared and confirmed by immunohistochemical staining.

Immunohistochemical staining was performed using anti-Crt17 antibodies in prepared tissue section slides. Tissue photographs were obtained at a microscope 400 magnification. The results are shown in Fig. 5 (red dotted circle; pore area).

As shown in Fig. 5, expression of Krt17 protein was confirmed in skin tissues such as that expressed in hair follicles, which is very important for hair regeneration. And the expression of Krt17 protein was decreased in the second group (aged mice immunized with mucosal immunity stimulated with PBS) compared with the first group (young mice). On the other hand, the expression of Krt17 protein was increased in the third group (aged rats immunized with FlaB / PspA recombinant protein) as compared to the second group (aged mice immunized with PBS). The tendency of Krt17 expression in the third group was similar to that in the first group. The expression pattern of Krt17 in the dorsal skin tissue was confirmed to be consistent with the protein expression of Krt17 identified in the immunoblotting result shown in Fig. Therefore, it was confirmed that the expression of Krt17 protein, which plays a crucial role in hair regeneration, is increased in aged rat skin tissues by continuously stimulating FlaB / PspA recombinant protein to mucosal immunostimulation in aged rats.

<110> SAM SUNG ELECTRONICS          INDUSTRY FOUNDATION OF CHONNAM NATIONAL UNIVERSITY <120> Composition or method for preventing or treating hair loss, and          screening method for a material preventing, treating, or          alleviating of hair loss <130> PN107008 <160> 22 <170> Kopatentin 2.0 <210> 1 <211> 612 <212> PRT <213> Artificial Sequence <220> <223> Recombinant fusion protein FlaB / PspA <400> 1 Met Ala Val Asn Val Asn Thr Asn Val Ala Ala Met Thr Ala Gln Arg   1 5 10 15 Tyr Leu Asn Asn Ala Asn Ser Ala Gln Gln Thr Ser Met Glu Arg Leu              20 25 30 Ser Ser Gly Phe Lys Ile Asn Ser Ala Lys Asp Asp Ala Ala Gly Leu          35 40 45 Gln Ile Ser Asn Arg Leu Asn Val Gln Ser Arg Gly Leu Asp Val Ala      50 55 60 Val Arg Asn Ala Asn Asp Gly Ile Ser Ile Ala Gln Thr Ala Glu Gly  65 70 75 80 Ala Met Asn Glu Thr Thr Asn Ile Leu Gln Arg Met Met Arg Asp Leu Ser                  85 90 95 Leu Gln Ser Ala Asn Gly Ser Asn Ser Lys Ser Glu Arg Val Ala Ile             100 105 110 Gln Glu Glu Val Thr Ala Leu Asn Asp Glu Leu Asn Arg Ile Ala Glu         115 120 125 Thr Thr Ser Phe Gly Gly Asn Lys Leu Leu Asn Gly Thr Tyr Gly Thr     130 135 140 Lys Ala Met Gln Ile Gly Ala Asp Asn Gly Glu Ala Val Met Leu Ser 145 150 155 160 Leu Lys Asp Met Arg Ser Asp Asn Val Met Met Gly Gly Val Ser Tyr                 165 170 175 Gln Ala Glu Glu Gly Lys Asp Lys Asn Trp Asn Val Ala Ala Gly Asp             180 185 190 Asn Asp Leu Thr Ile Ala Leu Thr Asp Ser Phe Gly Asn Glu Gln Glu         195 200 205 Ile Glu Ile Asn Ala Lys Ala Gly Asp Asp Ile Glu Glu     210 215 220 Tyr Ile Asn Gly Gln Thr Asp Leu Val Lys Ala Ser Val Gly Glu Gly 225 230 235 240 Gly Lys Leu Gln Ile Phe Ala Gly Asn Asn Lys Val Gln Gly Glu Ile                 245 250 255 Ala Phe Ser Gly Ser Leu Ala Gly Glu Leu Gly Leu Gly Glu Gly Lys             260 265 270 Asn Val Thr Val Asp Thr Ile Asp Val Thr Thr Val Gln Gly Ala Gln         275 280 285 Glu Ser Val Ala Ile Val Asp Ala Ala Leu Lys Tyr Val Asp Ser His     290 295 300 Arg Ala Glu Leu Gly Ala Phe Gln Asn Arg Phe Asn His Ala Ile Ser 305 310 315 320 Asn Leu Asp Asn Ile Asn Glu Asn Val Asn Ala Ser Lys Ser Arg Ile                 325 330 335 Lys Asp Thr Asp Phe Ala Lys Glu Thr Thr Gln Leu Thr Lys Thr Gln             340 345 350 Ile Leu Ser Gln Ala Ser Ser Ile Leu Ala Gln Ala Lys Gln Ala         355 360 365 Pro Asn Ser Ala Leu Ser Leu Leu Gly Val Asp Ser Pro Val Ala Ser     370 375 380 Gln Ser Lys Ala Glu Lys Asp Tyr Asp Ala Ala Lys Lys Asp Ala Lys 385 390 395 400 Asn Ala Lys Lys Ala Val Glu Asp Ala Gln Lys Ala Leu Asp Asp Ala                 405 410 415 Lys Ala Ala Gln Lys Lys Tyr Asp Glu Asp Gln Lys Lys Thr Glu Glu             420 425 430 Lys Ala Ala Leu Glu Lys Ala Ala Ser Glu Glu Met Asp Lys Ala Val         435 440 445 Ala Ala Val Gln Gln Ala Tyr Leu Ala Tyr Gln Gln Ala Thr Asp Lys     450 455 460 Ala Ala Lys Asp Ala Ala Asp Lys Met Ile Asp Glu Ala Lys Lys Arg 465 470 475 480 Glu Glu Glu Ala Lys Thr Lys Phe Asn Thr Val Arg Ala Met Val Val                 485 490 495 Pro Glu Pro Glu Gln Leu Ala Glu Thr Lys Lys Lys Ser Glu Glu Ala             500 505 510 Lys Gln Lys Ala Pro Glu Leu Thr Lys Lys Leu Glu Glu Ala Lys Ala         515 520 525 Lys Leu Glu Glu Ala Glu Lys Lys Ala Thr Glu Ala Lys Gln Lys Val     530 535 540 Asp Ala Glu Glu Val Ala Pro Gln Ala Lys Ile Ala Glu Leu Glu Asn 545 550 555 560 Gln Val His Arg Leu Glu Gln Glu Leu Lys Glu Ile Asp Glu Ser Glu                 565 570 575 Ser Glu Asp Tyr Ala Lys Glu Gly Phe Arg Ala Pro Leu Gln Ser Lys             580 585 590 Leu Asp Ala Lys Lys Ala Lys Leu Ser Lys Leu Glu Glu Leu Ser Asp         595 600 605 Lys Ile Asp Glu     610 <210> 2 <211> 1836 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid encoding recombinant fusion protein FlaB / PspA <400> 2 atggcagtga atgtaaatac aaacgtagca gcaatgacag cacagcgtta cctgaataac 60 gcaaacagcg cacaacaaac ttcgatggag cgtctgtctt caggtttcaa aatcaacagt 120 gcaaaagatg acgcagccgg tctgcaaatc tctaaccgct tgaacgtaca aagtcgcggt 180 ctagacgttg cggtacgtaa cgccaacgac ggtatctcaa tcgcacaaac cgcagaaggt 240 gcgatgaacg agaccaccaa catcctacaa cgtatgcgtg acctatctct acaatccgcg 300 aacggctcaa actcaaaatc agagcgcgtg gcgattcaag aagaagtgac agcattgaat 360 gacgagctaa accgtattgc agaaaccacg tcttttggtg gtaacaagct gctaaacggt 420 acttacggca cgaaagcaat gcaaattggt gcggataacg gtgaagcggt catgctttca 480 ctgaaagaca tgcgctctga caacgtgatg atgggcggcg tgagctacca agctgaagaa 540 ggcaaagaca agaactggaa tgtggccgca ggcgacaacg acttgacgat tgcactgaca 600 gacagctttg gtaacgagca agagatcgaa atcaacgcga aagcgggtga tgacatcgaa 660 gagctagcga cgtacatcaa cggtcaaact gaccttgtaa aagcgtcagt gggtgaaggc 720 ggcaagctac agatctttgc tggtaacaac aaagttcaag gtgaaattgc tttctcaggt 780 agcctagctg gtgaacttgg cctaggcgaa ggcaaaaacg tcacggtaga cacgattgac 840 gtgacaaccg tacaaggtgc gcaagagtcg gtagcgattg tggatgcggc actgaaatac 900 gtagacccc accgtgcaga gctgggtgca ttccagaacc gtttcaacca tgcaatcagc 960 aactggaca acatcaacga aaacgtgaac gcgtcgaaga gccgaatcaa agataccgac 1020 ttcgcgaaag aaacgactca gttgaccaag acacaaattc tatcgcaagc atcaagttcc 1080 attcttgcgc aagcgaaaca agcgccaaac tcagcgctaa gtctactagg cgtcgactct 1140 cccgtagcca gtcagtctaa agctgagaaa gactatgatg cagcgaagaa agatgctaag 1200 aatgcgaaaa aagcagtaga agatgctcaa aaggctttag atgatgcaaa agctgctcag 1260 aaaaaatatg acgaggatca gaagaaaact gaggagaaag ccgcgctaga aaaagcagcg 1320 tctgaagaga tggataaggc agtggcagca gttcaacaag cgtatctagc ctatcaacaa 1380 gctacagaca aagccgcaaa agacgcagca gataagatga tagatgaagc taagaaacgc 1440 gaagaagagg caaaaactaa atttaatact gttcgagcaa tggtagttcc tgagccagag 1500 cagttggctg agactaagaa aaaatcagaa gaagctaaac aaaaagcacc agaacttact 1560 aaaaaactag aagaagctaa agcaaaatta gaagaggctg agaaaaaagc tactgaagcc 1620 aaacaaaaag tggatgctga agaagtcgct cctcaagcta aaatcgctga attggaaaat 1680 caagttcata gactagaaca agagctcaaa gagattgatg agtctgaatc agaagattat 1740 gctaaagaag gtttccgtgc tcctcttcaa tctaaattgg atgccaaaaa agctaaacta 1800 tcaaaacttg aagagttaag tgataagatt gatgag 1836 <210> 3 <211> 376 <212> PRT <213> Artificial Sequence <220> <223> FlaB protein <400> 3 Met Ala Val Asn Val Asn Thr Asn Val Ala Ala Met Thr Ala Gln Arg   1 5 10 15 Tyr Leu Asn Asn Ala Asn Ser Ala Gln Gln Thr Ser Met Glu Arg Leu              20 25 30 Ser Ser Gly Phe Lys Ile Asn Ser Ala Lys Asp Asp Ala Ala Gly Leu          35 40 45 Gln Ile Ser Asn Arg Leu Asn Val Gln Ser Arg Gly Leu Asp Val Ala      50 55 60 Val Arg Asn Ala Asn Asp Gly Ile Ser Ile Ala Gln Thr Ala Glu Gly  65 70 75 80 Ala Met Asn Glu Thr Thr Asn Ile Leu Gln Arg Met Met Arg Asp Leu Ser                  85 90 95 Leu Gln Ser Ala Asn Gly Ser Asn Ser Lys Ser Glu Arg Val Ala Ile             100 105 110 Gln Glu Glu Val Thr Ala Leu Asn Asp Glu Leu Asn Arg Ile Ala Glu         115 120 125 Thr Thr Ser Phe Gly Gly Asn Lys Leu Leu Asn Gly Thr Tyr Gly Thr     130 135 140 Lys Ala Met Gln Ile Gly Ala Asp Asn Gly Glu Ala Val Met Leu Ser 145 150 155 160 Leu Lys Asp Met Arg Ser Asp Asn Val Met Met Gly Gly Val Ser Tyr                 165 170 175 Gln Ala Glu Glu Gly Lys Asp Lys Asn Trp Asn Val Ala Ala Gly Asp             180 185 190 Asn Asp Leu Thr Ile Ala Leu Thr Ser Phe Gly Asn Glu Gln Glu Ile         195 200 205 Glu Ile Asn Ala Lys Ala Gly Asp Asp Ile Glu Glu Leu Ala Thr Tyr     210 215 220 Ile Asn Gly Gln Thr Asp Leu Val Lys Ala Ser Val Gly Glu Gly Gly 225 230 235 240 Lys Leu Gln Ile Phe Ala Gly Asn Asn Lys Val Gln Gly Glu Ile Ala                 245 250 255 Phe Ser Gly Ser Leu Ala Gly Glu Leu Gly Leu Gly Glu Gly Lys Asn             260 265 270 Val Thr Val Asp Thr Ile Asp Val Thr Thr Val Gln Gly Ala Gln Glu         275 280 285 Ser Val Ala Ile Val Asp Ala Ala Leu Lys Tyr Val Asp Ser His Arg     290 295 300 Ala Glu Leu Gly Ala Phe Gln Asn Arg Phe Asn His Ala Ile Ser Asn 305 310 315 320 Leu Asp Asn Ile Asn Glu Asn Val Asn Ala Ser Lys Ser Arg Ile Lys                 325 330 335 Asp Thr Asp Phe Ala Lys Glu Thr Thr Gln Leu Thr Lys Thr Gln Ile             340 345 350 Leu Ser Gln Ala Ser Ser Ile Leu Ala Gln Ala Lys Gln Ala Pro         355 360 365 Asn Ser Ala Leu Ser Leu     370 375 <210> 4 <211> 1131 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid encoding FlaB protein <400> 4 atggcagtga atgtaaatac aaacgtagca gcaatgacag cacagcgtta cctgaataac 60 gcaaacagcg cacaacaaac ttcgatggag cgtctgtctt caggtttcaa aatcaacagt 120 gcaaaagatg acgcagccgg tctgcaaatc tctaaccgct tgaacgtaca aagtcgcggt 180 ctagacgttg cggtacgtaa cgccaacgac ggtatctcaa tcgcacaaac cgcagaaggt 240 gcgatgaacg agaccaccaa catcctacaa cgtatgcgtg acctatctct acaatccgcg 300 aacggctcaa actcaaaatc agagcgcgtg gcgattcaag aagaagtgac agcattgaat 360 gacgagctaa accgtattgc agaaaccacg tcttttggtg gtaacaagct gctaaacggt 420 acttacggca cgaaagcaat gcaaattggt gcggataacg gtgaagcggt catgctttca 480 ctgaaagaca tgcgctctga caacgtgatg atgggcggcg tgagctacca agctgaagaa 540 ggcaaagaca agaactggaa tgtggccgca ggcgacaacg acttgacgat tgcactgaca 600 gacagctttg gtaacgagca agagatcgaa atcaacgcga aagcgggtga tgacatcgaa 660 gagctagcga cgtacatcaa cggtcaaact gaccttgtaa aagcgtcagt gggtgaaggc 720 ggcaagctac agatctttgc tggtaacaac aaagttcaag gtgaaattgc tttctcaggt 780 agcctagctg gtgaacttgg cctaggcgaa ggcaaaaacg tcacggtaga cacgattgac 840 gtgacaaccg tacaaggtgc gcaagagtcg gtagcgattg tggatgcggc actgaaatac 900 gtagacccc accgtgcaga gctgggtgca ttccagaacc gtttcaacca tgcaatcagc 960 aactggaca acatcaacga aaacgtgaac gcgtcgaaga gccgaatcaa agataccgac 1020 ttcgcgaaag aaacgactca gttgaccaag acacaaattc tatcgcaagc atcaagttcc 1080 attcttgcgc aagcgaaaca agcgccaaac tcagcgctaa gtctactagg c 1131 <210> 5 <211> 230 <212> PRT <213> Artificial Sequence <220> <223> PspA protein <400> 5 Ser Pro Val Ala Ser Gln Ser Lys Ala Glu Lys Asp Tyr Asp Ala Ala   1 5 10 15 Lys Lys Asp Ala Lys Asn Ala Lys Lys Ala Val Glu Asp Ala Gln Lys              20 25 30 Ala Leu Asp Asp Ala Lys Ala Ala Gln Lys Lys Tyr Asp Glu Asp Gln          35 40 45 Lys Lys Thr Glu Glu Lys Ala Ala Leu Glu Lys Ala Ser Glu Glu Met      50 55 60 Asp Lys Ala Val Ala Val Gln Gln Ala Tyr Leu Ala Tyr Gln Gln  65 70 75 80 Ala Thr Asp Lys Ala Ala Lys Asp Ala Ala Asp Lys Met Ile Asp Glu                  85 90 95 Ala Lys Lys Arg Glu Glu Glu Ala Lys Thr Lys Phe Asn Thr Val Arg             100 105 110 Ala Met Val Val Pro Glu Pro Gln Leu Ala Glu Thr Lys Lys Lys Ser         115 120 125 Glu Glu Ala Lys Gln Lys Ala Pro Glu Leu Thr Lys Lys Leu Glu Glu     130 135 140 Ala Lys Ala Lys Leu Glu Glu Ala Glu Lys Lys Ala Thr Glu Ala Lys 145 150 155 160 Gln Lys Val Asp Ala Glu Glu Val Ala Pro Gln Ala Lys Ile Ala Glu                 165 170 175 Leu Glu Gln Val His Arg Leu Glu Gln Glu Leu Lys Glu Ile Asp Glu             180 185 190 Ser Glu Ser Glu Asp Tyr Ala Lys Glu Gly Phe Arg Ala Pro Leu Gln         195 200 205 Ser Lys Leu Asp Ala Lys Lys Ala Lys Leu Ser Lys Leu Glu Glu Leu     210 215 220 Ser Asp Lys Ile Asp Glu 225 230 <210> 6 <211> 702 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid encoding PspA protein <400> 6 tctcccgtag ccagtcagtc taaagctgag aaagactatg atgcagcgaa gaaagatgct 60 aagaatgcga aaaaagcagt agaagatgct caaaaggctt tagatgatgc aaaagctgct 120 cagaaaaaat atgacgagga tcagaagaaa actgaggaga aagccgcgct agaaaaagca 180 gcgtctgaag agatggataa ggcagtggca gcagttcaac aagcgtatct agcctatcaa 240 caagctacag acaaagccgc aaaagacgca gcagataaga tgatagatga agctaagaaa 300 cgcgaagaag aggcaaaaac taaatttaat actgttcgag caatggtagt tcctgagcca 360 gagcagttgg ctgagactaa gaaaaaatca gaagaagcta aacaaaaagc accagaactt 420 actaaaaaac tagaagaagc taaagcaaaa ttagaagagg ctgagaaaaa agctactgaa 480 gccaaacaaa aagtggatgc tgaagaagtc gctcctcaag ctaaaatcgc tgaattggaa 540 aatcaagttc atagactaga acaagagctc aaagagattg atgagtctga atcagaagat 600 tatgctaaag aaggtttccg tgctcctctt caatctaaat tggatgccaa aaaagctaaa 660 ctatcaaaac ttgaagagtt aagtgataag attgatgagt aa 702 <210> 7 <211> 432 <212> PRT <213> Artificial Sequence <220> <223> Human Keratin 17 protein <400> 7 Met Thr Thr Ser Ile Arg Gln Phe Thr Ser Ser Ser Ile Lys Gly   1 5 10 15 Ser Ser Gly Leu Gly Gly Gly Ser Ser Ser Thr Ser Cys Arg Leu Ser              20 25 30 Gly Gly Leu Gly Ala Gly Ser Cys Arg Leu Gly Ser Ala Gly Gly Leu          35 40 45 Gly Ser Thr Leu Gly Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser      50 55 60 Ser Gly Gly Gly Tyr Gly Ser Ser Phe Gly Gly Val Asp Gly Leu Leu  65 70 75 80 Ala Gly Gly Glu Lys Ala Thr Met Gln Asn Leu Asn Asp Arg Leu Ala                  85 90 95 Ser Tyr Leu Asp Lys Val Arg Ala Leu Glu Glu Ala Asn Thr Glu Leu             100 105 110 Glu Val Lys Ile Arg Asp Trp Tyr Gln Arg Gln Ala Pro Gly Pro Ala         115 120 125 Arg Asp Tyr Ser Gln Tyr Tyr Arg Thr Ile Glu Glu Leu Gln Asn Lys     130 135 140 Ile Leu Thr Ala Thr Val Asp Asn Ala Asn Ile Leu Leu Gln Ile Asp 145 150 155 160 Asn Ala Arg Leu Ala Asp Asp Phe Arg Thr Lys Phe Glu Thr Glu                 165 170 175 Gln Ala Leu Arg Leu Ser Val Glu Ala Asp Ile Asn Gly Leu Arg Arg             180 185 190 Val Leu Asp Glu Leu Thr Leu Ala Arg Ala Asp Leu Glu Met Gln Ile         195 200 205 Glu Asn Leu Lys Glu Glu Leu Ala Tyr Leu Lys Lys Asn His Glu Glu     210 215 220 Glu Met Asn Ala Leu Arg Gly Gln Val Gly Gly Glu Ile Asn Val Glu 225 230 235 240 Met Asp Ala Ala Pro Gly Val Asp Leu Ser Arg Ile Leu Asn Glu Met                 245 250 255 Arg Asp Gln Tyr Glu Lys Met Ala Glu Lys Asn Arg Lys Asp Ala Glu             260 265 270 Asp Trp Phe Phe Ser Lys Thr Glu Glu Leu Asn Arg Glu Val Ala Thr         275 280 285 Asn Ser Glu Leu Val Gln Ser Gly Lys Ser Glu Ile Ser Glu Leu Arg     290 295 300 Arg Thr Met Gln Ala Leu Glu Ile Glu Leu Gln Ser Gln Leu Ser Met 305 310 315 320 Lys Ala Ser Leu Glu Gly Asn Leu Ala Glu Thr Glu Asn Arg Tyr Cys                 325 330 335 Val Gln Leu Ser Gln Ile Gln Gly Leu Ile Gly Ser Val Glu Glu Gln             340 345 350 Leu Ala Gln Leu Arg Cys Glu Met Glu Gln Gln Asn Gln Glu Tyr Lys         355 360 365 Ile Leu Leu Asp Val Lys Thr Arg Leu Glu Gln Glu Ile Ala Thr Tyr     370 375 380 Arg Arg Leu Leu Glu Gly Glu Asp Ala His Leu Thr Gln Tyr Lys Lys 385 390 395 400 Glu Pro Thr Thr Arg Gln Val Arg Thr Ile Val Glu Glu Val Gln                 405 410 415 Asp Gly Lys Val Ser Ser Arg Glu Gln Val His Gln Thr Thr Arg             420 425 430 <210> 8 <211> 1574 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid encoding human Keratin 17 protein <400> 8 atcgctacgc ccacttggtg gcctataaag gaagcgggcg aaccccggca gccctacaca 60 acttggggcc cctctcctct ccagcccttc tcctgtgtgc ctgcctcctg ccgccgccac 120 catgaccacc tccatccgcc agttcacctc ctccagctcc atcaagggct cctccggcct 180 ggggggcggc tcgtcccgca cctcctgccg gctgtctggc ggcctgggtg ccggctcctg 240 caggctggga tctgctggcg gcctgggcag caccctcggg ggtagcagct actccagctg 300 ctacagcttt ggctctggtg gtggctatgg cagcagcttt gggggtgttg atgggctgct 360 ggctggaggt gagaaggcca ccatgcagaa cctcaatgac cgcctggcct cctacctgga 420 caaggtgcgt gccctggagg aggccaacac tgagctggag gtgaagatcc gtgactggta 480 ccagaggcag gccccggggc ccgcccgtga ctacagccag tactacagga caattgagga 540 gctgcagaac aagatcctca cagccaccgt ggacaatgcc aacatcctgc tacagattga 600 caatgcccgt ctggctgctg atgacttccg caccaagttt gagacagagc aggccctgcg 660 cctgagtgtg gaggccgaca tcaatggcct gcgcagggtg ctggatgagc tgaccctggc 720 cagagccgac ctggagatgc agattgagaa cctcaaggag gagctggcct acctgaagaa 780 gaaccacgag gaggagatga acgccctgcg aggccaggtg ggtggtgaga tcaatgtgga 840 gatggacgct gccccaggcg tggacctgag ccgcatcctc aacgagatgc gtgaccagta 900 tgagaagatg gcagagaaga accgcaagga tgccgaggat tggttcttca gcaagacaga 960 ggaactgaac cgcgaggtgg ccaccaacag tgagctggtg cagagtggca agagtgagat 1020 ctcggagctc cggcgcacca tgcaggcctt ggagatagag ctgcagtccc agctcagcat 1080 gaaagcatcc ctggagggca acctggcgga gacagagaac cgctactgcg tgcagctgtc 1140 ccagatccag gggctgattg gcagcgtgga ggagcagctg gcccagcttc gctgcgagat 1200 ggagcagcag aaccaggaat acaaaatcct gctggatgtg aagacgcggc tggagcagga 1260 gattgccacc taccgccgcc tgctggaggg agaggatgcc cacctgactc agtacaagaa 1320 agaaccggtg accacccgtc aggtgcgtac cattgtggaa gaggtccagg atggcaaggt 1380 catctcctcc cgcgagcagg tccaccagac cacccgctga ggactcagct accccggccg 1440 gccacccagg aggcagggag gcagccgccc catctgcccc acagtctccg gcctctccag 1500 cctcagcccc ctgcttcagt cccttcccca tgcttccttg cctgatgaca ataaagcttg 1560 ttgactcagc tatg 1574 <210> 9 <211> 433 <212> PRT <213> Artificial Sequence <220> <223> Mouse Keratin 17 protein <400> 9 Met Thr Thr Thr Ile Arg Gln Phe Thr Ser Ser Ser Ile Lys Gly   1 5 10 15 Ser Ser Gly Leu Gly Gly Gly Ser Ser Ser Thr Ser Cys Arg Leu Ser              20 25 30 Gly Ser Leu Gly Ala Gly Ser Cys Arg Leu Gly Ser Ala Ser Gly Leu          35 40 45 Gly Ser Ala Leu Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser      50 55 60 Thr Gly Ser Gly Tyr Gly Gly Asn Phe Gly Gly Val Asp Gly Leu Leu  65 70 75 80 Ala Gly Gly Glu Lys Ala Thr Met Gln Asn Leu Asn Asp Arg Leu Ala                  85 90 95 Ser Tyr Leu Asp Lys Val Arg Ala Leu Glu Glu Ala Asn Thr Glu Leu             100 105 110 Glu Val Lys Ile Arg Asp Trp Tyr Gln Lys Gln Ala Pro Gly Pro Ala         115 120 125 Arg Asp Tyr Ser Ala Tyr Tyr His Thr Ile Glu Asp Leu Lys Asn Lys     130 135 140 Ile Leu Val Ala Thr Val Asp Asn Ala Ser Ile Leu Leu Gln Ile Asp 145 150 155 160 Asn Ala Arg Leu Ala Asp Asp Phe Arg Thr Lys Phe Glu Thr Glu                 165 170 175 Gln Ala Leu Arg Met Ser Val Glu Ala Asp Ile Asn Gly Leu Arg Arg             180 185 190 Val Leu Asp Glu Leu Thr Leu Ala Arg Ala Asp Leu Glu Met Gln Ile         195 200 205 Glu Asn Leu Lys Glu Glu Leu Ala Tyr Leu Lys Lys Asn His Glu Glu     210 215 220 Glu Met Asn Ala Leu Arg Gly Gln Val Gly Gly Glu Ile Asn Val Glu 225 230 235 240 Met Asp Ala Ala Pro Gly Val Asp Leu Ser Arg Ile Leu Ser Glu Met                 245 250 255 Arg Asp Gln Tyr Glu Lys Met Ala Glu Lys Asn Arg Lys Asp Ala Glu             260 265 270 Asp Trp Phe Phe Ser Lys Thr Glu Glu Leu Asn Arg Glu Val Ala Thr         275 280 285 Asn Ser Glu Leu Val Gln Ser Gly Lys Ser Glu Ile Ser Glu Leu Arg     290 295 300 Arg Thr Met Gln Ala Leu Glu Ile Glu Leu Gln Ser Gln Leu Ser Met 305 310 315 320 Lys Ala Ser Leu Glu Gly Ser Leu Ala Glu Thr Glu Asn Arg Tyr Cys                 325 330 335 Val Gln Leu Ser Gln Ile Gln Gly Leu Ile Gly Ser Val Glu Glu Gln             340 345 350 Leu Ala Gln Leu Arg Cys Glu Met Glu Gln Gln Asn Gln Glu Tyr Lys         355 360 365 Ile Leu Leu Asp Val Lys Thr Arg Leu Glu Gln Glu Ile Ala Thr Tyr     370 375 380 Arg Arg Leu Leu Glu Gly Glu Asp Ala His Leu Thr Gln Tyr Lys Pro 385 390 395 400 Lys Glu Pro Thr Thr Arg Gln Val Arg Thr Ile Val Glu Glu Val                 405 410 415 Gln Asp Gly Lys Val Ser Ser Ser Glu Gln Val His Gln Thr Thr             420 425 430 Arg     <210> 10 <211> 1532 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid encoding mouse Keratin 17 protein <400> 10 ccacatccgt tgcccgctgc caccatgacc accaccatcc gccagtttac ctcctccagc 60 tctatcaagg gctcctctgg cctgggtgga ggttcatctc ggacctcctg ccgactgtct 120 ggcagcctgg gtgcaggctc ctgcaggctg gggtcagcta gtggcctggg tagtgctctt 180 gggagcaaca gttattccag ctgctacagc tttggcactg gcagtggtta tggaggcaac 240 tttgggggtg tcgatgggct gctggctgga ggggagaagg ccaccatgca gaacctcaat 300 gaccgcctgg cctcctacct ggacaaggtg cgtgccctgg aagaggccaa cactgagctg 360 gaggtgaaga tccgagattg gtaccagaag caggccccgg ggccagccag agactacagc 420 gcttattacc ataccattga ggatctgaag aacaagatcc ttgtggccac cgtggacaat 480 gccagcatcc tgctccagat tgacaatgct cgtctggcag ccgatgactt ccgtaccaag 540 tttgagacag agcaggctct gcgcatgagc gtggaggccg acatcaatgg cctgcgccgg 600 gtgctggatg agctgaccct ggccagagcc gacctggaga tgcagattga gaatctcaag 660 gaggagctgg cctacctgaa gaagaaccac gaggaggaga tgaatgctct gagaggccag 720 gtgggcggcg aaatcaacgt ggagatggat gccgctcccg gtgtggacct gagccgcatc 780 ctgtcagaga tgcgtgatca gtacgagaag atggcggaga agaaccgcaa ggatgccgaa 840 gactggttct tcagcaagac cgaggagctg aaccgcgagg tggccaccaa cagcgagctg 900 gtgcagagcg gcaagagcga gatctccgag ctcaggcgca ccatgcaggc cctggagatt 960 gagctgcagt cccagctcag catgaaagca tctctggagg gcagcctggc agagacagag 1020 aaccgctact gcgtgcagct gtctcagatc caggggctga tcggcagtgt ggaggagcag 1080 ctggctcagc tgcgctgcga gatggagcag cagaaccagg agtacaagat cctgctggat 1140 gtgaagacaa ggctggagca ggagatcgcc acctaccgcc gtctgctgga gggagaggat 1200 gcccacctga ctcagtacaa gccaaaagaa cctgtgacca cccgccaggt gcgcaccatt 1260 gtggaagaag ttcaggatgg caaggtcatc tcatcccggg aacaggtgca ccagaccacc 1320 cgttaaggac tcagctcctt ccgcccagtt ccccgaggct gcagagaggc agcttccctc 1380 tccgctccgg catcaccctc ctgctacagc ctctccccag cattcctatg cttgagacca 1440 ttaaagcttg ctgacctgaa gtgaactgtg gcctttgttc tgaacactga aataaatgac 1500 catggtgaca aaaaaaaaaa aaaaaaaaaa aa 1532 <210> 11 <211> 1464 <212> PRT <213> Artificial Sequence <220> <223> Human collagen type 1 alpha-1 protein <400> 11 Met Phe Ser Phe Val Asp Leu Arg Leu Leu Leu Leu Leu Ala Ala Thr   1 5 10 15 Ala Leu Leu Thr His Gly Gln Glu Glu Gly Gln Val Glu Gly Gln Asp              20 25 30 Glu Asp Ile Pro Pro Ile Thr Cys Val Gln Asn Gly Leu Arg Tyr His          35 40 45 Asp Arg Asp Val Trp Lys Pro Glu Pro Cys Arg Ile Cys Val Cys Asp      50 55 60 Asn Gly Lys Val Leu Cys Asp Asp Val Ile Cys Asp Glu Thr Lys Asn  65 70 75 80 Cys Pro Gly Ala Glu Val Pro Glu Gly Glu Cys Cys Pro Val Cys Pro                  85 90 95 Asp Gly Ser Glu Ser Pro Thr Asp Gln Glu Thr Thr Gly Val Glu Gly             100 105 110 Pro Lys Gly Asp Thr Gly Pro Arg Gly Pro Arg Gly Pro Ala Gly Pro         115 120 125 Pro Gly Arg Asp Gly Ile Pro Gly Gln Pro Gly Leu Pro Gly Pro Pro     130 135 140 Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Leu Gly Gly Asn Phe Ala 145 150 155 160 Pro Gln Leu Ser Tyr Gly Tyr Asp Glu Lys Ser Thr Gly Gly Ile Ser                 165 170 175 Val Pro Gly Pro Met Gly Pro Ser Gly Pro Arg Gly Leu Pro Gly Pro             180 185 190 Pro Gly Ala Pro Gly Pro Gly Gly Phe Gly Gly Pro Pro Gly Gly Pro         195 200 205 Gly Glu Pro Gly Ala Ser Gly Pro Met Gly Pro Arg Gly Pro Pro Gly     210 215 220 Pro Pro Gly Lys Asn Gly Asp Asp Gly Gly Ala Gly Lys Pro Gly Arg 225 230 235 240 Pro Gly Glu Arg Gly Pro Pro Gly Pro Gln Gly Ala Arg Gly Leu Pro                 245 250 255 Gly Thr Ala Gly Leu Pro Gly Met Lys Gly His Arg Gly Phe Ser Gly             260 265 270 Leu Asp Gly Ala Lys Gly Asp Ala Gly Pro Ala Gly Pro Lys Gly Glu         275 280 285 Pro Gly Ser Pro Gly Glu Asn Gly Ala Pro Gly Gln Met Gly Pro Arg     290 295 300 Gly Leu Pro Gly Glu Arg Gly Arg Pro Gly Ala Pro Gly Pro Ala Gly 305 310 315 320 Ala Arg Gly Asn Asp Gly Ala Thr Gly Ala Gly Pro Pro Gly Pro                 325 330 335 Thr Gly Pro Ala Gly Pro Pro Gly Phe Pro Gly Ala Val Gly Ala Lys             340 345 350 Gly Glu Ala Gly Pro Gln Gly Pro Arg Gly Ser Glu Gly Pro Gln Gly         355 360 365 Val Arg Gly Glu Pro Gly Pro Pro Gly Pro Ala Gly Ala Ala Gly Pro     370 375 380 Ala Gly Asn Pro Gly Ala Asp Gly Gln Pro Gly Ala Lys Gly Ala Asn 385 390 395 400 Gly Ala Pro Gly Ile Ala Gly Ala Pro Gly Phe Pro Gly Ala Arg Gly                 405 410 415 Pro Ser Gly Pro Gln Gly Pro Gly Gly Pro Pro Gly Pro Lys Gly Asn             420 425 430 Ser Gly Glu Pro Gly Ala Pro Gly Ser Lys Gly Asp Thr Gly Ala Lys         435 440 445 Gly Glu Pro Gly Pro Val Gly Val Gly Gly Pro Pro Gly Pro Ala Gly     450 455 460 Glu Glu Gly Lys Arg Gly Ala Arg Gly Glu Pro Gly Pro Thr Gly Leu 465 470 475 480 Pro Gly Pro Pro Gly Gly Arg Gly Gly Pro Gly Ser Arg Gly Phe Pro                 485 490 495 Gly Ala Asp Gly Val Ala Gly Pro Lys Gly Pro Ala Gly Glu Arg Gly             500 505 510 Ser Pro Gly Pro Ala Gly Pro Lys Gly Ser Pro Gly Glu Ala Gly Arg         515 520 525 Pro Gly Gly Aly Gly Leu Pro Gly Ala Lys Gly Leu Thr Gly Ser Pro     530 535 540 Gly Ser Pro Gly Pro Asp Gly Lys Thr Gly Pro Pro Gly Pro Ala Gly 545 550 555 560 Gln Asp Gly Arg Pro Gly Pro Pro Gly Pro Pro Gly Ala Arg Gly Gln                 565 570 575 Ala Gly Val Met Gly Phe Pro Gly Pro Lys Gly Ala Ala Gly Glu Pro             580 585 590 Gly Lys Ala Gly Glu Arg Gly Val Pro Gly Pro Gly Ala Val Gly         595 600 605 Pro Ala Gly Lys Asp Gly Glu Ala Gly Ala Gln Gly Pro Pro Gly Pro     610 615 620 Ala Gly Pro Ala Gly Glu Arg Gly Glu Gln Gly Pro Ala Gly Ser Pro 625 630 635 640 Gly Phe Gln Gly Leu Pro Gly Pro Ala Gly Pro Pro Gly Glu Ala Gly                 645 650 655 Lys Pro Gly Glu Gly Gly Val Pro Gly Asp Leu Gly Ala Pro Gly Pro             660 665 670 Ser Gly Ala Arg Gly Glu Arg Gly Phe Pro Gly Glu Arg Gly Val Gln         675 680 685 Gly Pro Pro Gly Pro Ala Gly Pro Arg Gly Ala Asn Gly Ala Pro Gly     690 695 700 Asn Asp Gly Ala Lys Gly Asp Ala Gly Ala Pro Gly Ala Pro Gly Ser 705 710 715 720 Gln Gly Ala Pro Gly Leu Gly Gly Met Pro Gly Gly Gly Aly Gly Ala                 725 730 735 Gly Leu Pro Gly Pro Lys Gly Asp Arg Gly Asp Ala Gly Pro Lys Gly             740 745 750 Ala Asp Gly Ser Pro Gly Lys Asp Gly Val Arg Gly Leu Thr Gly Pro         755 760 765 Ile Gly Pro Pro Gly Pro Ala Gly Ala Pro Gly Asp Lys Gly Glu Ser     770 775 780 Gly Pro Ser Gly Pro Ala Gly Pro Thr Gly Ala Arg Gly Ala Pro Gly 785 790 795 800 Asp Arg Gly Glu Pro Gly Pro Pro Gly Pro Ala Gly Phe Ala Gly Pro                 805 810 815 Pro Gly Ala Asp Gly Gln Pro Gly Ala Lys Gly Glu Gly Pro Gly Asp Ala             820 825 830 Gly Ala Lys Gly Asp Ala Gly Pro Pro Gly Pro Ala Gly Pro Ala Gly         835 840 845 Pro Pro Gly Pro Ile Gly Asn Val Gly Ala Pro Gly Ala Lys Gly Ala     850 855 860 Arg Gly Ser Ala Gly Pro Pro Gly Ala Thr Gly Phe Pro Gly Ala Ala 865 870 875 880 Gly Arg Val Gly Pro Pro Gly Pro Ser Gly Asn Ala Gly Pro Pro Gly                 885 890 895 Pro Pro Gly Pro Ala Gly Lys Glu Gly Gly Lys Gly Pro Arg Gly Glu             900 905 910 Thr Gly Pro Ala Gly Arg Pro Gly Glu Val Gly Pro Pro Gly Pro Pro         915 920 925 Gly Pro Ala Gly Gly Lys Gly Ser Pro Gly Ala Asp Gly Pro Ala Gly     930 935 940 Ala Pro Gly Thr Pro Gly Pro Gln Gly Ile Ala Gly Gln Arg Gly Val 945 950 955 960 Val Gly Leu Pro Gly Gln Arg Gly Glu Arg Gly Phe Pro Gly Leu Pro                 965 970 975 Gly Pro Ser Gly Glu Pro Gly Lys Gln Gly Pro Ser Gly Ala Ser Gly             980 985 990 Glu Arg Gly Pro Pro Gly Pro Met Gly Pro Pro Gly Leu Ala Gly Pro         995 1000 1005 Pro Gly Glu Ser Gly Arg Glu Gly Ala Pro Gly Ala Glu Gly Ser Pro    1010 1015 1020 Gly Arg Asp Gly Ser Pro Gly Ala Lys Gly Asp Arg Gly Glu Thr Gly 1025 1030 1035 1040 Pro Ala Gly Pro Pro Gly Ala Pro Gly Ala Pro Gly Ala Pro Gly Pro                1045 1050 1055 Val Gly Pro Ala Gly Lys Ser Gly Asp Arg Gly Glu Thr Gly Pro Ala            1060 1065 1070 Gly Pro Ala Gly Pro Val Gly Pro Val Gly Ala Arg Gly Pro Ala Gly        1075 1080 1085 Pro Gln Gly Pro Arg Gly Asp Lys Gly Glu Thr Gly Glu Gln Gly Asp    1090 1095 1100 Arg Gly Ile Lys Gly His Arg Gly Phe Ser Gly Leu Gln Gly Pro Pro 1105 1110 1115 1120 Gly Pro Pro Gly Ser Ser Gly                1125 1130 1135 Pro Ala Gly Pro Arg Gly Pro Pro Gly Ser Ala Gly Ala Pro Gly Lys            1140 1145 1150 Asp Gly Leu Asn Gly Leu Pro Gly Pro Ile Gly Pro Pro Gly Pro Arg        1155 1160 1165 Gly Arg Thr Gly Asp Ala Gly Pro Val Gly Pro Pro Gly Pro Pro Gly    1170 1175 1180 Pro Pro Gly Pro Pro Gly Pro Pro Ser Ala Gly Phe Asp Phe Ser Phe 1185 1190 1195 1200 Leu Pro Gln Pro Pro Gln Glu Lys Ala His Asp Gly Gly Arg Tyr Tyr                1205 1210 1215 Arg Ala Asp Asp Ala Asn Val Val Arg Asp Arg Asp Leu Glu Val Asp            1220 1225 1230 Thr Thr Leu Lys Ser Leu Ser Gln Gln Ile Glu Asn Ile Arg Ser Pro        1235 1240 1245 Glu Gly Ser Arg Lys Asn Pro Ala Arg Thr Cys Arg Asp Leu Lys Met    1250 1255 1260 Cys His Ser Asp Trp Lys Ser Gly Glu Tyr Trp Ile Asp Pro Asn Gln 1265 1270 1275 1280 Gly Cys Asn Leu Asp Ala Ile Lys Val Phe Cys Asn Met Glu Thr Gly                1285 1290 1295 Glu Thr Cys Val Tyr Pro Thr Gln Pro Ser Val Ala Gln Lys Asn Trp            1300 1305 1310 Tyr Ile Ser Lys Asn Pro Lys Asp Lys Arg His Val Trp Phe Gly Glu        1315 1320 1325 Ser Met Thr Asp Gly Phe Gln Phe Glu Tyr Gly Gly Gln Gly Ser Asp    1330 1335 1340 Pro Ala Asp Val Ala Ile Gln Leu Thr Phe Leu Arg Leu Met Ser Thr 1345 1350 1355 1360 Glu Ala Ser Gln Asn Ile Thr Tyr His Cys Lys Asn Ser Val Ala Tyr                1365 1370 1375 Met Asp Gln Gln Thr Gly Asn Leu Lys Lys Ala Leu Leu Leu Gln Gly            1380 1385 1390 Ser Asn Glu Ile Glu Ile Arg Ala Glu Gly Asn Ser Arg Phe Thr Tyr        1395 1400 1405 Ser Val Thr Val Asp Gly Cys Thr Ser His Thr Gly Ala Trp Gly Lys    1410 1415 1420 Thr Val Ile Glu Tyr Lys Thr Thr Lys Thr Ser Arg Leu Pro Ile Ile 1425 1430 1435 1440 Asp Val Ala Pro Leu Asp Val Gly Ala Pro Asp Gln Glu Phe Gly Phe                1445 1450 1455 Asp Val Gly Pro Val Cys Phe Leu            1460 <210> 12 <211> 5927 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid encoding human collagen type 1 alpha-1 protein <400> 12 tcgtcggagc agacgggagt ttctcctcgg ggtcggagca ggaggcacgc ggagtgtgag 60 gccacgcatg agcggacgct aaccccctcc ccagccacaa agagtctaca tgtctagggt 120 ctagacatgt tcagctttgt ggacctccgg ctcctgctcc tcttagcggc caccgccctc 180 ctgacgcacg gccaagagga aggccaagtc gagggccaag acgaagacat cccaccaatc 240 acctgcgtac agaacggcct caggtaccat gaccgagacg tgtggaaacc cgagccctgc 300 cggatctgcg tctgcgacaa cggcaaggtg ttgtgcgatg acgtgatctg tgacgagacc 360 aagaactgcc ccggcgccga agtccccgag ggcgagtgct gtcccgtctg ccccgacggc 420 tcagagtcac ccaccgacca agaaaccacc ggcgtcgagg gacccaaggg agacactggc 480 ccccgaggcc caaggggacc cgcaggcccc cctggccgag atggcatccc tggacagcct 540 ggacttcccg gaccccccgg accccccgga cctcccggac cccctggcct cggaggaaac 600 tttgctcccc agctgtctta tggctatgat gagaaatcaa ccggaggaat ttccgtgcct 660 ggccccatgg gtccctctgg tcctcgtggt ctccctggcc cccctggtgc acctggtccc 720 caaggcttcc aaggtccccc tggtgagcct ggcgagcctg gagcttcagg tcccatgggt 780 ccccgaggtc ccccaggtcc ccctggaaag aatggagatg atggggaagc tggaaaacct 840 gt; gctggcctcc ctggaatgaa gggacacaga ggtttcagtg gtttggatgg tgccaaggga 960 gatgctggtc ctgctggtcc taagggtgag cctggcagcc ctggtgaaaa tggagctcct 1020 ggtcagatgg gcccccgtgg cctgcctggt gagagaggtc gccctggagc ccctggccct 1080 gctggtgctc gtggaaatga tggtgctact ggtgctgccg ggccccctgg tcccaccggc 1140 cccgctggtc ctcctggctt ccctggtgct gttggtgcta agggtgaagc tggtccccaa 1200 gggccccgag gctctgaagg tccccagggt gtgcgtggtg agcctggccc ccctggccct 1260 gctggtgctg ctggccctgc tggaaaccct ggtgctgatg gacagcctgg tgctaaaggt 1320 gccaatggtg ctcctggtat tgctggtgct cctggcttcc ctggtgcccg aggcccctct 1380 ggaccccagg gccccggcgg ccctcctggt cccaagggta acagcggtga acctggtgct 1440 cctggcagca aaggagacac tggtgctaag ggagagcctg gccctgttgg tgttcaagga 1500 ccccctggcc ctgctggaga ggaaggaaag cgaggagctc gaggtgaacc cggacccact 1560 ggcctgcccg gaccccctgg cgagcgtggt ggacctggta gccgtggttt ccctggcgca 1620 gatggtgttg ctggtcccaa gggtcccgct ggtgaacgtg gttctcctgg ccctgctggc 1680 cccaaaggat ctcctggtga agctggtcgt cccggtgaag ctggtctgcc tggtgccaag 1740 ggtctgactg gaagccctgg cagccctggt cctgatggca aaactggccc ccctggtccc 1800 gccggtcaag atggtcgccc cggaccccca ggcccacctg gtgcccgtgg tcaggctggt 1860 gtgatgggat tccctggacc taaaggtgct gctggagagc ccggcaaggc tggagagcga 1920 ggtgttcccg gaccccctgg cgctgtcggt cctgctggca aagatggaga ggctggagct 1980 cagggacccc ctggccctgc tggtcccgct ggcgagagag gtgaacaagg ccctgctggc 2040 tcccccggat tccagggtct ccctggtcct gctggtcctc caggtgaagc aggcaaacct 2100 gt; agaggtttcc ctggcgagcg tggtgtgcaa ggtccccctg gtcctgctgg tccccgaggg 2220 gccaacggtg ctcccggcaa cgatggtgct aagggtgatg ctggtgcccc tggagctccc 2280 ggtagccagg gcgcccctgg ccttcaggga atgcctggtg aacgtggtgc agctggtctt 2340 ccagggccta agggtgacag aggtgatgct ggtcccaaag gtgctgatgg ctctcctggc 2400 aaagatggcg tccgtggtct gactggcccc attggtcctc ctggccctgc tggtgcccct 2460 ggtgacaagg gtgaaagtgg tcccagcggc cctgctggtc ccactggagc tcgtggtgcc 2520 cccggagacc gtggtgagcc tggtcccccc ggccctgctg gctttgctgg cccccctggt 2580 gctgacggcc aacctggtgc taaaggcgaa cctggtgatg ctggtgctaa aggcgatgct 2640 ggtccccctg gccctgccgg acccgctgga ccccctggcc ccattggtaa tgttggtgct 2700 cctggagcca aaggtgctcg cggcagcgct ggtccccctg gtgctactgg tttccctggt 2760 gctgctggcc gagtcggtcc tcctggcccc tctggaaatg ctggaccccc tggccctcct 2820 ggtcctgctg gcaaagaagg cggcaaaggt ccccgtggtg agactggccc tgctggacgt 2880 cctggtgaag ttggtccccc tggtccccct ggccctgctg gcgagaaagg atcccctggt 2940 gctgatggtc ctgctggtgc tcctggtact cccgggcctc aaggtattgc tggacagcgt 3000 ggtgtggtcg gcctgcctgg tcagagagga gagagaggct tccctggtct tcctggcccc 3060 tctggtgaac ctggcaaaca aggtccctct ggagcaagtg gtgaacgtgg tccccctggt 3120 cccatgggcc cccctggatt ggctggaccc cctggtgaat ctggacgtga gggggctcct 3180 ggtgccgaag gttcccctgg acgagacggt tctcctggcg ccaagggtga ccgtggtgag 3240 accggccccg ctggaccccc tggtgctcct ggtgctcctg gtgcccctgg ccccgttggc 3300 cctgctggca agagtggtga tcgtggtgag actggtcctg ctggtcccgc cggtcctgtc 3360 ggccctgttg gcgcccgtgg ccccgccgga ccccaaggcc cccgtggtga caagggtgag 3420 acaggcgaac agggcgacag aggcataaag ggtcaccgtg gcttctctgg cctccagggt 3480 ccccctggcc ctcctggctc tcctggtgaa caaggtccct ctggagcctc tggtcctgct 3540 ggtccccgag gtccccctgg ctctgctggt gctcctggca aagatggact caacggtctc 3600 cctggcccca ttgggccccc tggtcctcgc ggtcgcactg gtgatgctgg tcctgttggt 3660 ccccccggcc ctcctggacc tcctggtccc cctggtcctc ccagcgctgg tttcgacttc 3720 agcttcctgc cccagccacc tcaagagaag gctcacgatg gtggccgcta ctaccgggct 3780 gatgatgcca atgtggttcg tgaccgtgac ctcgaggtgg acaccaccct caagagcctg 3840 agccagcaga tcgagaacat ccggagccca gagggcagcc gcaagaaccc cgcccgcacc 3900 tgccgtgacc tcaagatgtg ccactctgac tggaagagtg gagagtactg gattgacccc 3960 aaccaaggct gcaacctgga tgccatcaaa gtcttctgca acatggagac tggtgagacc 4020 tgcgtgtacc ccactcagcc cagtgtggcc cagaagaact ggtacatcag caagaacccc 4080 aaggacaaga ggcatgtctg gttcggcgag agcatgaccg atggattcca gttcgagtat 4140 ggcggccagg gctccgaccc tgccgatgtg gccatccagc tgaccttcct gcgcctgatg 4200 tccaccgagg cctcccagaa catcacctac cactgcaaga acagcgtggc ctacatggac 4260 cagcagactg gcaacctcaa gaaggccctg ctcctccagg gctccaacga gatcgagatc 4320 cgcgccgagg gcaacagccg cttcacctac agcgtcactg tcgatggctg cacgagtcac 4380 accggagcct ggggcaagac agtgattgaa tacaaaacca ccaagacctc ccgcctgccc 4440 atcatcgatg tggccccctt ggacgttggt gccccagacc aggaattcgg cttcgacgtt 4500 ggccctgtct gcttcctgta aactccctcc atcccaacct ggctccctcc cacccaacca 4560 actttccccc caacccggaa acagacaagc aacccaaact gaaccccctc aaaagccaaa 4620 aaatgggaga caatttcaca tggactttgg aaaatatttt tttcctttgc attcatctct 4680 caaacttagt ttttatcttt gaccaaccga acatgaccaa aaaccaaaag tgcattcaac 4740 cttaccaaaa aaaaaaaaaa aaaaagaata aataaataac tttttaaaaa aggaagcttg 4800 gtccacttgc ttgaagaccc atgcgggggt aagtcccttt ctgcccgttg ggcttatgaa 4860 accccaatgc tgccctttct gctcctttct ccacaccccc cttggggcct cccctccact 4920 ccttcccaaa tctgtctccc cagaagacac aggaaacaat gtattgtctg cccagcaatc 4980 aaaggcaatg ctcaaacacc caagtggccc ccaccctcag cccgctcctg cccgcccagc 5040 acccccaggc cctgggggac ctggggttct cagactgcca aagaagcctt gccatctggc 5100 gctcccatgg ctcttgcaac atctcccctt cgtttttgag ggggtcatgc cgggggagcc 5160 accagcccct cactgggttc ggaggagagt caggaagggc cacgacaaag cagaaacatc 5220 ggatttgggg aacgcgtgtc aatcccttgt gccgcagggc tgggcgggag agactgttct 5280 gttccttgtg taactgtgtt gctgaaagac tacctcgttc ttgtcttgat gtgtcaccgg 5340 ggcaactgcc tgggggcggg gatgggggca gggtggaagc ggctccccat tttataccaa 5400 aggtgctaca tctatgtgat gggtggggtg gggagggaat cactggtgct atagaaattg 5460 agatgccccc ccaggccagc aaatgttcct ttttgttcaa agtctatttt tattccttga 5520 tatttttctt tttttttttt tttttttgtg gatggggact tgtgaatttt tctaaaggtg 5580 ctatttaaca tgggaggaga gcgtgtgcgg ctccagccca gcccgctgct cactttccac 5640 cctctctcca cctgcctctg gcttctcagg cctctgctct ccgacctctc tcctctgaaa 5700 ccctcctcca cagctgcagc ccatcctccc ggctccctcc tagtctgtcc tgcgtcctct 5760 gtccccgggt ttcagagaca acttcccaaa gcacaaagca gtttttcccc ctaggggtgg 5820 gaggaagcaa aagactctgt acctattttg tatgtgtata ataatttgag atgtttttaa 5880 ttattttgat tgctggaata aagcatgtgg aaatgaccca aacataa 5927 <210> 13 <211> 1453 <212> PRT <213> Artificial Sequence <220> <223> Mouse collagen type 1 alpha-1 protein <400> 13 Met Phe Ser Phe Val Asp Leu Arg Leu Leu Leu Leu Leu Gly Ala Thr   1 5 10 15 Ala Leu Leu Thr His Gly Gln Glu Asp Ile Pro Glu Val Ser Cys Ile              20 25 30 His Asn Gly Leu Arg Val Pro Asn Gly Glu Thr Trp Lys Pro Glu Val          35 40 45 Cys Leu Ile Cys Ile Cys His Asn Gly Thr Ala Val Cys Asp Asp Val      50 55 60 Gln Cys Asn Glu Glu Leu Asp Cys Pro Asn Pro Gln Arg Arg Glu Gly  65 70 75 80 Glu Cys Cys Ala Phe Cys Pro Glu Glu Tyr Val Ser Pro Asn Ser Glu                  85 90 95 Asp Val Gly Val Glu Gly Pro Lys Gly Asp Pro Gly Pro Gln Gly Pro             100 105 110 Arg Gly Pro Gly Pro Pro Gly Arg Asp Gly Ile Pro Gly Gln Pro         115 120 125 Gly Leu Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly     130 135 140 Leu Gly Gly Asn Phe Ala Ser Gln Met Ser Tyr Gly Tyr Asp Glu Lys 145 150 155 160 Ser Ala Gly Val Ser Val Pro Gly Pro Met Gly Pro Ser Gly Pro Arg                 165 170 175 Gly Leu Pro Gly Pro Pro Gly Ala Pro Gly Pro Gly Gly Phe Gln Gly             180 185 190 Pro Pro Gly Gly Pro Gly Gly Pro Gly Gly Ser Gly Pro Met Gly Pro         195 200 205 Arg Gly Pro Pro Gly Pro Pro Gly Lys Asn Gly Asp Asp Gly Glu Ala     210 215 220 Gly Lys Pro Gly Arg Pro Gly Glu Arg Gly Pro Pro Gly Pro Gln Gly 225 230 235 240 Ala Arg Gly Leu Pro Gly Thr Ala Gly Leu Pro Gly Met Lys Gly His                 245 250 255 Arg Gly Phe Ser Gly Leu Asp Gly Ala Lys Gly Asp Ala Gly Pro Ala             260 265 270 Gly Pro Lys Gly Gly Pro Gly Ser Pro Gly Gly Asn Gly Ala Pro Gly         275 280 285 Gln Met Gly Pro Arg Gly Leu Pro Gly Glu Arg Gly Arg Pro Gly Pro     290 295 300 Pro Gly Thr Ala Gly Ala Arg Gly Asn Asp Gly Ala Val Gly Ala Ala 305 310 315 320 Gly Pro Pro Gly Pro Thr Gly Pro Thr Gly Pro Pro Gly Phe Pro Gly                 325 330 335 Ala Val Gly Ala Lys Gly Aly Gly Aly Gly Aly Gly Aly Arg Gly Ser             340 345 350 Glu Gly Pro Gln Gly Val Arg Gly Glu Pro Gly Pro Pro Gly Pro Ala         355 360 365 Gly Ala Ala Gly Pro Ala Gly Asn Pro Gly Ala Asp Gly     370 375 380 Ala Lys Gly Ala Asn Gly Ala Pro Gly Ile Ala Gly Ala Pro Gly Phe 385 390 395 400 Pro Gly Ala Arg Gly Pro Ser Gly Pro Gln Gly Pro Ser Gly Pro Pro                 405 410 415 Gly Pro Lys Gly Asn Ser Gly Glu Pro Gly Ala Pro Gly Asn Lys Gly             420 425 430 Asp Thr Gly Ala Lys Gly Glu Pro Gly Ala Thr Gly Val Gln Gly Pro         435 440 445 Pro Gly Pro Ala Gly Glu Glu Gly Lys Arg Gly Ala Arg Gly Glu Pro     450 455 460 Gly Pro Ser Gly Leu Pro Gly Pro Pro Gly Gly Arg Gly Gly Pro Gly 465 470 475 480 Ser Arg Gly Phe Pro Gly Ala Asp Gly Val Ala Gly Pro Lys Gly Pro                 485 490 495 Ser Gly Glu Arg Gly Ala Pro Gly Pro Ala Gly Pro Lys Gly Ser Pro             500 505 510 Gly Glu Ala Gly Arg Pro Gly Gly Ala Gly Leu Pro Gly Ala Lys Gly         515 520 525 Leu Thr Gly Ser Pro Gly Ser Pro Gly Pro Asp Gly Lys Thr Gly Pro     530 535 540 Pro Gly Pro Ala Gly Gln Asp Gly Arg Pro Gly Pro Ala Gly Pro Pro 545 550 555 560 Gly Ala Arg Gly Gln Ala Gly Val Met Gly Phe Pro Gly Pro Lys Gly                 565 570 575 Thr Ala Gly Glu Pro Gly Lys Ala Gly Glu Arg Gly Leu Pro Gly Pro             580 585 590 Pro Gly Ala Val Gly Pro Ala Gly Lys Asp Gly Gly Ala Gly Ala Gln         595 600 605 Gly Ala Pro Gly Pro Ala Gly Pro Ala Gly Glu Arg Gly Glu Gln Gly     610 615 620 Pro Ala Gly Ser Pro Gly Phe Gln Gly Leu Pro Gly Pro Ala Gly Pro 625 630 635 640 Pro Gly Glu Ala Gly Lys Pro Gly Glu Gln Gly Val Pro Gly Asp Leu                 645 650 655 Gly Ala Pro Gly Pro Ser Gly Ala Arg Gly Glu Arg Gly Phe Pro Gly             660 665 670 Glu Arg Gly Val Gln Gly Pro Pro Gly Pro Ala Gly Pro Arg Gly Asn         675 680 685 Asn Gly Ala Pro Gly Asn Asp Gly Ala Lys Gly Asp Thr Gly Ala Pro     690 695 700 Gly Ala Pro Gly Ser Gln Gly Ala Pro Gly Leu Gln Gly Met Pro Gly 705 710 715 720 Glu Arg Gly Ala Gly Leu Pro Gly Pro Lys Gly Asp Arg Gly Asp                 725 730 735 Ala Gly Pro Lys Gly Ala Asp Gly Ser Pro Gly Lys Asp Gly Ala Arg             740 745 750 Gly Leu Thr Gly Pro Gly Aly Gly Pro Gly Aly Gly Ala Pro Gly         755 760 765 Asp Lys Gly Glu Ala Gly Pro Ser Gly Pro Pro Gly Pro Thr Gly Ala     770 775 780 Arg Gly Ala Pro Gly Asp Arg Gly Glu Ala Gly Pro Pro Gly Pro Ala 785 790 795 800 Gly Phe Ala Gly Pro Pro Gly Ala Asp Gly Gln Pro Gly Ala Lys Gly                 805 810 815 Glu Pro Gly Asp Thr Gly Val Lys Gly Asp Ala Gly Pro Pro Gly Pro             820 825 830 Ala Gly Pro Ala Gly Pro Gly Aly Pro         835 840 845 Gly Pro Lys Gly Pro Arg Gly Ala Ala Gly Pro Pro Gly Ala Thr Gly     850 855 860 Phe Pro Gly Ala Ala Gly Arg Val Gly Pro Pro Gly Pro Ser Gly Asn 865 870 875 880 Ala Gly Pro Pro Gly Pro Pro Gly Pro Val Gly Lys Gly Gly Gly Lys                 885 890 895 Gly Pro Arg Gly Glu Thr Gly Pro Ala Gly Arg Pro Gly Glu Val Gly             900 905 910 Pro Pro Gly Pro Pro Gly Pro Ala Gly Glu Lys Gly Ser Pro Gly Ala         915 920 925 Asp Gly Pro Ala Gly Ser Pro Gly Thr Pro Gly Pro Gln Gly Ile Ala     930 935 940 Gly Gln Arg Gly Val Val Gly Leu Pro Gly Gln Arg Gly Glu Arg Gly 945 950 955 960 Phe Pro Gly Leu Pro Gly Pro Ser Gly Glu Pro Gly Lys Gln Gly Pro                 965 970 975 Ser Gly Ser Ser Gly Glu Arg Gly Pro Pro Gly Pro Met Gly Pro Pro             980 985 990 Gly Leu Ala Gly Pro Pro Gly Glu Ser Gly Arg Gly Gly Ser Pro Gly         995 1000 1005 Ala Glu Gly Ser Pro Gly Arg Asp Gly Ala Pro Gly Ala Lys Gly Asp    1010 1015 1020 Arg Gly Glu Thr Gly Pro Ala Gly Pro Pro Gly Ala Pro Gly Ala Pro 1025 1030 1035 1040 Gly Ala Pro Gly Pro Val Gly Pro Ala Gly Lys Asn Gly Asp Arg Gly                1045 1050 1055 Glu Thr Gly Pro Ala Gly Ala Gly Ala Gly Ala            1060 1065 1070 Arg Gly Pro Ala Gly Pro Gln Gly Pro Arg Gly Asp Lys Gly Glu Thr        1075 1080 1085 Gly Glu Gln Gly Asp Arg Gly Ile Lys Gly His Arg Gly Phe Ser Gly    1090 1095 1100 Leu Gln Gly Pro Pro Gly Ser Pro Gly Ser Pro Gly Glu Gln Gly Pro 1105 1110 1115 1120 Ser Gly Ala Ser Gly Pro Ala Gly Pro Arg Gly Pro Pro Gly Ser Ala                1125 1130 1135 Gly Ser Pro Gly Lys Asp Gly Leu Asn Gly Leu Pro Gly Pro Ile Gly            1140 1145 1150 Pro Pro Gly Pro Arg Gly Arg Thr Gly Asp Ser Gly Pro Ala Gly Pro        1155 1160 1165 Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Ser Gly Gly    1170 1175 1180 Tyr Asp Phe Ser Phe Leu Pro Gln Pro Pro Gln Glu Lys Ser Gln Asp 1185 1190 1195 1200 Gly Gly Arg Tyr Tyr Arg Ala Asp Asp Ala Asn Val Val Arg Asp Arg                1205 1210 1215 Asp Leu Glu Val Asp Thr Thr Leu Lys Ser Leu Ser Gln Gln Ile Glu            1220 1225 1230 Asn Ile Arg Ser Pro Glu Gly Ser Arg Lys Asn Pro Ala Arg Thr Cys        1235 1240 1245 Arg Asp Leu Lys Met Cys His Ser Asp Trp Lys Ser Gly Glu Tyr Trp    1250 1255 1260 Ile Asp Pro Asn Gln Gly Cys Asn Leu Asp Ala Ile Lys Val Tyr Cys 1265 1270 1275 1280 Asn Met Glu Thr Gly Gln Thr Cys Val Phe Pro Thr Gln Pro Ser Val                1285 1290 1295 Pro Gln Lys Asn Trp Tyr Ile Ser Pro Asn Pro Lys Glu Lys Lys His            1300 1305 1310 Val Trp Phe Gly Glu Ser Met Thr Asp Gly Phe Pro Phe Glu Tyr Gly        1315 1320 1325 Ser Glu Gly Ser Asp Pro Ala Asp Val Ala Ile Gln Leu Thr Phe Leu    1330 1335 1340 Arg Leu Met Ser Thr Glu Ala Ser Gln Asn Ile Thr Tyr His Cys Lys 1345 1350 1355 1360 Asn Ser Val Ala Tyr Met Asp Gln Gln Thr Gly Asn Leu Lys Lys Ala                1365 1370 1375 Leu Leu Leu Glu Gly Ser Asn Glu Ile Glu Leu Arg Gly Glu Gly Asn            1380 1385 1390 Ser Arg Phe Thr Tyr Ser Thr Leu Val Asp Gly Cys Thr Ser His Thr        1395 1400 1405 Gly Thr Trp Gly Lys Thr Val Ile Glu Tyr Lys Thr Thr Lys Thr Ser    1410 1415 1420 Arg Leu Pro Ile Ile Asp Val Ala Pro Leu Asp Ile Gly Ala Pro Asp 1425 1430 1435 1440 Gln Glu Phe Gly Leu Asp Ile Gly Pro Ala Cys Phe Val                1445 1450 <210> 14 <211> 4709 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid encoding mouse collagen type 1 alpha-1 protein <400> 14 ctcgggacgg agcaggaggc acgcggagtg aggccacgca tgagccgaag ctaacccccc 60 accccagccg caaagagtct acatgtctag ggtctagaca tgttcagctt tgtggacctc 120 cggctcctgc tcctcttagg ggccactgcc ctcctgacgc atggccaaga agacatccct 180 gaagtcagct gcatacacaa tggcctaagg gtccccaatg gtgagacgtg gaaacccgag 240 gtatgcttga tctgtatctg ccacaatggc acggctgtgt gcgatgacgt gcaatgcaat 300 gaagaactgg actgtcccaa cccccaaaga cgggagggcg agtgctgtgc tttctgcccg 360 gaagaatacg tatcaccaaa ctcagaagat gtaggagtcg agggacccaa gggagaccct 420 ggcccccaag gcccaagggg acccgttggc ccccctggac gagatggcat ccctggacag 480 cctggacttc ctggtcctcc tggtccccct gggccccccg gaccccctgg ccttggagga 540 aactttgctt cccagatgtc ctatggctat gatgaaaaat cagctggagt ttccgtgcct 600 gt; caaggtttcc aaggcccccc tggtgaacct ggcgagcctg gcggttcagg tccaatgggt 720 ccccgaggtc cccctggccc tcctggcaag aatggagatg atggggaagc tggcaagccc 780 ggccgtcctg gtgagcgtgg acctcctgga cctcagggtg ctcgtggatt gcctggaaca 840 gctggcctcc ctggaatgaa gggacaccga ggcttcagtg gtttggatgg tgccaaagga 900 gatgctggtc ctgctggtcc taagggagag cccggcagtc ctggtgaaaa cggagctcct 960 ggccagatgg gtccccgagg tctgcccggt gagagaggtc gccctggacc tcctggcact 1020 gctggtgctc gcggtaacga tggtgctgtt ggtgctgctg gaccccctgg tcccaccggc 1080 cccactggcc ctcctggctt ccctggtgca gttggtgcta agggtgaagc tggtccccaa 1140 ggagctagag gctctgaagg tccccagggt gtgcgtggtg agcccggacc ccctggccct 1200 gctggtgctg ccggccctgc tggaaaccct ggtgctgatg gacaacctgg cgctaaaggt 1260 gccaatggtg ctcctggtat tgctggtgct cctggcttcc ctggtgcccg aggcccctct 1320 ggaccccagg gccccagcgg ccctccaggt cccaagggta acagtggtga acctggtgct 1380 cctggcaaca aaggagacac tggtgccaaa ggagaacccg gtgctactgg agttcaaggt 1440 cccccaggcc ctgccggaga agaaggaaaa cgaggagccc gtggtgagcc tggaccttcc 1500 ggactgcctg gacctcctgg cgagcgtggt ggacctggta gccgtggttt ccctggtgct 1560 gatggtgttg ctggccccaa gggtccttcc ggtgaacgtg gtgctcccgg acctgctggt 1620 cccaaaggtt ctcctggtga agctggtcgc cccggtgaag ctggtctccc tggtgccaag 1680 ggtctcactg gcagtcctgg cagccctggt cctgatggca aaaccggccc ccctggtccc 1740 gctggtcaag atggtcgccc tggacccgca ggtcctcctg gagcccgtgg ccaggctggt 1800 gtgatgggat tccctggacc taagggtacc gctggagaac ctggaaaggc tggagagcga 1860 ggccttcccg gaccccctgg cgctgttggt cctgctggca aagatggaga agctggagct 1920 cagggagccc ctggccctgc tggtcctgct ggtgagagag gtgaacaagg tcccgctggc 1980 tcccctggat tccagggtct tcctggtcct gccggtcctc ctggtgaagc aggcaagcct 2040 gt; agaggtttcc ctggtgaacg tggtgtacaa ggtcccccag gtcctgctgg tccccgagga 2160 aacaatggtg cccccggcaa cgatggtgcc aagggtgata ctggtgcccc cggagctccc 2220 ggtagccagg gtgcccccgg tcttcaggga atgcctggtg aacgtggtgc agctggtctt 2280 ccaggtccta agggtgacag aggtgatgct ggtcccaaag gtgctgatgg ttctcctggt 2340 aaagatggtg cccgtggtct gactggtccc attggtcctc ctggccctgc tggtgcccct 2400 ggtgacaagg gtgaagctgg tcccagtggt cctcccggtc ccaccggagc ccgtggtgct 2460 cccggagacc gtggtgaggc tggtccccct ggtcctgctg gctttgccgg cccccctggt 2520 gctgatggcc aacctggtgc gaaaggtgaa cctggtgata ctggtgttaa aggtgatgct 2580 ggtcctcctg gccctgctgg tcctgctgga ccccccggcc ccattggtaa cgttggtgct 2640 cctggaccca aaggtcctcg tggtgctgct ggtccccctg gtgctactgg cttccctggt 2700 gt; ggtcccgttg gcaaagaagg gggcaaaggt ccccgtggtg agactggccc tgctggacgt 2820 cctggtgaag ttggtccccc aggtcccccc ggtcctgctg gtgagaaagg atctcctggt 2880 gctgatggac ctgctggctc tcctggtacc cctggacctc agggtattgc tggacaacgt 2940 ggtgtggtcg gtcttcccgg tcagagagga gaaagaggct tccctggtct tcctggcccc 3000 tctggtgaac ctggcaaaca aggtccttct ggatcaagtg gtgaacgcgg tccccctggc 3060 cccatggggc cccctggatt ggctggtccc cctggtgaat ctggacgtga gggatcccct 3120 ggtgctgaag gctcccctgg aagggatggt gctcccgggg ccaagggtga ccgtggtgag 3180 actggccccg ctggcccccc tggtgcccct ggtgctcccg gtgctcccgg ccctgttggt 3240 cccgctggca agaatggcga tcgtggtgag actggtcctg ctggtcctgc tggtcccatt 3300 ggccctgctg gtgcccgtgg ccctgctgga ccccaaggcc cccgtggtga caagggtgag 3360 acaggcgaac aaggtgacag aggcataaag ggtcatcgtg gcttctctgg tctccagggt 3420 cctcctggtt ctcctggttc tcctggtgaa caaggcccct ctggagcttc aggtcctgca 3480 ggcccccggg gtccccctgg ctctgctggt tctcctggca aagacggact caacggtctc 3540 cctggcccca ttggtccccc tggtcctcga ggtcgcactg gtgacagcgg ccctgctggt 3600 ccccccggcc ctcctggacc ccctggccct cctggacctc ccagtggcgg ttatgacttc 3660 agcttcctgc ctcagccacc tcaagagaag tctcaagatg gtggccgcta ctaccgggcc 3720 gatgatgcta acgtggttcg tgaccgtgac cttgaggtgg acaccaccct caagagcctg 3780 agtcagcaga ttgagaacat ccgcagcccc gaaggcagcc gcaagaaccc tgcccgcaca 3840 tgccgcgacc tcaagatgtg ccactctgac tggaagagcg gagagtactg gatcgaccct 3900 aaccaaggct gcaacctgga cgccatcaag gtctactgca acatggagac aggtcagacc 3960 tgtgtgttcc ctactcagcc gtctgtgcct cagaagaact ggtacatcag cccgaacccc 4020 aaggaaaaga agcacgtctg gtttggagag agcatgaccg atggattccc gttcgagtac 4080 ggaagcgagg gctccgaccc cgccgatgtc gctatccagc tgaccttcct gcgcctaatg 4140 tccaccgagg cctcccagaa catcacctat cactgcaaga acagcgtagc ctacatggac 4200 cagcagactg gcaacctcaa gaaggccctg ctcctccagg gatccaacga gatcgagctc 4260 agaggcgaag gcaacagtcg cttcacctac agcacccttg tggacggctg cacgagtcac 4320 accggaactt ggggcaagac agtcatcgaa tacaaaacca ccaagacctc ccgcctgccc 4380 atcatcgatg tggctccctt ggacattggt gccccagacc aggaattcgg actagacatt 4440 ggccctgcct gcttcgtgta aactccctcc accccaatct ggttccctcc cacccagccc 4500 acttttcccc aaccctggaa acagacgaac aacccaaact caatttcccc caaaagccaa 4560 aaatatggga gataatttca catggacttt ggaaaacatt ttttttcctt tgcattcacc 4620 tttcaaactt agtttttacc tttgaccaac tgaacgtgac caaaaaccaa aagtgcattc 4680 aaccttacca aaaaagaaaa aaaaaaaaa 4709 <210> 15 <211> 2871 <212> PRT <213> Artificial Sequence <220> <223> Human Fibrillin 1 protein <400> 15 Met Arg Arg Gly Arg Leu Leu Glu Ile Ala Leu Gly Phe Thr Val Leu   1 5 10 15 Leu Ala Ser Tyr Thr Ser Gly Ala Asp Ala Asn Leu Glu Ala Gly              20 25 30 Asn Val Lys Glu Thr Arg Ala Ser Arg Ala Lys Arg Arg Gly Gly Gly          35 40 45 Gly His Asp Ala Leu Lys Gly Pro Asn Val Cys Gly Ser Arg Tyr Asn      50 55 60 Ala Tyr Cys Cys Pro Gly Trp Lys Thr Leu Pro Gly Gly Asn Gln Cys  65 70 75 80 Ile Val Pro Ile Cys Arg His Ser Cys Gly Asp Gly Phe Cys Ser Arg                  85 90 95 Pro Asn Met Cys Thr Cys Pro Ser Gly Gln Ile Ala Pro Ser Cys Gly             100 105 110 Ser Arg Ser Ser Gln His Cys Asn Ile Arg Cys Met Asn Gly Gly Ser         115 120 125 Cys Ser Asp Asp His Cys Leu Cys Gln Lys Gly Tyr Ile Gly Thr His     130 135 140 Cys Gly Gln Pro Val Cys Glu Ser Gly Cys Leu Asn Gly Gly Arg Cys 145 150 155 160 Val Ala Pro Asn Arg Cys Ala Cys Thr Tyr Gly Phe Thr Gly Pro Gln                 165 170 175 Cys Glu Arg Asp Tyr Arg Thr Gly Pro Cys Phe Thr Val Ser Ser Asn             180 185 190 Gln Met Cys Gln Gly Gln Leu Ser Gly Ile Val Cys Thr Lys Thr Leu         195 200 205 Cys Cys Ala Thr Val Gly Arg Ala Trp Gly His Pro Cys Glu Met Cys     210 215 220 Pro Ala Gln Pro His Pro Cys Arg Arg Gly Phe Ile Pro Asn Ile Arg 225 230 235 240 Thr Gly Ala Cys Gln Asp Val Asp Glu Cys Gln Ala Ile Pro Gly Leu                 245 250 255 Cys Gln Gly Gly Asn Cys Ile Asn Thr Val Gly Ser Phe Glu Cys Lys             260 265 270 Cys Pro Ala Gly His Lys Leu Asn Glu Val Ser Gln Lys Cys Glu Asp         275 280 285 Ile Asp Glu Cys Ser Thr Ile Pro Gly Ile Cys Glu Gly Gly Glu Cys     290 295 300 Thr Asn Thr Val Ser Ser Tyr Phe Cys Lys Cys Pro Pro Gly Phe Tyr 305 310 315 320 Thr Ser Pro Asp Gly Thr Arg Cys Ile Asp Val Arg Pro Gly Tyr Cys                 325 330 335 Tyr Thr Ala Leu Thr Asn Gly Arg Cys Ser Asn Gln Leu Pro Gln Ser             340 345 350 Ile Thr Lys Met Gln Cys Cys Cys Asp Ala Gly Arg Cys Trp Ser Pro         355 360 365 Gly Val Thr Val Ala Pro Glu Met Cys Pro Ile Arg Ala Thr Glu Asp     370 375 380 Phe Asn Lys Leu Cys Ser Val Pro Met Val Ile Pro Gly Arg Pro Glu 385 390 395 400 Tyr Pro Pro Pro Leu Gly Pro Ile Pro Pro Val Leu Pro Val Pro                 405 410 415 Pro Gly Phe Pro Pro Gly Pro Gln Ile Pro Val Pro Arg Pro Pro Val             420 425 430 Glu Tyr Leu Tyr Pro Ser Arg Glu Pro Pro Arg Val Leu Pro Val Asn         435 440 445 Val Thr Asp Tyr Cys Gln Leu Val Arg Tyr Leu Cys Gln Asn Gly Arg     450 455 460 Cys Ile Pro Thr Pro Gly Ser Tyr Arg Cys Glu Cys Asn Lys Gly Phe 465 470 475 480 Gln Leu Asp Leu Arg Gly Glu Cys Ile Asp Val Asp Glu Cys Glu Lys                 485 490 495 Asn Pro Cys Ala Gly Gly Glu Cys Ile Asn Asn Gln Gly Ser Tyr Thr             500 505 510 Cys Gln Cys Arg Ala Gly Tyr Gln Ser Thr Leu Thr Arg Thr Glu Cys         515 520 525 Arg Asp Ile Asp Glu Cys Leu Gln Asn Gly Arg Ile Cys Asn Asn Gly     530 535 540 Arg Cys Ile Asn Thr Asp Gly Ser Phe His Cys Val Cys Asn Ala Gly 545 550 555 560 Phe His Val Thr Arg Asp Gly Lys Asn Cys Glu Asp Met Asp Glu Cys                 565 570 575 Ser Ile Arg Asn Met Cys Leu Asn Gly Met Cys Ile Asn Glu Asp Gly             580 585 590 Ser Phe Lys Cys Ile Cys Lys Pro Gly Phe Gln Leu Ala Ser Asp Gly         595 600 605 Arg Tyr Cys Lys Asp Ile Asn Glu Cys Glu Thr Pro Gly Ile Cys Met     610 615 620 Asn Gly Arg Cys Val Asn Thr Asp Gly Ser Tyr Arg Cys Glu Cys Phe 625 630 635 640 Pro Gly Leu Ala Val Gly Leu Asp Gly Arg Val Cys Val Asp Thr His                 645 650 655 Met Arg Ser Thr Cys Tyr Gly Gly Tyr Lys Arg Gly Gln Cys Ile Lys             660 665 670 Pro Leu Phe Gly Ala Val Thr Lys Ser Glu Cys Cys Cys Ala Ser Thr         675 680 685 Glu Tyr Ala Phe Gly Glu Pro Cys Gln Pro Cys Pro Ala Gln Asn Ser     690 695 700 Ala Glu Tyr Gln Ala Leu Cys Ser Ser Gly Pro Gly Met Thr Ser Ala 705 710 715 720 Gly Ser Asp Ile Asn Glu Cys Ala Leu Asp Pro Asp Ile Cys Pro Asn                 725 730 735 Gly Ile Cys Glu Asn Leu Arg Gly Thr Tyr Lys Cys Ile Cys Asn Ser             740 745 750 Gly Tyr Glu Val Asp Ser Thr Gly Lys Asn Cys Val Asp Ile Asn Glu         755 760 765 Cys Val Leu Asn Ser Leu Leu Cys Asp Asn Gly Gln Cys Arg Asn Thr     770 775 780 Pro Gly Ser Phe Val Cys Thr Cys Pro Lys Gly Phe Ile Tyr Lys Pro 785 790 795 800 Asp Leu Lys Thr Cys Glu Asp Ile Asp Glu Cys Glu Ser Ser Pro Cys                 805 810 815 Ile Asn Gly Val Cys Lys Asn Ser Pro Gly Ser Phe Ile Cys Glu Cys             820 825 830 Ser Ser Glu Ser Thr Leu Asp Pro Thr Lys Thr Ile Cys Ile Glu Thr         835 840 845 Ile Lys Gly Thr Cys Trp Gln Thr Val Ile Asp Gly Arg Cys Glu Ile     850 855 860 Asn Ile Asn Gly Ala Thr Leu Lys Ser Gln Cys Cys Ser Ser Leu Gly 865 870 875 880 Ala Ala Trp Gly Ser Pro Cys Thr Leu Cys Gln Val Asp Pro Ile Cys                 885 890 895 Gly Lys Gly Tyr Ser Arg Ile Lys Gly Thr Gln Cys Glu Asp Ile Asp             900 905 910 Glu Cys Glu Val Phe Pro Gly Val Cys Lys Asn Gly Leu Cys Val Asn         915 920 925 Thr Arg Gly Ser Phe Lys Cys Gln Cys Pro Ser Gly Met Thr Leu Asp     930 935 940 Ala Thr Gly Arg Ile Cys Leu Asp Ile Arg Leu Glu Thr Cys Phe Leu 945 950 955 960 Arg Tyr Glu Asp Glu Glu Cys Thr Leu Pro Ile Ala Gly Arg His Arg                 965 970 975 Met Asp Ala Cys Cys Cys Ser Val Gly Ala Ala Trp Gly Thr Glu Glu             980 985 990 Cys Glu Glu Cys Pro Met Arg Asn Thr Pro Glu Tyr Glu Glu Leu Cys         995 1000 1005 Pro Arg Gly Pro Gly Phe Ala Thr Lys Glu Ile Thr Asn Gly Lys Pro    1010 1015 1020 Phe Phe Lys Asp Ile Asn Glu Cys Lys Met Ile Pro Ser Leu Cys Thr 1025 1030 1035 1040 His Gly Lys Cys Arg Asn Thr Ile Gly Ser Phe Lys Cys Arg Cys Asp                1045 1050 1055 Ser Gly Phe Ala Leu Asp Ser Glu Glu Arg Asn Cys Thr Asp Ile Asp            1060 1065 1070 Glu Cys Arg Ile Ser Pro Asp Leu Cys Gly Arg Gly Gln Cys Val Asn        1075 1080 1085 Thr Pro Gly Asp Phe Glu Cys Lys Cys Asp Glu Gly Tyr Glu Ser Gly    1090 1095 1100 Phe Met Met Met Lys Asn Cys Met Asp Ile Asp Glu Cys Gln Arg Asp 1105 1110 1115 1120 Pro Leu Leu Cys Arg Gly Gly Val Cys His Asn Thr Glu Gly Ser Tyr                1125 1130 1135 Arg Cys Glu Cys Pro Pro Gly His Gln Leu Ser Pro Asn Ile Ser Ala            1140 1145 1150 Cys Ile Asp Ile Asn Glu Cys Glu Leu Ser Ala His Leu Cys Pro Asn        1155 1160 1165 Gly Arg Cys Val Asn Leu Ile Gly Lys Tyr Gln Cys Ala Cys Asn Pro    1170 1175 1180 Gly Tyr His Ser Thr Pro Asp Arg Leu Phe Cys Val Asp Ile Asp Glu 1185 1190 1195 1200 Cys Ser Ile Met Asn Gly Gly Cys Glu Thr Phe Cys Thr Asn Ser Glu                1205 1210 1215 Gly Ser Tyr Glu Cys Ser Cys Gln Pro Gly Phe Ala Leu Met Pro Asp            1220 1225 1230 Gln Arg Ser Cys Thr Asp Ile Asp Glu Cys Glu Asp Asn Pro Asn Ile        1235 1240 1245 Cys Asp Gly Gly Gln Cys Thr Asn Ile Pro Gly Glu Tyr Arg Cys Leu    1250 1255 1260 Cys Tyr Asp Gly Phe Met Ala Ser Glu Asp Met Lys Thr Cys Val Asp 1265 1270 1275 1280 Val Asn Glu Cys Asp Leu Asn Pro Asn Ile Cys Leu Ser Gly Thr Cys                1285 1290 1295 Glu Asn Thr Lys Gly Ser Phe Ile Cys His Cys Asp Met Gly Tyr Ser            1300 1305 1310 Gly Lys Lys Gly Lys Thr Gly Cys Thr Asp Ile Asn Glu Cys Glu Ile        1315 1320 1325 Gly Ala His Asn Cys Gly Lys His Ala Val Cys Thr Asn Thr Ala Gly    1330 1335 1340 Ser Phe Lys Cys Ser Cys Ser Pro Gly Trp Ile Gly Asp Gly Ile Lys 1345 1350 1355 1360 Cys Thr Asp Leu Asp Glu Cys Ser Asn Gly Thr His Met Cys Ser Gln                1365 1370 1375 His Ala Asp Cys Lys Asn Thr Met Gly Ser Tyr Arg Cys Leu Cys Lys            1380 1385 1390 Glu Gly Tyr Thr Gly Asp Gly Phe Thr Cys Thr Asp Leu Asp Glu Cys        1395 1400 1405 Ser Glu Asn Leu Asn Leu Cys Gly Asn Gly Gln Cys Leu Asn Ala Pro    1410 1415 1420 Gly Gly Tyr Arg Cys Glu Cys Asp Met Gly Phe Val Pro Ser Ala Asp 1425 1430 1435 1440 Gly Lys Ala Cys Glu Asp Ile Asp Glu Cys Ser Leu Pro Asn Ile Cys                1445 1450 1455 Val Phe Gly Thr Cys His Asn Leu Pro Gly Leu Phe Arg Cys Glu Cys            1460 1465 1470 Glu Ile Gly Tyr Glu Leu Asp Arg Ser Gly Gly Asn Cys Thr Asp Val        1475 1480 1485 Asn Glu Cys Leu Asp Pro Thr Thr Cys Ile Ser Gly Asn Cys Val Asn    1490 1495 1500 Thr Pro Gly Ser Tyr Ile Cys Asp Cys Pro Pro Asp Phe Glu Leu Asn 1505 1510 1515 1520 Pro Thr Arg Val Gly Cys Val Asp Thr Arg Ser Gly Asn Cys Tyr Leu                1525 1530 1535 Asp Ile Arg Pro Arg Gly Asp Asn Gly Asp Thr Ala Cys Ser Asn Glu            1540 1545 1550 Ile Gly Val Gly Val Ser Lys Ala Ser Cys Cys Cys Ser Leu Gly Lys        1555 1560 1565 Ala Trp Gly Thr Pro Cys Glu Met Cys Pro Ala Val Asn Thr Ser Glu    1570 1575 1580 Tyr Lys Ile Leu Cys Pro Gly Gly Glu Gly Phe Arg Pro Asn Pro Ile 1585 1590 1595 1600 Thr Val Ile Leu Glu Asp Ile Asp Glu Cys Gln Glu Leu Pro Gly Leu                1605 1610 1615 Cys Gln Gly Gly Lys Cys Ile Asn Thr Phe Gly Ser Phe Gln Cys Arg            1620 1625 1630 Cys Pro Thr Gly Tyr Tyr Leu Asn Glu Asp Thr Arg Val Cys Asp Asp        1635 1640 1645 Val Asn Glu Cys Glu Thr Pro Gly Ile Cys Gly Pro Gly Thr Cys Tyr    1650 1655 1660 Asn Thr Val Gly Asn Tyr Thr Cys Ile Cys Pro Pro Asp Tyr Met Gln 1665 1670 1675 1680 Val Asn Gly Gly Asn Asn Cys Met Asp Met Arg Arg Ser Leu Cys Tyr                1685 1690 1695 Arg Asn Tyr Tyr Ala Asp Asn Gln Thr Cys Asp Gly Glu Leu Leu Phe            1700 1705 1710 Asn Met Thr Lys Lys Met Cys Cys Cys Ser Tyr Asn Ile Gly Arg Ala        1715 1720 1725 Trp Asn Lys Pro Cys Glu Gln Cys Pro Ile Pro Ser Thr Asp Glu Phe    1730 1735 1740 Ala Thr Leu Cys Gly Ser Gln Arg Pro Gly Phe Val Ile Asp Ile Tyr 1745 1750 1755 1760 Thr Gly Leu Pro Val Asp Ile Asp Glu Cys Arg Glu Ile Pro Gly Val                1765 1770 1775 Cys Glu Asn Gly Val Cys Ile Asn Met Val Gly Ser Phe Arg Cys Glu            1780 1785 1790 Cys Pro Val Gly Phe Phe Tyr Asn Asp Lys Leu Leu Val Cys Glu Asp        1795 1800 1805 Ile Asp Glu Cys Gln Asn Gly Pro Val Cys Gln Arg Asn Ala Glu Cys    1810 1815 1820 Ile Asn Thr Ala Gly Ser Tyr Arg Cys Asp Cys Lys Pro Gly Tyr Arg 1825 1830 1835 1840 Phe Thr Ser Thr Gly Gln Cys Asn Asp Arg Asn Glu Cys Gln Glu Ile                1845 1850 1855 Pro Asn Ile Cys Ser His Gly Gln Cys Ile Asp Thr Val Gly Ser Phe            1860 1865 1870 Tyr Cys Leu Cys His Thr Gly Phe Lys Thr Asn Asp Asp Gln Thr Met        1875 1880 1885 Cys Leu Asp Ile Asn Glu Cys Glu Arg Asp Ala Cys Gly Asn Gly Thr    1890 1895 1900 Cys Arg Asn Thr Ile Gly Ser Phe Asn Cys Arg Cys Asn His Gly Phe 1905 1910 1915 1920 Ile Leu Ser His Asn Asn Asp Cys Ile Asp Val Asp Glu Cys Ala Ser                1925 1930 1935 Gly Asn Gly Asn Leu Cys Arg Asn Gly Gln Cys Ile Asn Thr Val Gly            1940 1945 1950 Ser Phe Gln Cys Gln Cys Asn Glu Gly Tyr Glu Val Ala Pro Asp Gly        1955 1960 1965 Arg Thr Cys Val Asp Ile Asn Glu Cys Leu Leu Glu Pro Arg Lys Cys    1970 1975 1980 Ala Pro Gly Thr Cys Gln Asn Leu Asp Gly Ser Tyr Arg Cys Ile Cys 1985 1990 1995 2000 Pro Pro Gly Tyr Ser Leu Gln Asn Glu Lys Cys Glu Asp Ile Asp Glu                2005 2010 2015 Cys Val Glu Glu Pro Glu Ile Cys Ala Leu Gly Thr Cys Ser Asn Thr            2020 2025 2030 Glu Gly Ser Phe Lys Cys Leu Cys Pro Glu Gly Phe Ser Leu Ser Ser        2035 2040 2045 Ser Gly Arg Arg Cys Gln Asp Leu Arg Met Ser Tyr Cys Tyr Ala Lys    2050 2055 2060 Phe Glu Gly Gly Lys Cys Ser Ser Pro Lys Ser Arg Asn His Ser Lys 2065 2070 2075 2080 Gln Glu Cys Cys Cys Ala Leu Lys Gly Glu Gly Trp Gly Asp Pro Cys                2085 2090 2095 Glu Leu Cys Pro Thr Glu Pro Asp Glu Ala Phe Arg Gln Ile Cys Pro            2100 2105 2110 Tyr Gly Ser Gly Ile Ile Val Gly Pro Asp Asp Ser Ala Val Asp Met        2115 2120 2125 Asp Glu Cys Lys Glu Pro Asp Val Cys Lys His Gly Gln Cys Ile Asn    2130 2135 2140 Thr Asp Gly Ser Tyr Arg Cys Glu Cys Pro Phe Gly Tyr Ile Leu Ala 2145 2150 2155 2160 Gly Asn Glu Cys Val Asp Thr Asp Glu Cys Ser Val Gly Asn Pro Cys                2165 2170 2175 Gly Asn Gly Thr Cys Lys Asn Val Ile Gly Gly Phe Glu Cys Thr Cys            2180 2185 2190 Glu Glu Gly Phe Glu Pro Gly Pro Met Met Thr Cys Glu Asp Ile Asn        2195 2200 2205 Glu Cys Ala Gln Asn Pro Leu Leu Cys Ala Phe Arg Cys Val Asn Thr    2210 2215 2220 Tyr Gly Ser Tyr Glu Cys Lys Cys Pro Val Gly Tyr Val Leu Arg Glu 2225 2230 2235 2240 Asp Arg Arg Met Cys Lys Asp Glu Asp Glu Cys Glu Glu Gly Lys His                2245 2250 2255 Asp Cys Thr Glu Lys Gln Met Glu Cys Lys Asn Leu Ile Gly Thr Tyr            2260 2265 2270 Met Cys Ile Cys Gly Pro Gly Tyr Gln Arg Arg Pro Asp Gly Glu Gly        2275 2280 2285 Cys Val Asp Glu Asn Glu Cys Gln Thr Lys Pro Gly Ile Cys Glu Asn    2290 2295 2300 Gly Arg Cys Leu Asn Thr Arg Gly Ser Tyr Thr Cys Glu Cys Asn Asp 2305 2310 2315 2320 Gly Phe Thr Ala Ser Pro Asn Gln Asp Glu Cys Leu Asp Asn Arg Glu                2325 2330 2335 Gly Tyr Cys Phe Thr Glu Val Leu Gln Asn Met Cys Gln Ile Gly Ser            2340 2345 2350 Ser Asn Arg Asn Pro Val Thr Lys Ser Glu Cys Cys Cys Asp Gly Gly        2355 2360 2365 Arg Gly Trp Gly Pro His Cys Glu Ile Cys Pro Phe Gln Gly Thr Val    2370 2375 2380 Ala Phe Lys Lys Leu Cys Pro His Gly Arg Gly Phe Met Thr Asn Gly 2385 2390 2395 2400 Ala Asp Ile Asp Glu Cys Lys Val Ile His Asp Val Cys Arg Asn Gly                2405 2410 2415 Glu Cys Val Asn Asp Arg Gly Ser Tyr His Cys Ile Cys Lys Thr Gly            2420 2425 2430 Tyr Thr Pro Asp Ile Thr Gly Thr Ser Cys Val Asp Leu Asn Glu Cys        2435 2440 2445 Asn Gln Ala Pro Lys Pro Cys Asn Phe Ile Cys Lys Asn Thr Glu Gly    2450 2455 2460 Ser Tyr Gln Cys Ser Cys Pro Lys Gly Tyr Ile Leu Gln Glu Asp Gly 2465 2470 2475 2480 Arg Ser Cys Lys Asp Leu Asp Glu Cys Ala Thr Lys Gln His Asn Cys                2485 2490 2495 Gln Phe Leu Cys Val Asn Thr Ile Gly Gly Phe Thr Cys Lys Cys Pro            2500 2505 2510 Pro Gly Phe Thr Gln His His Thr Ser Cys Ile Asp Asn Asn Glu Cys        2515 2520 2525 Thr Ser Asp Ile Asn Leu Cys Gly Ser Lys Gly Ile Cys Gln Asn Thr    2530 2535 2540 Pro Gly Ser Phe Thr Cys Glu Cys Gln Arg Gly Phe Ser Leu Asp Gln 2545 2550 2555 2560 Thr Gly Ser Ser Cys Glu Asp Val Asp Glu Cys Glu Gly Asn His Arg                2565 2570 2575 Cys Gln His Gly Cys Gln Asn Ile Ile Gly Gly Tyr Arg Cys Ser Cys            2580 2585 2590 Pro Gln Gly Tyr Leu Gln His Tyr Gln Trp Asn Gln Cys Val Asp Glu        2595 2600 2605 Asn Glu Cys Leu Ser Ala His Ile Cys Gly Gly Ala Ser Cys His Asn    2610 2615 2620 Thr Leu Gly Ser Tyr Lys Cys Met Cys Pro Ala Gly Phe Gln Tyr Glu 2625 2630 2635 2640 Gln Phe Ser Gly Gly Cys Gln Asp Ile Asn Glu Cys Gly Ser Ala Gln                2645 2650 2655 Ala Pro Cys Ser Tyr Gly Cys Ser Asn Thr Glu Gly Gly Tyr Leu Cys            2660 2665 2670 Gly Cys Pro Pro Gly Tyr Phe Arg Ile Gly Gln Gly His Cys Val Ser        2675 2680 2685 Gly Met Gly Met Gly Arg Gly Asn Pro Glu Pro Pro Val Ser Gly Glu    2690 2695 2700 Met Asp Asp Asn Ser Leu Ser Pro Glu Ala Cys Tyr Glu Cys Lys Ile 2705 2710 2715 2720 Asn Gly Tyr Pro Lys Arg Gly Arg Lys Arg Arg Ser Thr Asn Glu Thr                2725 2730 2735 Asp Ala Ser Asn Ile Glu Asp Gln Ser Glu Thr Glu Ala Asn Val Ser            2740 2745 2750 Leu Ala Ser Trp Asp Val Glu Lys Thr Ala Ile Phe Ala Phe Asn Ile        2755 2760 2765 Ser His Val Ser Asn Lys Val Arg Ile Leu Glu Leu Leu Pro Ala Leu    2770 2775 2780 Thr Thr Leu Thr Asn His Asn Arg Tyr Leu Ile Glu Ser Gly Asn Glu 2785 2790 2795 2800 Asp Gly Phe Phe Lys Ile Asn Gln Lys Glu Gly Ile Ser Tyr Leu His                2805 2810 2815 Phe Thr Lys Lys Lys Pro Val Ala Gly Thr Tyr Ser Leu Gln Ile Ser            2820 2825 2830 Ser Thr Pro Leu Tyr Lys Lys Lys Glu Leu Asn Gln Leu Glu Asp Lys        2835 2840 2845 Tyr Asp Lys Asp Tyr Leu Ser Gly Glu Leu Gly Asp Asn Leu Lys Met    2850 2855 2860 Lys Ile Gln Val Leu Leu His 2865 2870 <210> 16 <211> 11695 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid encoding human Fibrillin 1 protein <400> 16 agtatttctc tcgcgagaaa ccgctgcgcg gacgatactt gaagaggtgg ggaaaggagg 60 gggctgcggg agccgcggca gagactgtgg gtgccacaag cggacaggag ccacagctgg 120 gacagctgcg agcggagccg agcagtggct gtagcggcca cgactgggag cagccgccgc 180 cgcctcctcg ggagtcggag ccgccgcttc tccactggca ggggccgcct gaagtgggag 240 cagcgcctgg agaaggcggg aggagcccgg cccgggggac gggcggcggg atagcgggac 300 cccggcggcg cggtgcgctt cagggcgcag cggcggccgc agaccgagcc ccgggcgcgg 360 caagaggcgg cgggagccgg tggcggctcg gcatcatgcg tcgagggcgt ctgctggaga 420 tcgccctggg atttaccgtg cttttagcgt cctacacgag ccatggggcg gacgccaatt 480 tggaggctgg gaacgtgaag gaaaccagag ccagtcgggc caagagaaga ggcggtggag 540 gacacgacgc gcttaaagga cccaatgtct gtggatcacg ttataatgct tactgttgcc 600 ctggatggaa aaccttacct ggcggaaatc agtgtattgt ccccatttgc cggcattcct 660 gtggggatgg attttgttcg aggccaaata tgtgcacttg cccatctggt cagatagctc 720 cttcctgtgg ctccagatcc atacaacact gcaatattcg ctgtatgaat ggaggtagct 780 gcagtgacga tcactgtcta tgccagaaag gatacatagg gactcactgt ggacaacctg 840 tttgtgaaag tggctgtctc aatggaggaa ggtgtgtggc cccaaatcga tgtgcatgca 900 cttacggatt tactggaccc cagtgtgaaa gagattacag gacaggccca tgttttactg 960 tgatcagcaa ccagatgtgc cagggacaac tcagcgggat tgtctgcaca aaaacgctct 1020 gctgtgccac agtcggccga gcctggggcc acccctgtga gatgtgtcct gcccagcctc 1080 acccctgccg ccgtggcttc attccaaata tccgcacggg agcttgtcaa gatgtggatg 1140 aatgccaggc catccccggg ctctgtcagg gaggaaattg cattaatact gttgggtctt 1200 ttgagtgcaa atgccctgct ggacacaaac ttaatgaagt gtcacaaaaa tgtgaagata 1260 ttgatgaatg cagcaccatt cctggaatct gtgaaggggg tgaatgtaca aacacagtca 1320 gcagttactt ttgcaaatgt ccccctggtt tttacacctc tccagatggt accagatgca 1380 tagatgttcg cccaggatac tgttacacag ctctgacaaa cgggcgctgc tctaaccagc 1440 tgccacagtc cataaccaaa atgcagtgct gctgtgatgc cggccgatgc tggtctccag 1500 gggtcactgt cgcccctgag atgtgtccca tcagagcaac cgaggatttc aacaagctgt 1560 gctctgttcc tatggtaatt cctgggagac cagaatatcc tcccccaccc cttggcccca 1620 ttcctccagt tctccctgtt cctcctggct ttcctcctgg acctcaaatt ccggtccctc 1680 gaccaccagt ggaatatctg tatccatctc gggagccacc aagggtgctg ccagtaaacg 1740 ttactgatta ctgccagttg gtccgctatc tctgtcaaaa tggacgctgc attccaactc 1800 ctgggagtta ccggtgtgag tgcaacaaag ggttccagct ggacctccgt ggggagtgta 1860 ttgatgttga tgaatgtgag aaaaacccct gtgctggtgg tgagtgtatt aacaaccagg 1920 gttcgtacac ctgtcagtgc cgagctggat atcagagcac actcacgcgg acagaatgcc 1980 gagacattga tgagtgttta cagaatggcc ggatctgcaa taatggacgc tgcatcaaca 2040 cagatggcag ttttcattgc gtgtgtaatg cgggctttca tgttacacga gatgggaaga 2100 actgtgaaga tatggatgaa tgcagcataa ggaacatgtg ccttaatgga atgtgtatca 2160 atgaagatgg cagttttaaa tgtatttgca aacctggatt ccagctggca tcagatggac 2220 gttattgcaa agacattaac gagtgtgaaa cccctgggat ctgcatgaat gggcgttgcg 2280 tcaacactga tggctcctac agatgtgaat gcttccctgg actggctgtg ggtctggatg 2340 gccgtgtgtg tgttgacaca cacatgcgga gcacatgcta tggtggatac aagagaggcc 2400 agtgtatcaa acctttgttt ggtgctgtca ctaaatctga atgctgttgc gccagcactg 2460 agtatgcatt tggggaacct tgccagccgt gtcctgcaca gaattcagcg gaatatcagg 2520 cactctgcag cagtgggcca ggaatgacgt cagcaggcag tgatataaat gaatgtgcac 2580 tagatcctga tatttgccca aatggaatct gtgaaaacct tcgtgggacc tataaatgta 2640 tatgcaattc aggatatgaa gtggattcaa ctgggaaaaa ctgcgttgat attaatgaat 2700 gtgtactgaa cagtctcctt tgtgacaatg gacaatgtag aaatactcct ggaagttttg 2760 tctgtacctg ccccaaggga tttatctaca aacctgatct aaaaacatgt gaagacattg 2820 atgaatgcga atcaagtcct tgcattaatg gagtctgcaa gaacagccca ggctctttta 2880 tttgtgaatg ttcttctgaa agtactttgg atccaacaaa aaccatctgc atagaaacca 2940 tcaagggcac ttgctggcag actgtcattg atgggcgatg tgagatcaac atcaatggag 3000 ccaccttaaa gtcccagtgc tgctcctccc tcggtgctgc gtggggaagc ccgtgcaccc 3060 tatgccaagt tgatcccata tgtggtaaag ggtactcaag aattaaagga acacaatgtg 3120 aagatataga tgaatgtgaa gtgttcccag gagtgtgtaa aaatggcctg tgtgttaaca 3180 ctagggggtc attcaagtgt cagtgtccca gtggaatgac tttggatgcc acaggaagga 3240 tctgtcttga tatccgcctg gaaacctgct tcctgaggta cgaggacgag gagtgcaccc 3300 tgcctattgc tggccgccac cgcatggacg cctgctgctg ctccgtcggg gcagcctggg 3360 gtactgagga atgcgaggag tgtcccatga gaaatactcc tgagtacgag gagctgtgtc 3420 cgagaggacc cggatttgcc acaaaagaaa ttacaaatgg aaagcctttc ttcaaagata 3480 tcaatgagtg caagatgata cccagcctct gcacccacgg caagtgcaga aacaccattg 3540 gcagctttaa gtgcaggtgt gacagcggct ttgctcttga ttctgaagaa aggaactgca 3600 cagacattga cgaatgccgc atatctcctg acctctgtgg cagaggccag tgtgtgaaca 3660 cccctgggga ctttgaatgc aagtgtgacg aaggctatga aagtggattc atgatgatga 3720 agaactgcat ggatattgat gagtgtcaga gagatcctct cctatgccga ggtggtgttt 3780 gccataacac agagggaagt taccgctgtg aatgcccgcc tggccatcag ctgtccccca 3840 acatctccgc gtgtatcgac atcaatgaat gtgagctgag tgcacacctg tgccccaatg 3900 gccgttgcgt gaacctcata gggaagtatc agtgtgcctg caaccctggc taccattcaa 3960 ctcccgatag gctattttgt gttgacattg atgaatgcag cataatgaat ggtggttgtg 4020 aaaccttctg cacaaactct gaaggcagct atgaatgtag ctgtcagccg ggatttgcac 4080 taatgcctga ccagagatca tgcaccgaca tcgatgagtg tgaagataat cccaatatct 4140 gtgatggtgg tcagtgcaca aatatccctg gagagtacag gtgcttgtgt tatgatggat 4200 tcatggcatc tgaagacatg aagacttgtg tagatgtcaa tgagtgtgac ctgaatccaa 4260 atatctgcct aagtgggacc tgtgaaaaca cgaaaggctc atttatctgc cactgtgata 4320 tgggctactc cggcaaaaaa ggaaaaactg gctgtacaga catcaatgaa tgtgaaattg 4380 gagcacacaa ctgtggcaaa catgctgtat gtaccaatac agcaggaagc ttcaaatgta 4440 gctgcagtcc cgggtggatt ggagatggca ttaagtgcac tgatctggac gaatgttcca 4500 atggaaccca tatgtgcagc cagcatgcag actgcaagaa taccatggga tcttaccgct 4560 gtctgtgcaa ggaaggatac acaggtgatg gcttcacttg tacagacctt gatgagtgct 4620 ctgagaacct gaatctctgt ggcaatggcc agtgcctcaa tgcaccagga ggataccgct 4680 gtgaatgcga catgggcttc gtgcccagtg ctgacgggaa agcctgtgaa gatattgatg 4740 agtgctccct tccgaacatc tgtgtctttg gaacttgcca caacctccct ggcctgttcc 4800 gctgtgagtg tgagataggc tacgaactgg acagaagcgg cgggaactgc acagatgtga 4860 atgaatgcct ggatccaacc acgtgcatca gtgggaactg tgtcaacact ccaggcagct 4920 atatctgtga ctgcccacct gattttgaac tgaacccaac tcgagttggc tgtgttgata 4980 cccgctctgg aaattgctat ttggatattc gacctcgagg agacaatgga gatacagcct 5040 gcagcaatga aattggagtt ggtgtttcca aagcttcctg ctgctgttct ctgggtaaag 5100 cctggggtac tccttgtgag atgtgtcctg ctgtgaacac atccgagtac aaaattcttt 5160 gtcctggagg ggaaggtttc cgaccaaatc ctatcaccgt tatattggaa gatattgatg 5220 agtgccagga gctaccaggg ctgtgccaag gaggaaaatg tatcaacacc tttgggagtt 5280 tccagtgccg ctgtccaacc ggctactacc tgaatgaaga tacacgagtg tgtgatgatg 5340 tgaatgaatg tgagactcct ggaatctgtg gtccagggac atgttacaac accgttggca 5400 actacacctg tatctgtcct ccagactaca tgcaagtgaa tgggggaaat aattgcatgg 5460 atatgagaag aagtttgtgc tacagaaact actatgctga caaccagacc tgtgatggag 5520 aattgttatt caacatgacc aagaagatgt gctgctgttc ctacaacatt ggccgggcgt 5580 ggaacaagcc ctgtgaacag tgtcccatcc caagtacaga tgagtttgct acactctgtg 5640 gaagtcaaag gccaggcttt gtcatcgaca tttataccgg tttacccgtt gatattgatg 5700 agtgccggga gatcccaggg gtctgtgaaa atggagtgtg tatcaacatg gttggcagct 5760 tccgatgtga atgtccagtg ggattcttct ataatgacaa gttgttggtt tgtgaagata 5820 ttgacgagtg tcagaacggc ccagtgtgcc agcgcaacgc cgaatgcatc aacactgcag 5880 gcagctaccg ctgtgactgt aagcccggct accgcttcac ctccacagga cagtgcaatg 5940 atcgtaatga atgtcaagaa atccccaata tatgcagtca tgggcagtgc attgacacag 6000 ttggaagctt ttattgcctt tgccacactg gttttaaaac aaatgatgac caaaccatgt 6060 gcttggacat aaatgaatgt gaaagagatg cctgtgggaa tggaacttgc cggaacacaa 6120 ttggttcctt caactgccgc tgcaatcatg gtttcatcct ttctcacaac aatgactgta 6180 tagatgttga tgaatgtgca agtggaaatg ggaatctttg cagaaatggc caatgcatta 6240 atacagtggg gtctttccag tgccagtgca atgaaggcta tgaggtggct ccagatggga 6300 ggacctgtgt ggatatcaat gaatgtcttc tagaacccag aaaatgtgca ccaggtacct 6360 gtcaaaactt ggatgggtcc tacagatgca tttgcccacc tggatacagt cttcaaaatg 6420 agaagtgtga agatattgat gagtgtgtcg aagagccaga aatttgtgcc ctgggcacat 6480 gcagtaacac tgaaggcagc ttcaaatgtc tgtgtccaga agggttttcc ttgtcctcca 6540 gtggaagaag gtgccaagat ttgcgaatga gctactgtta tgcgaagttt gaaggaggaa 6600 agtgttcatc acccaaatcc agaaatcact ccaagcagga atgctgctgt gccttgaagg 6660 ggaaggctg gggagacccc tgcgagctct gccccacgga acctgatgag gccttccgcc 6720 agatatgtcc ttatggaagt gggatcatcg tgggacctga tgattcagca gttgatatgg 6780 acgaatgcaa agaacccgat gtctgtaaac atggacagtg catcaataca gatggttcct 6840 atcgctgcga gtgtcccttt ggttatattc tagcagggaa tgaatgtgta gatactgatg 6900 aatgttctgt tggcaatcct tgtggaaatg gaacctgcaa gaatgtgatt ggaggttttg 6960 aatgcacctg cgaggaggga tttgagcccg gtccaatgat gacatgtgaa gatataaatg 7020 aatgtgccca gaatcctctg ctctgtgcct tccgatgtgt gaacacttat gggtcatatg 7080 aatgcaaatg tcccgtggga tatgtgctca gagaagaccg taggatgtgc aaagatgagg 7140 atgagtgtga agagggaaaa catgactgta ctgaaaaaca aatggaatgc aagaacctca 7200 ttggcacata tatgtgcatc tgtggacccg ggtatcagcg gagacctgat ggagaaggct 7260 gtgtagatga gaatgaatgt cagacgaagc cagggatctg tgagaatggg cgctgcctca 7320 acacccgtgg gagctacacc tgtgagtgta atgatgggtt taccgccagc cccaaccagg 7380 acgagtgcct tgacaatcgg gaagggtact gcttcacaga ggtgctacaa aacatgtgtc 7440 agatcggctc cagcaacagg aaccccgtca ccaaatcgga atgctgctgt gacggaggga 7500 gaggctgggg tccccactgt gagatctgcc ctttccaggg gactgtggct ttcaagaaac 7560 tctgtcccca tggccgagga ttcatgacca atggagcaga tatcgatgaa tgcaaggtta 7620 ttcacgatgt ttgccgaaat ggggaatgtg tcaatgacag aggatcatat cattgcattt 7680 gtaaaactgg gtacactcca gatataactg ggacttcctg tgtagatctg aacgagtgca 7740 accaggctcc caaaccctgc aattttatct gcaaaaacac agaagggagt taccagtgtt 7800 catgcccgaa aggctacatt ctgcaagagg atggaaggag ctgcaaagat cttgatgagt 7860 gtgcaaccaa gcaacacaac tgccagttcc tatgtgttaa caccattggc ggcttcacat 7920 gcaaatgtcc tcccggattt acccaacacc atacgtcctg cattgataac aatgaatgca 7980 cctctgacat caatctgtgc gggtctaagg gcatttgcca gaacactcct ggaagcttca 8040 cctgtgaatg ccagcgggga ttctcacttg atcagaccgg ctccagctgt gaagacgtgg 8100 acgagtgtga gggtaaccac cgctgccagc atggctgcca gaacatcatt gggggctaca 8160 ggtgcagctg cccccagggc tacctccagc actaccagtg gaaccagtgt gttgatgaaa 8220 acgaatgcct cagcgctcac atctgcggag gagcctcctg tcacaacacc ctggggagct 8280 acaagtgcat gtgtcccgcc ggcttccagt atgaacagtt cagtggagga tgccaagaca 8340 tcaatgaatg tggctctgcg caggccccct gcagctatgg ctgttccaat accgagggcg 8400 gttacctgtg tggctgtcca cctggttact tccgcatagg ccaagggcac tgtgtttctg 8460 gaatgggcat gggccgagga aacccagagc cacctgtcag tggtgaaatg gatgacaatt 8520 cactctcccc agaggcttgt tacgagtgta agatcaatgg ctaccccaaa cggggcagga 8580 aacggagaag cacaaacgaa actgatgcct ccaatatcga ggatcagtct gagacagaag 8640 ccaatgtgag tcttgcaagt tgggatgttg agaagacagc catctttgct ttcaatattt 8700 cccacgtcag taacaaggtt cgaatcctag aactccttcc agctcttaca actctgacga 8760 atcacaacag atacttgatc gaatctggaa atgaagatgg cttctttaaa atcaaccaaa 8820 aggaagggat cagctacctc cacttcacaa agaagaagcc agtggctgga acctattcat 8880 tacaaatcag tagtactcca ctttataaaa agaaagaact taaccaacta gaagacaaat 8940 atgacaaaga ctacctcagt ggtgaactgg gtgataatct gaagatgaaa atccaggttt 9000 tgcttcatta attcaccatc cagagaccaa ataattaaaa gaaaaacaaa tatagatagg 9060 tagaactata ttttccccca atcagaatca tcatatcata ggtacaatct ttcaccaagt 9120 aaatttgtat aaataagcac tattctttgt attaccaaag caaggtacag gtgactaccc 9180 tagttcaaaa caaccacttt ctcaggcttc tcatgtgtgt agctaagcta ccttgtcata 9240 tgtgttgatt cttgaaaact gggacgtgta tttccattgg gggttggcca tttatgctga 9300 catgccatcc ttccagcaaa cgtacgggaa tgtgctttca attgatggac tactctattt 9360 tttgcaaatt tgtaaacttt gcttctccaa atacaagtac taggttgtcc atttatggta 9420 cctatttggt gctagtaaat tttcaaacta gatttataaa tgcactgtaa tatgtacaca 9480 acttagaaac caaattacaa gtattcagtt ccaatacttc attaatttca atcaaccaaa 9540 gttagttcag tagcttatct cagttatgag tataatacat tacatgtaaa ttaagtgtgt 9600 gtatactgta atcgtgctat tttttatcat tgaaacattt ataaactaga ataataatgc 9660 ccttaatgtg agggtttgta atggtgctta ttaagaccaa agacttgtta aatgtataca 9720 ccaagtggta atgaaatttc ggtgactggc ccacacgtgc atagaggtct gggaggacca 9780 ggaaacagcc tcagtggcca gaggatcacc agtgcatcct tcatcacagc atgtgcaata 9840 tgccaagatt accctcggtc attcctgtca acaaggggtc aatgtcataa atgtcacaat 9900 aaaacaatct cttctttttt ttagtttacc ccttggcttt gtgttcttgc atggatttgg 9960 ggttggaggg gccattccgg aggctaaata aagtctcctg gatttaaatt atcctgggtc 10020 tcttacttat ggcttatgaa agtaccaaat gtataaccac tagaagaaaa tttaacatat 10080 gagtcgatcc cttgttttat ccattgaaag tagcagagtc tggtgtcatt aacctgactt 10140 gcttgtgaga aatttagatt gtagagtcat ttctgaaaca tgacctaatt catcttgtga 10200 cttttaaata gtcttaaata ccaagttcag tcattgtctt agagcacatg aatttcatta 10260 taatagattt atcatgcccc cctctcaaat atacacagtt ttggcaagcc ttaggtgttc 10320 tgttccattt ttttttcccc taaacatctt tcgttagtca atgctcatct aattacaaag 10380 ggataatccc agactgtatc caattgctgt aacttttggt ttcttaatgt cataattttt 10440 aaagtctgtt ttattttaag tgcaatattg agtatttagc tgttaggctc aatccgtcga 10500 tatgaaataa ttttttaaat ccctaagggc aggaaagcat ttcgtggtag tgaaaataag 10560 aggaaataag atggcatgaa ggtggtgggc ggagaaacta ggtaggacac aggaaagtgc 10620 tctcaaaaat ctttgaagag ctcagctgaa aaaaatggag tagatttggc tcatactatt 10680 ccggaaggca aaaccagggt cagctgatgt cagccccagt ttaatacaca cggtcccaat 10740 tatagagcta ctcactgaaa gaatgggttt ccttgcattg tggtgagctc cctgtcacaa 10800 gatagaagag tttcagtcta ggcttaatgg caaccattgg acaaagatgc tttcttccac 10860 ctaacaggcc attaacatct taaaggtatt tttgtatctc taattttgtt tataataggt 10920 gctcaacaga atgagctgaa tggctgttac aaagggggtt tgtaccttgg gtaagagatt 10980 aaaatataac tcaaaatttc cttctaacgc tgcacctatg gaaccatgtg atagaggtgt 11040 attaaaattg ttatcgaaga atatatagca tatggtaaac aacagtttgc atatggaaaa 11100 tgtctttgat aatttaacca gaactgcatt atattcaata acggattttc tttataacaa 11160 acaacagggg aaaatggagt tggcacacag tggatcactt tgatattttt aatagtccaa 11220 gtctggattt tatttattcc tgagccaaca attttgaaca gcatattttc catgtttctg 11280 actgtaacaa aacattttcc tcattgttcc attgtaaata ttcctcttgt tggaactctt 11340 tttaatcctg agatttaaac ctgtaccttt caattgtctg tgacctttca atttcacttt 11400 caatagttga agaacttggc tttgtaaatc tctcagaagc ttgaaaatat cttgtctcta 11460 ccccctcagc ccatttcatt tgccaataat tattttgtaa gtagggttga aatgaactca 11520 gctggccttg tgaaatgttt aaacttgcac aaacaactac atttttgttc aacaaatagc 11580 agtttactca gccaaaatca ctttggatat tgccattaca aatactgtta aacttcagaa 11640 atcatgtctg taaattagat gagccaaaat aaaggacaat tgggttgatg ctgca 11695 <210> 17 <211> 2873 <212> PRT <213> Artificial Sequence <220> <223> Mouse Fibrillin 1 protein <400> 17 Met Arg Arg Gly Gly Leu Leu Glu Val Ala Leu Ala Phe Ala Leu Leu   1 5 10 15 Leu Glu Ser Tyr Thr Ser Gly Ala Asp Ala Asn Leu Glu Ala Gly              20 25 30 Ser Leu Lys Glu Thr Arg Ala Asn Arg Ala Lys Arg Arg Gly Gly Gly          35 40 45 Gly His Asp Ala Leu Lys Gly Pro Asn Val Cys Gly Ser Arg Tyr Asn      50 55 60 Ala Tyr Cys Cys Pro Gly Trp Lys Thr Leu Pro Gly Gly Asn Gln Cys  65 70 75 80 Ile Val Pro Ile Cys Arg His Ser Cys Gly Asp Gly Phe Cys Ser Arg                  85 90 95 Pro Asn Met Cys Thr Cys Pro Ser Gly Gln Ile Ser Pro Ser Cys Gly             100 105 110 Ser Arg Ser Ser Gln His Cys Ser Ile Arg Cys Met Asn Gly Gly Ser         115 120 125 Cys Ser Asp Asp His Cys Leu Cys Gln Lys Gly Tyr Ile Gly Thr His     130 135 140 Cys Gly Gln Pro Val Cys Glu Ser Gly Cys Leu Asn Gly Gly Arg Cys 145 150 155 160 Val Ala Pro Asn Arg Cys Ala Cys Thr Tyr Gly Phe Thr Gly Pro Gln                 165 170 175 Cys Glu Arg Asp Tyr Arg Thr Gly Pro Cys Phe Thr Val Val Ser Asn             180 185 190 Gln Met Cys Gln Gly Gln Leu Ser Gly Ile Val Cys Thr Lys Thr Leu         195 200 205 Cys Cys Ala Thr Val Gly Arg Ala Trp Gly His Pro Cys Glu Met Cys     210 215 220 Pro Ala Gln Pro His Pro Cys Arg Arg Gly Phe Ile Pro Asn Ile Arg 225 230 235 240 Thr Gly Ala Cys Gln Asp Val Asp Glu Cys Gln Ala Ile Pro Gly Met                 245 250 255 Cys Gln Gly Gly Asn Cys Ile Asn Thr Val Gly Ser Phe Glu Cys Lys             260 265 270 Cys Pro Ala Gly His Lys Phe Asn Glu Val Ser Gln Lys Cys Glu Asp         275 280 285 Ile Asp Glu Cys Ser Thr Ile Pro Gly Val Cys Asp Gly Gly Glu Cys     290 295 300 Thr Asn Thr Val Ser Ser Tyr Phe Cys Lys Cys Pro Pro Gly Phe Tyr 305 310 315 320 Thr Ser Pro Asp Gly Thr Arg Cys Val Asp Val Arg Pro Gly Tyr Cys                 325 330 335 Tyr Thr Ala Leu Ala Asn Gly Arg Cys Ser Asn Gln Leu Pro Gln Ser             340 345 350 Ile Thr Lys Met Gln Cys Cys Cys Asp Leu Gly Arg Cys Trp Ser Pro         355 360 365 Gly Val Thr Val Ala Pro Glu Met Cys Pro Ile Arg Ser Thr Glu Asp     370 375 380 Phe Asn Lys Leu Cys Ser Val Pro Leu Val Ile Pro Gly Arg Pro Glu 385 390 395 400 Tyr Pro Pro Pro Ile Gly Pro Leu Pro Pro Val Gln Pro Val Pro                 405 410 415 Pro Gly Tyr Pro Pro Gly Pro Val Ile Pro Ala Pro Arg Pro Pro Pro             420 425 430 Glu Tyr Pro Tyr Pro Ser Pro Ser Arg Glu Pro Pro Arg Val Leu Pro         435 440 445 Phe Asn Val Thr Asp Tyr Cys Gln Leu Val Arg Tyr Leu Cys Gln Asn     450 455 460 Gly Arg Cys Ile Pro Thr Pro Gly Ser Tyr Arg Cys Glu Cys Asn Lys 465 470 475 480 Gly Phe Gln Leu Asp Ile Arg Gly Glu Cys Ile Asp Val Asp Glu Cys                 485 490 495 Glu Lys Asn Pro Cys Thr Gly Gly Glu Cys Ile Asn Asn Gln Gly Ser             500 505 510 Tyr Thr Cys His Cys Arg Ala Gly Tyr Gln Ser Thr Leu Thr Arg Thr         515 520 525 Glu Cys Arg Asp Ile Asp Glu Cys Leu Gln Asn Gly Arg Ile Cys Asn     530 535 540 Asn Gly Arg Cys Ile Asn Thr Asp Gly Ser Phe His Cys Val Cys Asn 545 550 555 560 Ala Gly Phe His Val Thr Arg Asp Gly Lys Asn Cys Glu Asp Met Asp                 565 570 575 Glu Cys Ser Ile Arg Asn Met Cys Leu Asn Gly Met Cys Ile Asn Glu             580 585 590 Asp Gly Ser Phe Lys Cys Ile Cys Lys Pro Gly Phe Gln Leu Ala Ser         595 600 605 Asp Gly Arg Tyr Cys Lys Asp Ile Asn Glu Cys Glu Thr Pro Gly Ile     610 615 620 Cys Met Asn Gly Arg Cys Val Asn Thr Asp Gly Ser Tyr Arg Cys Glu 625 630 635 640 Cys Phe Pro Gly Leu Ala Val Gly Leu Asp Gly Arg Val Cys Val Asp                 645 650 655 Thr His Met Arg Ser Thr Cys Tyr Gly Gly Tyr Arg Arg Gly Gln Cys             660 665 670 Val Lys Pro Leu Phe Gly Ala Val Thr Lys Ser Glu Cys Cys Cys Ala         675 680 685 Ser Thr Glu Tyr Ala Phe Gly Glu Pro Cys Gln Pro Cys Pro Ala Gln     690 695 700 Asn Ser Ala Glu Tyr Gln Ala Leu Cys Ser Ser Gly Pro Gly Met Thr 705 710 715 720 Ser Ala Gly Thr Asp Ile Asn Glu Cys Ala Leu Asp Pro Asp Ile Cys                 725 730 735 Pro Asn Gly Ile Cys Glu Asn Leu Arg Gly Thr Tyr Lys Cys Ile Cys             740 745 750 Asn Ser Gly Tyr Glu Val Asp Ile Thr Gly Lys Asn Cys Val Asp Ile         755 760 765 Asn Glu Cys Val Leu Asn Ser Leu Leu Cys Asp Asn Gly Gln Cys Arg     770 775 780 Asn Thr Pro Gly Ser Phe Val Cys Thr Cys Pro Lys Gly Phe Val Tyr 785 790 795 800 Lys Pro Asp Leu Lys Thr Cys Glu Asp Ile Asp Glu Cys Glu Ser Ser                 805 810 815 Pro Cys Ile Asn Gly Val Cys Lys Asn Ser Pro Gly Ser Phe Ile Cys             820 825 830 Glu Cys Ser Pro Glu Ser Thr Leu Asp Pro Thr Lys Thr Ile Cys Ile         835 840 845 Glu Thr Ile Lys Gly Thr Cys Trp Gln Thr Val Ile Asp Gly Arg Cys     850 855 860 Glu Ile Asn Ile Asn Gly Ala Thr Leu Lys Ser Glu Cys Cys Ser Ser 865 870 875 880 Leu Gly Ala Ala Trp Gly Ser Pro Cys Thr Ile Cys Gln Leu Asp Pro                 885 890 895 Ile Cys Gly Lys Gly Phe Ser Arg Ile Lys Gly Thr Gln Cys Glu Asp             900 905 910 Ile Asn Glu Cys Glu Val Phe Pro Gly Val Cys Lys Asn Gly Leu Cys         915 920 925 Val Asn Ser Arg Gly Ser Phe Lys Cys Glu Cys Pro Asn Gly Met Thr     930 935 940 Leu Asp Ala Thr Gly Arg Ile Cys Leu Asp Ile Arg Leu Glu Thr Cys 945 950 955 960 Phe Leu Lys Tyr Asp Asp Glu Glu Cys Thr Leu Pro Ile Ala Gly Arg                 965 970 975 His Arg Met Asp Ala Cys Cys Cys Ser Val Gly Ala Ala Trp Gly Thr             980 985 990 Glu Glu Cys Glu Glu Cys Pro Leu Arg Asn Ser Arg Glu Tyr Glu Glu         995 1000 1005 Leu Cys Pro Arg Gly Pro Gly Phe Ala Thr Lys Asp Ile Thr Asn Gly    1010 1015 1020 Lys Pro Phe Phe Lys Asp Ile Asn Glu Cys Lys Met Ile Pro Ser Leu 1025 1030 1035 1040 Cys Thr His Gly Lys Cys Arg Asn Thr Ile Gly Ser Phe Lys Cys Arg                1045 1050 1055 Cys Asp Ser Gly Phe Ala Leu Asp Ser Glu Glu Arg Asn Cys Thr Asp            1060 1065 1070 Ile Asp Glu Cys Arg Ile Ser Pro Asp Leu Cys Gly Arg Gly Gln Cys        1075 1080 1085 Val Asn Thr Pro Gly Asp Phe Glu Cys Lys Cys Asp Glu Gly Tyr Glu    1090 1095 1100 Ser Gly Phe Met Met Met Lys Asn Cys Met Asp Ile Asp Glu Cys Gln 1105 1110 1115 1120 Arg Asp Pro Leu Leu Cys Arg Gly Gly Ile Cys His Asn Thr Glu Gly                1125 1130 1135 Ser Tyr Arg Cys Glu Cys Pro Pro Gly His Gln Leu Ser Pro Asn Ile            1140 1145 1150 Ser Ala Cys Ile Asp Ile Asn Glu Cys Glu Leu Ser Ala Asn Leu Cys        1155 1160 1165 Pro His Gly Arg Cys Val Asn Leu Ile Gly Lys Tyr Gln Cys Ala Cys    1170 1175 1180 Asn Pro Gly Tyr His Pro Thr His Asp Arg Leu Phe Cys Val Asp Ile 1185 1190 1195 1200 Asp Glu Cys Ser Ile Met Asn Gly Gly Cys Glu Thr Phe Cys Thr Asn                1205 1210 1215 Ser Asp Gly Ser Tyr Glu Cys Ser Cys Gln Pro Gly Phe Ala Leu Met            1220 1225 1230 Pro Asp Gln Arg Ser Cys Thr Asp Ile Asp Glu Cys Glu Asp Asn Pro        1235 1240 1245 Asn Ile Cys Asp Gly Gly Gln Cys Thr Asn Ile Pro Gly Glu Tyr Arg    1250 1255 1260 Cys Leu Cys Tyr Asp Gly Phe Met Ala Ser Glu Asp Met Lys Thr Cys 1265 1270 1275 1280 Val Asp Val Asn Glu Cys Asp Leu Asn Pro Asn Ile Cys Leu Ser Gly                1285 1290 1295 Thr Cys Glu Asn Thr Lys Gly Ser Phe Ile Cys His Cys Asp Met Gly            1300 1305 1310 Tyr Ser Gly Lys Lys Gly Lys Thr Gly Cys Thr Asp Ile Asn Glu Cys        1315 1320 1325 Glu Ile Gly Ala His Asn Cys Gly Arg His Ala Val Cys Thr Asn Thr    1330 1335 1340 Ala Gly Ser Phe Lys Cys Ser Cys Ser Pro Gly Trp Ile Gly Asp Gly 1345 1350 1355 1360 Ile Lys Cys Thr Asp Leu Asp Glu Cys Ser Asn Gly Thr His Met Cys                1365 1370 1375 Ser Gln His Ala Asp Cys Lys Asn Thr Met Gly Ser Tyr Arg Cys Leu            1380 1385 1390 Cys Lys Asp Gly Tyr Thr Gly Asp Gly Phe Thr Cys Thr Asp Leu Asp        1395 1400 1405 Glu Cys Ser Glu Asn Leu Asn Leu Cys Gly Asn Gly Gin Cys Leu Asn    1410 1415 1420 Ala Pro Gly Gly Tyr Arg Cys Glu Cys Asp Met Gly Phe Val Ser Ser 1425 1430 1435 1440 Ala Asp Gly Lys Ala Cys Glu Asp Ile Asp Glu Cys Ser Leu Pro Asn                1445 1450 1455 Ile Cys Val Phe Gly Thr Cys His Asn Leu Pro Gly Leu Phe Arg Cys            1460 1465 1470 Glu Cys Glu Ile Gly Tyr Glu Leu Asp Arg Ser Gly Gly Asn Cys Thr        1475 1480 1485 Asp Val Asn Glu Cys Leu Asp Pro Thr Thr Cys Ile Ser Gly Asn Cys    1490 1495 1500 Val Asn Thr Pro Gly Ser Tyr Thr Cys Asp Cys Pro Pro Asp Phe Glu 1505 1510 1515 1520 Leu Asn Pro Thr Arg Val Gly Cys Val Asp Thr Arg Ser Gly Asn Cys                1525 1530 1535 Tyr Leu Asp Ile Arg Pro Arg Gly Asp Asn Gly Asp Thr Ala Cys Ser            1540 1545 1550 Asn Glu Ile Gly Val Gly Val Ser Lys Ala Ser Cys Cys Cys Ser Leu        1555 1560 1565 Gly Lys Ala Trp Gly Thr Pro Cys Glu Leu Cys Pro Ser Val Asn Thr    1570 1575 1580 Ser Glu Tyr Lys Ile Leu Cys Pro Gly Gly Glu Gly Phe Arg Pro Asn 1585 1590 1595 1600 Pro Ile Thr Val Ile Leu Glu Asp Ile Asp Glu Cys Gln Glu Leu Pro                1605 1610 1615 Gly Leu Cys Gln Gly Gly Lys Cys Ile Asn Thr Phe Gly Ser Phe Gln            1620 1625 1630 Cys Arg Cys Pro Thr Gly Tyr Tyr Leu Asn Glu Asp Thr Arg Val Cys        1635 1640 1645 Asp Asp Val Asn Glu Cys Glu Thr Pro Gly Ile Cys Gly Pro Gly Thr    1650 1655 1660 Cys Tyr Asn Thr Val Gly Asn Tyr Thr Cys Ile Cys Pro Pro Asp Tyr 1665 1670 1675 1680 Met Gln Val Asn Gly Gly Asn Asn Cys Met Asp Met Arg Arg Ser Leu                1685 1690 1695 Cys Tyr Arg Asn Tyr Tyr Ala Asp Asn Gln Thr Cys Asp Gly Glu Leu            1700 1705 1710 Leu Phe Asn Met Thr Lys Lys Met Cys Cys Cys Ser Tyr Asn Ile Gly        1715 1720 1725 Arg Ala Trp Asn Lys Pro Cys Glu Gln Cys Pro Ile Pro Ser Thr Asp    1730 1735 1740 Glu Phe Ala Thr Leu Cys Gly Ser Gln Arg Pro Gly Phe Val Ile Asp 1745 1750 1755 1760 Ile Tyr Thr Gly Leu Pro Val Asp Ile Asp Glu Cys Arg Glu Ile Pro                1765 1770 1775 Gly Val Cys Glu Asn Gly Val Cys Ile Asn Met Val Gly Ser Phe Arg            1780 1785 1790 Cys Glu Cys Pro Val Gly Phe Phe Tyr Asn Asp Lys Leu Leu Val Cys        1795 1800 1805 Glu Asp Ile Asp Glu Cys Gln Asn Gly Pro Val Cys Gln Arg Asn Ala    1810 1815 1820 Glu Cys Ile Asn Thr Ala Gly Ser Tyr Arg Cys Asp Cys Lys Pro Gly 1825 1830 1835 1840 Tyr Arg Leu Thr Ser Thr Gly Gln Cys Asn Asp Arg Asn Glu Cys Gln                1845 1850 1855 Glu Ile Pro Asn Ile Cys Ser His Gly Gln Cys Ile Asp Thr Val Gly            1860 1865 1870 Ser Phe Tyr Cys Leu Cys His Thr Gly Phe Lys Thr Asn Val Asp Gln        1875 1880 1885 Thr Met Cys Leu Asp Ile Asn Glu Cys Glu Arg Asp Ala Cys Gly Asn    1890 1895 1900 Gly Thr Cys Arg Asn Thr Ile Gly Ser Phe Asn Cys Arg Cys Asn His 1905 1910 1915 1920 Gly Phe Ile Leu Ser His Asn Asn Asp Cys Ile Asp Val Asp Glu Cys                1925 1930 1935 Ala Thr Gly Asn Gly Asn Leu Cys Arg Asn Gly Gln Cys Val Asn Thr            1940 1945 1950 Val Gly Ser Phe Gln Cys Arg Cys Asn Glu Gly Tyr Glu Val Ala Pro        1955 1960 1965 Asp Gly Arg Thr Cys Val Asp Ile Asn Glu Cys Val Leu Asp Pro Gly    1970 1975 1980 Lys Cys Ala Pro Gly Thr Cys Gln Asn Leu Asp Gly Ser Tyr Arg Cys 1985 1990 1995 2000 Ile Cys Pro Pro Gly Tyr Ser Leu Gln Asn Asp Lys Cys Glu Asp Ile                2005 2010 2015 Asp Glu Cys Val Glu Glu Pro Glu Ile Cys Ala Leu Gly Thr Cys Ser            2020 2025 2030 Asn Thr Glu Gly Ser Phe Lys Cys Leu Cys Pro Glu Gly Phe Ser Leu        2035 2040 2045 Ser Ser Thr Gly Arg Arg Cys Gln Asp Leu Arg Met Ser Tyr Cys Tyr    2050 2055 2060 Ala Lys Phe Glu Gly Gly Lys Cys Ser Ser Pro Lys Ser Arg Asn His 2065 2070 2075 2080 Ser Lys Gln Glu Cys Cys Cys Ala Leu Lys Gly Glu Gly Trp Gly Asp                2085 2090 2095 Pro Cys Glu Leu Cys Pro Thr Glu Pro Asp Glu Ala Phe Arg Gln Ile            2100 2105 2110 Cys Pro Phe Gly Ser Gly Ile Ile Val Gly Pro Asp Asp Ser Ala Val        2115 2120 2125 Asp Met Asp Glu Cys Lys Glu Pro Asp Val Cys Arg His Gly Gln Cys    2130 2135 2140 Ile Asn Thr Asp Gly Ser Tyr Arg Cys Glu Cys Pro Phe Gly Tyr Ile 2145 2150 2155 2160 Leu Glu Gly Asn Glu Cys Val Asp Thr Asp Glu Cys Ser Val Gly Asn                2165 2170 2175 Pro Cys Gly Asn Gly Thr Cys Lys Asn Val Ile Gly Gly Phe Glu Cys            2180 2185 2190 Thr Cys Glu Glu Gly Phe Glu Pro Gly Pro Met Met Thr Cys Glu Asp        2195 2200 2205 Ile Asn Glu Cys Ala Gln Asn Pro Leu Leu Cys Ala Phe Arg Cys Val    2210 2215 2220 Asn Thr Tyr Gly Ser Tyr Glu Cys Lys Cys Pro Val Gly Tyr Val Leu 2225 2230 2235 2240 Arg Glu Asp Arg Arg Met Cys Lys Asp Glu Asp Glu Cys Ala Glu Gly                2245 2250 2255 Lys His Asp Cys Thr Glu Lys Gln Met Glu Cys Lys Asn Leu Ile Gly            2260 2265 2270 Thr Tyr Met Cys Ile Cys Gly Pro Gly Tyr Gln Arg Arg Pro Asp Gly        2275 2280 2285 Glu Gly Cys Ile Asp Glu Asn Glu Cys Gln Thr Lys Pro Gly Ile Cys    2290 2295 2300 Glu Asn Gly Arg Cys Leu Asn Thr Leu Gly Ser Tyr Thr Cys Glu Cys 2305 2310 2315 2320 Asn Asp Gly Phe Thr Ala Ser Pro Thr Gln Asp Glu Cys Leu Asp Asn                2325 2330 2335 Arg Glu Gly Tyr Cys Phe Ser Glu Val Leu Gln Asn Met Cys Gln Ile            2340 2345 2350 Gly Ser Ser Asn Arg Asn Pro Val Thr Lys Ser Glu Cys Cys Cys Asp        2355 2360 2365 Gly Gly Arg Gly Trp Gly Pro His Cys Glu Ile Cys Pro Phe Glu Gly    2370 2375 2380 Thr Val Ala Tyr Lys Lys Leu Cys Pro His Gly Arg Gly Phe Met Thr 2385 2390 2395 2400 Asn Gly Ala Asp Ile Asp Glu Cys Lys Val Ile His Asp Val Cys Arg                2405 2410 2415 Asn Gly Glu Cys Val Asn Asp Arg Gly Ser Tyr His Cys Ile Cys Lys            2420 2425 2430 Thr Gly Tyr Thr Pro Asp Ile Thr Gly Thr Ala Cys Val Asp Leu Asn        2435 2440 2445 Glu Cys Asn Gln Ala Pro Lys Pro Cys Asn Phe Ile Cys Lys Asn Thr    2450 2455 2460 Glu Gly Ser Tyr Gln Cys Ser Cys Pro Lys Gly Tyr Ile Leu Gln Glu 2465 2470 2475 2480 Asp Gly Arg Ser Cys Lys Asp Leu Asp Glu Cys Ala Thr Lys Gln His                2485 2490 2495 Asn Cys Gln Phe Leu Cys Val Asn Thr Ile Gly Gly Phe Thr Cys Lys            2500 2505 2510 Cys Pro Pro Gly Phe Thr Gln His His Thr Ala Cys Ile Asp Asn Asn        2515 2520 2525 Glu Cys Thr Ser Asp Ile Asn Leu Cys Gly Ser Lys Gly Val Cys Gln    2530 2535 2540 Asn Thr Pro Gly Ser Phe Thr Cys Glu Cys Gln Arg Gly Phe Ser Leu 2545 2550 2555 2560 Asp Gln Ser Gly Ala Ser Cys Glu Asp Val Asp Glu Cys Glu Gly Asn                2565 2570 2575 His Arg Cys Gln His Gly Cys Gln Asn Ile Gly Gly Tyr Arg Cys            2580 2585 2590 Ser Cys Pro Gln Gly Tyr Leu Gln His Tyr Gln Trp Asn Gln Cys Val        2595 2600 2605 Asp Glu Asn Glu Cys Leu Ser Ala His Val Cys Gly Gly Ala Ser Cys    2610 2615 2620 His Asn Thr Leu Gly Ser Tyr Lys Cys Met Cys Pro Thr Gly Phe Gln 2625 2630 2635 2640 Tyr Glu Gln Phe Ser Gly Gly Cys Gln Asp Ile Asn Glu Cys Gly Ser                2645 2650 2655 Ser Gln Ala Pro Cys Ser Tyr Gly Cys Ser Asn Thr Glu Gly Gly Tyr            2660 2665 2670 Leu Cys Gly Cys Pro Pro Gly Tyr Phe Arg Ile Gly Gln Gly His Cys        2675 2680 2685 Val Ser Gly Met Gly Met Gly Arg Gly Gly Pro Glu Pro Pro Ala Ser    2690 2695 2700 Ser Glu Met Asp Asp Asn Ser Leu Ser Pro Glu Ala Cys Tyr Glu Cys 2705 2710 2715 2720 Lys Ile Asn Gly Tyr Pro Lys Arg Gly Arg Lys Arg Arg Ser Thr Asn                2725 2730 2735 Glu Thr Asp Ala Ser Asp Ile Gln Asp Gly Ser Glu Met Glu Ala Asn            2740 2745 2750 Val Ser Leu Ala Ser Trp Asp Val Glu Lys Pro Ala Ser Phe Ala Phe        2755 2760 2765 Asn Ile Ser His Val Asn Asn Lys Val Arg Ile Leu Glu Leu Leu Pro    2770 2775 2780 Ala Leu Thr Thr Leu Met Asn His Asn Arg Tyr Leu Ile Glu Ser Gly 2785 2790 2795 2800 Asn Glu Asp Gly Phe Phe Lys Ile Asn Gln Lys Glu Gly Val Ser Tyr                2805 2810 2815 Leu His Phe Thr Lys Lys Lys Pro Val Ala Gly Thr Tyr Ser Leu Gln            2820 2825 2830 Ile Ser Ser Thr Pro Leu Tyr Lys Lys Lys Glu Leu Asn Gln Leu Glu        2835 2840 2845 Asp Arg Tyr Asp Lys Asp Tyr Leu Ser Gly Glu Leu Gly Asp Asn Leu    2850 2855 2860 Lys Met Lys Ile Gln Ile Leu Leu His 2865 2870 <210> 18 <211> 9900 <212> DNA <213> Artificial Sequence <220> Nucleic acid encoding mouse Fibrillin 1 protein <400> 18 agagttgggg cagagactgt gggtgccaca ggcggccaca gctgggacag ctgcggagca 60 gagcagccac cgccgcctga gagtccgagc cgctagtcca gacaggcagg gactacccga 120 agtgggagca gtccctggag aagaaagctg taggacccag gccggggacc tctctgcatc 180 aggacagccg gacagtgaga cagcgggacc ccggagactc gggccgctgg aaggcgcggc 240 ggcggcggcg gcggcggcgg cggagcgagt ggcggccggc ggcaccatgc ggcgaggagg 300 gctgctggag gtcgcgctgg cgttcgccct gctcctcgag tcctacacga gccatggggc 360 ggacgccaat ttggaggctg ggagcctgaa ggagaccaga gccaatcggg ccaagagaag 420 aggcggcgga ggacacgatg cgctgaaagg acccaatgtc tgtggatcac gttataatgc 480 atactgttgt cctggatgga aaaccttacc tggtggaaat cagtgtattg ttcccatttg 540 ccggcattcc tgtggggatg gattctgctc gaggccaaat atgtgcactt gcccgtctgg 600 tcagatatct ccttcctgtg gctccagatc catccaacac tgcagcatcc gctgtatgaa 660 tgggggcagc tgcagcgatg accactgtct gtgccagaaa gggtacatcg gcactcactg 720 tggacagcct gtctgtgaaa gtggctgtct caacggaggg aggtgtgtgg ccccaaatcg 780 gtgtgcttgc acgtacggct ttactggacc ccagtgtgaa agagattaca gaacaggccc 840 atgttttact gtggtaagca accagatgtg ccagggacag ctcagcggga ttgtctgcac 900 caaaacactt tgctgtgcca ccgtgggccg agcctggggc cacccctgtg agatgtgtcc 960 tgcccagcct cacccctgcc gccgcggctt cattcccaac atccgcactg gagcttgtca 1020 agatgtggat gaatgtcagg ccatcccagg gatgtgtcaa ggaggaaatt gcattaatac 1080 cgttggatct tttgagtgca aatgccctgc tggacacaaa tttaatgaag tgtcacaaaa 1140 atgtgaagat attgacgagt gcagcaccat tcctggagtc tgcgatggcg gggaatgtac 1200 aaacactgtc agcagctact tctgcaaatg tccccctggt ttttacacct ctcctgatgg 1260 caccagatgc gtagatgttc gccctggtta ctgctacaca gctctggcaa acgggcgctg 1320 ctctaaccag ctgccacagt ccataaccaa aatgcagtgc tgttgcgatc ttggccggtg 1380 ctggtctcca ggggttactg ttgctcccga gatgtgtccc atcaggtcaa ctgaggattt 1440 caacaagctg tgctctgtcc ctctggtaat tcccgggaga ccagaatatc ctcccccacc 1500 cattggcccc cttcctccag ttcagcccgt tcctcctggc tatcctcctg ggcctgtgat 1560 tccagcccct cggccaccgc cagaatatcc atatccatct ccgtctcggg aaccaccaag 1620 ggtgctgcct ttcaacgtta ctgactactg tcaactggtc cgctatctct gtcaaaatgg 1680 gcgctgcatt ccaactcccg gtagctaccg ctgcgagtgc aacaagggct tccagctgga 1740 tatccgtggc gaatgcatcg acgtggatga gtgtgagaag aacccatgca ctggtggcga 1800 gtgcatcaac aaccagggct cctacacctg tcactgcaga gctggctacc agagcacact 1860 caccagaact gagtgcagag acatagatga gtgtcttcag aatggccgga tctgcaacaa 1920 tggtcgctgt atcaacacag acggcagctt ccactgcgta tgcaatgcgg gctttcatgt 1980 cacgcgggac ggaaagaact gtgaagatat ggatgagtgc agcatccgaa acatgtgcct 2040 aaacggaatg tgtattaatg aagatggcag tttcaagtgt atttgcaaac ctgggttcca 2100 actggcatca gatggccgct actgcaaaga tatcaatgag tgtgagacac ctgggatctg 2160 catgaacgga cgctgtgtga acacggatgg ctcctacaga tgcgaatgct tccccggatt 2220 ggctgtgggt ctagacggac gtgtgtgtgt tgacacacac atgcggagca catgctatgg 2280 aggatacagg agaggccagt gcgtgaagcc gttgtttggt gctgttacca aatcggaatg 2340 ctgttgtgcc agcactgagt atgcctttgg ggaaccctgc cagccgtgtc ctgcacagaa 2400 ttcagcggaa tatcaggcac tctgcagcag tggaccggga atgacatcag caggcactga 2460 tataaacgaa tgtgcattag atcctgatat ttgcccaaat ggaatttgtg aaaatctccg 2520 tgggacctac aaatgtatat gcaactcggg atatgaagta gacataactg ggaaaaactg 2580 tgtcgatatt aatgagtgtg tgctgaacag tctactttgt gacaatggac aatgtcgaaa 2640 cacacctgga agttttgtct gcacctgccc caaaggattt gtgtacaaac ctgacctaaa 2700 aacctgtgaa gacattgatg aatgtgaatc gagtccttgc attaatggag tctgcaagaa 2760 cagccctggc tccttcattt gtgaatgttc tcctgaaagt actctggacc caacaaaaac 2820 catctgcata gaaaccatca agggcacttg ctggcagact gtcatcgacg ggcgctgtga 2880 gatcaacatc aacggagcca ccttgaagtc cgagtgctgc tcctcccttg gtgctgcgtg 2940 ggggagcccg tgcaccatct gtcaacttga tcccatttgt ggtaaagggt tctcaagaat 3000 taaaggcacg caatgtgaag atatcaatga gtgtgaagtg ttcccgggag tatgcaagaa 3060 cggcctgtgt gtcaactcca ggggttcatt caagtgcgag tgtcccaatg gaatgacttt 3120 ggatgctaca ggaagaatct gtcttgacat ccgcctggag acctgcttcc tcaagtatga 3180 cgatgaagag tgcaccttgc ccatcgctgg ccgccaccga atggatgcct gctgctgctc 3240 tgttggggca gcctggggaa cggaagagtg tgaggagtgt ccattgagaa acagccggga 3300 gtatgaggaa ctctgtcccc gaggacctgg gtttgccaca aaagacatta caaatgggaa 3360 acctttcttc aaagatatca atgagtgcaa gatgataccc agcctctgta cccacggcaa 3420 gtgcaggaac accattggca gcttcaagtg taggtgtgac agtggctttg ctctggattc 3480 tgaagagagg aactgtacag acattgatga gtgccgcata tctcctgacc tctgtggccg 3540 aggccagtgt gtgaacaccc cgggggactt tgaatgcaag tgtgatgaag gctatgaaag 3600 tggcttcatg atgatgaaga actgcatgga tattgatgaa tgtcagagag atcctctcct 3660 gtgtcgagga ggcatttgcc acaacacaga gggaagctat cgctgcgaat gtcctcctgg 3720 tcaccaattg tccccaaaca tctctgcatg cattgacatc aacgagtgtg agctgagtgc 3780 gaatctctgt ccccatgggc gttgtgtgaa cctcataggg aagtaccagt gtgcctgcaa 3840 ccctggctac caccccactc atgacaggct cttctgtgtc gatattgatg aatgcagcat 3900 aatgaacggt ggttgtgaga ccttctgcac aaactctgac gggagctatg aatgtagctg 3960 tcagccaggc ttcgcgctaa tgccagacca gcgatcgtgc acagacattg atgagtgtga 4020 agacaacccc aatatctgtg atggtggcca gtgcacaaac atacctgggg agtacaggtg 4080 cctgtgctat gatgggttca tggcatctga agacatgaag acttgtgtgg atgtcaatga 4140 gtgtgacctg aatccaaaca tctgccttag tgggacctgt gaaaatacta aaggctcgtt 4200 catctgccac tgtgatatgg gatattcagg gaagaaagga aaaacgggct gtacagatat 4260 caatgaatgt gagatcggag cacacaactg tggcagacat gctgtatgca caaatacagc 4320 cgggagcttc aagtgcagct gcagtcccgg ctggattgga gacggcatta agtgcacaga 4380 tctggatgaa tgctctaatg gaacccacat gtgcagccaa cacgcggact gcaagaacac 4440 catggggtca tatcgctgtc tctgtaagga tggctataca ggggatggct tcacctgtac 4500 agacctcgac gagtgctccg agaacctgaa cctctgtggc aatggccagt gcctcaacgc 4560 ccctggcggg taccgctgtg aatgcgacat gggcttcgtg cccagtgctg acgggaaggc 4620 ctgtgaagat atcgatgagt gctcccttcc aaacatctgt gtctttggaa cttgccacaa 4680 cctcccgggc ctcttccgtt gcgagtgtga gattggctat gaactggacc gaagtggtgg 4740 aaactgcaca gatgttaatg agtgtctgga tcccaccacc tgcatcagtg gaaactgtgt 4800 caacactccc ggtagttaca catgcgattg tcctccggat tttgagctga atccaactcg 4860 tgtcggctgt gtcgatactc gctctggaaa ctgctatctg gatatccgac cccggggaga 4920 caatggagat acagcctgca gcaatgaaat tggagttggt gtctctaagg cttcctgctg 4980 ttgttcactg ggtaaagctt ggggaacccc atgtgagctg tgtccttctg tgaacacatc 5040 tgagtataaa attctttgcc ctggaggaga aggttttcgt ccaaatccca tcaccgttat 5100 attggaagac atcgatgagt gccaggagct tccagggctg tgccaagggg ggaagtgcat 5160 caataccttt ggcagcttcc agtgtcgctg tccaactggt tactacctga atgaagacac 5220 tcgagtgtgt gatgatgtga acgaatgtga gactcctgga atctgtggtc cggggacctg 5280 ttacaacacc gttggcaact atacctgcat ttgtcctcca gactacatgc aagtgaacgg 5340 gggaaataat tgcatggaca tgagaagaag tctatgctac agaaactatt acgctgacaa 5400 ccagacctgc gatggagaac tcctgttcaa catgaccaag aagatgtgct gttgctccta 5460 caacatcggc agagcctgga acaaaccctg tgaacagtgc cccatcccaa gcacagatga 5520 gtttgctacc ctctgtggga gccagaggcc cggcttcgtg attgacattt atacgggttt 5580 acccgtggat attgatgaat gccgggagat ccctggggtc tgtgaaaatg gagtgtgcat 5640 caacatggtt ggcagcttcc ggtgtgagtg tcccgtggga ttcttctata acgacaagtt 5700 actggtttgt gaagatatcg acgagtgtca gaatggccct gtgtgccagc gaaatgcgga 5760 atgcatcaac actgcaggca gctaccgctg tgactgtaag cccggctacc gccttacctc 5820 cacaggtcaa tgcaacgatc gaaacgagtg ccaagaaatc ccgaacatat gcagtcatgg 5880 ccagtgcatc gacaccgtgg gaagcttcta ctgcctttgt cacactggct tcaaaacaaa 5940 tgtggatcag accatgtgct tagacataaa tgagtgtgag agagacgcct gtgggaacgg 6000 gacttgcaga aacacgattg gctccttcaa ctgtcgctgt aaccatggct tcatactgtc 6060 tcacaacaat gactgcatag atgttgatga gtgtgcaact ggaaacggga acctttgcag 6120 aaatggccag tgtgtcaata ccgtgggctc ctttcagtgc aggtgcaatg aaggctatga 6180 ggtggctccg gacggcagga cctgtgtgga tatcaacgag tgtgttctgg atcctgggaa 6240 atgtgcacct ggaacctgtc agaacctgga tggctcctac agatgcattt gcccgcctgg 6300 gtatagtcta cagaatgaca agtgtgaaga tattgatgag tgtgttgaag agccagaaat 6360 ctgtgccttg gggacctgca gcaacactga gggtagcttc aaatgtctgt gtccagaggg 6420 gttctccctg tcctccactg gaagaaggtg ccaagatttg cgaatgagct actgctatgc 6480 gaagtttgaa ggtgggaagt gttcatcacc caaatccaga aaccattcca agcaggagtg 6540 ctgctgtgct ttgaagggag aaggctgggg agatccttgt gagttgtgcc ccactgagcc 6600 agatgaggct ttccgccaga tctgcccctt tggaagtggg atcattgtgg gccctgatga 6660 ctcagcagtt gatatggacg aatgcaaaga acctgatgtc tgtagacatg ggcagtgcat 6720 taacacagac ggctcctatc gatgcgagtg tccttttggt tatattctgg aagggaatga 6780 gtgtgtggat accgatgaat gctctgtggg caatccttgt ggaaatggga cctgcaagaa 6840 tgtgattgga ggttttgaat gtacctgtga ggaggggttc gagcctggcc caatgatgac 6900 ttgtgaagat ataaatgaat gtgcccagaa tcctctgctc tgcgccttcc gctgtgtaaa 6960 tacctacggg tcctatgaat gcaaatgccc tgttggatac gttctccgag aagacaggag 7020 gatgtgtaaa gatgaggatg agtgtgcaga gggaaaacac gactgtactg agaagcaaat 7080 ggagtgtaag aacctcattg gtacctacat gtgcatctgc ggccctgggt accagcgcag 7140 acccgatgga gagggctgca tagatgagaa tgagtgtcag accaagcccg ggatctgtga 7200 gaatgggcgt tgcctcaaca ccctgggtag ctacacttgt gagtgtaacg atggcttcac 7260 agccagcccc actcaggatg agtgcttgga caaccgggaa gggtactgct tttcggaggt 7320 cttgcaaaac atgtgccaga ttggctcaag caacaggaac cccgtcacca agtccgagtg 7380 ctgctgtgat ggagggagag gctggggacc ccactgtgag atctgccctt tcgagggcac 7440 agtggcttac aagaagctct gtccccacgg ccgaggattc atgaccaacg gagcagatat 7500 tgatgagtgc aaggttattc atgatgtttg ccgaaatggg gagtgtgtca acgacagagg 7560 gtcctatcac tgcatctgta aaactggcta cactccggat ataacaggga ccgcctgtgt 7620 agatctgaat gaatgcaacc aggctcccaa accctgcaat tttatatgca aaaacacaga 7680 agggagttac cagtgttcct gcccgaaggg ctacattctg caagaggatg gaaggagctg 7740 caaagatctt gacgagtgtg caaccaagca gcataactgt cagttcctgt gtgttaacac 7800 catcggtggc ttcacatgca aatgccctcc tgggtttacc cagcatcaca ctgcctgcat 7860 tgataacaat gagtgcacgt ctgatatcaa cctgtgtggg tccaagggtg tttgccagaa 7920 cactccagga agcttcacct gtgaatgcca acgggggttc tcactcgatc agagtggtgc 7980 cagctgtgaa gatgtggacg agtgtgaggg taaccaccgc tgtcaacatg gctgccagaa 8040 catcatcgga ggctataggt gtagctgccc ccagggctac ctccagcact accaatggaa 8100 ccagtgtgta gatgaaaacg agtgcctgag tgcacatgtc tgtggaggag cctcctgcca 8160 caacaccctg gggagttaca agtgcatgtg tcccaccggc ttccagtacg aacagttcag 8220 tggaggctgc caagacatca atgagtgtgg ctcatcccag gccccctgca gttacggttg 8280 ctctaatact gagggtggct acctgtgtgg ctgtccacca ggatacttcc ggataggcca 8340 agggcattgt gtttctggaa tgggcatggg ccgaggcggc ccagagccac ctgccagcag 8400 cgagatggac gacaactcac tgtccccaga ggcctgctat gagtgtaaga tcaacggcta 8460 cccaaaacga ggccggaaac ggagaagcac gaacgaaacg gatgcctccg acatccagga 8520 cgggtctgag atggaagcca acgtgagcct cgccagctgg gatgtggaga agccggctag 8580 ctttgctttc aatatttccc atgtcaataa caaggtccga atcctagagc tcctgccggc 8640 cctcacaact ctgatgaacc acaacagata cttgattgaa tctggaaatg aagatggctt 8700 ctttaaaatc aaccagaaag aaggggtcag ctacctccac ttcacgaaga agaagccggt 8760 ggctgggacc tactccttac aaatcagcag caccccactt tataaaaaga aagaacttaa 8820 ccagttagaa gacagatatg acaaagacta cctcagtggt gaactgggcg ataacctgaa 8880 gatgaaaatt cagatcttgc tgcattaatt caccatccag agaccaaata attaaatgaa 8940 aaagcaacct taggcaggta gaattatatt ttccccaagc cagaaccttc acatcatggt 9000 acaattgttc accgagtcga tctgtataaa tgagcaccac tcttgaatgg caacacccag 9060 gtacagtgat gatcctagtt caaccaacca ctttctcagg cttctcgtga gtagctcagc 9120 taccctgtca tgcgtattga ttcctgaaaa ctgggacatg aatatccgct gaggttggcc 9180 attcacgccg atgggctatc ttcccagcct ccgcacagga acgcgcttcc atctgatgga 9240 ctgttccgcg ttggtcttca gatcttgaaa ctttgcttct ccgagtgcaa gcagtaggtt 9300 tctgttgtct gtttggtgct agtaaattct caaaatagat ttattgatgc actgtaataa 9360 agacacgagt taggaaccaa attgccaagt actcagttca aatacttcat ttcaatcaac 9420 caaagttagt tcagtagctt atctcactta tgagtatggt gcagtacatg taaattaagt 9480 gtgtgtacac tgtaacgtgc tatttttatc attgaaacat ttataaacta caataataaa 9540 gcccttaatg tgagggtttg taatggtgct tattaagacc aaagacttgt taaacatcta 9600 cccaaatgg tagtggattc tctgagactg gcccacttgt gcactgaggt tggggaggac 9660 aaggaagcag cctcagccac cagaggatca ccaccgcatc ctccatcaca cagcatgtgc 9720 aatacgccaa aatcactctc agtcattcct gtcaacaagg ggttaatgtc atgatgtcac 9780 aataaagtga tcctcccctc cctccccatt ttagtttaca ccttggtttt atgttcttgt 9840 gtggattaag gctggagggg cctttctgga ggtgaaataa agtctcctgg gtttaaagta 9900                                                                         9900 <210> 19 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Human Decorin protein <400> 19 Met Lys Ala Thr Ile Leu Leu Leu   1 5 10 15 Gly Pro Phe Gln Gln Arg Gly Leu Phe Asp Phe Met Leu Glu Asp Glu              20 25 30 Ala Ser Gly Ile Gly Pro Glu Val Pro Asp Asp Arg Asp Phe Glu Pro          35 40 45 Ser Leu Gly Pro Val Cys Pro Phe Arg Cys Gln Cys His Leu Arg Val      50 55 60 Val Gln Cys Ser Asp Leu Gly Leu Asp Lys Val Pro Lys Asp Leu Pro  65 70 75 80 Pro Asp Thr Thr Leu Leu Asp Leu Gln Asn Asn Lys Ile Thr Glu Ile                  85 90 95 Lys Asp Gly Asp Phe Lys Asn Leu Lys Asn Leu His Ala Leu Ile Leu             100 105 110 Val Asn Asn Lys Ile Ser Lys Val Ser Pro Gly Ala Phe Thr Pro Leu         115 120 125 Val Lys Leu Glu Arg Leu Tyr Leu Ser Lys Asn Gln Leu Lys Glu Leu     130 135 140 Pro Glu Lys Met Pro Lys Thr Leu Gln Glu Leu Arg Ala His Glu Asn 145 150 155 160 Glu Ile Thr Lys Val Arg Lys Val Thr Phe Asn Gly Leu Asn Gln Met                 165 170 175 Ile Val Ile Glu Leu Gly Thr Asn Pro Leu Lys Ser Ser Gly Ile Glu             180 185 190 Asn Gly Ala Phe Gln Gly Met Lys Lys Leu Ser Tyr Ile Arg Ile Ala         195 200 205 Asp Thr Asn Ile Thr Ser Ile Pro Gln Gly Leu Pro Pro Ser Leu Thr     210 215 220 Glu Leu His Leu Asp Gly Asn Lys Ile Ser Arg Val Asp Ala Ala Ser 225 230 235 240 Leu Lys Gly Leu Asn Asn Leu Ala Lys Leu Gly Leu Ser Phe Asn Ser                 245 250 255 Ile Ser Ala Val Asp Asn Gly Ser Leu Ala Asn Thr Pro His Leu Arg             260 265 270 Glu Leu His Leu Asp Asn Asn Lys Leu Thr Arg Val Pro Gly Gly Leu         275 280 285 Ala Glu His Lys Tyr Ile Gln Val Val Tyr Leu His Asn Asn Asn Ile     290 295 300 Ser Val Val Gly Ser Ser Asp Phe Cys Pro Pro Gly His Asn Thr Lys 305 310 315 320 Lys Ala Ser Tyr Ser Gly Val Ser Leu Phe Ser Asn Pro Val Gln Tyr                 325 330 335 Trp Glu Ile Gln Pro Ser Thr Phe Arg Cys Val Tyr Val Arg Ser Ala             340 345 350 Ile Gln Leu Gly Asn Tyr Lys         355 <210> 20 <211> 2305 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid encoding human Decorin protein <400> 20 gaatctacaa taagacaaat ttcaaatcaa gttgctccac tatactgcat aagcagttta 60 gaatcttaag cagatgcaaa aagaataaag caaatgggag gaaaaaaaag gccgataaag 120 tttctggcta caatacaaga gacatatcat taccatatga tctaatgtgg gtgtcagccg 180 gattgtgttc attgagggaa accttatttt ttaactgtgc tatggagtag aagcaggagg 240 ttttcaacct agtcacagag cagcacctac cccctcctcc tttccacacc tgcaaactct 300 tttacttggg ctgaatattt agtgtaatta catctcagct ttgagggctc ctgtggcaaa 360 ttcccggatt aaaaggttcc ctggttgtga aaatacatga gataaatcat gaaggccact 420 atcatcctcc ttctgcttgc acaagtttcc tgggctggac cgtttcaaca gagaggctta 480 tttgacttta tgctagaaga tgaggcttct gggataggcc cagaagttcc tgatgaccgc 540 gacttcgagc cctccctagg cccagtgtgc cccttccgct gtcaatgcca tcttcgagtg 600 gtccagtgtt ctgatttggg tctggacaaa gtgccaaagg atcttccccc tgacacaact 660 ctgctagacc tgcaaaacaa caaaataacc gaaatcaaag atggagactt taagaacctg 720 aagaaccttc acgcattgat tcttgtcaac aataaaatta gcaaagttag tcctggagca 780 tttacacctt tggtgaagtt ggaacgactt tatctgtcca agaatcagct gaaggaattg 840 ccagaaaaaa tgcccaaaac tcttcaggag ctgcgtgccc atgagaatga gatcaccaaa 900 gtgcgaaaag ttactttcaa tggactgaac cagatgattg tcatagaact gggcaccaat 960 ccgctgaaga gctcaggaat tgaaaatggg gctttccagg gaatgaagaa gctctcctac 1020 atccgcattg ctgataccaa tatcaccagc attcctcaag gtcttcctcc ttcccttacg 1080 gaattacatc ttgatggcaa caaaatcagc agagttgatg cagctagcct gaaaggactg 1140 aataatttgg ctaagttggg attgagtttc aacagcatct ctgctgttga caatggctct 1200 ctggccaaca cgcctcatct gagggagctt cacttggaca acaacaagct taccagagta 1260 cctggtgggc tggcagagca taagtacatc caggttgtct accttcataa caacaatatc 1320 tctgtagttg gatcaagtga cttctgccca cctggacaca acaccaaaaa ggcttcttat 1380 tcgggtgtga gtcttttcag caacccggtc cagtactggg agatacagcc atccaccttc 1440 agatgtgtct acgtgcgctc tgccattcaa ctcggaaact ataagtaatt ctcaagaaag 1500 ccctcatttt tataacctgg caaaatcttg ttaatgtcat tgctaaaaaa taaataaaag 1560 ctagatactg gaaacctaac tgcaatgtgg atgttttacc cacatgactt attatgcata 1620 aagccaaatt tccagtttaa gtaattgcct acaataaaaa gaaattttgc ctgccatttt 1680 cagaatcatc ttttgaagct ttctgttgat gttaactgag ctactagaga tattcttatt 1740 tcactaaatg taaaatttgg agtaaatata tatgtcaata tttagtaaag cttttctttt 1800 ttaatttcca ggaaaaaata aaaagagtat gagtcttctg taattcattg agcagttagc 1860 tcatttgaga taaagtcaaa tgccaaacac tagctctgta ttaatcccca tcattactgg 1920 taaagcctca tttgaatgtg tgaattcaat acaggctatg taaaattttt actaatgtca 1980 ttattttgaa aaaataaatt taaaaataca ttcaaaatta ctattgtata caagcttaat 2040 tgttaatatt ccctaaacac aattttatga agggagaaga cattggtttg ttgacaataa 2100 cagtacatct tttcaagttc tcagctattt cttctacctc tccctatctt acatttgagt 2160 atggtaactt atgtcatcta tgttgaatgt aagcttataa agcacaaagc atacatttcc 2220 tgactggtct agagaactga tgtttcaatt tacccctctg ctaaataaat attaaaacta 2280 tcatgtgaaa aaaaaaaaaa aaaaa 2305 <210> 21 <211> 354 <212> PRT <213> Artificial Sequence <220> <223> Mouse Decorin protein <400> 21 Met Lys Ala Thr Leu Ile Phe Phe Leu Leu Ala Gln Val Ser Trp Ala   1 5 10 15 Gly Pro Phe Glu Gln Arg Gly Leu Phe Asp Phe Met Leu Glu Asp Glu              20 25 30 Ala Ser Gly Ile Ile Pro Tyr Asp Pro Asp Asn Pro Leu Ile Ser Met          35 40 45 Cys Pro Tyr Arg Cys Gln Cys His Leu Arg Val Val Gln Cys Ser Asp      50 55 60 Leu Gly Leu Asp Lys Val Pro Trp Asp Phe Pro Pro Asp Thr Thr Leu  65 70 75 80 Leu Asp Leu Gln Asn Asn Lys Ile Thr Glu Ile Lys Glu Gly Ala Phe                  85 90 95 Lys Asn Leu Lys Asp Leu His Thr Leu Ile Leu Val Asn Asn Lys Ile             100 105 110 Ser Lys Ile Ser Pro Glu Ala Phe Lys Pro Leu Val Lys Leu Glu Arg         115 120 125 Leu Tyr Leu Ser Lys Asn Gln Leu Lys Glu Leu Pro Glu Lys Met Pro     130 135 140 Arg Thr Leu Gln Glu Leu Arg Val His Glu Asn Glu Ile Thr Lys Leu 145 150 155 160 Arg Lys Ser Asp Phe Asn Gly Leu Asn Asn Val Leu Val Ile Glu Leu                 165 170 175 Gly Asn Pro Leu Lys Asn Ser Gly Ile Glu Asn Gly Ala Phe Gln             180 185 190 Gly Leu Lys Ser Leu Ser Tyr Ile Arg Ile Ser Asp Thr Asn Ile Thr         195 200 205 Ala Ile Pro Gln Gly Leu Pro Thr Ser Leu Thr Glu Val His Leu Asp     210 215 220 Gly Asn Lys Ile Thr Lys Val Asp Ala Pro Ser Leu Lys Gly Leu Ile 225 230 235 240 Asn Leu Ser Lys Leu Gly Leu Ser Phe Asn Ser Ile Thr Val Met Glu                 245 250 255 Asn Gly Ser Leu Ala Asn Val Pro His Leu Arg Glu Leu His Leu Asp             260 265 270 Asn Asn Lys Leu Leu Arg Val Pro Ala Gly Leu Ala Gln His Lys Tyr         275 280 285 Ile Gln Val Val Tyr Leu His Asn Asn Asn Ser Ser Ala Val Gly Gln     290 295 300 Asn Asp Phe Cys Arg Ala Gly His Pro Ser Arg Lys Ala Ser Tyr Ser 305 310 315 320 Ala Val Ser Leu Tyr Gly Asn Pro Val Arg Tyr Trp Glu Ile Phe Pro                 325 330 335 Asn Thr Phe Arg Cys Val Tyr Val Arg Ser Ala Ile Gln Leu Gly Asn             340 345 350 Tyr Lys         <210> 22 <211> 1886 <212> DNA <213> Artificial Sequence <220> <223> Nucleic acid encoding mouse Decorin protein <400> 22 gggggaggga gaagggggcc gataaagttt ctggctacaa tacaagagac gtatcattac 60 catatgatct aatgtgggtg tcagctggat gcgctcacgc agtgaaacct tagttcttaa 120 ctgtgctatg gagtagaagc aggaggtttt caacccagtg acagtcacag ggcagcacca 180 ccccctcctc cttctttcca cacctgcaaa cccttttgcc tgggctgcat agttagtgtt 240 aattacatcg cagctttgag ggctcctgtg gcaaataccc ggattaaaag gtcgtgaaaa 300 tacatgagat aatcatgaag gcaactctca tcttcttcct tctggcacaa gtctcttggg 360 ctggaccatt tgaacagaga ggcttatttg acttcatgct agaagatgag gcttctggca 420 taatccctta tgaccctgac aatcccctga tatctatgtg cccctaccga tgccagtgtc 480 atcttcgagt ggtgcagtgt tctgatctgg gtttggacaa agtgccctgg gattttccac 540 ccgacacaac cttgctagac ctgcaaaaca acaaaattac agagatcaaa gaaggggcct 600 tcaagaacct gaaggacttg cataccttga tccttgtcaa caacaagatc agcaaaatca 660 gtccagaggc attcaaacct ctcgtgaagt tggaaaggct ttacctgtct aagaaccaac 720 taaaggaact gcctgaaaaa atgcccagaa ctctccagga acttcgtgtc catgagaatg 780 agatcaccaa gctgcggaaa tccgacttca atggactgaa caatgtgctt gtcatagaac 840 tgggcggcaa cccactgaaa aactctggga ttgaaaacgg agccttccag ggactgaaga 900 gtctctcata cattcgcatc tcagacacca acataactgc gatccctcaa ggtctgccta 960 cttctctcac tgaagtgcat ctagatggca acaagatcac caaggttgat gcacccagcc 1020 tgaaaggact gattaatttg tctaaactgg gattgagctt caacagcatc accgttatgg 1080 agaatggcag tctggccaat gttcctcatc tgagggaact ccacttggac aacaacaaac 1140 tcctcagggt gcctgctggg ctggcacagc ataagtatat ccaggtcgtc taccttcaca 1200 acaacaacat ctccgcagtt gggcaaaatg acttctgccg agctggacac ccctctcgaa 1260 aggcttccta ctcggctgtg agtctttacg gcaaccctgt ccggtattgg gaaatctttc 1320 caaacacctt cagatgtgtc tatgtgcgtt ctgccattca acttggaaac tacaagtaac 1380 cctcagacgg cctaattctt ataatctgga aaaacacccc aatatgtcaa tatcattgct 1440 aaaaagaaaa aatactaaaa aagaaagaaa gaatgctaga ttctggaaat tcaagcacac 1500 tgtgcatgcc ttttccacat gacttattat gcaagctgaa tatacagatt gaataattgc 1560 ctacaataaa aatattttac ttgtagtatt cagaatcact tttaaagttg tctgtagttg 1620 tgaactgagt tatcaaagtc tgatgtaatc ataaatgtca accacttagt aaagcgttaa 1680 aaggaacaga atacaaagtc tctgtaattc atagagctaa attaactctt ttgacataaa 1740 gtcaaatgcc gccgaactct agcaatgtat taatctcctt tattattggt gaagccttat 1800 ttgagtatgt aagttcaata tgggctatgt aaaattttca ctgtcatatt gaaaaaaata 1860 aaattttaaa aatgcattca aaagat 1886

Claims (15)

An activator that increases the amount of keratin 17 (Krt17) transcript or the protein encoded thereby;
An activator that increases the amount of collagen type 1 alpha 1 (Col1a1) transcript or the protein encoded thereby;
An inhibitor that reduces the amount of fibrillin 1 (Fbn1) transcript or the amount of protein encoded thereby; And
A pharmaceutical composition for prevention or treatment of hair loss comprising at least one substance selected from the group consisting of decorin (Dcn) transcripts or inhibitors that reduce the amount of protein encoded thereby. The pharmaceutical composition for preventing or treating hair loss according to claim 1, wherein the active agent is a transcription activator or a protein active agent (agonist). The pharmaceutical composition according to claim 1, wherein the inhibitor is a transcription repressor or a protein active antagonist. The pharmaceutical composition for prevention or treatment of hair loss according to claim 1, wherein the active agent is a transcription factor, a natural extract, a chemical substance, or a combination thereof. The method of claim 1, wherein the inhibitor is selected from the group consisting of antisense oligonucleotides, small interference RNA (siRNA), small hairpin RNA or short hairpin RNA, microRNA (miRNA) Or a combination thereof. &Lt; RTI ID = 0.0 &gt; A &lt; / RTI &gt; The pharmaceutical composition for prevention or treatment of hair loss according to claim 1, further comprising a recombinant fusion protein comprising plaslan or a fragment thereof and a protein or fragment thereof of Streptococcus pneumoniae. [Claim 7] The pharmaceutical composition for preventing or treating hair loss according to claim 6, wherein the plasgelin is an FlaB protein of Vibrio vulnificus. [Claim 7] The pharmaceutical composition for prevention or treatment of hair loss according to claim 6, wherein the protein of pneumococci is pneumococcal surface protein A (PsaA). An activator that increases the amount of the Krt17 transcript or the protein encoded thereby;
An activator that increases the amount of the Colla1 transcript or the protein encoded thereby;
An inhibitor that reduces the amount of Fbn1 transcript or the amount of protein encoded thereby; And
Wherein the composition comprises at least one substance selected from the group consisting of prodrugs of Dcn or inhibitors which decrease the amount of proteins encoded thereby. A method for preventing or treating hair loss comprising administering to a subject a pharmaceutical composition for preventing or treating hair loss of claim 1. 11. The method of claim 10, further comprising the step of administering to said subject a recombinant fusion protein comprising plageline or a fragment thereof and a protein or fragment thereof of Streptococcus pneumoniae. Comprising administering to the subject a cosmetic composition for prevention or amelioration of hair loss of claim 9. 13. The method of claim 12, further comprising administering to said subject a recombinant fusion protein comprising plasgel or a fragment thereof and a protein or fragment thereof of S. pneumoniae. Incubating the test substance with cells expressing Krt17, Col1a1, Fbn1, Dcn, or a combination thereof;
Measuring the amount of the transcript of Krt17, Col1a1, Fbn1, Dcn, or a combination thereof, or the protein encoded thereby; And
And screening the test substance for which the amount of the transcript or protein measured is higher or lower than that of the control. 15. The method of claim 14,
Determining a substance for prevention, treatment, or amelioration of hair loss when the amount of Krt17 transcript or Krt17 protein is increased as compared with the control;
Determining a substance for prevention, treatment, or amelioration of hair loss when the amount of Col1a1 transcript or the amount of Col1a1 protein is increased as compared with the control;
Treating or improving hair loss when the amount of Fbn1 transcript or Fbn1 protein is decreased as compared with the control;
Determining a substance to prevent, treat, or ameliorate hair loss if the amount of Dcn transcript or Dcn protein is decreased as compared with the control; Or a combination thereof.

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