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Q02487

- DSC2_HUMAN

UniProt

Q02487 - DSC2_HUMAN

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Protein
Desmocollin-2
Gene
DSC2, CDHF2, DSC3
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms.

GO - Molecular functioni

  1. calcium ion binding Source: InterPro
  2. protein binding Source: IntAct
Complete GO annotation...

GO - Biological processi

  1. bundle of His cell to Purkinje myocyte communication Source: BHF-UCL
  2. cardiac muscle cell-cardiac muscle cell adhesion Source: UniProt
  3. cell adhesion Source: ProtInc
  4. homophilic cell adhesion Source: InterPro
  5. regulation of heart rate by cardiac conduction Source: BHF-UCL
  6. ventricular cardiac muscle cell action potential Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

Calcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Desmocollin-2
Alternative name(s):
Cadherin family member 2
Desmocollin-3
Desmosomal glycoprotein II
Desmosomal glycoprotein III
Gene namesi
Name:DSC2
Synonyms:CDHF2, DSC3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 18

Organism-specific databases

HGNCiHGNC:3036. DSC2.

Subcellular locationi

Cell membrane; Single-pass type I membrane protein. Cell junctiondesmosome 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini136 – 694559Extracellular Reviewed prediction
Add
BLAST
Transmembranei695 – 71521Helical; Reviewed prediction
Add
BLAST
Topological domaini716 – 901186Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. cell-cell adherens junction Source: Ensembl
  2. cytoplasmic vesicle Source: UniProt
  3. desmosome Source: UniProtKB
  4. extracellular vesicular exosome Source: UniProt
  5. integral component of membrane Source: UniProtKB-KW
  6. intercalated disc Source: UniProt
  7. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Arrhythmogenic right ventricular dysplasia, familial, 11 (ARVD11) [MIM:610476]: A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias.
Note: The disease is caused by mutations affecting the gene represented in this entry.3 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti203 – 2031R → C in ARVD11; fails to undergo complete processing into a mature form; fails to localize at the desmosomes. 1 Publication
VAR_065687
Natural varianti231 – 2311I → T in ARVD11. 1 Publication
VAR_065688
Natural varianti275 – 2751T → M in ARVD11; can be processed into a mature form but shows a higher pro-protein to mature protein ratio; only a proportion of the partly functional mutant is incorporated into the desmosomes. 1 Publication
VAR_065689
Natural varianti340 – 3401T → A in ARVD11. 1 Publication
VAR_065690

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

MIMi610476. phenotype.
Orphaneti293899. Familial isolated arrhythmogenic ventricular dysplasia, biventricular form.
293888. Familial isolated arrhythmogenic ventricular dysplasia, left dominant form.
293910. Familial isolated arrhythmogenic ventricular dysplasia, right dominant form.
PharmGKBiPA27489.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727 Reviewed prediction
Add
BLAST
Propeptidei28 – 135108 Reviewed prediction
PRO_0000003869Add
BLAST
Chaini136 – 901766Desmocollin-2
PRO_0000003870Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi34 – 341N-linked (GlcNAc...) Reviewed prediction
Glycosylationi166 – 1661N-linked (GlcNAc...) Reviewed prediction
Glycosylationi392 – 3921N-linked (GlcNAc...) (complex)2 Publications
Glycosylationi546 – 5461N-linked (GlcNAc...)1 Publication
Glycosylationi629 – 6291N-linked (GlcNAc...)1 Publication
Modified residuei864 – 8641Phosphoserine Reviewed prediction

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ02487.
PaxDbiQ02487.
PRIDEiQ02487.

PTM databases

PhosphoSiteiQ02487.

Expressioni

Tissue specificityi

Expressed in epithelia, myocardium and lymph nodes.

Gene expression databases

ArrayExpressiQ02487.
BgeeiQ02487.
CleanExiHS_DSC2.
HS_DSC3.
GenevestigatoriQ02487.

Organism-specific databases

HPAiHPA011911.
HPA012615.

Interactioni

Subunit structurei

Interacts with DSP, PKP2 and JUP.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
F1M7L92EBI-6900677,EBI-6900770From a different organism.
GJA1P173022EBI-6900677,EBI-1103439
GJA1Q6TYA93EBI-6900677,EBI-6901331From a different organism.

Protein-protein interaction databases

BioGridi108158. 8 interactions.
IntActiQ02487. 7 interactions.
STRINGi9606.ENSP00000280904.

Structurei

3D structure databases

ProteinModelPortaliQ02487.
SMRiQ02487. Positions 137-669.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini136 – 243108Cadherin 1
Add
BLAST
Domaini244 – 355112Cadherin 2
Add
BLAST
Domaini356 – 471116Cadherin 3
Add
BLAST
Domaini472 – 579108Cadherin 4
Add
BLAST
Domaini580 – 694115Cadherin 5
Add
BLAST

Domaini

Calcium may be bound by the cadherin-like repeats Reviewed prediction.
Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain By similarity.

Sequence similaritiesi

Contains 5 cadherin domains.

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG304955.
HOGENOMiHOG000231253.
HOVERGENiHBG102801.
InParanoidiQ02487.
KOiK07601.
OMAiPLNYEER.
OrthoDBiEOG74BJR7.
PhylomeDBiQ02487.
TreeFamiTF316817.

Family and domain databases

Gene3Di2.60.40.60. 6 hits.
4.10.900.10. 1 hit.
InterProiIPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR009124. Cadherin/Desmocollin.
IPR020894. Cadherin_CS.
IPR000233. Cadherin_cytoplasmic-dom.
IPR014868. Cadherin_pro_dom.
IPR027397. Catenin_binding_dom.
IPR009122. Desmosomal_cadherin.
[Graphical view]
PANTHERiPTHR24025. PTHR24025. 1 hit.
PfamiPF00028. Cadherin. 4 hits.
PF01049. Cadherin_C. 1 hit.
PF08758. Cadherin_pro. 1 hit.
[Graphical view]
PRINTSiPR00205. CADHERIN.
PR01818. DESMOCADHERN.
PR01820. DESMOCOLLIN.
SMARTiSM00112. CA. 5 hits.
SM01055. Cadherin_pro. 1 hit.
[Graphical view]
SUPFAMiSSF49313. SSF49313. 6 hits.
PROSITEiPS00232. CADHERIN_1. 3 hits.
PS50268. CADHERIN_2. 5 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 2A (identifier: Q02487-1) [UniParc]FASTAAdd to Basket

Also known as: DGII

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

MEAARPSGSW NGALCRLLLL TLAILIFASD ACKNVTLHVP SKLDAEKLVG    50
RVNLKECFTA ANLIHSSDPD FQILEDGSVY TTNTILLSSE KRSFTILLSN 100
TENQEKKKIF VFLEHQTKVL KKRHTKEKVL RRAKRRWAPI PCSMLENSLG 150
PFPLFLQQVQ SDTAQNYTIY YSIRGPGVDQ EPRNLFYVER DTGNLYCTRP 200
VDREQYESFE IIAFATTPDG YTPELPLPLI IKIEDENDNY PIFTEETYTF 250
TIFENCRVGT TVGQVCATDK DEPDTMHTRL KYSIIGQVPP SPTLFSMHPT 300
TGVITTTSSQ LDRELIDKYQ LKIKVQDMDG QYFGLQTTST CIINIDDVND 350
HLPTFTRTSY VTSVEENTVD VEILRVTVED KDLVNTANWR ANYTILKGNE 400
NGNFKIVTDA KTNEGVLCVV KPLNYEEKQQ MILQIGVVNE APFSREASPR 450
SAMSTATVTV NVEDQDEGPE CNPPIQTVRM KENAEVGTTS NGYKAYDPET 500
RSSSGIRYKK LTDPTGWVTI DENTGSIKVF RSLDREAETI KNGIYNITVL 550
ASDQGGRTCT GTLGIILQDV NDNSPFIPKK TVIICKPTMS SAEIVAVDPD 600
EPIHGPPFDF SLESSTSEVQ RMWRLKAIND TAARLSYQND PPFGSYVVPI 650
TVRDRLGMSS VTSLDVTLCD CITENDCTHR VDPRIGGGGV QLGKWAILAI 700
LLGIALLFCI LFTLVCGASG TSKQPKVIPD DLAQQNLIVS NTEAPGDDKV 750
YSANGFTTQT VGASAQGVCG TVGSGIKNGG QETIEMVKGG HQTSESCRGA 800
GHHHTLDSCR GGHTEVDNCR YTYSEWHSFT QPRLGEKVYL CNQDENHKHA 850
QDYVLTYNYE GRGSVAGSVG CCSERQEEDG LEFLDNLEPK FRTLAEACMK 900
R 901
Length:901
Mass (Da):99,962
Last modified:February 1, 1994 - v1
Checksum:i30F7E3D33ECA67CC
GO
Isoform 2B (identifier: Q02487-2) [UniParc]FASTAAdd to Basket

Also known as: DGIII

The sequence of this isoform differs from the canonical sequence as follows:
     837-847: KVYLCNQDENH → ESIRGHTLIKN
     848-901: Missing.

Show »
Length:847
Mass (Da):93,769
Checksum:iA53588B1D490CD8F
GO

Sequence cautioni

The sequence CAA40141.1 differs from that shown. Reason: Erroneous initiation.
The sequence CAA40142.1 differs from that shown. Reason: Erroneous initiation.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti11 – 111N → S.1 Publication
Corresponds to variant rs868333 [ dbSNP | Ensembl ].
VAR_029480
Natural varianti203 – 2031R → C in ARVD11; fails to undergo complete processing into a mature form; fails to localize at the desmosomes. 1 Publication
VAR_065687
Natural varianti231 – 2311I → T in ARVD11. 1 Publication
VAR_065688
Natural varianti275 – 2751T → M in ARVD11; can be processed into a mature form but shows a higher pro-protein to mature protein ratio; only a proportion of the partly functional mutant is incorporated into the desmosomes. 1 Publication
VAR_065689
Natural varianti340 – 3401T → A in ARVD11. 1 Publication
VAR_065690
Natural varianti358 – 3581T → I.1 Publication
Corresponds to variant rs139399951 [ dbSNP | Ensembl ].
VAR_062391
Natural varianti596 – 5961A → V.1 Publication
Corresponds to variant rs148185335 [ dbSNP | Ensembl ].
VAR_065691
Natural varianti638 – 6381Q → H.1 Publication
VAR_065692
Natural varianti776 – 7761I → V.2 Publications
Corresponds to variant rs1893963 [ dbSNP | Ensembl ].
VAR_024388
Natural varianti798 – 7981R → Q.3 Publications
Corresponds to variant rs61731921 [ dbSNP | Ensembl ].
VAR_062392

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei837 – 84711KVYLCNQDENH → ESIRGHTLIKN in isoform 2B.
VSP_000657Add
BLAST
Alternative sequencei848 – 90154Missing in isoform 2B.
VSP_000658Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X56807 mRNA. Translation: CAA40141.1. Different initiation.
X56807 mRNA. Translation: CAA40142.1. Different initiation.
BC063291 mRNA. Translation: AAH63291.1.
CCDSiCCDS11892.1. [Q02487-1]
CCDS11893.1. [Q02487-2]
PIRiA40390. IJHUDB.
B40390. IJHUDA.
RefSeqiNP_004940.1. NM_004949.3. [Q02487-2]
NP_077740.1. NM_024422.3. [Q02487-1]
UniGeneiHs.95612.

Genome annotation databases

EnsembliENST00000251081; ENSP00000251081; ENSG00000134755. [Q02487-2]
ENST00000280904; ENSP00000280904; ENSG00000134755. [Q02487-1]
GeneIDi1824.
KEGGihsa:1824.
UCSCiuc002kwk.4. human. [Q02487-2]
uc002kwl.4. human. [Q02487-1]

Polymorphism databases

DMDMi461968.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X56807 mRNA. Translation: CAA40141.1 . Different initiation.
X56807 mRNA. Translation: CAA40142.1 . Different initiation.
BC063291 mRNA. Translation: AAH63291.1 .
CCDSi CCDS11892.1. [Q02487-1 ]
CCDS11893.1. [Q02487-2 ]
PIRi A40390. IJHUDB.
B40390. IJHUDA.
RefSeqi NP_004940.1. NM_004949.3. [Q02487-2 ]
NP_077740.1. NM_024422.3. [Q02487-1 ]
UniGenei Hs.95612.

3D structure databases

ProteinModelPortali Q02487.
SMRi Q02487. Positions 137-669.
ModBasei Search...

Protein-protein interaction databases

BioGridi 108158. 8 interactions.
IntActi Q02487. 7 interactions.
STRINGi 9606.ENSP00000280904.

PTM databases

PhosphoSitei Q02487.

Polymorphism databases

DMDMi 461968.

Proteomic databases

MaxQBi Q02487.
PaxDbi Q02487.
PRIDEi Q02487.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000251081 ; ENSP00000251081 ; ENSG00000134755 . [Q02487-2 ]
ENST00000280904 ; ENSP00000280904 ; ENSG00000134755 . [Q02487-1 ]
GeneIDi 1824.
KEGGi hsa:1824.
UCSCi uc002kwk.4. human. [Q02487-2 ]
uc002kwl.4. human. [Q02487-1 ]

Organism-specific databases

CTDi 1824.
GeneCardsi GC18M028670.
GeneReviewsi DSC2.
HGNCi HGNC:3036. DSC2.
HPAi HPA011911.
HPA012615.
MIMi 125645. gene.
610476. phenotype.
neXtProti NX_Q02487.
Orphaneti 293899. Familial isolated arrhythmogenic ventricular dysplasia, biventricular form.
293888. Familial isolated arrhythmogenic ventricular dysplasia, left dominant form.
293910. Familial isolated arrhythmogenic ventricular dysplasia, right dominant form.
PharmGKBi PA27489.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG304955.
HOGENOMi HOG000231253.
HOVERGENi HBG102801.
InParanoidi Q02487.
KOi K07601.
OMAi PLNYEER.
OrthoDBi EOG74BJR7.
PhylomeDBi Q02487.
TreeFami TF316817.

Miscellaneous databases

ChiTaRSi DSC2. human.
GeneWikii DSC2.
GenomeRNAii 1824.
NextBioi 7437.
PROi Q02487.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q02487.
Bgeei Q02487.
CleanExi HS_DSC2.
HS_DSC3.
Genevestigatori Q02487.

Family and domain databases

Gene3Di 2.60.40.60. 6 hits.
4.10.900.10. 1 hit.
InterProi IPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR009124. Cadherin/Desmocollin.
IPR020894. Cadherin_CS.
IPR000233. Cadherin_cytoplasmic-dom.
IPR014868. Cadherin_pro_dom.
IPR027397. Catenin_binding_dom.
IPR009122. Desmosomal_cadherin.
[Graphical view ]
PANTHERi PTHR24025. PTHR24025. 1 hit.
Pfami PF00028. Cadherin. 4 hits.
PF01049. Cadherin_C. 1 hit.
PF08758. Cadherin_pro. 1 hit.
[Graphical view ]
PRINTSi PR00205. CADHERIN.
PR01818. DESMOCADHERN.
PR01820. DESMOCOLLIN.
SMARTi SM00112. CA. 5 hits.
SM01055. Cadherin_pro. 1 hit.
[Graphical view ]
SUPFAMi SSF49313. SSF49313. 6 hits.
PROSITEi PS00232. CADHERIN_1. 3 hits.
PS50268. CADHERIN_2. 5 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Desmosomal glycoproteins II and III. Cadherin-like junctional molecules generated by alternative splicing."
    Parker A.E., Wheeler G.N., Arnemann J., Pidsley S.C., Ataliotis P., Thomas C.L., Rees D.A., Magee A.I., Buxton R.S.
    J. Biol. Chem. 266:10438-10445(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2A AND 2B).
    Tissue: Keratinocyte.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2A).
    Tissue: Placenta.
  3. "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
    Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
    J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-546.
    Tissue: Plasma.
  4. "Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry."
    Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A.
    J. Proteome Res. 5:1493-1503(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-392 AND ASN-629.
    Tissue: Saliva.
  5. "Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2."
    Syrris P., Ward D., Evans A., Asimaki A., Gandjbakhch E., Sen-Chowdhry S., McKenna W.J.
    Am. J. Hum. Genet. 79:978-984(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN ARVD11.
  6. Cited for: GLYCOSYLATION AT ASN-392.
  7. "Mechanistic insights into arrhythmogenic right ventricular cardiomyopathy caused by desmocollin-2 mutations."
    Gehmlich K., Syrris P., Peskett E., Evans A., Ehler E., Asimaki A., Anastasakis A., Tsatsopoulou A., Vouliotis A.I., Stefanadis C., Saffitz J.E., Protonotarios N., McKenna W.J.
    Cardiovasc. Res. 90:77-87(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH DSP; PKP2 AND JUP, VARIANTS ARVD11 CYS-203 AND MET-275, CHARACTERIZATION OF VARIANTS ARVD11 CYS-203 AND MET-275.
  8. Cited for: VARIANTS ILE-358; VAL-776 AND GLN-798.
  9. "Comprehensive desmosome mutation analysis in North Americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy."
    den Haan A.D., Tan B.Y., Zikusoka M.N., Llado L.I., Jain R., Daly A., Tichnell C., James C., Amat-Alarcon N., Abraham T., Russell S.D., Bluemke D.A., Calkins H., Dalal D., Judge D.P.
    Circ. Cardiovasc. Genet. 2:428-435(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS SER-11; VAL-596; HIS-638; VAL-776 AND GLN-798.
  10. "Role of genetic testing in arrhythmogenic right ventricular cardiomyopathy/dysplasia."
    Barahona-Dussault C., Benito B., Campuzano O., Iglesias A., Leung T.L., Robb L., Talajic M., Brugada R.
    Clin. Genet. 77:37-48(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS ARVD11 THR-231 AND ALA-340, VARIANT GLN-798.

Entry informationi

Entry nameiDSC2_HUMAN
AccessioniPrimary (citable) accession number: Q02487
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: July 9, 2014
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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