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O00622

- CYR61_HUMAN

UniProt

O00622 - CYR61_HUMAN

Protein

Protein CYR61

Gene

CYR61

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 1 (01 Jul 1997)
      Previous versions | rss
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    Functioni

    Promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion. Appears to play a role in wound healing by up-regulating, in skin fibroblasts, the expression of a number of genes involved in angiogenesis, inflammation and matrix remodeling including VEGA-A, VEGA-C, MMP1, MMP3, TIMP1, uPA, PAI-1 and integrins alpha-3 and alpha-5. CYR61-mediated gene regulation is dependent on heparin-binding. Down-regulates the expression of alpha-1 and alpha-2 subunits of collagen type-1. Promotes cell adhesion and adhesive signaling through integrin alpha-6/beta-1, cell migration through integrin alpha-v/beta-5 and cell proliferation through integrin alpha-v/beta-3.1 Publication

    GO - Molecular functioni

    1. extracellular matrix binding Source: Ensembl
    2. heparin binding Source: UniProtKB-KW

    GO - Biological processi

    1. anatomical structure morphogenesis Source: ProtInc
    2. apoptotic process involved in heart morphogenesis Source: Ensembl
    3. atrial septum morphogenesis Source: Ensembl
    4. atrioventricular valve morphogenesis Source: Ensembl
    5. cell proliferation Source: ProtInc
    6. chemotaxis Source: UniProtKB-KW
    7. chondroblast differentiation Source: Ensembl
    8. chorio-allantoic fusion Source: Ensembl
    9. extracellular matrix organization Source: Ensembl
    10. intussusceptive angiogenesis Source: Ensembl
    11. labyrinthine layer blood vessel development Source: Ensembl
    12. negative regulation of apoptotic process Source: Ensembl
    13. osteoblast differentiation Source: Ensembl
    14. positive regulation of apoptotic process Source: Ensembl
    15. positive regulation of BMP signaling pathway Source: BHF-UCL
    16. positive regulation of cartilage development Source: Ensembl
    17. positive regulation of cell migration Source: BHF-UCL
    18. positive regulation of cell-substrate adhesion Source: Ensembl
    19. positive regulation of ceramide biosynthetic process Source: Ensembl
    20. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
    21. positive regulation of osteoblast differentiation Source: BHF-UCL
    22. positive regulation of osteoblast proliferation Source: BHF-UCL
    23. positive regulation of phospholipase activity Source: Ensembl
    24. positive regulation of protein kinase activity Source: BHF-UCL
    25. positive regulation of protein phosphorylation Source: BHF-UCL
    26. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    27. reactive oxygen species metabolic process Source: Ensembl
    28. regulation of cell growth Source: InterPro
    29. regulation of ERK1 and ERK2 cascade Source: BHF-UCL
    30. ventricular septum development Source: Ensembl
    31. wound healing, spreading of cells Source: BHF-UCL

    Keywords - Biological processi

    Cell adhesion, Chemotaxis

    Keywords - Ligandi

    Growth factor binding, Heparin-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein CYR61
    Alternative name(s):
    CCN family member 1
    Cysteine-rich angiogenic inducer 61
    Insulin-like growth factor-binding protein 10
    Short name:
    IBP-10
    Short name:
    IGF-binding protein 10
    Short name:
    IGFBP-10
    Protein GIG1
    Gene namesi
    Name:CYR61
    Synonyms:CCN1, GIG1, IGFBP10
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:2654. CYR61.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA27126.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424Sequence AnalysisAdd
    BLAST
    Chaini25 – 381357Protein CYR61PRO_0000014398Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi286 ↔ 323By similarity
    Disulfide bondi303 ↔ 337By similarity
    Disulfide bondi314 ↔ 353By similarity
    Disulfide bondi317 ↔ 355By similarity
    Disulfide bondi322 ↔ 359By similarity

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    MaxQBiO00622.
    PaxDbiO00622.
    PRIDEiO00622.

    PTM databases

    PhosphoSiteiO00622.

    Miscellaneous databases

    PMAP-CutDBO00622.

    Expressioni

    Gene expression databases

    ArrayExpressiO00622.
    BgeeiO00622.
    CleanExiHS_CYR61.
    GenevestigatoriO00622.

    Organism-specific databases

    HPAiHPA029853.

    Interactioni

    Subunit structurei

    Interaction with integrins is heparin- and cell-type-dependent and promotes cell adhesion. In skin fibroblasts it binds ITGA6/ITGB1, in endothelial cells, binds ITGAV/ITGB3 and in platelets, ITGA2B/ITGB3. Binds, in vitro, ITGAV/ITGB5.

    Protein-protein interaction databases

    BioGridi109712. 9 interactions.
    IntActiO00622. 5 interactions.
    MINTiMINT-4993925.
    STRINGi9606.ENSP00000398736.

    Structurei

    3D structure databases

    ProteinModelPortaliO00622.
    SMRiO00622. Positions 295-360.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini25 – 9470IGFBP N-terminalPROSITE-ProRule annotationAdd
    BLAST
    Domaini98 – 16467VWFCPROSITE-ProRule annotationAdd
    BLAST
    Domaini228 – 27346TSP type-1PROSITE-ProRule annotationAdd
    BLAST
    Domaini286 – 36075CTCKPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni279 – 31537Heparin-bindingBy similarityAdd
    BLAST

    Sequence similaritiesi

    Belongs to the CCN family.Curated
    Contains 1 CTCK (C-terminal cystine knot-like) domain.PROSITE-ProRule annotation
    Contains 1 IGFBP N-terminal domain.PROSITE-ProRule annotation
    Contains 1 TSP type-1 domain.PROSITE-ProRule annotation
    Contains 1 VWFC domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG82014.
    HOGENOMiHOG000231462.
    HOVERGENiHBG000635.
    InParanoidiO00622.
    KOiK06829.
    OMAiKCIVQTT.
    OrthoDBiEOG7N8ZXB.
    PhylomeDBiO00622.
    TreeFamiTF326070.

    Family and domain databases

    InterProiIPR006207. Cys_knot_C.
    IPR006208. Glyco_hormone_CN.
    IPR009030. Growth_fac_rcpt_N_dom.
    IPR000867. IGFBP-like.
    IPR012395. IGFBP_CNN.
    IPR017891. Insulin_GF-bd_Cys-rich_CS.
    IPR000884. Thrombospondin_1_rpt.
    IPR001007. VWF_C.
    [Graphical view]
    PfamiPF00007. Cys_knot. 1 hit.
    PF00219. IGFBP. 1 hit.
    PF00090. TSP_1. 1 hit.
    PF00093. VWC. 1 hit.
    [Graphical view]
    PIRSFiPIRSF036495. IGFBP_rP_CNN. 1 hit.
    SMARTiSM00041. CT. 1 hit.
    SM00121. IB. 1 hit.
    SM00209. TSP1. 1 hit.
    SM00214. VWC. 1 hit.
    [Graphical view]
    SUPFAMiSSF57184. SSF57184. 1 hit.
    SSF82895. SSF82895. 1 hit.
    PROSITEiPS01185. CTCK_1. 1 hit.
    PS01225. CTCK_2. 1 hit.
    PS00222. IGFBP_N_1. 1 hit.
    PS51323. IGFBP_N_2. 1 hit.
    PS50092. TSP1. 1 hit.
    PS01208. VWFC_1. 1 hit.
    PS50184. VWFC_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    O00622-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSSRIARALA LVVTLLHLTR LALSTCPAAC HCPLEAPKCA PGVGLVRDGC    50
    GCCKVCAKQL NEDCSKTQPC DHTKGLECNF GASSTALKGI CRAQSEGRPC 100
    EYNSRIYQNG ESFQPNCKHQ CTCIDGAVGC IPLCPQELSL PNLGCPNPRL 150
    VKVTGQCCEE WVCDEDSIKD PMEDQDGLLG KELGFDASEV ELTRNNELIA 200
    VGKGSSLKRL PVFGMEPRIL YNPLQGQKCI VQTTSWSQCS KTCGTGISTR 250
    VTNDNPECRL VKETRICEVR PCGQPVYSSL KKGKKCSKTK KSPEPVRFTY 300
    AGCLSVKKYR PKYCGSCVDG RCCTPQLTRT VKMRFRCEDG ETFSKNVMMI 350
    QSCKCNYNCP HANEAAFPFY RLFNDIHKFR D 381
    Length:381
    Mass (Da):42,027
    Last modified:July 1, 1997 - v1
    Checksum:iFC0BD39C078CA0B1
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti165 – 1651E → Q in CAA72167. (PubMed:9536281)Curated
    Sequence conflicti210 – 2101L → I in AAB84227. 1 PublicationCurated
    Sequence conflicti220 – 2201L → R in AAB84227. 1 PublicationCurated
    Sequence conflicti369 – 3691F → L in AAG59863. (PubMed:11810026)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti334 – 3341R → W.1 Publication
    Corresponds to variant rs9658587 [ dbSNP | Ensembl ].
    VAR_018934

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U62015 mRNA. Translation: AAB58319.1.
    Y11307 mRNA. Translation: CAA72167.1.
    Y12084 mRNA. Translation: CAA72802.1.
    AF003594 mRNA. Translation: AAB61240.1.
    AF031385 mRNA. Translation: AAB84227.1.
    Z98053 mRNA. Translation: CAB10848.1.
    AF307860 Genomic DNA. Translation: AAG59863.1.
    AY443495 Genomic DNA. Translation: AAR05446.1.
    BC001271 mRNA. Translation: AAH01271.1.
    BC009199 mRNA. Translation: AAH09199.1.
    BC016952 mRNA. Translation: AAH16952.1.
    CCDSiCCDS706.1.
    RefSeqiNP_001545.2. NM_001554.4.
    UniGeneiHs.8867.

    Genome annotation databases

    EnsembliENST00000451137; ENSP00000398736; ENSG00000142871.
    GeneIDi3491.
    KEGGihsa:3491.
    UCSCiuc001dle.3. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U62015 mRNA. Translation: AAB58319.1 .
    Y11307 mRNA. Translation: CAA72167.1 .
    Y12084 mRNA. Translation: CAA72802.1 .
    AF003594 mRNA. Translation: AAB61240.1 .
    AF031385 mRNA. Translation: AAB84227.1 .
    Z98053 mRNA. Translation: CAB10848.1 .
    AF307860 Genomic DNA. Translation: AAG59863.1 .
    AY443495 Genomic DNA. Translation: AAR05446.1 .
    BC001271 mRNA. Translation: AAH01271.1 .
    BC009199 mRNA. Translation: AAH09199.1 .
    BC016952 mRNA. Translation: AAH16952.1 .
    CCDSi CCDS706.1.
    RefSeqi NP_001545.2. NM_001554.4.
    UniGenei Hs.8867.

    3D structure databases

    ProteinModelPortali O00622.
    SMRi O00622. Positions 295-360.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109712. 9 interactions.
    IntActi O00622. 5 interactions.
    MINTi MINT-4993925.
    STRINGi 9606.ENSP00000398736.

    PTM databases

    PhosphoSitei O00622.

    Proteomic databases

    MaxQBi O00622.
    PaxDbi O00622.
    PRIDEi O00622.

    Protocols and materials databases

    DNASUi 3491.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000451137 ; ENSP00000398736 ; ENSG00000142871 .
    GeneIDi 3491.
    KEGGi hsa:3491.
    UCSCi uc001dle.3. human.

    Organism-specific databases

    CTDi 3491.
    GeneCardsi GC01P086046.
    HGNCi HGNC:2654. CYR61.
    HPAi HPA029853.
    MIMi 602369. gene.
    neXtProti NX_O00622.
    PharmGKBi PA27126.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG82014.
    HOGENOMi HOG000231462.
    HOVERGENi HBG000635.
    InParanoidi O00622.
    KOi K06829.
    OMAi KCIVQTT.
    OrthoDBi EOG7N8ZXB.
    PhylomeDBi O00622.
    TreeFami TF326070.

    Miscellaneous databases

    ChiTaRSi CYR61. human.
    GeneWikii CYR61.
    GenomeRNAii 3491.
    NextBioi 13730.
    PMAP-CutDB O00622.
    PROi O00622.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O00622.
    Bgeei O00622.
    CleanExi HS_CYR61.
    Genevestigatori O00622.

    Family and domain databases

    InterProi IPR006207. Cys_knot_C.
    IPR006208. Glyco_hormone_CN.
    IPR009030. Growth_fac_rcpt_N_dom.
    IPR000867. IGFBP-like.
    IPR012395. IGFBP_CNN.
    IPR017891. Insulin_GF-bd_Cys-rich_CS.
    IPR000884. Thrombospondin_1_rpt.
    IPR001007. VWF_C.
    [Graphical view ]
    Pfami PF00007. Cys_knot. 1 hit.
    PF00219. IGFBP. 1 hit.
    PF00090. TSP_1. 1 hit.
    PF00093. VWC. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF036495. IGFBP_rP_CNN. 1 hit.
    SMARTi SM00041. CT. 1 hit.
    SM00121. IB. 1 hit.
    SM00209. TSP1. 1 hit.
    SM00214. VWC. 1 hit.
    [Graphical view ]
    SUPFAMi SSF57184. SSF57184. 1 hit.
    SSF82895. SSF82895. 1 hit.
    PROSITEi PS01185. CTCK_1. 1 hit.
    PS01225. CTCK_2. 1 hit.
    PS00222. IGFBP_N_1. 1 hit.
    PS51323. IGFBP_N_2. 1 hit.
    PS50092. TSP1. 1 hit.
    PS01208. VWFC_1. 1 hit.
    PS50184. VWFC_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The human growth factor-inducible immediate early gene, CYR61, maps to chromosome 1p."
      Jay P., Berge-Lefranc J.-L., Marsollier C., Mejean C., Taviaux S., Berta P.
      Oncogene 14:1753-1757(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Chromosomal mapping and expression of the human cyr61 gene in tumour cells from the nervous system."
      Martinerie C., Viegas-Pequignot E., Nguyen V.C., Perbal B.
      Mol. Pathol. 50:310-316(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Muscarinic acetylcholine receptors induce the expression of the immediate early growth regulatory gene CYR61."
      Albrecht C., von Der Kammer H., Mayhaus M., Klaudiny J., Schweizer M., Nitsch R.M.
      J. Biol. Chem. 275:28929-28936(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "Human growth-factor inducible gene product CYR61, complete sequence."
      Kolesnikova T.V., Lau L.F.
      Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Placenta.
    5. "Cloning of HumCyr61 gene expressing down-regulatedly in rhabdomyosarcoma."
      Bi A.B., Yu L.
      Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    6. "Regulation of hCYR61 by vitamin D, serum and cytokines in fetal human osteoblasts."
      Schuetze N., Lechner A., Groll C., Koehrle J., Jakob F.
      Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    7. "Organization and expression of the Cyr61 gene in normal human fibroblasts."
      Leng E., Malcolm T., Tai G., Estable M., Sadowski I.
      J. Biomed. Sci. 9:59-67(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    8. NIEHS SNPs program
      Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT TRP-334.
    9. "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].
      Tissue: Lung, Placenta and Skin.
    10. "The angiogenic factor Cyr61 activates a genetic program for wound healing in human skin fibroblasts."
      Chen C.-C., Mo F.-E., Lau L.F.
      J. Biol. Chem. 276:47329-47337(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN WOUND HEALING.
    11. "Adhesion of human umbilical vein endothelial cells to the immediate-early gene product Cyr61 is mediated through integrin alphavbeta3."
      Kireeva M.L., Lam S.C., Lau L.F.
      J. Biol. Chem. 273:3090-3096(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH INTEGRIN ALPHA-V/BETA-3.
    12. "Activation-dependent adhesion of human platelets to Cyr61 and Fisp12/mouse connective tissue growth factor is mediated through integrin alpha(IIb)beta(3)."
      Jedsadayanmata A., Chen C.-C., Kireeva M.L., Lau L.F., Lam S.C.
      J. Biol. Chem. 274:24321-24327(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH INTEGRIN ALPHA-IIB/BETA-3.
    13. "Adhesion of human skin fibroblasts to Cyr61 is mediated through integrin alpha 6beta 1 and cell surface heparan sulfate proteoglycans."
      Chen N., Chen C.-C., Lau L.F.
      J. Biol. Chem. 275:24953-24961(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH INTEGRIN ALPHA-6/BETA-1.
    14. "CYR61 stimulates human skin fibroblast migration through Integrin alpha vbeta 5 and enhances mitogenesis through integrin alpha vbeta 3, independent of its carboxyl-terminal domain."
      Grzeszkiewicz T.M., Kirschling D.J., Chen N., Lau L.F.
      J. Biol. Chem. 276:21943-21950(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH INTEGRIN ALPHA-V/BETA-6.

    Entry informationi

    Entry nameiCYR61_HUMAN
    AccessioniPrimary (citable) accession number: O00622
    Secondary accession number(s): O14934, O43775, Q9BZL7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: July 1, 1997
    Last modified: October 1, 2014
    This is version 134 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 1
      Human chromosome 1: 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