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Protein

Protein CYR61

Gene

CYR61

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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: GO_Central
  3. integrin binding Source: GO_Central

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

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 matrix Source: UniProtKB
  2. proteinaceous extracellular matrix Source: GO_Central
Complete GO annotation...

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

BgeeiO00622.
CleanExiHS_CYR61.
ExpressionAtlasiO00622. baseline and differential.
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 35-133.
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

        10         20         30         40         50
MSSRIARALA LVVTLLHLTR LALSTCPAAC HCPLEAPKCA PGVGLVRDGC
60 70 80 90 100
GCCKVCAKQL NEDCSKTQPC DHTKGLECNF GASSTALKGI CRAQSEGRPC
110 120 130 140 150
EYNSRIYQNG ESFQPNCKHQ CTCIDGAVGC IPLCPQELSL PNLGCPNPRL
160 170 180 190 200
VKVTGQCCEE WVCDEDSIKD PMEDQDGLLG KELGFDASEV ELTRNNELIA
210 220 230 240 250
VGKGSSLKRL PVFGMEPRIL YNPLQGQKCI VQTTSWSQCS KTCGTGISTR
260 270 280 290 300
VTNDNPECRL VKETRICEVR PCGQPVYSSL KKGKKCSKTK KSPEPVRFTY
310 320 330 340 350
AGCLSVKKYR PKYCGSCVDG RCCTPQLTRT VKMRFRCEDG ETFSKNVMMI
360 370 380
QSCKCNYNCP HANEAAFPFY RLFNDIHKFR D
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliO00622.
SMRiO00622. Positions 35-133.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiO00622.

Proteomic databases

MaxQBiO00622.
PaxDbiO00622.
PRIDEiO00622.

Protocols and materials databases

DNASUi3491.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3491.
GeneCardsiGC01P086046.
HGNCiHGNC:2654. CYR61.
HPAiHPA029853.
MIMi602369. gene.
neXtProtiNX_O00622.
PharmGKBiPA27126.
GenAtlasiSearch...

Phylogenomic databases

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

Miscellaneous databases

ChiTaRSiCYR61. human.
GeneWikiiCYR61.
GenomeRNAii3491.
NextBioi13730.
PMAP-CutDBO00622.
PROiO00622.
SOURCEiSearch...

Gene expression databases

BgeeiO00622.
CleanExiHS_CYR61.
ExpressionAtlasiO00622. baseline and differential.
GenevestigatoriO00622.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: February 4, 2015
This is version 137 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.