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O00622 (CYR61_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:CYR61
Synonyms:CCN1, GIG1, IGFBP10
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length381 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10

Subunit structure

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.

Subcellular location

Secreted.

Sequence similarities

Belongs to the CCN family.

Contains 1 CTCK (C-terminal cystine knot-like) domain.

Contains 1 IGFBP N-terminal domain.

Contains 1 TSP type-1 domain.

Contains 1 VWFC domain.

Ontologies

Keywords
   Biological processCell adhesion
Chemotaxis
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   LigandGrowth factor binding
Heparin-binding
   PTMDisulfide bond
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanatomical structure morphogenesis

Traceable author statement Ref.1. Source: ProtInc

apoptotic process involved in heart morphogenesis

Inferred from electronic annotation. Source: Ensembl

atrial septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

atrioventricular valve morphogenesis

Inferred from electronic annotation. Source: Ensembl

cell proliferation

Traceable author statement Ref.1. Source: ProtInc

chemotaxis

Inferred from electronic annotation. Source: UniProtKB-KW

chondroblast differentiation

Inferred from electronic annotation. Source: Ensembl

chorio-allantoic fusion

Inferred from electronic annotation. Source: Ensembl

extracellular matrix organization

Inferred from electronic annotation. Source: Ensembl

intussusceptive angiogenesis

Inferred from electronic annotation. Source: Ensembl

labyrinthine layer blood vessel development

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of BMP signaling pathway

Inferred from genetic interaction PubMed 20675382. Source: BHF-UCL

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of cartilage development

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell migration

Inferred from direct assay PubMed 20675382. Source: BHF-UCL

positive regulation of cell-substrate adhesion

Inferred from electronic annotation. Source: Ensembl

positive regulation of ceramide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of osteoblast differentiation

Inferred from direct assay PubMed 20675382. Source: BHF-UCL

positive regulation of osteoblast proliferation

Inferred from direct assay PubMed 20675382. Source: BHF-UCL

positive regulation of phospholipase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase activity

Inferred from direct assay PubMed 20675382. Source: BHF-UCL

positive regulation of protein phosphorylation

Inferred from direct assay PubMed 20675382. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 20675382. Source: BHF-UCL

reactive oxygen species metabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of ERK1 and ERK2 cascade

Inferred from direct assay PubMed 20675382. Source: BHF-UCL

regulation of cell growth

Inferred from electronic annotation. Source: InterPro

ventricular septum development

Inferred from electronic annotation. Source: Ensembl

wound healing, spreading of cells

Inferred from direct assay PubMed 20675382. Source: BHF-UCL

   Cellular_componentextracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionextracellular matrix binding

Inferred from electronic annotation. Source: Ensembl

heparin binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 381357Protein CYR61
PRO_0000014398

Regions

Domain25 – 9470IGFBP N-terminal
Domain98 – 16467VWFC
Domain228 – 27346TSP type-1
Domain286 – 36075CTCK
Region279 – 31537Heparin-binding By similarity

Amino acid modifications

Disulfide bond286 ↔ 323 By similarity
Disulfide bond303 ↔ 337 By similarity
Disulfide bond314 ↔ 353 By similarity
Disulfide bond317 ↔ 355 By similarity
Disulfide bond322 ↔ 359 By similarity

Natural variations

Natural variant3341R → W. Ref.8
Corresponds to variant rs9658587 [ dbSNP | Ensembl ].
VAR_018934

Experimental info

Sequence conflict1651E → Q in CAA72167. Ref.2
Sequence conflict2101L → I in AAB84227. Ref.5
Sequence conflict2201L → R in AAB84227. Ref.5
Sequence conflict3691F → L in AAG59863. Ref.7

Sequences

Sequence LengthMass (Da)Tools
O00622 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: FC0BD39C078CA0B1

FASTA38142,027
        10         20         30         40         50         60 
MSSRIARALA LVVTLLHLTR LALSTCPAAC HCPLEAPKCA PGVGLVRDGC GCCKVCAKQL 

        70         80         90        100        110        120 
NEDCSKTQPC DHTKGLECNF GASSTALKGI CRAQSEGRPC EYNSRIYQNG ESFQPNCKHQ 

       130        140        150        160        170        180 
CTCIDGAVGC IPLCPQELSL PNLGCPNPRL VKVTGQCCEE WVCDEDSIKD PMEDQDGLLG 

       190        200        210        220        230        240 
KELGFDASEV ELTRNNELIA VGKGSSLKRL PVFGMEPRIL YNPLQGQKCI VQTTSWSQCS 

       250        260        270        280        290        300 
KTCGTGISTR VTNDNPECRL VKETRICEVR PCGQPVYSSL KKGKKCSKTK KSPEPVRFTY 

       310        320        330        340        350        360 
AGCLSVKKYR PKYCGSCVDG RCCTPQLTRT VKMRFRCEDG ETFSKNVMMI QSCKCNYNCP 

       370        380 
HANEAAFPFY RLFNDIHKFR D 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001545.2. NM_001554.4.
UniGeneHs.8867.

3D structure databases

ProteinModelPortalO00622.
SMRO00622. Positions 25-161, 232-273, 303-364.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109712. 9 interactions.
IntActO00622. 5 interactions.
MINTMINT-4993925.
STRING9606.ENSP00000398736.

PTM databases

PhosphoSiteO00622.

Proteomic databases

PaxDbO00622.
PRIDEO00622.

Protocols and materials databases

DNASU3491.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000451137; ENSP00000398736; ENSG00000142871.
GeneID3491.
KEGGhsa:3491.
UCSCuc001dle.3. human.

Organism-specific databases

CTD3491.
GeneCardsGC01P086046.
HGNCHGNC:2654. CYR61.
HPAHPA029853.
MIM602369. gene.
neXtProtNX_O00622.
PharmGKBPA27126.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG82014.
HOGENOMHOG000231462.
HOVERGENHBG000635.
InParanoidO00622.
KOK06829.
OMAKCIVQTT.
OrthoDBEOG7N8ZXB.
PhylomeDBO00622.
TreeFamTF326070.

Gene expression databases

ArrayExpressO00622.
BgeeO00622.
CleanExHS_CYR61.
GenevestigatorO00622.

Family and domain databases

InterProIPR006207. 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]
PfamPF00007. Cys_knot. 1 hit.
PF00219. IGFBP. 1 hit.
PF00090. TSP_1. 1 hit.
PF00093. VWC. 1 hit.
[Graphical view]
PIRSFPIRSF036495. IGFBP_rP_CNN. 1 hit.
SMARTSM00041. CT. 1 hit.
SM00121. IB. 1 hit.
SM00209. TSP1. 1 hit.
SM00214. VWC. 1 hit.
[Graphical view]
SUPFAMSSF57184. SSF57184. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEPS01185. 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]
ProtoNetSearch...

Other

ChiTaRSCYR61. human.
GeneWikiCYR61.
GenomeRNAi3491.
NextBio13730.
PMAP-CutDBO00622.
PROO00622.
SOURCESearch...

Entry information

Entry nameCYR61_HUMAN
AccessionPrimary (citable) accession number: O00622
Secondary accession number(s): O14934, O43775, Q9BZL7
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM