O00622 (CYR61_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	CYR61
Synonyms:	CCN1, GIG1, IGFBP10

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	381 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Cell adhesion Chemotaxis
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Growth factor binding Heparin-binding
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process involved in heart morphogenesis Inferred from electronic annotation. Source: Compara atrial septum morphogenesis Inferred from electronic annotation. Source: Compara atrioventricular valve morphogenesis Inferred from electronic annotation. Source: Compara cell proliferation Traceable author statement Ref.1. Source: ProtInc chemotaxis Inferred from electronic annotation. Source: UniProtKB-KW chondroblast differentiation Inferred from electronic annotation. Source: Compara chorio-allantoic fusion Inferred from electronic annotation. Source: Compara extracellular matrix organization Inferred from electronic annotation. Source: Compara intussusceptive angiogenesis Inferred from electronic annotation. Source: Compara labyrinthine layer blood vessel development Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara osteoblast differentiation Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of cartilage development Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of ceramide biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of protein kinase activity 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: Compara 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: Compara wound healing, spreading of cells Inferred from direct assay PubMed 20675382. Source: BHF-UCL
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	extracellular matrix binding Inferred from electronic annotation. Source: Compara heparin binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 381	357	Protein CYR61		PRO_0000014398
Regions
	Domain	25 – 94	70	IGFBP N-terminal
	Domain	98 – 164	67	VWFC
	Domain	228 – 273	46	TSP type-1
	Domain	286 – 360	75	CTCK
	Region	279 – 315	37	Heparin-binding By similarity
Amino acid modifications
	Disulfide bond	286 ↔ 323		By similarity
	Disulfide bond	303 ↔ 337		By similarity
	Disulfide bond	314 ↔ 353		By similarity
	Disulfide bond	317 ↔ 355		By similarity
	Disulfide bond	322 ↔ 359		By similarity
Natural variations
	Natural variant	334	1	R → W. Ref.8 Corresponds to variant rs9658587 [ dbSNP | Ensembl ].		VAR_018934
Experimental info
	Sequence conflict	165	1	E → Q in CAA72167. Ref.2
	Sequence conflict	210	1	L → I in AAB84227. Ref.5
	Sequence conflict	220	1	L → R in AAB84227. Ref.5
	Sequence conflict	369	1	F → L in AAG59863. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	O00622 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: FC0BD39C078CA0B1	FASTA	381	42,027
	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

References

	« Hide 'large scale' referencesShow '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

NIEHS-SNPs

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.
IPI	IPI00299219.
RefSeq	NP_001545.2. NM_001554.4.
UniGene	Hs.8867.
3D structure databases
ProteinModelPortal	O00622.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00622. 5 interactions.
MINT	MINT-4993925.
STRING	9606.ENSP00000398736.
PTM databases
PhosphoSite	O00622.
Proteomic databases
PaxDb	O00622.
PRIDE	O00622.
Protocols and materials databases
DNASU	3491.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000451137; ENSP00000398736; ENSG00000142871.
GeneID	3491.
KEGG	hsa:3491.
UCSC	uc001dle.3. human.
Organism-specific databases
CTD	3491.
GeneCards	GC01P086046.
HGNC	HGNC:2654. CYR61.
HPA	HPA029853.
MIM	602369. gene.
neXtProt	NX_O00622.
PharmGKB	PA27126.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG82014.
HOGENOM	HOG000231462.
HOVERGEN	HBG000635.
InParanoid	O00622.
KO	K06829.
OMA	KCIVQTT.
OrthoDB	EOG4J3WH3.
PhylomeDB	O00622.
Enzyme and pathway databases
Pathway_Interaction_DB	amb2_neutrophils_pathway. amb2 Integrin signaling.
Gene expression databases
ArrayExpress	O00622.
Bgee	O00622.
CleanEx	HS_CYR61.
Genevestigator	O00622.
GermOnline	ENSG00000142871. Homo sapiens.
Family and domain databases
InterPro	IPR006208. Cys_knot. IPR006207. Cys_knot_C. IPR000867. IGFBP-like. IPR012395. IGFBP_CNN. IPR017891. Insulin_GF-bd_Cys-rich_CS. IPR000884. Thrombospondin_1_rpt. IPR001007. VWF_C. [Graphical view]
Pfam	PF00007. Cys_knot. 1 hit. PF00219. IGFBP. 1 hit. PF00090. TSP_1. 1 hit. PF00093. VWC. 1 hit. [Graphical view]
PIRSF	PIRSF036495. IGFBP_rP_CNN. 1 hit.
SMART	SM00041. CT. 1 hit. SM00121. IB. 1 hit. SM00209. TSP1. 1 hit. SM00214. VWC. 1 hit. [Graphical view]
SUPFAM	SSF82895. TSP1. 1 hit.
PROSITE	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]
ProtoNet	Search...
Other
ChiTaRS	CYR61. human.
GenomeRNAi	3491.
NextBio	13730.
PMAP-CutDB	O00622.
SOURCE	Search...

Entry information

Entry name

CYR61_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.