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Symbol CYR61 contributors: mct/pgu - updated : 29-04-2012
HGNC name cysteine-rich, angiogenic inducer, 61
HGNC id 2654
Location 1p22.3      Physical location : 86.046.443 - 86.049.646
Synonym name
  • insulin-like growth factor binding protein 10
  • cysteine-rich heparin binding protein 61
  • related protein 4, immediate early gene, low affinity
  • connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed 1
  • Synonym symbol(s) IGFBP10, IGFBPRP4, GIG1, CCN1
    TYPE functioning gene
    STRUCTURE 3.21 kb     5 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    motif repetitive sequence
    text structure CA repeat in the promoter
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC148418 1p22.3 dnaj-like protein LOC391051 1 similar to urate oxidase (EC - baboon DLAD 1p31.1 similar to urate oxidase (EC - baboon RPF1 1p22.3 similar to urate oxidase (EC - baboon GNG5 1p22 guanine nucleotide binding protein (G protein), gamma 5 SPATA1 1p22.3 spermatogenesis associated 1 CTBS 1p22 chitobiase, di-N-acetyl- FLJ35487 1p22.3 hypothetical protein FLJ35487 SSX2IP 1p22 synovial sarcoma, X breakpoint 2 interacting protein EDG7 1p22.3-p31.1 endothelial differentiation, lysophosphatidic acid G-protein-coupled receptor, 7 MCOLN2 1p22 mucolipin 2 MCOLN3 1p22.3 mucolipin 3 NYD-SP29 1p22.3 testis development protein NYD-SP29 FLJ13815 1p22.3 hypothetical protein FLJ13815 gm117 1p22.3 gm117 BCL10 1p22 B-cell CLL/lymphoma 10 DDAH1 1p22 dimethylarginine dimethylaminohydrolase 1 CYR61 1p31.p22 cysteine-rich, angiogenic inducer, 61 FLJ20729 1p22.3 hypothetical protein FLJ20729 COL24A1 1p22.3-p22.2 collagen, type XXIV, alpha 1 KIAA1229 1p22.3 KIAA1229 protein CLCA2 1p31-p22 chloride channel, calcium activated, family member 2 CLCA1 1p31-p22 chloride channel, calcium activated, family member 1 CLCA4 1p31-p22 chloride channel, calcium activated, family member 4 CLCA3 1p31-p22 chloride channel, calcium activated, family member 3 SH3GLB1 1p22 SH3-domain GRB2-like endophilin B1 LOC391052 1 similar to dJ612B15.1 (novel protein similar to 60S ribosomal protein L17 (RPL17)) SEP15 1p31 similar to dJ612B15.1 (novel protein similar to 60S ribosomal protein L17 (RPL17))
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2037 42 381 - 2008 18575751
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     stomach   highly
    Reproductivefemale systemplacenta    Homo sapiens
     female systemovary  highly
     male systemprostate  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage
    cell lines tumor cell lines derived from the nervous system
    at STAGE
    physiological period embryo, pregnancy
  • expressed in the extravillous trophoblast
  • invariant cysteine residues, 11 N terminal, 6 C terminal
  • a N terminal IGFBP motif
  • a central domain lacking cysteine residues
  • a cysteine knot domain (at the C terminus), U45F type C domain
  • mono polymer aggregate
    interspecies homolog to murine Cyr61
  • CCN (CYR61/CTGF/NOV) protein family of matricellular proteins
  • growth factor-inducible immediate-early gene family consisting of CYR61/CCN1, connective tissue growth factor/CCN2, and nephroblastoma overexpressed/CCN3
  • growth factor-inducible, immediate-early genes family
  • CATEGORY regulatory , signaling
        plasma membrane
    text extracellular matrix protein
    basic FUNCTION
  • putatively involved in the control of cell proliferation
  • growth factor regulated gene in osteoblasts
  • matricellular inducer of angiogenesis essential for successful vascular development
  • promoting adhesion, migration, and proliferation of endothelial cells and fibroblasts
  • involved throughout the clinical progression of breast cancer to an invasive phenotype
  • tumor suppressor in hepatocarcinogenesis and is involved in DNA damage response
  • acts as a suppressor of melanoma cell motility, invasion and angiogenesis
  • acts as a negative regulator of melanoma cell migration and invasion
  • key player in global cellular and tissue organization
  • matricellular protein involved in both wound healing and cancer cell invasion
  • critical role in acid-induced esophageal epithelial cell transformation
  • regulates diverse cellular functions, including cell adhesion, migration, differentiation and survival in a cell-type- and context-dependent manner, and potent inducer of angiogenesis
  • induces cellular senescence in granulation tissue and curbs the fibrogenic response during cutaneous wound healing, also a potent angiogenic inducer which may promote tumour growth
    a component
    small molecule
  • ligand of multiple integrins, including alpha 6 beta 1 integrins (alpha 6 beta 1, alpha V beta 5 and beta 3) to mediate disparate activities in a cell type-specific manner
  • interacting with CREB1 (acts as a negative regulator of CCN1/CYR61 transcription)
  • KLK12-mediated proteolysis of CYR61 and WISP3 can reduce or abolish the binding of VEGFA, BMP2, and TGFB1
  • modulates the VEGFC expression of decidual natural killer cells via PI3K/AKT pathway
  • cell & other
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in non-small cell lung cancer (NSCLC), with poor prognosis
    constitutional     --over  
    in dilated inflammatory cardiomyopathy hearts
    tumoral     --low  
    in prostate cancer, uterine leiomyoma, rhabdomyosarcoma, embryonic rhabdomyosarcoma, and non-small cell lung carcinoma
    tumoral     --over  
    in highly metastatic melanoma cells causes a decrease in tumor angiogenesis, which is accompanied by melanoma cell apoptosis
    tumoral     --low  
    in hepatocellular carcinoma
    tumoral     --low  
    in gastric carcinoma compared with nontumoral mucosa, and might contribute to the progression of cancer by promoting MMP7 expression
    constitutional     --over  
    in granulation tissues during cutaneous wound healing
    constitutional     --other  
    deregulated in preeclampsia
  • to Graves disease
  • to Graves ophthalmopathy
  • Variant & Polymorphism
    Candidate gene candidate gene for AVSD (atrioventricular septal defect)
    Therapy target
  • potential therapeutic target in prostatic hyperplastic growth
  • specific regions of CYR61 could be targeted for therapeutic benefit to inhibit particular aspects of malignancy in breast cancer
  • SNP rs3753793 in CYR61 were associated with Graves disease
  • SNPs rs3753793, rs6682848, rs12756618, and rs1378228 in CYR61 were associated with Graves ophthalmopathy