CCN1_MOUSE
ID CCN1_MOUSE Reviewed; 379 AA.
AC P18406;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=CCN family member 1;
DE AltName: Full=3CH61;
DE AltName: Full=Cellular communication network factor 1;
DE AltName: Full=Cysteine-rich angiogenic inducer 61;
DE AltName: Full=Insulin-like growth factor-binding protein 10;
DE Short=IBP-10;
DE Short=IGF-binding protein 10;
DE Short=IGFBP-10;
DE AltName: Full=Protein CYR61;
DE Flags: Precursor;
GN Name=Ccn1 {ECO:0000312|MGI:MGI:88613};
GN Synonyms=Cyr61 {ECO:0000303|PubMed:2062642, ECO:0000303|PubMed:2355916},
GN Igfbp10;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Fibroblast;
RX PubMed=2355916; DOI=10.1128/mcb.10.7.3569-3577.1990;
RA O'Brien T.P., Yang G.P., Sanders L., Lau L.F.;
RT "Expression of cyr61, a growth factor-inducible immediate-early gene.";
RL Mol. Cell. Biol. 10:3569-3577(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=A/J; TISSUE=Embryonic fibroblast;
RX PubMed=2062642; DOI=10.1093/nar/19.12.3261;
RA Latinkic B.V., O'Brien T.P., Lau L.F.;
RT "Promoter function and structure of the growth factor-inducible immediate
RT early gene cyr61.";
RL Nucleic Acids Res. 19:3261-3267(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP HEPARIN-BINDING DOMAIN.
RX PubMed=10821835; DOI=10.1074/jbc.m003040200;
RA Chen N., Chen C.-C., Lau L.F.;
RT "Adhesion of human skin fibroblasts to Cyr61 is mediated through integrin
RT alpha 6beta 1 and cell surface heparan sulfate proteoglycans.";
RL J. Biol. Chem. 275:24953-24961(2000).
CC -!- FUNCTION: Promotes cell proliferation, chemotaxis, angiogenesis and
CC cell adhesion. Appears to play a role in wound healing by up-
CC regulating, in skin fibroblasts, the expression of a number of genes
CC involved in angiogenesis, inflammation and matrix remodeling including
CC VEGA-A, VEGA-C, MMP1, MMP3, TIMP1, uPA, PAI-1 and integrins alpha-3 and
CC alpha-5 (By similarity). CCN1-mediated gene regulation is dependent on
CC heparin-binding (By similarity). Down-regulates the expression of
CC alpha-1 and alpha-2 subunits of collagen type-1 (By similarity).
CC Promotes cell adhesion and adhesive signaling through integrin alpha-
CC 6/beta-1, cell migration through integrin alpha-1/beta-5 and cell
CC proliferation through integrin alpha-v/beta-3 (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interaction with integrins is heparin- and cell-type-dependent
CC and promotes cell adhesion. {ECO:0000250, ECO:0000269|PubMed:10821835}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Low in kidney, adrenal gland, testes, brain, and
CC ovary, moderate in heart, uterus, and skeletal muscle, highest in lung.
CC -!- DEVELOPMENTAL STAGE: Expressed from G(0)/G(1) through mid-G(1) in
CC normal cells, and at a constant level in rapidly growing cells.
CC -!- INDUCTION: By growth factors.
CC -!- SIMILARITY: Belongs to the CCN family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M32490; AAA37512.1; -; mRNA.
DR EMBL; X56790; CAA40109.1; -; Genomic_DNA.
DR EMBL; BC066019; AAH66019.1; -; mRNA.
DR CCDS; CCDS17895.1; -.
DR PIR; A35669; A35669.
DR RefSeq; NP_034646.1; NM_010516.2.
DR AlphaFoldDB; P18406; -.
DR SMR; P18406; -.
DR BioGRID; 200553; 16.
DR IntAct; P18406; 15.
DR STRING; 10090.ENSMUSP00000029846; -.
DR iPTMnet; P18406; -.
DR PhosphoSitePlus; P18406; -.
DR PaxDb; P18406; -.
DR PeptideAtlas; P18406; -.
DR PRIDE; P18406; -.
DR ProteomicsDB; 277939; -.
DR Antibodypedia; 19796; 600 antibodies from 38 providers.
DR DNASU; 16007; -.
DR Ensembl; ENSMUST00000029846; ENSMUSP00000029846; ENSMUSG00000028195.
DR GeneID; 16007; -.
DR KEGG; mmu:16007; -.
DR UCSC; uc008rqq.2; mouse.
DR CTD; 3491; -.
DR MGI; MGI:88613; Ccn1.
DR VEuPathDB; HostDB:ENSMUSG00000028195; -.
DR eggNOG; ENOG502QQQQ; Eukaryota.
DR GeneTree; ENSGT00940000155151; -.
DR HOGENOM; CLU_063247_1_0_1; -.
DR InParanoid; P18406; -.
DR OMA; CPLEVPK; -.
DR OrthoDB; 999958at2759; -.
DR PhylomeDB; P18406; -.
DR TreeFam; TF326070; -.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 16007; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Ccn1; mouse.
DR PRO; PR:P18406; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P18406; protein.
DR Bgee; ENSMUSG00000028195; Expressed in endoderm of midgut and 250 other tissues.
DR ExpressionAtlas; P18406; baseline and differential.
DR Genevisible; P18406; MM.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0050840; F:extracellular matrix binding; IDA:MGI.
DR GO; GO:0019838; F:growth factor binding; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; IBA:GO_Central.
DR GO; GO:0005178; F:integrin binding; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0003278; P:apoptotic process involved in heart morphogenesis; IMP:MGI.
DR GO; GO:0060413; P:atrial septum morphogenesis; IMP:MGI.
DR GO; GO:0003181; P:atrioventricular valve morphogenesis; IMP:MGI.
DR GO; GO:0007155; P:cell adhesion; IDA:MGI.
DR GO; GO:0098609; P:cell-cell adhesion; IDA:MGI.
DR GO; GO:0006935; P:chemotaxis; ISO:MGI.
DR GO; GO:0060591; P:chondroblast differentiation; IDA:MGI.
DR GO; GO:0060710; P:chorio-allantoic fusion; IMP:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IDA:MGI.
DR GO; GO:0002041; P:intussusceptive angiogenesis; IMP:MGI.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; IBA:GO_Central.
DR GO; GO:0001649; P:osteoblast differentiation; IGI:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IGI:MGI.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISO:MGI.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISO:MGI.
DR GO; GO:0061036; P:positive regulation of cartilage development; IMP:MGI.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IDA:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:MGI.
DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IDA:MGI.
DR GO; GO:2000304; P:positive regulation of ceramide biosynthetic process; IDA:MGI.
DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; ISO:MGI.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IGI:MGI.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:MGI.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISO:MGI.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:MGI.
DR GO; GO:0033690; P:positive regulation of osteoblast proliferation; ISO:MGI.
DR GO; GO:0010518; P:positive regulation of phospholipase activity; IDA:MGI.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:2000309; P:positive regulation of tumor necrosis factor (ligand) superfamily member 11 production; ISO:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IDA:MGI.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0003281; P:ventricular septum development; IMP:MGI.
DR GO; GO:0044319; P:wound healing, spreading of cells; ISO:MGI.
DR Gene3D; 2.20.100.10; -; 1.
DR InterPro; IPR006207; Cys_knot_C.
DR InterPro; IPR006208; Glyco_hormone_CN.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR000867; IGFBP-like.
DR InterPro; IPR012395; IGFBP_CNN.
DR InterPro; IPR017891; Insulin_GF-bd_Cys-rich_CS.
DR InterPro; IPR043973; TSP1_CCN.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR InterPro; IPR001007; VWF_dom.
DR Pfam; PF00007; Cys_knot; 1.
DR Pfam; PF00219; IGFBP; 1.
DR Pfam; PF19035; TSP1_CCN; 1.
DR Pfam; PF00093; VWC; 1.
DR PIRSF; PIRSF036495; IGFBP_rP_CNN; 1.
DR SMART; SM00041; CT; 1.
DR SMART; SM00121; IB; 1.
DR SMART; SM00209; TSP1; 1.
DR SMART; SM00214; VWC; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR SUPFAM; SSF82895; SSF82895; 1.
DR PROSITE; PS01185; CTCK_1; 1.
DR PROSITE; PS01225; CTCK_2; 1.
DR PROSITE; PS00222; IGFBP_N_1; 1.
DR PROSITE; PS51323; IGFBP_N_2; 1.
DR PROSITE; PS50092; TSP1; 1.
DR PROSITE; PS01208; VWFC_1; 1.
DR PROSITE; PS50184; VWFC_2; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Chemotaxis; Disulfide bond; Growth factor binding;
KW Heparin-binding; Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..379
FT /note="CCN family member 1"
FT /id="PRO_0000014399"
FT DOMAIN 25..94
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 98..164
FT /note="VWFC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 226..271
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 284..358
FT /note="CTCK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT REGION 277..313
FT /note="Heparin-binding"
FT /evidence="ECO:0000269|PubMed:10821835"
FT MOD_RES 184
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00622"
FT DISULFID 284..321
FT /evidence="ECO:0000250"
FT DISULFID 301..335
FT /evidence="ECO:0000250"
FT DISULFID 312..351
FT /evidence="ECO:0000250"
FT DISULFID 315..353
FT /evidence="ECO:0000250"
FT DISULFID 320..357
FT /evidence="ECO:0000250"
SQ SEQUENCE 379 AA; 41709 MW; FA6B5014B56A8EE9 CRC64;
MSSSTFRTLA VAVTLLHLTR LALSTCPAAC HCPLEAPKCA PGVGLVRDGC GCCKVCAKQL
NEDCSKTQPC DHTKGLECNF GASSTALKGI CRAQSEGRPC EYNSRIYQNG ESFQPNCKHQ
CTCIDGAVGC IPLCPQELSL PNLGCPNPRL VKVSGQCCEE WVCDEDSIKD SLDDQDDLLG
LDASEVELTR NNELIAIGKG SSLKRLPVFG TEPRVLFNPL HAHGQKCIVQ TTSWSQCSKS
CGTGISTRVT NDNPECRLVK ETRICEVRPC GQPVYSSLKK GKKCSKTKKS PEPVRFTYAG
CSSVKKYRPK YCGSCVDGRC CTPLQTRTVK MRFRCEDGEM FSKNVMMIQS CKCNYNCPHP
NEASFRLYSL FNDIHKFRD
