ID CCN2_RAT Reviewed; 347 AA. AC Q9R1E9; Q53YJ0; Q9WVS1; DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 24-JAN-2024, entry version 158. DE RecName: Full=CCN family member 2 {ECO:0000305}; DE AltName: Full=Cellular communication network factor 2; DE AltName: Full=Connective tissue growth factor; DE AltName: Full=Connective tissue growth-related protein; DE Flags: Precursor; GN Name=Ccn2 {ECO:0000312|RGD:621392}; Synonyms=Ctgf; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10679821; RX DOI=10.1002/(sici)1097-4644(20000401)77:1<103::aid-jcb11>3.0.co;2-g; RA Xu J., Smock S.L., Safadi F.F., Rosenzweig A.B., Odgren P.R., RA Marks S.C. Jr., Owen T.A., Popoff S.N.; RT "Cloning the full-length cDNA for rat connective tissue growth factor: RT implications for skeletal development."; RL J. Cell. Biochem. 77:103-115(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10393331; DOI=10.1093/oxfordjournals.jbchem.a022414; RA Shimo T., Nakanishi T., Nishida T., Asano M., Kanyama M., Kuboki T., RA Tamatani T., Tezuka K., Takemura M., Matsumura T., Takigawa M.; RT "Connective tissue growth factor induces the proliferation, migration, and RT tube formation of vascular endothelial cells in vitro, and angiogenesis in RT vivo."; RL J. Biochem. 126:137-145(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Wistar; RA Ma L.N., Zou Y.L.; RT "Connective tissue growth related gene."; RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Major connective tissue mitoattractant secreted by vascular CC endothelial cells. Promotes proliferation and differentiation of CC chondrocytes (By similarity). Mediates heparin- and divalent cation- CC dependent cell adhesion in many cell types including fibroblasts, CC myofibroblasts, endothelial and epithelial cells (By similarity). CC Enhances fibroblast growth factor-induced DNA synthesis (By CC similarity). {ECO:0000250|UniProtKB:P29279}. CC -!- SUBUNIT: Monomer. Interacts with TSKU. {ECO:0000250|UniProtKB:P29279}. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000250|UniProtKB:P29268}. Secreted CC {ECO:0000250|UniProtKB:P29268}. 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; AF120275; AAD39132.1; -; mRNA. DR EMBL; AB023068; BAA82125.1; -; mRNA. DR EMBL; AY596447; AAT08023.1; -; Transcribed_RNA. DR RefSeq; NP_071602.1; NM_022266.2. DR AlphaFoldDB; Q9R1E9; -. DR SMR; Q9R1E9; -. DR STRING; 10116.ENSRNOP00000020528; -. DR PhosphoSitePlus; Q9R1E9; -. DR jPOST; Q9R1E9; -. DR PaxDb; 10116-ENSRNOP00000020528; -. DR GeneID; 64032; -. DR KEGG; rno:64032; -. DR AGR; RGD:621392; -. DR CTD; 1490; -. DR RGD; 621392; Ccn2. DR VEuPathDB; HostDB:ENSRNOG00000015036; -. DR eggNOG; ENOG502QQDX; Eukaryota. DR HOGENOM; CLU_063247_1_0_1; -. DR InParanoid; Q9R1E9; -. DR OrthoDB; 2970572at2759; -. DR PhylomeDB; Q9R1E9; -. DR TreeFam; TF326070; -. DR PRO; PR:Q9R1E9; -. DR Proteomes; UP000002494; Chromosome 1. DR Bgee; ENSRNOG00000015036; Expressed in lung and 20 other cell types or tissues. DR ExpressionAtlas; Q9R1E9; baseline and differential. DR GO; GO:0005938; C:cell cortex; IDA:RGD. DR GO; GO:0031012; C:extracellular matrix; ISO:RGD. DR GO; GO:0005576; C:extracellular region; ISO:RGD. DR GO; GO:0005615; C:extracellular space; IDA:RGD. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD. DR GO; GO:0001968; F:fibronectin binding; IDA:RGD. DR GO; GO:0008083; F:growth factor activity; IDA:RGD. DR GO; GO:0008201; F:heparin binding; ISO:RGD. DR GO; GO:0005178; F:integrin binding; ISO:RGD. DR GO; GO:0001525; P:angiogenesis; ISO:RGD. DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; IMP:RGD. DR GO; GO:0001502; P:cartilage condensation; ISO:RGD. DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central. DR GO; GO:0016477; P:cell migration; ISO:RGD. DR GO; GO:0007160; P:cell-matrix adhesion; ISO:RGD. DR GO; GO:0071398; P:cellular response to fatty acid; IEP:RGD. DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD. DR GO; GO:0002062; P:chondrocyte differentiation; ISO:RGD. DR GO; GO:0035988; P:chondrocyte proliferation; ISO:RGD. DR GO; GO:0061448; P:connective tissue development; ISO:RGD. DR GO; GO:0071897; P:DNA biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0070278; P:extracellular matrix constituent secretion; IMP:RGD. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; ISO:RGD. DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISO:RGD. DR GO; GO:0035556; P:intracellular signal transduction; IDA:RGD. DR GO; GO:0030324; P:lung development; IEP:RGD. DR GO; GO:0007019; P:microtubule depolymerization; IMP:RGD. DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD. DR GO; GO:0001503; P:ossification; ISO:RGD. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD. DR GO; GO:0060452; P:positive regulation of cardiac muscle contraction; IMP:RGD. DR GO; GO:0050867; P:positive regulation of cell activation; IMP:RGD. DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:RGD. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD. DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IMP:RGD. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD. DR GO; GO:0070318; P:positive regulation of G0 to G1 transition; IMP:RGD. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD. DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:RGD. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:RGD. DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISO:RGD. DR GO; GO:0072593; P:reactive oxygen species metabolic process; ISO:RGD. DR GO; GO:0032330; P:regulation of chondrocyte differentiation; ISO:RGD. DR GO; GO:0043200; P:response to amino acid; IEP:RGD. DR GO; GO:0034059; P:response to anoxia; IEP:RGD. DR GO; GO:0032355; P:response to estradiol; IEP:RGD. DR GO; GO:0070542; P:response to fatty acid; IEP:RGD. DR GO; GO:0051385; P:response to mineralocorticoid; IEP:RGD. DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD. DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR GO; GO:0001894; P:tissue homeostasis; ISO:RGD. DR Gene3D; 2.20.100.10; Thrombospondin type-1 (TSP1) repeat; 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 PANTHER; PTHR11348:SF7; CCN FAMILY MEMBER 2; 1. DR PANTHER; PTHR11348; CONNECTIVE TISSUE GROWTH FACTOR-RELATED; 1. 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; SSF57603; FnI-like domain; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF82895; TSP-1 type 1 repeat; 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. DR Genevisible; Q9R1E9; RN. PE 2: Evidence at transcript level; KW Cell adhesion; Disulfide bond; DNA synthesis; Extracellular matrix; KW Heparin-binding; Reference proteome; Secreted; Signal. FT SIGNAL 1..24 FT /evidence="ECO:0000255" FT CHAIN 25..347 FT /note="CCN family member 2" FT /id="PRO_0000014405" FT DOMAIN 25..96 FT /note="IGFBP N-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DOMAIN 99..165 FT /note="VWFC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220" FT DOMAIN 196..241 FT /note="TSP type-1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DOMAIN 254..328 FT /note="CTCK" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039" FT REGION 245..347 FT /note="Heparin-binding" FT /evidence="ECO:0000250|UniProtKB:P29279" FT DISULFID 27..52 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 31..54 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 33..55 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 41..58 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 66..80 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 72..93 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 254..291 FT /evidence="ECO:0000250" FT DISULFID 271..305 FT /evidence="ECO:0000250" FT DISULFID 282..321 FT /evidence="ECO:0000250" FT DISULFID 285..323 FT /evidence="ECO:0000250" FT DISULFID 290..327 FT /evidence="ECO:0000250" FT CONFLICT 35 FT /note="A -> R (in Ref. 2; BAA82125)" FT /evidence="ECO:0000305" FT CONFLICT 94 FT /note="T -> P (in Ref. 2; BAA82125)" FT /evidence="ECO:0000305" SQ SEQUENCE 347 AA; 37756 MW; CFBE1A19766B7B16 CRC64; MLASVAGPVS LALVLLLCTR PATGQDCSAQ CQCAAEAAPR CPAGVSLVLD GCGCCRVCAK QLGELCTERD PCDPHKGLFC DFGSPANRKI GVCTAKDGAP CVFGGSVYRS GESFQSSCKY QCTCLDGAVG CVPLCSMDVR LPSPDCPFPR RVKLPGKCCE EWVCDEPKDR TVVGPALAAY RLEDTFGPDP TMMRANCLVQ TTEWSACSKT CGMGISTRVT NDNTFCRLEK QSRLCMVRPC EADLEENIKK GKKCIRTPKI AKPVKFELSG CTSVKTYRAK FCGVCTDGRC CTPHRTTTLP VEFKCPDGEI MKKNMMFIKT CACHYNCPGD NDIFESLYYR KMYGDMA //