ID CCN2_MOUSE Reviewed; 348 AA.
AC P29268; G5E830; Q922U0;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 3.
DT 27-MAR-2024, entry version 189.
DE RecName: Full=CCN family member 2;
DE AltName: Full=Cellular communication network factor 2;
DE AltName: Full=Connective tissue growth factor;
DE AltName: Full=Hypertrophic chondrocyte-specific protein 24;
DE AltName: Full=Protein FISP-12;
DE Flags: Precursor;
GN Name=Ccn2 {ECO:0000312|MGI:MGI:95537};
GN Synonyms=betaIG-M2 {ECO:0000303|PubMed:2029337}, Ctgf,
GN Fisp-12 {ECO:0000303|PubMed:1888698}, Fisp12 {ECO:0000303|PubMed:10082563},
GN Hcs24;
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 [GENOMIC DNA / MRNA].
RX PubMed=1888698;
RA Ryseck R.-P., Macdonald-Bravo H., Mattei M.-G., Bravo R.;
RT "Structure, mapping, and expression of fisp-12, a growth factor-inducible
RT gene encoding a secreted cysteine-rich protein.";
RL Cell Growth Differ. 2:225-233(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2029337; DOI=10.1089/dna.1991.10.293;
RA Brunner A., Chinn J., Neubauer M.G., Purchio A.F.;
RT "Identification of a gene family regulated by transforming growth factor-
RT beta.";
RL DNA Cell Biol. 10:293-300(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9184077; DOI=10.1006/excr.1997.3548;
RA Kireeva M.L., Latinkic B.V., Kolesnikova T.V., Chen C.-C., Yang G.P.,
RA Abler A.S., Lau L.F.;
RT "Cyr61 and Fisp12 are both ECM-associated signaling molecules: activities,
RT metabolism, and localization during development.";
RL Exp. Cell Res. 233:63-77(1997).
RN [7]
RP FUNCTION.
RX PubMed=10082563; DOI=10.1128/mcb.19.4.2958;
RA Babic A.M., Chen C.-C., Lau L.F.;
RT "Fisp12/mouse connective tissue growth factor mediates endothelial cell
RT adhesion and migration through integrin alphavbeta3, promotes endothelial
RT cell survival, and induces angiogenesis in vivo.";
RL Mol. Cell. Biol. 19:2958-2966(1999).
RN [8]
RP INTERACTION WITH TSKU.
RX PubMed=30232710; DOI=10.1007/s12079-018-0487-x;
RA Ohta K., Aoyama E., Ahmad S.A.I., Ito N., Anam M.B., Kubota S.,
RA Takigawa M.;
RT "CCN2/CTGF binds the small leucine rich proteoglycan protein Tsukushi.";
RL J. Cell Commun. Signal. 13:113-118(2019).
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 ECO:0000269|PubMed:10082563, ECO:0000269|PubMed:9184077}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with TSKU
CC (PubMed:30232710). {ECO:0000250|UniProtKB:P29279,
CC ECO:0000269|PubMed:30232710}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:9184077}. Secreted
CC {ECO:0000269|PubMed:9184077}.
CC -!- TISSUE SPECIFICITY: Testis, spleen, kidney, lung, heart, and brain
CC (lowest level in testis and highest in lung).
CC -!- INDUCTION: By growth factors.
CC -!- SIMILARITY: Belongs to the CCN family. {ECO:0000305}.
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DR EMBL; M70641; AAA37627.1; -; Genomic_DNA.
DR EMBL; M70642; AAA37628.1; -; mRNA.
DR EMBL; M80263; AAA73135.1; -; mRNA.
DR EMBL; AC099695; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466540; EDL04783.1; -; Genomic_DNA.
DR EMBL; BC006783; AAH06783.1; -; mRNA.
DR CCDS; CCDS23751.1; -.
DR PIR; A40578; A40578.
DR RefSeq; NP_034347.2; NM_010217.2.
DR AlphaFoldDB; P29268; -.
DR SMR; P29268; -.
DR BioGRID; 199679; 4.
DR IntAct; P29268; 1.
DR STRING; 10090.ENSMUSP00000020171; -.
DR PhosphoSitePlus; P29268; -.
DR CPTAC; non-CPTAC-3782; -.
DR MaxQB; P29268; -.
DR PaxDb; 10090-ENSMUSP00000020171; -.
DR PeptideAtlas; P29268; -.
DR ProteomicsDB; 284143; -.
DR Pumba; P29268; -.
DR ABCD; P29268; 1 sequenced antibody.
DR Antibodypedia; 3916; 1076 antibodies from 43 providers.
DR DNASU; 14219; -.
DR Ensembl; ENSMUST00000020171.12; ENSMUSP00000020171.6; ENSMUSG00000019997.12.
DR GeneID; 14219; -.
DR KEGG; mmu:14219; -.
DR UCSC; uc011xbr.1; mouse.
DR AGR; MGI:95537; -.
DR CTD; 1490; -.
DR MGI; MGI:95537; Ccn2.
DR VEuPathDB; HostDB:ENSMUSG00000019997; -.
DR eggNOG; ENOG502QQDX; Eukaryota.
DR GeneTree; ENSGT00940000155019; -.
DR HOGENOM; CLU_063247_1_0_1; -.
DR InParanoid; P29268; -.
DR OMA; ERDPCDH; -.
DR OrthoDB; 2970572at2759; -.
DR PhylomeDB; P29268; -.
DR TreeFam; TF326070; -.
DR BioGRID-ORCS; 14219; 0 hits in 77 CRISPR screens.
DR ChiTaRS; Ccn2; mouse.
DR PRO; PR:P29268; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P29268; Protein.
DR Bgee; ENSMUSG00000019997; Expressed in aorta tunica media and 348 other cell types or tissues.
DR ExpressionAtlas; P29268; baseline and differential.
DR Genevisible; P29268; MM.
DR GO; GO:0005938; C:cell cortex; ISO:MGI.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0001968; F:fibronectin binding; ISO:MGI.
DR GO; GO:0008083; F:growth factor activity; ISO:MGI.
DR GO; GO:0008201; F:heparin binding; IDA:MGI.
DR GO; GO:0005178; F:integrin binding; IDA:MGI.
DR GO; GO:0001525; P:angiogenesis; IDA:MGI.
DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; ISO:MGI.
DR GO; GO:0001502; P:cartilage condensation; IDA:MGI.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IDA:MGI.
DR GO; GO:0007160; P:cell-matrix adhesion; IDA:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IDA:MGI.
DR GO; GO:0035988; P:chondrocyte proliferation; IMP:MGI.
DR GO; GO:0061448; P:connective tissue development; IMP:MGI.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0070278; P:extracellular matrix constituent secretion; ISO:MGI.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IDA:MGI.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0007019; P:microtubule depolymerization; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI.
DR GO; GO:0001503; P:ossification; IMP:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0060452; P:positive regulation of cardiac muscle contraction; ISO:MGI.
DR GO; GO:0050867; P:positive regulation of cell activation; ISO:MGI.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0070318; P:positive regulation of G0 to G1 transition; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISO:MGI.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IDA:MGI.
DR GO; GO:0032330; P:regulation of chondrocyte differentiation; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0001894; P:tissue homeostasis; IMP:MGI.
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.
PE 1: Evidence at protein level;
KW Cell adhesion; Disulfide bond; DNA synthesis; Extracellular matrix;
KW Heparin-binding; Reference proteome; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..348
FT /note="CCN family member 2"
FT /id="PRO_0000014403"
FT DOMAIN 26..97
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 100..166
FT /note="VWFC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 197..242
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 255..329
FT /note="CTCK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT REGION 246..348
FT /note="Heparin-binding"
FT /evidence="ECO:0000250|UniProtKB:P29279"
FT DISULFID 28..53
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DISULFID 32..55
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DISULFID 34..56
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DISULFID 42..59
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DISULFID 67..81
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DISULFID 73..94
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DISULFID 255..292
FT /evidence="ECO:0000250"
FT DISULFID 272..306
FT /evidence="ECO:0000250"
FT DISULFID 283..322
FT /evidence="ECO:0000250"
FT DISULFID 286..324
FT /evidence="ECO:0000250"
FT DISULFID 291..328
FT /evidence="ECO:0000250"
FT CONFLICT 24
FT /note="M -> T (in Ref. 1; AAA37627/AAA37628, 2; AAA73135
FT and 5; AAH06783)"
FT /evidence="ECO:0000305"
FT CONFLICT 161
FT /note="E -> K (in Ref. 1; AAA37627/AAA37628)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 348 AA; 37824 MW; 9BD99E6D0BEFC7BC CRC64;
MLASVAGPIS LALVLLALCT RPAMGQDCSA QCQCAAEAAP HCPAGVSLVL DGCGCCRVCA
KQLGELCTER DPCDPHKGLF CDFGSPANRK IGVCTAKDGA PCVFGGSVYR SGESFQSSCK
YQCTCLDGAV GCVPLCSMDV RLPSPDCPFP RRVKLPGKCC EEWVCDEPKD RTAVGPALAA
YRLEDTFGPD PTMMRANCLV QTTEWSACSK TCGMGISTRV TNDNTFCRLE KQSRLCMVRP
CEADLEENIK KGKKCIRTPK IAKPVKFELS GCTSVKTYRA KFCGVCTDGR CCTPHRTTTL
PVEFKCPDGE IMKKNMMFIK TCACHYNCPG DNDIFESLYY RKMYGDMA
//
