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   25-MAY-2022, entry version 179.
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; 3.
DR   IntAct; P29268; 1.
DR   STRING; 10090.ENSMUSP00000020171; -.
DR   PhosphoSitePlus; P29268; -.
DR   CPTAC; non-CPTAC-3782; -.
DR   MaxQB; P29268; -.
DR   PaxDb; P29268; -.
DR   PeptideAtlas; P29268; -.
DR   PRIDE; P29268; -.
DR   ProteomicsDB; 284143; -.
DR   ABCD; P29268; 1 sequenced antibody.
DR   Antibodypedia; 3916; 949 antibodies from 43 providers.
DR   DNASU; 14219; -.
DR   Ensembl; ENSMUST00000020171; ENSMUSP00000020171; ENSMUSG00000019997.
DR   GeneID; 14219; -.
DR   KEGG; mmu:14219; -.
DR   UCSC; uc011xbr.1; mouse.
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; QDCGGQC; -.
DR   OrthoDB; 999958at2759; -.
DR   PhylomeDB; P29268; -.
DR   TreeFam; TF326070; -.
DR   BioGRID-ORCS; 14219; 0 hits in 72 CRISPR screens.
DR   ChiTaRS; Ccn2; mouse.
DR   PRO; PR:P29268; -.
DR   Proteomes; UP000000589; Chromosome 10.
DR   RNAct; P29268; protein.
DR   Bgee; ENSMUSG00000019997; Expressed in decidua and 369 other tissues.
DR   Genevisible; P29268; MM.
DR   GO; GO:0005938; C:cell cortex; ISO:MGI.
DR   GO; GO:0005801; C:cis-Golgi network; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; 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: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:0008022; F:protein C-terminus binding; ISO:MGI.
DR   GO; GO:0001525; P:angiogenesis; IDA:MGI.
DR   GO; GO:0001502; P:cartilage condensation; IDA:MGI.
DR   GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR   GO; GO:0030154; P:cell differentiation; IDA:MGI.
DR   GO; GO:0016477; P:cell migration; IDA:MGI.
DR   GO; GO:0007160; P:cell-matrix adhesion; IDA:MGI.
DR   GO; GO:0035988; P:chondrocyte proliferation; IMP:MGI.
DR   GO; GO:0061448; P:connective tissue development; IMP:MGI.
DR   GO; GO:0060401; P:cytosolic calcium ion transport; ISO: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:0060548; P:negative regulation of cell death; 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: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:0010942; P:positive regulation of cell death; 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:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic 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; -; 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; 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        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
//