CCN3_HUMAN
ID CCN3_HUMAN Reviewed; 357 AA.
AC P48745; B2R5X7; Q6I9S3; Q96BY5; Q9UDE4;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=CCN family member 3 {ECO:0000305};
DE AltName: Full=Cellular communication network factor 3 {ECO:0000312|HGNC:HGNC:7885};
DE AltName: Full=Insulin-like growth factor-binding protein 9;
DE Short=IBP-9;
DE Short=IGF-binding protein 9;
DE Short=IGFBP-9;
DE AltName: Full=Nephro blastoma-overexpressed gene protein homolog;
DE AltName: Full=Protein NOV homolog;
DE Short=NovH;
DE Flags: Precursor;
GN Name=CCN3 {ECO:0000312|HGNC:HGNC:7885}; Synonyms=IGFBP9, NOV, NOVH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=7520150;
RA Martinerie C., Huff V., Joubert I., Badzioch M., Saunders G.F.,
RA Strong L.C., Perbal B.;
RT "Structural analysis of the human nov proto-oncogene and expression in
RT Wilms tumor.";
RL Oncogene 9:2729-2732(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RX PubMed=8622864;
RA Martinerie C., Chevalier G., Rauscher F.J. III, Perbal B.;
RT "Regulation of nov by WT1: a potential role for nov in nephrogenesis.";
RL Oncogene 12:1479-1492(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Jiang D., Gou D., Li W.;
RT "Cloning, sequencing and expression of human nov gene.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 26-102, AND TISSUE SPECIFICITY.
RX PubMed=1756408;
RA Martinerie C., Perbal B.;
RT "Expression of a gene encoding a novel potential IGF binding protein in
RT human tissues.";
RL C. R. Acad. Sci. III, Sci. Vie 313:345-351(1991).
RN [8]
RP PROTEIN SEQUENCE OF 32-46.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [9]
RP INTERACTION WITH FBLN1.
RX PubMed=9927660; DOI=10.1073/pnas.96.3.869;
RA Perbal B., Martinerie C., Sainson R., Werner M., He B., Roizman B.;
RT "The C-terminal domain of the regulatory protein NOVH is sufficient to
RT promote interaction with fibulin 1C: a clue for a role of NOVH in cell-
RT adhesion signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:869-874(1999).
RN [10]
RP FUNCTION, AND INTERACTION WITH NOTCH1.
RX PubMed=12050162; DOI=10.1074/jbc.m203727200;
RA Sakamoto K., Yamaguchi S., Ando R., Miyawaki A., Kabasawa Y., Takagi M.,
RA Li C.L., Perbal B., Katsube K.;
RT "The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with
RT Notch1 extracellular domain and inhibits myoblast differentiation via Notch
RT signaling pathway.";
RL J. Biol. Chem. 277:29399-29405(2002).
RN [11]
RP FUNCTION, AND INTERACTION WITH ITGA5; ITGAV; ITGB1 AND ITGB3.
RX PubMed=12695522; DOI=10.1074/jbc.m302028200;
RA Lin C.G., Leu S.J., Chen N., Tebeau C.M., Lin S.X., Yeung C.Y., Lau L.F.;
RT "CCN3 (NOV) is a novel angiogenic regulator of the CCN protein family.";
RL J. Biol. Chem. 278:24200-24208(2003).
RN [12]
RP NOMENCLATURE.
RX PubMed=12665631; DOI=10.1136/mp.56.2.127;
RA Brigstock D.R., Goldschmeding R., Katsube K.I., Lam S.C., Lau L.F.,
RA Lyons K., Naus C., Perbal B., Riser B., Takigawa M., Yeger H.;
RT "Proposal for a unified CCN nomenclature.";
RL Mol. Pathol. 56:127-128(2003).
RN [13]
RP FUNCTION, INTERACTION WITH GJA1, AND SUBCELLULAR LOCATION.
RX PubMed=15181016; DOI=10.1074/jbc.m404073200;
RA Gellhaus A., Dong X., Propson S., Maass K., Klein-Hitpass L., Kibschull M.,
RA Traub O., Willecke K., Perbal B., Lye S.J., Winterhager E.;
RT "Connexin43 interacts with NOV: a possible mechanism for negative
RT regulation of cell growth in choriocarcinoma cells.";
RL J. Biol. Chem. 279:36931-36942(2004).
RN [14]
RP INTERACTION WITH GJA1.
RX PubMed=15213231; DOI=10.1074/jbc.m403952200;
RA Fu C.T., Bechberger J.F., Ozog M.A., Perbal B., Naus C.C.;
RT "CCN3 (NOV) interacts with connexin43 in C6 glioma cells: possible
RT mechanism of connexin-mediated growth suppression.";
RL J. Biol. Chem. 279:36943-36950(2004).
RN [15]
RP FUNCTION, AND INTERACTION WITH ITGAV AND ITGB5.
RX PubMed=15611078; DOI=10.1074/jbc.m404903200;
RA Lin C.G., Chen C.C., Leu S.J., Grzeszkiewicz T.M., Lau L.F.;
RT "Integrin-dependent functions of the angiogenic inducer NOV (CCN3):
RT implication in wound healing.";
RL J. Biol. Chem. 280:8229-8237(2005).
RN [16]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=17463287; DOI=10.1126/science.1136031;
RA Gupta R., Hong D., Iborra F., Sarno S., Enver T.;
RT "NOV (CCN3) functions as a regulator of human hematopoietic stem or
RT progenitor cells.";
RL Science 316:590-593(2007).
RN [17]
RP FUNCTION.
RX PubMed=20139355; DOI=10.1161/atvbaha.110.203356;
RA Shimoyama T., Hiraoka S., Takemoto M., Koshizaka M., Tokuyama H.,
RA Tokuyama T., Watanabe A., Fujimoto M., Kawamura H., Sato S., Tsurutani Y.,
RA Saito Y., Perbal B., Koseki H., Yokote K.;
RT "CCN3 inhibits neointimal hyperplasia through modulation of smooth muscle
RT cell growth and migration.";
RL Arterioscler. Thromb. Vasc. Biol. 30:675-682(2010).
RN [18]
RP FUNCTION, INDUCTION BY LAMINAR SHEAR STRESS; STATINS AND TNF, AND TISSUE
RP SPECIFICITY.
RX PubMed=21063504; DOI=10.1007/s12079-010-0095-x;
RA Lin Z., Natesan V., Shi H., Hamik A., Kawanami D., Hao C.,
RA Mahabaleshwar G.H., Wang W., Jin Z.G., Atkins G.B., Firth S.M., Rittie L.,
RA Perbal B., Jain M.K.;
RT "A novel role of CCN3 in regulating endothelial inflammation.";
RL J. Cell Commun. Signal. 4:141-153(2010).
RN [19]
RP FUNCTION.
RX PubMed=21871891; DOI=10.1016/j.febslet.2011.08.024;
RA Janune D., Kubota S., Nishida T., Kawaki H., Perbal B., Iida S.,
RA Takigawa M.;
RT "Novel effects of CCN3 that may direct the differentiation of
RT chondrocytes.";
RL FEBS Lett. 585:3033-3040(2011).
RN [20]
RP FUNCTION.
RX PubMed=21344378; DOI=10.1002/jcp.22672;
RA Tzeng H.E., Chen J.C., Tsai C.H., Kuo C.C., Hsu H.C., Hwang W.L.,
RA Fong Y.C., Tang C.H.;
RT "CCN3 increases cell motility and MMP-13 expression in human chondrosarcoma
RT through integrin-dependent pathway.";
RL J. Cell. Physiol. 226:3181-3189(2011).
RN [21]
RP INDUCTION BY TNF AND IL1B.
RX PubMed=24722330; DOI=10.1371/journal.pone.0094912;
RA Liu J., Ren Y., Kang L., Zhang L.;
RT "Overexpression of CCN3 inhibits inflammation and progression of
RT atherosclerosis in apolipoprotein E-deficient mice.";
RL PLoS ONE 9:E94912-E94912(2014).
CC -!- FUNCTION: Immediate-early protein playing a role in various cellular
CC processes including proliferation, adhesion, migration, differentiation
CC and survival (PubMed:15181016, PubMed:15611078, PubMed:12695522,
CC PubMed:21344378, PubMed:12050162). Acts by binding to integrins or
CC membrane receptors such as NOTCH1 (PubMed:12695522, PubMed:21344378,
CC PubMed:15611078). Essential regulator of hematopoietic stem and
CC progenitor cell function (PubMed:17463287). Inhibits myogenic
CC differentiation through the activation of Notch-signaling pathway
CC (PubMed:12050162). Inhibits vascular smooth muscle cells proliferation
CC by increasing expression of cell-cycle regulators such as CDKN2B or
CC CDKN1A independently of TGFB1 signaling (PubMed:20139355). Ligand of
CC integrins ITGAV:ITGB3 and ITGA5:ITGB1, acts directly upon endothelial
CC cells to stimulate pro-angiogenic activities and induces angiogenesis.
CC In endothelial cells, supports cell adhesion, induces directed cell
CC migration (chemotaxis) and promotes cell survival (PubMed:12695522).
CC Also plays a role in cutaneous wound healing acting as integrin
CC receptor ligand. Supports skin fibroblast adhesion through ITGA5:ITGB1
CC and ITGA6:ITGB1 and induces fibroblast chemotaxis through ITGAV:ITGB5.
CC Seems to enhance bFGF-induced DNA synthesis in fibroblasts
CC (PubMed:15611078). Involved in bone regeneration as a negative
CC regulator (By similarity). Enhances the articular chondrocytic
CC phenotype, whereas it repressed the one representing endochondral
CC ossification (PubMed:21871891). Impairs pancreatic beta-cell function,
CC inhibits beta-cell proliferation and insulin secretion (By similarity).
CC Plays a role as negative regulator of endothelial pro-inflammatory
CC activation reducing monocyte adhesion, its anti-inflammatory effects
CC occur secondary to the inhibition of NF-kappaB signaling pathway
CC (PubMed:21063504). Contributes to the control and coordination of
CC inflammatory processes in atherosclerosis (By similarity). Attenuates
CC inflammatory pain through regulation of IL1B- and TNF-induced MMP9,
CC MMP2 and CCL2 expression. Inhibits MMP9 expression through ITGB1
CC engagement (PubMed:21871891). {ECO:0000250|UniProtKB:Q64299,
CC ECO:0000269|PubMed:12050162, ECO:0000269|PubMed:12695522,
CC ECO:0000269|PubMed:15181016, ECO:0000269|PubMed:15611078,
CC ECO:0000269|PubMed:17463287, ECO:0000269|PubMed:20139355,
CC ECO:0000269|PubMed:21063504, ECO:0000269|PubMed:21344378,
CC ECO:0000269|PubMed:21871891}.
CC -!- SUBUNIT: Interacts with FBLN1. Interacts (via CTCK domain) with NOTCH1
CC (via the EGF-like repeat region) (PubMed:12050162). Interacts with
CC GJA1/CX43 (PubMed:15181016, PubMed:15213231). Interacts with
CC ITGA5:ITGB1, ITGAV:ITGB3 and ITGAV:ITGB5 (PubMed:12695522,
CC PubMed:15611078). Interacts with ZDHHC22; the interaction may lead to
CC CCN3 palmitoylation (By similarity). {ECO:0000250|UniProtKB:Q64299,
CC ECO:0000269|PubMed:12050162, ECO:0000269|PubMed:12695522,
CC ECO:0000269|PubMed:15181016, ECO:0000269|PubMed:15213231,
CC ECO:0000269|PubMed:15611078, ECO:0000269|PubMed:9927660}.
CC -!- INTERACTION:
CC P48745; X5D778: ANKRD11; NbExp=3; IntAct=EBI-3904822, EBI-17183751;
CC P48745; Q9BWW8: APOL6; NbExp=3; IntAct=EBI-3904822, EBI-11574440;
CC P48745; Q6NUJ2: C11orf87; NbExp=3; IntAct=EBI-3904822, EBI-6660291;
CC P48745; P27658: COL8A1; NbExp=3; IntAct=EBI-3904822, EBI-747133;
CC P48745; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-3904822, EBI-6658203;
CC P48745; O43559: FRS3; NbExp=3; IntAct=EBI-3904822, EBI-725515;
CC P48745; P49639: HOXA1; NbExp=4; IntAct=EBI-3904822, EBI-740785;
CC P48745; Q6L8G9: KRTAP5-6; NbExp=3; IntAct=EBI-3904822, EBI-10250562;
CC P48745; Q5T7P2: LCE1A; NbExp=3; IntAct=EBI-3904822, EBI-11962058;
CC P48745; Q9BYE3: LCE3D; NbExp=3; IntAct=EBI-3904822, EBI-6658837;
CC P48745; Q8N5G2: MACO1; NbExp=3; IntAct=EBI-3904822, EBI-2683507;
CC P48745; Q8IV28: NID2; NbExp=3; IntAct=EBI-3904822, EBI-10261509;
CC P48745; Q12837: POU4F2; NbExp=3; IntAct=EBI-3904822, EBI-17236143;
CC P48745; Q6P9E2: RECK; NbExp=3; IntAct=EBI-3904822, EBI-10253121;
CC P48745; Q96KP6: TNIP3; NbExp=3; IntAct=EBI-3904822, EBI-2509913;
CC P48745; Q9Y3S2: ZNF330; NbExp=3; IntAct=EBI-3904822, EBI-373456;
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasm
CC {ECO:0000269|PubMed:15181016}. Cell junction, gap junction
CC {ECO:0000269|PubMed:15181016}. Note=Localizes at the gap junction in
CC presence of GJA1. {ECO:0000250|UniProtKB:Q9QZQ5}.
CC -!- TISSUE SPECIFICITY: Expressed in endiothelial cells (at protein level)
CC (PubMed:21063504). Expressed in bone marrow, thymic cells and
CC nephroblastoma. Increased expression in Wilms tumor of the stromal
CC type. {ECO:0000269|PubMed:1756408, ECO:0000269|PubMed:21063504}.
CC -!- DEVELOPMENTAL STAGE: Expressed in primitive compartments of umbilical
CC vein cord. {ECO:0000269|PubMed:17463287}.
CC -!- INDUCTION: Expression is down-regulated by WT1. Expression is down-
CC regulated by pro-inflammatory stimuli such as TNF or IL1B
CC (PubMed:24722330, PubMed:21063504). Expression is induced by laminar
CC shear stress and statins (PubMed:21063504).
CC {ECO:0000269|PubMed:21063504, ECO:0000269|PubMed:24722330,
CC ECO:0000269|PubMed:8622864}.
CC -!- PTM: May be palmitoylated on Cys-244, which is important for
CC extracellular secretion. {ECO:0000250|UniProtKB:Q64299}.
CC -!- SIMILARITY: Belongs to the CCN family. {ECO:0000305}.
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DR EMBL; X78351; CAA55146.1; -; Genomic_DNA.
DR EMBL; X78352; CAA55146.1; JOINED; Genomic_DNA.
DR EMBL; X78353; CAA55146.1; JOINED; Genomic_DNA.
DR EMBL; X78354; CAA55146.1; JOINED; Genomic_DNA.
DR EMBL; X96584; CAA65403.1; -; mRNA.
DR EMBL; AY082381; AAL92490.1; -; mRNA.
DR EMBL; AK312355; BAG35274.1; -; mRNA.
DR EMBL; CR457432; CAG33713.1; -; mRNA.
DR EMBL; BC015028; AAH15028.1; -; mRNA.
DR CCDS; CCDS6328.1; -.
DR PIR; I38069; I38069.
DR RefSeq; NP_002505.1; NM_002514.3.
DR AlphaFoldDB; P48745; -.
DR SMR; P48745; -.
DR BioGRID; 110918; 39.
DR CORUM; P48745; -.
DR IntAct; P48745; 21.
DR MINT; P48745; -.
DR STRING; 9606.ENSP00000259526; -.
DR DrugBank; DB00030; Insulin human.
DR TCDB; 8.A.87.1.6; the tbc1 domain (tbc1) family.
DR GlyGen; P48745; 2 sites.
DR iPTMnet; P48745; -.
DR PhosphoSitePlus; P48745; -.
DR SwissPalm; P48745; -.
DR BioMuta; NOV; -.
DR DMDM; 1352515; -.
DR jPOST; P48745; -.
DR MassIVE; P48745; -.
DR MaxQB; P48745; -.
DR PaxDb; P48745; -.
DR PeptideAtlas; P48745; -.
DR PRIDE; P48745; -.
DR ProteomicsDB; 55942; -.
DR Antibodypedia; 13650; 394 antibodies from 36 providers.
DR DNASU; 4856; -.
DR Ensembl; ENST00000259526.4; ENSP00000259526.3; ENSG00000136999.5.
DR GeneID; 4856; -.
DR KEGG; hsa:4856; -.
DR MANE-Select; ENST00000259526.4; ENSP00000259526.3; NM_002514.4; NP_002505.1.
DR UCSC; uc003yoq.3; human.
DR CTD; 4856; -.
DR DisGeNET; 4856; -.
DR GeneCards; CCN3; -.
DR HGNC; HGNC:7885; CCN3.
DR HPA; ENSG00000136999; Tissue enriched (adrenal).
DR MIM; 164958; gene.
DR neXtProt; NX_P48745; -.
DR OpenTargets; ENSG00000136999; -.
DR PharmGKB; PA31687; -.
DR VEuPathDB; HostDB:ENSG00000136999; -.
DR eggNOG; ENOG502QR9V; Eukaryota.
DR GeneTree; ENSGT00940000159963; -.
DR HOGENOM; CLU_063247_1_0_1; -.
DR InParanoid; P48745; -.
DR OMA; CHTNCPQ; -.
DR OrthoDB; 999958at2759; -.
DR PhylomeDB; P48745; -.
DR TreeFam; TF326070; -.
DR PathwayCommons; P48745; -.
DR SignaLink; P48745; -.
DR SIGNOR; P48745; -.
DR BioGRID-ORCS; 4856; 12 hits in 1069 CRISPR screens.
DR ChiTaRS; NOV; human.
DR GeneWiki; NOV_(gene); -.
DR GenomeRNAi; 4856; -.
DR Pharos; P48745; Tbio.
DR PRO; PR:P48745; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P48745; protein.
DR Bgee; ENSG00000136999; Expressed in right coronary artery and 166 other tissues.
DR ExpressionAtlas; P48745; baseline and differential.
DR Genevisible; P48745; HS.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005921; C:gap junction; IMP:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; IBA:GO_Central.
DR GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR GO; GO:0005112; F:Notch binding; IPI:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IDA:UniProtKB.
DR GO; GO:1990523; P:bone regeneration; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0033627; P:cell adhesion mediated by integrin; IDA:UniProtKB.
DR GO; GO:0060326; P:cell chemotaxis; IDA:UniProtKB.
DR GO; GO:0002062; P:chondrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0035767; P:endothelial cell chemotaxis; IDA:UniProtKB.
DR GO; GO:0071603; P:endothelial cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0010761; P:fibroblast migration; IDA:UniProtKB.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; IMP:UniProtKB.
DR GO; GO:0060548; P:negative regulation of cell death; IBA:GO_Central.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:UniProtKB.
DR GO; GO:1902731; P:negative regulation of chondrocyte proliferation; IMP:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0046676; P:negative regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0090027; P:negative regulation of monocyte chemotaxis; IMP:UniProtKB.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; IDA:UniProtKB.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:1904057; P:negative regulation of sensory perception of pain; ISS:UniProtKB.
DR GO; GO:0060392; P:negative regulation of SMAD protein signal transduction; ISS:UniProtKB.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0014909; P:smooth muscle cell migration; IDA:UniProtKB.
DR GO; GO:0048659; P:smooth muscle cell proliferation; IDA:UniProtKB.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; ISS:UniProtKB.
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 junction; Cytoplasm; Direct protein sequencing; Disulfide bond;
KW Gap junction; Glycoprotein; Growth factor; Lipoprotein; Palmitate;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..31
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 32..357
FT /note="CCN family member 3"
FT /id="PRO_0000014415"
FT DOMAIN 32..105
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 108..174
FT /note="VWFC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT DOMAIN 205..250
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 264..338
FT /note="CTCK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT LIPID 244
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q64299"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 264..301
FT /evidence="ECO:0000250"
FT DISULFID 281..315
FT /evidence="ECO:0000250"
FT DISULFID 292..331
FT /evidence="ECO:0000250"
FT DISULFID 295..333
FT /evidence="ECO:0000250"
FT DISULFID 300..337
FT /evidence="ECO:0000250"
FT VARIANT 42
FT /note="R -> Q (in dbSNP:rs2279112)"
FT /id="VAR_049568"
FT VARIANT 233
FT /note="R -> H (in dbSNP:rs11538929)"
FT /id="VAR_049569"
FT CONFLICT 26..27
FT /note="LG -> CL (in Ref. 7)"
FT /evidence="ECO:0000305"
FT CONFLICT 97
FT /note="N -> K (in Ref. 5; CAG33713 and 6; AAH15028)"
FT /evidence="ECO:0000305"
FT CONFLICT 231
FT /note="R -> G (in Ref. 4; BAG35274)"
FT /evidence="ECO:0000305"
FT CONFLICT 357
FT /note="M -> I (in Ref. 5; CAG33713)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 357 AA; 39162 MW; 035D5BF4576BD85B CRC64;
MQSVQSTSFC LRKQCLCLTF LLLHLLGQVA ATQRCPPQCP GRCPATPPTC APGVRAVLDG
CSCCLVCARQ RGESCSDLEP CDESSGLYCD RSADPSNQTG ICTAVEGDNC VFDGVIYRSG
EKFQPSCKFQ CTCRDGQIGC VPRCQLDVLL PEPNCPAPRK VEVPGECCEK WICGPDEEDS
LGGLTLAAYR PEATLGVEVS DSSVNCIEQT TEWTACSKSC GMGFSTRVTN RNRQCEMLKQ
TRLCMVRPCE QEPEQPTDKK GKKCLRTKKS LKAIHLQFKN CTSLHTYKPR FCGVCSDGRC
CTPHNTKTIQ AEFQCSPGQI VKKPVMVIGT CTCHTNCPKN NEAFLQELEL KTTRGKM
