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 17-JUN-2020, entry version 167. 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 Plays also 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=3; 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 proinflammatory 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}. 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; 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 SMR; P48745; -. DR BioGRID; 110918; 15. DR CORUM; P48745; -. DR IntAct; P48745; 19. DR STRING; 9606.ENSP00000259526; -. DR DrugBank; DB00071; Insulin pork. DR TCDB; 8.A.87.1.6; the tbc1 domain (tbc1) family. 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; 368 antibodies. DR DNASU; 4856; -. DR Ensembl; ENST00000259526; ENSP00000259526; ENSG00000136999. DR GeneID; 4856; -. DR KEGG; hsa:4856; -. DR UCSC; uc003yoq.3; human. DR CTD; 4856; -. DR DisGeNET; 4856; -. DR EuPathDB; HostDB:ENSG00000136999.4; -. 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 eggNOG; ENOG410IH0W; Eukaryota. DR eggNOG; ENOG4111F77; LUCA. DR GeneTree; ENSGT00940000159963; -. DR HOGENOM; CLU_063247_1_0_1; -. DR InParanoid; P48745; -. DR KO; K23571; -. DR OMA; CHTNCPQ; -. DR OrthoDB; 999958at2759; -. DR PhylomeDB; P48745; -. DR TreeFam; TF326070; -. DR SignaLink; P48745; -. DR SIGNOR; P48745; -. DR BioGRID-ORCS; 4856; 0 hits in 786 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 left adrenal gland and 185 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:0005520; F:insulin-like growth factor binding; IEA:InterPro. 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 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; 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; 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 Polymorphism; 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 //