{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P48745","secondaryAccessions":["B2R5X7","Q6I9S3","Q96BY5","Q9UDE4"],"uniProtkbId":"CCN3_HUMAN","entryAudit":{"firstPublicDate":"1996-02-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1996-02-01","entryVersion":196,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"CCN family member 3"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:7885"}],"value":"Cellular communication network factor 3"}},{"fullName":{"value":"Insulin-like growth factor-binding protein 9"},"shortNames":[{"value":"IBP-9"},{"value":"IGF-binding protein 9"},{"value":"IGFBP-9"}]},{"fullName":{"value":"Nephro blastoma-overexpressed gene protein homolog"}},{"fullName":{"value":"Protein NOV homolog"},"shortNames":[{"value":"NovH"}]}],"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:7885"}],"value":"CCN3"},"synonyms":[{"value":"IGFBP9"},{"value":"NOV"},{"value":"NOVH"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q64299"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12050162"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12695522"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15181016"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15611078"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17463287"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20139355"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21063504"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21344378"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21871891"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38987585"}],"value":"Immediate-early protein playing a role in various cellular processes including proliferation, adhesion, migration, differentiation and survival (PubMed:12050162, PubMed:12695522, PubMed:15181016, PubMed:15611078, PubMed:21344378). Acts by binding to integrins or membrane receptors such as NOTCH1 (PubMed:12695522, PubMed:15611078, PubMed:21344378). Essential regulator of hematopoietic stem and progenitor cell function (PubMed:17463287). Inhibits myogenic differentiation through the activation of Notch-signaling pathway (PubMed:12050162). Inhibits vascular smooth muscle cells proliferation by increasing expression of cell-cycle regulators such as CDKN2B or CDKN1A independently of TGFB1 signaling (PubMed:20139355). Ligand of integrins ITGAV:ITGB3 and ITGA5:ITGB1, acts directly upon endothelial cells to stimulate pro-angiogenic activities and induces angiogenesis. In endothelial cells, supports cell adhesion, induces directed cell migration (chemotaxis) and promotes cell survival (PubMed:12695522). Also plays a role in cutaneous wound healing acting as integrin receptor ligand. Supports skin fibroblast adhesion through ITGA5:ITGB1 and ITGA6:ITGB1 and induces fibroblast chemotaxis through ITGAV:ITGB5. Seems to enhance bFGF-induced DNA synthesis in fibroblasts (PubMed:15611078). Involved in bone regeneration as a negative regulator (By similarity). Enhances the articular chondrocytic phenotype, whereas it repressed the one representing endochondral ossification (PubMed:21871891). Impairs pancreatic beta-cell function, inhibits beta-cell proliferation and insulin secretion (By similarity). Plays a role as negative regulator of endothelial pro-inflammatory activation reducing monocyte adhesion, its anti-inflammatory effects occur secondary to the inhibition of NF-kappaB signaling pathway (PubMed:21063504). Contributes to the control and coordination of inflammatory processes in atherosclerosis (By similarity). Attenuates inflammatory pain through regulation of IL1B- and TNF-induced MMP9, MMP2 and CCL2 expression. Inhibits MMP9 expression through ITGB1 engagement (PubMed:21871891). Brain osteoanabolic hormone (By similarity). Drives osteogenesis in osteochondral skeletal stem cells (PubMed:38987585). During lactation, maintains the maternal skeleton and viability of offspring (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q64299"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12050162"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12695522"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15181016"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15213231"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15611078"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9927660"}],"value":"Interacts with FBLN1. Interacts (via CTCK domain) with NOTCH1 (via the EGF-like repeat region) (PubMed:12050162). Interacts with GJA1/CX43 (PubMed:15181016, PubMed:15213231). Interacts with ITGA5:ITGB1, ITGAV:ITGB3 and ITGAV:ITGB5 (PubMed:12695522, PubMed:15611078). Interacts with ZDHHC22; the interaction may lead to CCN3 palmitoylation (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"X5D778","geneName":"ANKRD11","intActId":"EBI-17183751"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"Q9BWW8","geneName":"APOL6","intActId":"EBI-11574440"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"Q6NUJ2","geneName":"C11orf87","intActId":"EBI-6660291"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"P27658","geneName":"COL8A1","intActId":"EBI-747133"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"Q86YD7","geneName":"FAM90A1","intActId":"EBI-6658203"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"O43559","geneName":"FRS3","intActId":"EBI-725515"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"P49639","geneName":"HOXA1","intActId":"EBI-740785"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"Q6L8G9","geneName":"KRTAP5-6","intActId":"EBI-10250562"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"Q5T7P2","geneName":"LCE1A","intActId":"EBI-11962058"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"Q9BYE3","geneName":"LCE3D","intActId":"EBI-6658837"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"Q8N5G2","geneName":"MACO1","intActId":"EBI-2683507"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"Q8IV28","geneName":"NID2","intActId":"EBI-10261509"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"Q12837","geneName":"POU4F2","intActId":"EBI-17236143"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"Q6P9E2","geneName":"RECK","intActId":"EBI-10253121"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"Q96KP6","geneName":"TNIP3","intActId":"EBI-2509913"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P48745","intActId":"EBI-3904822"},"interactantTwo":{"uniProtKBAccession":"Q9Y3S2","geneName":"ZNF330","intActId":"EBI-373456"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9QZQ5"}],"value":"Localizes at the gap junction in presence of GJA1"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q64299"}],"value":"Secreted","id":"SL-0243"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15181016"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15181016"}],"value":"Cell junction, gap junction","id":"SL-0124"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1756408"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21063504"}],"value":"Expressed in endothelial cells (at protein level) (PubMed:21063504). 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