Ccn3
Developmental stage
Up-regulated in the early phase of bone regeneration (PubMed:23653360). Expressed in arcuate nucleus ESR1/KISS1 neurons of lactating dams. Weaning reduces expression in arcuate nucleus ESR1 neurons when examined 3 or 7 days after removal of pups. Not expressed in arcuate nucleus ESR1 neurons in virgin females, nor during the early and later stages of pregnancy (PubMed:38987585).
Function
Immediate-early protein playing a role in various cellular processes including proliferation, adhesion, migration, differentiation and survival. Acts by binding to integrins or membrane receptors such as NOTCH1. Essential regulator of hematopoietic stem and progenitor cell function. Inhibits myogenic differentiation through the activation of Notch-signaling pathway. Inhibits vascular smooth muscle cells proliferation by increasing expression of cell-cycle regulators such as CDKN2B or CDKN1A independently of TGFB1 signaling. 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. 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 (By similarity). Involved in bone regeneration as a negative regulator (PubMed:23653360). Enhances the articular chondrocytic phenotype, whereas it repressed the one representing endochondral ossification (By similarity). Impairs pancreatic beta-cell function, inhibits beta-cell proliferation and insulin secretion (PubMed:23705021). 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 (By similarity). Contributes to the control and coordination of inflammatory processes in atherosclerosis (PubMed:24722330). Attenuates inflammatory pain through regulation of IL1B- and TNF-induced MMP9, MMP2 and CCL2 expression. Inhibits MMP9 expression through ITGB1 engagement (By similarity). Brain osteoanabolic hormone (PubMed:38987585). During lactation, maintains the maternal skeleton and viability of offspring (PubMed:38987585). In this context, may act on osteochondral skeletal stem cells (PubMed:38987585).
Post-translational modifications
May be palmitoylated on Cys-241, which is important for extracellular secretion.
Sequence Similarities
Belongs to the CCN family.
Tissue Specificity
Expressed in large vessels including the ascending aorta, carotid arteries, and the thoracic aorta, in medium-sized vessels such as coronary arteries and small pulmonary veins and also in small vessels. In addition, also found to be present in the heart (at protein level) (PubMed:21063504). Expressed in astrocytes (at protein level) (PubMed:15213231). Detected in brain, bone, lung and muscle tissues (PubMed:20139355, PubMed:23653360). Expressed in skin, expression highly increases 5 days post-wounding, peaking on the 7th day to decline after 9 days (PubMed:15611078). Expressed in pancreatic ducts and beta-cell islets (PubMed:23705021). Expressed in the brain, in arcuate nucleus ESR1/KISS1 neurons, during lactation (at protein level) (PubMed:38987585).
Cellular localization
- Secreted
- Cytoplasm
- Cell junction
- Gap junction
- Localizes at the gap junction in presence of GJA1.
Alternative names
Nov, Ccn3, CCN family member 3, Cellular communication network factor 3, Nephroblastoma-overexpressed gene protein homolog, Protein NOV homolog, NovH