Q64299 · CCN3_MOUSE
- ProteinCCN family member 3
- GeneCcn3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids354 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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).
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).
GO annotations
Keywords
- Molecular function
Names & Taxonomy
Protein names
- Recommended nameCCN family member 3
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ64299
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes at the gap junction in presence of GJA1.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mutants develop normally but have enhanced arterial neointimal hyperplasia in response to injury (PubMed:20139355).
Animals show an accelerated bone regeneration comparing to in wild-type mice (PubMed:24722330).
Animals show an accelerated bone regeneration comparing to in wild-type mice (PubMed:24722330).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 227 | No effect on extracellular secretion. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 229 | No effect on extracellular secretion. | ||||
Sequence: N → Q | ||||||
Mutagenesis | 241 | Abolishes extracellular secretion. Inhibits axonal growth of callosal projections when overexpressed. | ||||
Sequence: C → A | ||||||
Mutagenesis | 246 | Reduces extracellular secretion. No significant effect on axonal growth of callosal projections when overexpressed. | ||||
Sequence: C → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 10 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation, lipidation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-21 | |||||
Sequence: MSLFLRKRCLCLGFLLFHLLS | ||||||
Chain | PRO_0000014416 | 22-354 | CCN family member 3 | |||
Sequence: QVSASLRCPSRCPPKCPSISPTCAPGVRSVLDGCSCCPVCARQRGESCSEMRPCDQSSGLYCDRSADPNNQTGICMVPEGDNCVFDGVIYRNGEKFEPNCQYFCTCRDGQIGCLPRCQLDVLLPGPDCPAPRKVAVPGECCEKWTCGSDEQGTQGTLGGLALPAYRPEATVGVEVSDSSINCIEQTTEWSACSKSCGMGVSTRVTNRNRQCEMVKQTRLCIVRPCEQEPEEVTDKKGKKCLRTKKSLKAIHLQFENCTSLYTYKPRFCGVCSDGRCCTPHNTKTIQVEFQCLPGEIIKKPVMVIGTCTCYSNCPQNNEAFLQDLELKTSRGEI | ||||||
Disulfide bond | 29↔55 | |||||
Sequence: CPSRCPPKCPSISPTCAPGVRSVLDGC | ||||||
Disulfide bond | 33↔57 | |||||
Sequence: CPPKCPSISPTCAPGVRSVLDGCSC | ||||||
Disulfide bond | 37↔58 | |||||
Sequence: CPSISPTCAPGVRSVLDGCSCC | ||||||
Disulfide bond | 44↔61 | |||||
Sequence: CAPGVRSVLDGCSCCPVC | ||||||
Disulfide bond | 69↔83 | |||||
Sequence: CSEMRPCDQSSGLYC | ||||||
Disulfide bond | 75↔96 | |||||
Sequence: CDQSSGLYCDRSADPNNQTGIC | ||||||
Glycosylation | 91 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Lipidation | 241 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Disulfide bond | 261↔298 | |||||
Sequence: CLRTKKSLKAIHLQFENCTSLYTYKPRFCGVCSDGRCC | ||||||
Glycosylation | 277 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 278↔312 | |||||
Sequence: CTSLYTYKPRFCGVCSDGRCCTPHNTKTIQVEFQC | ||||||
Disulfide bond | 289↔328 | |||||
Sequence: CGVCSDGRCCTPHNTKTIQVEFQCLPGEIIKKPVMVIGTC | ||||||
Disulfide bond | 292↔330 | |||||
Sequence: CSDGRCCTPHNTKTIQVEFQCLPGEIIKKPVMVIGTCTC | ||||||
Disulfide bond | 297↔334 | |||||
Sequence: CCTPHNTKTIQVEFQCLPGEIIKKPVMVIGTCTCYSNC |
Post-translational modification
May be palmitoylated on Cys-241, which is important for extracellular secretion.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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 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).
Induction
Expression is reduced in atherosclerosis progression.
Developmental stage
Up-regulated in the early phase of bone regeneration.
Gene expression databases
Interaction
Subunit
Interacts with FBLN1. Interacts (via CTCK domain) with NOTCH1 (via the EGF-like repeat region). Interacts with GJA1/CX43. Interacts with ITGA5:ITGB1, ITGAV:ITGB3 and ITGAV:ITGB5. Interacts with ZDHHC22; the interaction may lead to CCN3 palmitoylation (PubMed:29287726).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 25-99 | IGFBP N-terminal | ||||
Sequence: ASLRCPSRCPPKCPSISPTCAPGVRSVLDGCSCCPVCARQRGESCSEMRPCDQSSGLYCDRSADPNNQTGICMVP | ||||||
Domain | 102-168 | VWFC | ||||
Sequence: DNCVFDGVIYRNGEKFEPNCQYFCTCRDGQIGCLPRCQLDVLLPGPDCPAPRKVAVPGECCEKWTCG | ||||||
Domain | 202-247 | TSP type-1 | ||||
Sequence: NCIEQTTEWSACSKSCGMGVSTRVTNRNRQCEMVKQTRLCIVRPCE | ||||||
Domain | 261-335 | CTCK | ||||
Sequence: CLRTKKSLKAIHLQFENCTSLYTYKPRFCGVCSDGRCCTPHNTKTIQVEFQCLPGEIIKKPVMVIGTCTCYSNCP |
Sequence similarities
Belongs to the CCN family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length354
- Mass (Da)38,928
- Last updated1996-11-01 v1
- Checksum08ECE8CFC67829DE
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 6 | in Ref. 3; BAC30363 | ||||
Sequence: R → G |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X97863 EMBL· GenBank· DDBJ | CAA66457.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Y09257 EMBL· GenBank· DDBJ | CAA70454.1 EMBL· GenBank· DDBJ | mRNA | ||
X96585 EMBL· GenBank· DDBJ | CAA65404.1 EMBL· GenBank· DDBJ | mRNA | ||
AK039481 EMBL· GenBank· DDBJ | BAC30363.1 EMBL· GenBank· DDBJ | mRNA | ||
AK081944 EMBL· GenBank· DDBJ | BAC38378.1 EMBL· GenBank· DDBJ | mRNA | ||
BC003774 EMBL· GenBank· DDBJ | AAH03774.1 EMBL· GenBank· DDBJ | mRNA |