Q64299 · CCN3_MOUSE

  • Protein
    CCN family member 3
  • Gene
    Ccn3
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

GO annotations

AspectTerm
Cellular Componentaxon
Cellular Componentcollagen-containing extracellular matrix
Cellular Componentcytoplasm
Cellular Componentdendrite
Cellular Componentextracellular matrix
Cellular Componentextracellular region
Cellular Componentextracellular space
Cellular Componentgap junction
Cellular Componentintracellular membrane-bounded organelle
Cellular Componentneuronal cell body
Molecular Functiongrowth factor activity
Molecular Functionheparin binding
Molecular Functionintegrin binding
Molecular FunctionNotch binding
Biological Processangiogenesis
Biological Processbone regeneration
Biological Processcell adhesion
Biological Processcell adhesion mediated by integrin
Biological Processcell chemotaxis
Biological Processchondrocyte differentiation
Biological Processendothelial cell chemotaxis
Biological Processendothelial cell-cell adhesion
Biological Processfibroblast migration
Biological Processhematopoietic stem cell homeostasis
Biological Processnegative regulation of cell growth
Biological Processnegative regulation of chondrocyte proliferation
Biological Processnegative regulation of inflammatory response
Biological Processnegative regulation of insulin secretion
Biological Processnegative regulation of monocyte chemotaxis
Biological Processnegative regulation of myotube differentiation
Biological Processnegative regulation of non-canonical NF-kappaB signal transduction
Biological Processnegative regulation of sensory perception of pain
Biological Processnegative regulation of SMAD protein signal transduction
Biological Processpositive regulation of cell differentiation
Biological Processpositive regulation of Notch signaling pathway
Biological Processregulation of gene expression
Biological Processsignal transduction
Biological Processsmooth muscle cell migration
Biological Processsmooth muscle cell proliferation
Biological Processtype B pancreatic cell proliferation

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    CCN family member 3
  • Alternative names
    • Cellular communication network factor 3
    • Nephroblastoma-overexpressed gene protein homolog
    • Protein NOV homolog (NovH)

Gene names

    • Name
      Ccn3
    • Synonyms
      Nov

Organism names

  • Taxonomic identifier
  • Strains
    • 129/Sv
    • ICR
    • C57BL/6J
    • Czech II
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q64299
  • Secondary accessions
    • Q8CA67

Proteomes

Organism-specific databases

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).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis227No effect on extracellular secretion.
Mutagenesis229No effect on extracellular secretion.
Mutagenesis241Abolishes extracellular secretion. Inhibits axonal growth of callosal projections when overexpressed.
Mutagenesis246Reduces extracellular secretion. No significant effect on axonal growth of callosal projections when overexpressed.

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.

Go to variant viewer

PTM/Processing

Features

Showing features for signal, chain, disulfide bond, glycosylation, lipidation.

TypeIDPosition(s)Description
Signal1-21
ChainPRO_000001441622-354CCN family member 3
Disulfide bond29↔55
Disulfide bond33↔57
Disulfide bond37↔58
Disulfide bond44↔61
Disulfide bond69↔83
Disulfide bond75↔96
Glycosylation91N-linked (GlcNAc...) asparagine
Lipidation241S-palmitoyl cysteine
Disulfide bond261↔298
Glycosylation277N-linked (GlcNAc...) asparagine
Disulfide bond278↔312
Disulfide bond289↔328
Disulfide bond292↔330
Disulfide bond297↔334

Post-translational modification

May be palmitoylated on Cys-241, which is important for extracellular secretion.

Keywords

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).

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.

TypeIDPosition(s)Description
Domain25-99IGFBP N-terminal
Domain102-168VWFC
Domain202-247TSP type-1
Domain261-335CTCK

Sequence similarities

Belongs to the CCN family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    354
  • Mass (Da)
    38,928
  • Last updated
    1996-11-01 v1
  • Checksum
    08ECE8CFC67829DE
MSLFLRKRCLCLGFLLFHLLSQVSASLRCPSRCPPKCPSISPTCAPGVRSVLDGCSCCPVCARQRGESCSEMRPCDQSSGLYCDRSADPNNQTGICMVPEGDNCVFDGVIYRNGEKFEPNCQYFCTCRDGQIGCLPRCQLDVLLPGPDCPAPRKVAVPGECCEKWTCGSDEQGTQGTLGGLALPAYRPEATVGVEVSDSSINCIEQTTEWSACSKSCGMGVSTRVTNRNRQCEMVKQTRLCIVRPCEQEPEEVTDKKGKKCLRTKKSLKAIHLQFENCTSLYTYKPRFCGVCSDGRCCTPHNTKTIQVEFQCLPGEIIKKPVMVIGTCTCYSNCPQNNEAFLQDLELKTSRGEI

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict6in Ref. 3; BAC30363

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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