CCN proteins are a family of

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...

(ECM)-associated proteins involved in

intercellular signaling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a Cell (biology), cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property ...

. Due to their dynamic role within the ECM they are considered matricellular proteins.

Background

The acronym CCN is derived from the first three members of the family discovered, namely

CYR61 Cysteine-rich angiogenic inducer 61 (CYR61) or CCN family member 1 (CCN1), is a matricellular protein that in humans is encoded by the ''CYR61'' gene. CYR61 is a secreted, extracellular matrix (ECM)-associated signaling protein of the CCN family ...

(cysteine-rich angiogenic protein 61 or CCN1),

CTGF CTGF, also known as CCN2 or connective tissue growth factor, is a matricellular protein of the CCN family of extracellular matrix-associated heparin-binding proteins (see also CCN intercellular signaling protein). CTGF has important roles in many b ...

(connective tissue growth factor or CCN2), and NOV (nephroblastoma overexpressed or CCN3). Together with three Wnt-induced secreted proteins, they comprise the CCN family of matricellular proteins. These proteins have now been renamed CCN1-6 by international consensus. Members of the CCN protein family are characterized by having four conserved

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

-rich domains, which include the insulin-like growth factor-binding domain (IGFBP), the

Von Willebrand factor type C domain Von Willebrand factor, type C (VWFC or VWC)is a protein domain is found in various blood plasma proteins: complement factors B, C2, CR3 and CR4; the integrins (I-domains); collagen types VI, VII, XII and XIV; and other extracellular proteins. Fu ...

(VWC), the thrombospondin type 1 repeat (TSR), and a

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

domain (CT) with a

cysteine knot A cystine knot is a protein structural motif containing three disulfide bridges (formed from pairs of cysteine residues). The sections of polypeptide that occur between two of them form a loop through which a third disulfide bond passes, forming ...

motif. CCN proteins have been shown to play important roles in many cellular processes, including

cell adhesion Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...

, migration, proliferation, differentiation, survival,

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

, and

senescence Senescence () or biological aging is the gradual deterioration of functional characteristics in living organisms. The word ''senescence'' can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence inv ...

. They are also involved in biological processes including

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...

, inflammation,

fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

, wound healing and

tumorigenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abno ...

. CCN proteins likely constitute a hub for the coordination of cell signaling and communication.

Members

The CCN protein family includes the following six proteins: * CCN1:

(cysteine-rich angiogenic protein 61) * CCN2:

(connective tissue growth factor) * CCN3: NOV (nephroblastoma overexpressed) * CCN4:

WISP1 WNT1-inducible-signaling pathway protein 1 (WISP-1), also known as CCN4, is a matricellular protein that in humans is encoded by the ''WISP1'' gene. Structure WISP-1 is highly homologous to CYR61 (CCN1) and CTGF (CCN2), and is a member of the ...

(WNT1 inducible signaling pathway protein-1) * CCN5:

WISP2 WNT1-inducible-signaling pathway protein 2, or WISP-2 (also named CCN5) is a matricellular protein that in humans is encoded by the ''WISP2'' gene. Function The CCN family of proteins regulates diverse cellular functions, including cell adhesi ...

(WNT1 inducible signaling pathway protein-2) * CCN6:

WISP3 WNT1-inducible-signaling pathway protein 3 (WISP3, also named CCN6) is a matricellular protein that in humans is encoded by the ''WISP3'' gene. Structure It is a member of the CCN family (CCN intercellular signaling protein) of secreted, extrac ...

(WNT1 inducible signaling pathway protein-3)

References

External links

* {{Intercellular signaling peptides and proteins

Background

Members

References

Further reading

External links