WNT1-inducible-signaling pathway protein 3 (WISP3, also named CCN6) is a

matricellular protein A matricellular protein is a dynamically expressed non-structural protein that is present in the extracellular matrix (ECM). Rather than serving as stable structural elements in the ECM, these proteins are rapidly turned over and have regulatory rol ...

that in humans is encoded by the ''WISP3''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Structure

It is a member of the CCN family (

CCN intercellular signaling protein CCN proteins are a family of extracellular matrix (ECM)-associated proteins involved in intercellular signaling. Due to their dynamic role within the ECM they are considered matricellular proteins. Background The acronym CCN is derived from the fi ...

) of secreted, extracellular matrix (ECM)-associated signaling matricellular proteins. The CCN acronym is derived from the first three members of the family identified, 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 inducer 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 ...

(connective tissue growth factor, or CCN2), and NOV (nephroblastoma overexpressed, or CCN3). These proteins, together with

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 t ...

(CCN4), and

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 ...

(CCN5) comprise the six-member CCN family in vertebrates. CCN proteins characteristically contain an N-terminal secretory signal peptide followed by four structurally distinct domains with homologies to insulin-like growth factor binding protein (

IGFBP The insulin-like growth factor-binding protein (IGFBP) serves as a transport protein for insulin-like growth factor 1 (IGF-1). Function Approximately 98% of IGF-1 is always bound to one of six binding proteins (IGF-BP). IGFBP-3, the most abund ...

), von Willebrand type C repeats ( vWC), thrombospondin type 1 repeat (TSR), and 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 within the C-terminal (CT) domain.

Function

The CCN family of proteins regulates diverse cellular functions, including cell adhesion, migration, proliferation, survival, and differentiation.

Clinical significance

Mutations in the human WISP3 gene are associated with

progressive pseudorheumatoid dysplasia Progressive pseudorheumatoid disyplasia (PPD or PPAC) is a disorder of bone and cartilage that affects many joints. The disorder leads to stiff joints, short stature Short stature refers to a height of a human which is below typical. Whether a ...

, a juvenile onset autosomal recessive skeletal disorder, indicating that the gene is essential for normal postnatal skeletal growth and cartilage homeostasis. However, mice with WISP3 knockout or overexpression are normal and suffer no apparent developmental defect. Loss of WISP3 expression is associated with aggressive inflammatory breast cancer and breast cancer with axillary lymph node metastasis, suggesting that WISP3/CCN6 may function as a suppressor of breast cancer growth and metastasis.

References

CCN proteins {{gene-6-stub