WNT1-inducible-signaling pathway protein 2, or WISP-2 (also named CCN5) 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 ''WISP2''
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 b ...
.
Function
The CCN family of proteins regulates diverse cellular functions, 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
Migration, migratory, or migrate may refer to: Human migration
* Human migration, physical movement by humans from one region to another
** International migration, when peoples cross state boundaries and stay in the host state for some minimum l ...
,
proliferation
Proliferation may refer to:
Weapons
*Nuclear proliferation, the spread of nuclear weapons, material, and technology
*Chemical weapon proliferation, the spread of chemical weapons, material, and technology
* Small arms proliferation, the spread of ...
,
differentiation
Differentiation may refer to:
Business
* Differentiation (economics), the process of making a product different from other similar products
* Product differentiation, in marketing
* Differentiated service, a service that varies with the identity ...
.
Structure
WISP-2 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 fir ...
) of secreted,
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 struc ...
(ECM)-associated signaling
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 ...
s. 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 ...
(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 Nov or NOV may refer to:
* November, the 11th month of the year in the Julian and Gregorian calendars
* Nav, Asalem (also , Nov or Nāv), a village in Gilan Province, Iran
* Nov, Golan Heights, an Israeli moshav (a cooperative agricultural communi ...
. 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
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe ...
/CCN4, WISP2 (CCN5, this gene), and
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, extra ...
(CCN6) comprise the six-member CCN family in vertebrates. CCN proteins characteristically contain an
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
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
Thrombospondins (TSPs) are a family of secreted glycoproteins with antiangiogenic functions. Due to their dynamic role within the extracellular matrix they are considered matricellular proteins. The first member of the family, thrombospondin 1 (T ...
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
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 ...
(CT) domain. However, WISP-2 is unique among this family of proteins by lacking precisely the CT domain.
Clinical significance
WISP-2 (CCN5) inhibits the proliferation of
vascular smooth muscle
Vascular smooth muscle is the type of smooth muscle that makes up most of the walls of blood vessels.
Structure
Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood ...
cells, human uterine myometrial cells, and leiomyoma cells. Ectopic expression of WISP-2 also inhibits the motility and invasiveness of breast carcinoma cells. WISP-2 also inhibits cardiac
hypertrophy
Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number.Updated by Linda J ...
and
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 permane ...
, an effect that appears linked to the absence of the CT domain.
References
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CCN proteins