WNT1-inducible-signaling pathway protein 3

WNT1-inducible-signaling pathway protein 3[5][6] (WISP3, also named CCN6) is a matricellular protein that in humans is encoded by the WISP3 gene.

CCN6
Identifiers
Aliases	CCN6, LIBC, PPAC, PPD, WISP-3, WNT1 inducible signaling pathway protein 3, WISP3, cellular communication network factor 6
External IDs	OMIM: 603400 MGI: 2685581 HomoloGene: 77038 GeneCards: CCN6
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q21 Start 112,054,072 bp[1] End 112,070,969 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10|10 B1 Start 39,150,970 bp[2] End 39,163,794 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • insulin-like growth factor binding • growth factor activity • integrin binding • heparin binding Cellular component • extracellular region • extracellular • endoplasmic reticulum • extracellular matrix • mitochondrion Biological process • cell-cell signaling • regulation of cell growth • signal transduction • cell adhesion • negative regulation of cell death • regulation of receptor activity • regulation of mitochondrial membrane potential • regulation of reactive oxygen species biosynthetic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8838	327743
Ensembl	ENSG00000112761	ENSMUSG00000062074
UniProt	O95389	D3Z5L9
RefSeq (mRNA)	NM_003880 NM_130396 NM_198239	NM_001127376
RefSeq (protein)	NP_003871 NP_937882	NP_001120848
Location (UCSC)	Chr 6: 112.05 – 112.07 Mb	Chr 10: 39.15 – 39.16 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

It is a member of the CCN family (CCN intercellular signaling protein) 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, or CCN1), CTGF (connective tissue growth factor, or CCN2), and NOV (nephroblastoma overexpressed, or CCN3). These proteins, together with WISP1 (CCN4), and WISP2 (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), von Willebrand type C repeats (vWC), thrombospondin type 1 repeat (TSR), and a cysteine knot 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.[7][8][9]

Clinical significance

Mutations in the human WISP3 gene are associated with progressive pseudorheumatoid dysplasia, a juvenile onset autosomal recessive skeletal disorder, indicating that the gene is essential for normal postnatal skeletal growth and cartilage homeostasis.[10] However, mice with WISP3 knockout or overexpression are normal and suffer no apparent developmental defect.[11][12] 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.[6]

References

1. GRCh38: Ensembl release 89: ENSG00000112761 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000062074 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Jun JI, Lau LF (December 2011). "Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets". Nat Rev Drug Discov. 10 (12): 945–63. doi:10.1038/nrd3599. PMC 3663145. PMID 22129992.
6. Huang W, Pal A, Kleer CG (March 2012). "On how CCN6 suppresses breast cancer growth and invasion". J Cell Commun Signal. 6 (1): 5–10. doi:10.1007/s12079-011-0148-9. PMC 3271195. PMID 21842227.
7. Chen CC, Lau LF (April 2009). "Functions and mechanisms of action of CCN matricellular proteins". Int. J. Biochem. Cell Biol. 41 (4): 771–83. doi:10.1016/j.biocel.2008.07.025. PMC 2668982. PMID 18775791.
8. Holbourn KP, Acharya KR, Perbal B (October 2008). "The CCN family of proteins: structure-function relationships". Trends Biochem. Sci. 33 (10): 461–73. doi:10.1016/j.tibs.2008.07.006. PMC 2683937. PMID 18789696.
9. Leask A, Abraham DJ (December 2006). "All in the CCN family: essential matricellular signaling modulators emerge from the bunker". J. Cell Sci. 119 (Pt 23): 4803–10. doi:10.1242/jcs.03270. PMID 17130294.
10. Hurvitz JR, Suwairi WM, Van Hul W, El-Shanti H, Superti-Furga A, Roudier J, Holderbaum D, Pauli RM, Herd JK, Van Hul EV, Rezai-Delui H, Legius E, Le Merrer M, Al-Alami J, Bahabri SA, Warman ML (September 1999). "Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia". Nat. Genet. 23 (1): 94–8. doi:10.1038/12699. PMID 10471507.
11. Kutz WE, Gong Y, Warman ML (January 2005). "WISP3, the gene responsible for the human skeletal disease progressive pseudorheumatoid dysplasia, is not essential for skeletal function in mice". Mol. Cell. Biol. 25 (1): 414–21. doi:10.1128/MCB.25.1.414-421.2005. PMC 538768. PMID 15601861.
12. Nakamura Y, Cui Y, Fernando C, Kutz WE, Warman ML (June 2009). "Normal growth and development in mice over-expressing the CCN family member WISP3". J Cell Commun Signal. 3 (2): 105–13. doi:10.1007/s12079-009-0040-z. PMC 2721080. PMID 19401829.