WNT1-inducible-signaling pathway protein 3

Last updated
CCN6
Identifiers
Aliases CCN6 , LIBC, PPAC, PPD, WISP-3, WNT1 inducible signaling pathway protein 3, WISP3, cellular communication network factor 6, PPRD
External IDs OMIM: 603400 MGI: 2685581 HomoloGene: 77038 GeneCards: CCN6
Orthologs
SpeciesHumanMouse
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

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.

Contents

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]

Related Research Articles

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<span class="mw-page-title-main">CTGF</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">FGD1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Sulfate transporter</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">CYR61</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">LRP5</span> Protein-coding gene in the species Homo sapiens

Low-density lipoprotein receptor-related protein 5 is a protein that in humans is encoded by the LRP5 gene. LRP5 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway. Mutations in LRP5 can lead to considerable changes in bone mass. A loss-of-function mutation causes osteoporosis pseudoglioma syndrome with a decrease in bone mass, while a gain-of-function mutation causes drastic increases in bone mass.

<span class="mw-page-title-main">NOV (gene)</span> Protein-coding gene in the species Homo sapiens

NOV also known as CCN3 is a matricellular protein that in humans is encoded by the NOV gene.

<span class="mw-page-title-main">FGF9</span> Protein-coding gene in the species Homo sapiens

Glia-activating factor is a protein that in humans is encoded by the FGF9 gene.

<span class="mw-page-title-main">WNT1-inducible-signaling pathway protein 1</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">WNT1-inducible-signaling pathway protein 2</span> Protein-coding gene in the species Homo sapiens

WNT1-inducible-signaling pathway protein 2, or WISP-2 is a matricellular protein that in humans is encoded by the WISP2 gene.

<span class="mw-page-title-main">MTA3</span> Protein-coding gene in the species Homo sapiens

Metastasis-associated protein MTA3 is a protein that in humans is encoded by the MTA3 gene. MTA3 protein localizes in the nucleus as well as in other cellular compartments MTA3 is a component of the nucleosome remodeling and deacetylate (NuRD) complex and participates in gene expression. The expression pattern of MTA3 is opposite to that of MTA1 and MTA2 during mammary gland tumorigenesis. However, MTA3 is also overexpressed in a variety of human cancers.

<span class="mw-page-title-main">Homeobox protein goosecoid</span> Protein-coding gene in the species Homo sapiens

Homeobox protein goosecoid(GSC) is a homeobox protein that is encoded in humans by the GSC gene. Like other homeobox proteins, goosecoid functions as a transcription factor involved in morphogenesis. In Xenopus, GSC is thought to play a crucial role in the phenomenon of the Spemann-Mangold organizer. Through lineage tracing and timelapse microscopy, the effects of GSC on neighboring cell fates could be observed. In an experiment that injected cells with GSC and observed the effects of uninjected cells, GSC recruited neighboring uninjected cells in the dorsal blastopore lip of the Xenopus gastrula to form a twinned dorsal axis, suggesting that the goosecoid protein plays a role in the regulation and migration of cells during gastrulation.

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.

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 roles. They characteristically contain binding sites for ECM structural proteins and cell surface receptors, and may sequester and modulate activities of specific growth factors.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000112761 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 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. S2CID   31389994.
  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.


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