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WISP2 (Wnt-1-inducible signaling parthway protein-2)

Identity

Other namesCCN5
rCop-1
CT58
CTGF-L
HGNC (Hugo) WISP2
LocusID (NCBI) 8839
Location 20q13.12
Location_base_pair Starts at 43343885 and ends at 43356452 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note WISP-2 is a member of the connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (nov) (CCN) family and is upregulated in the mouse mammary epithelial cell line C57MG transformed by Wnt-1 and in several non-invasive human breast tumor cell lines. WISP-2 is a serum and PMA (phorbol 12-myristate 13-acetate)-induced early responsive gene. Blocking the expression of this gene by WISP-2 antisense oligos or siRNA drastically reduce serum or PMA-induced cell proliferation in MCF-7 cells. Therefore, these studies suggest that WISP-2 signaling may be essential for mitogen-induced breast tumor cell proliferation.

WISP-2 expression is enhanced by important modulators of human breast cancer cell proliferation such as estrogen, progesterone and epidermal growth factor ( EGF) in MCF-7 cells. These effects, inhibited by appropriate antagonists, indicate that steroids and growth factor-induced upregulation of WISP-2 may be mediated through receptors.

The expression profile of WISP-2 gene in breast tumor biopsy tissue specimens are similar with that of in vitro studies and suggest that WISP-2 mRNA and protein levels are significantly higher in tumor samples as compared to the normal breast samples, and this expression is significantly correlated with the expression of estrogen receptor protein. However, within the tumor specimens, expression was predominant in the non-invasive carcinoma lesions as well as benign hyperplastic areas adjacent to the invasive tumors. Together, these findings suggest that bi-phasic regulation of WISP-2 signaling may be critical for initial events of growth, survivability and invasion of breast tumor cells.

WISP-2 also acts as a negative regulator in some cells including vascular smooth muscle cells.

DNA/RNA

Note Until now, three genes have been identified and isolated as members of WISP sub-family. WISP-1/CCN4, WISP-2/CCN5 and WISP-3/CCN6 genes were localized in human chromosomes 8q24.1-q24.3, 20q12-q13 and 6q22-23, respectively and exhibit tissue specific patterns of expression. Nucleotide and protein sequence alignment studies have demonstrated a 30-40% sequence homology within WISP genes and their modular architecture is similar except in their C-terminal domains, which is absent in the WISP-2 gene.
 
  Modular structure of individual genes of WISP sub-family of CCN family. Module shown with color boxes are the predicted primary translational.

Protein

Description The translation products of most of the CCN family members are secreted proteins of 35-40 kDa and have been shown to contain four distinct structural modules: 1) an IGF-binding protein type (IGFBP) domain, 2) a Von Willebrand type C (VWC) domain; 3) a Thrombospondin-1 (TSP-1) domain and 4) a C-terminal Cysteine-knot (CT) domain (10). Although the functional roles of these multiple modules are unclear, they raise interesting questions as to the contribution of each individual module to the biological properties of the full-length proteins.
Expression Epithelial cells and vascular smooth muscle cells
Localisation Adrenal gland, breast, colon, pancreas, uterus and ovary.
Function Positive regulator of epithelial cells and negative regulator of vascular smooth muscle cells.

Mutations

Somatic Amplified in breast tumor cells.

Implicated in

Disease Breast cancer
  
Disease Colon cancer
  
Disease Macronodular adrenal hyperplasia
  

External links

Nomenclature
HGNC (Hugo)WISP2   12770
Cards
AtlasWISP2ID42814ch20q12
Entrez_Gene (NCBI)WISP2  8839  WNT1 inducible signaling pathway protein 2
GeneCards (Weizmann)WISP2
Ensembl (Hinxton)ENSG00000064205 [Gene_View]  chr20:43343885-43356452 [Contig_View]  WISP2 [Vega]
ICGC DataPortalENSG00000064205
AceView (NCBI)WISP2
Genatlas (Paris)WISP2
WikiGenes8839
SOURCE (Princeton)NM_003881
Genomic and cartography
GoldenPath (UCSC)WISP2  -  20q13.12   chr20:43343885-43356452 +  20q13.12   [Description]    (hg19-Feb_2009)
EnsemblWISP2 - 20q13.12 [CytoView]
Mapping of homologs : NCBIWISP2 [Mapview]
OMIM603399   
Gene and transcription
Genbank (Entrez)AF074604 AF083500 AF100780 AK129660 AK313853
RefSeq transcript (Entrez)NM_003881
RefSeq genomic (Entrez)AC_000152 NC_000020 NC_018931 NT_011362 NW_001838666 NW_004929418
Consensus coding sequences : CCDS (NCBI)WISP2
Cluster EST : UnigeneHs.592145 [ NCBI ]
CGAP (NCI)Hs.592145
Alternative Splicing : Fast-db (Paris)GSHG0018771
Alternative Splicing GalleryENSG00000064205
Gene ExpressionWISP2 [ NCBI-GEO ]     WISP2 [ SEEK ]   WISP2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO76076 (Uniprot)
NextProtO76076  [Medical]
With graphics : InterProO76076
Splice isoforms : SwissVarO76076 (Swissvar)
Domaine pattern : Prosite (Expaxy)IGFBP_N_1 (PS00222)    IGFBP_N_2 (PS51323)    TSP1 (PS50092)    VWFC_1 (PS01208)    VWFC_2 (PS50184)   
Domains : Interpro (EBI)Growth_fac_rcpt_N_dom    IGFBP-like    Insulin_GF-bd_Cys-rich_CS    Thrombospondin_1_rpt    VWF_C   
Related proteins : CluSTrO76076
Domain families : Pfam (Sanger)IGFBP (PF00219)    TSP_1 (PF00090)    VWC (PF00093)   
Domain families : Pfam (NCBI)pfam00219    pfam00090    pfam00093   
Domain families : Smart (EMBL)IB (SM00121)  TSP1 (SM00209)  VWC (SM00214)  
DMDM Disease mutations8839
Blocks (Seattle)O76076
Human Protein AtlasENSG00000064205
Peptide AtlasO76076
HPRD16020
IPIIPI00022052   IPI00442992   IPI00447485   
Protein Interaction databases
DIP (DOE-UCLA)O76076
IntAct (EBI)O76076
FunCoupENSG00000064205
BioGRIDWISP2
IntegromeDBWISP2
STRING (EMBL)WISP2
Ontologies - Pathways
QuickGOO76076
Ontology : AmiGOregulation of cell growth  insulin-like growth factor binding  extracellular space  plasma membrane  cell adhesion  signal transduction  cell-cell signaling  extracellular vesicular exosome  
Ontology : EGO-EBIregulation of cell growth  insulin-like growth factor binding  extracellular space  plasma membrane  cell adhesion  signal transduction  cell-cell signaling  extracellular vesicular exosome  
Protein Interaction DatabaseWISP2
Wikipedia pathwaysWISP2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)WISP2
SNP (GeneSNP Utah)WISP2
SNP : HGBaseWISP2
Genetic variants : HAPMAPWISP2
1000_GenomesWISP2 
ICGC programENSG00000064205 
CONAN: Copy Number AnalysisWISP2 
Somatic Mutations in Cancer : COSMICWISP2 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
DECIPHER (Syndromes)20:43343885-43356452
Mutations and Diseases : HGMDWISP2
OMIM603399   
MedgenWISP2
GENETestsWISP2
Disease Genetic AssociationWISP2
Huge Navigator WISP2 [HugePedia]  WISP2 [HugeCancerGEM]
Genomic VariantsWISP2  WISP2 [DGVbeta]
Exome VariantWISP2
dbVarWISP2
ClinVarWISP2
snp3D : Map Gene to Disease8839
General knowledge
Homologs : HomoloGeneWISP2
Homology/Alignments : Family Browser (UCSC)WISP2
Phylogenetic Trees/Animal Genes : TreeFamWISP2
Chemical/Protein Interactions : CTD8839
Chemical/Pharm GKB GenePA37373
Clinical trialWISP2
Cancer Resource (Charite)ENSG00000064205
Other databases
Probes
Litterature
PubMed32 Pubmed reference(s) in Entrez
CoreMineWISP2
GoPubMedWISP2
iHOPWISP2

Bibliography

WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors.
Pennica D, Swanson TA, Welsh JW, Roy MA, Lawrence DA, Lee J, Brush J, Taneyhill LA, Deuel B, Lew M, Watanabe C, Cohen RL, Melhem MF, Finley GG, Quirke P, Goddard AD, Hillan KJ, Gurney AL, Botstein D, Levine AJ
Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (25) : 14717-14722.
PMID 9843955
 
Identification and cloning of a connective tissue growth factor-like cDNA from human osteoblasts encoding a novel regulator of osteoblast functions.
Kumar S, Hand AT, Connor JR, Dodds RA, Ryan PJ, Trill JJ, Fisher SM, Nuttall ME, Lipshutz DB, Zou C, Hwang SM, Votta BJ, James IE, Rieman DJ, Gowen M, Lee JC
The Journal of biological chemistry. 1999 ; 274 (24) : 17123-17131.
PMID 10358067
 
Differential expression of WISP-1 and WISP-2 genes in normal and transformed human breast cell lines.
Saxena N, Banerjee S, Sengupta K, Zoubine MN, Banerjee SK
Molecular and cellular biochemistry. 2001 ; 228 (1-2) : 99-104.
PMID 11855747
 
WISP-2 gene in human breast cancer: estrogen and progesterone inducible expression and regulation of tumor cell proliferation.
Banerjee S, Saxena N, Sengupta K, Tawfik O, Mayo MS, Banerjee SK
Neoplasia (New York, N.Y.). 2003 ; 5 (1) : 63-73.
PMID 12659671
 
Estrogen-induced genes, WISP-2 and pS2, respond divergently to protein kinase pathway.
Inadera H
Biochemical and biophysical research communications. 2003 ; 309 (2) : 272-278.
PMID 12951045
 
Gene array analysis of macronodular adrenal hyperplasia confirms clinical heterogeneity and identifies several candidate genes as molecular mediators.
Bourdeau I, Antonini SR, Lacroix A, Kirschner LS, Matyakhina L, Lorang D, Libutti SK, Stratakis CA
Oncogene. 2004 ; 23 (8) : 1575-1585.
PMID 14767469
 
The growth arrest-specific gene CCN5 is deficient in human leiomyomas and inhibits the proliferation and motility of cultured human uterine smooth muscle cells.
Mason HR, Lake AC, Wubben JE, Nowak RA, Castellot JJ Jr
Molecular human reproduction. 2004 ; 10 (3) : 181-187.
PMID 14981145
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written12-2004Sushanta K. Banerjee, Snigdha Banerjee
Division of Hematology/Oncology, Depatment of Medicine, and Department of Anatomy and Cell Biology University of Kansas Medical Center and Research Director, Cancer Research Unit, VA Medical Center, Kansas City, MO 64128, USA

Citation

This paper should be referenced as such :
Banerjee, SK ; Banerjee, S
WISP2 (wnt-1-inducible signaling parthway protein-2)
Atlas Genet Cytogenet Oncol Haematol. 2005;9(1):15-16.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/WISP2ID42814ch20q12.html

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indexed on : Sat Nov 8 16:39:46 CET 2014

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