WISP3 (WNT-1 inducible signaling pathway protein 3)

Identity

Other names	PPD
	CCN6
	LIBC
	PPAC
	Wnt1 signaling pathway protein 3
HGNC	WISP3
Location	6q22-q23

DNA/RNA

Description	5 exons spanning 967kb of genomic
Transcription	Alternative splicing generates at least three transcript variants, their sizes are 1212bp, 1307 bp and 1068 bp

Protein

Description	WISP3 contains four conserved cysteine-rich domains: insulin-like growth factor-binding domain, von Willebrand factor type C module, thrombospondin domain and C-terminal cystine knot-like domain. It has three isoforms: 1) variant 1, 354 aa, 39292 Da; 2) variant 2, 331 aa, This variant differs from variant 1 in two regions. It has an alternate 5' end which results in a different N-terminus. It also uses two alternative donor and acceptor sites in the middle coding region which result in a few internal aa differences between variant 1 and 2. 3) variant 3, 372 aa, This variant differs in the 5' UTR and CDS, compared to variant 1. The resulting protein is longer and has a distinct N-terminus, compared to variant 1.
Expression	Predominant expression in adult kidney and testis and fetal kidney. Weaker expression found in placenta, ovary, prostate and small intestine. Also expressed in skeletally-derived cells such as synoviocytes and articular cartilage chondrocytes.
Localisation	Secreted (Probable).
Function	It is a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family and may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. It is over-expressed in colon tumors. It is essential for normal postnatal skeletal growth and cartilage homeostasis. It acts as a putative growth regulator contributing to the inflammatory breast cancer by regulating tumor cell growth, invasion and angiogenesis.
Homology	Wnt1-inducible signaling proteins

Mutations

Germinal	Various types of mutations have been described, dispersed throughout the gene, including nucleotide substitutions, small deletions and small insertions. There are patients who are compound heterozygous, heterozygous or homozygous. The mutations cause progressive pseudorheumatoid dysplasia.
Somatic	Somatic mutations that cause reading frameshifts at a polyadenosine tract within the WISP3 coding sequence have been observed at higher-than-expected rates in gastrointestinal tumors from patients with mutations in the mismatch repair pathway.

Implicated in

Entity	Arthropathy, progressive pseudorheumatoid, of childhood
Disease	Mutations in the WISP3 gene result in an arthropathy of childhood beginning at about age 3-8. Usually several joints were affected with pain and soft tissue swelling. The proximal interphalangeal joints of the hand were most commonly affected and the hips and elbows next most often involved.
Entity	Inflammatory breast cancer
Oncogenesis	Loss of WISP3 is one of the key genetic alterations in the development of IBC.
Entity	Rheumatoid arthritis
Entity	Colon cancer
Oncogenesis	Frameshifts, non-sense mutations and non-synonymous changes involving cysteines or affect a splice-donor site.

External links

	Nomenclature
HGNC	WISP3   12771
Entrez_Gene	WISP3  8838  WNT1 inducible signaling pathway protein 3
	Cards
Atlas	WISP3ID469ch6q22
GeneCards	WISP3
Ensembl	WISP3 [Search_View]   ENSG00000112761 [Gene_View]
Genatlas	WISP3
GeneLynx	WISP3
eGenome	WISP3
euGene	8838
	Genomic and cartography
GoldenPath	WISP3  -     chr6:112481971-112497580 +  6q21   [Description]    (hg18-Mar_2006)
Ensembl	WISP3 - 6q21 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	WISP3
	Gene and transcription
Genbank	AB075040 [ ENTREZ ]
Genbank	AF100781 [ ENTREZ ]
Genbank	AF143679 [ ENTREZ ]
Genbank	AY358349 [ ENTREZ ]
Genbank	AY358350 [ ENTREZ ]
RefSeq	NM_003880 [ SRS ]    NM_003880 [ ENTREZ ]
RefSeq	NM_130396 [ SRS ]    NM_130396 [ ENTREZ ]
RefSeq	NM_198239 [ SRS ]    NM_198239 [ ENTREZ ]
RefSeq	AC_000049 [ SRS ]    AC_000049 [ ENTREZ ]
RefSeq	AC_000138 [ SRS ]    AC_000138 [ ENTREZ ]
RefSeq	NC_000006 [ SRS ]    NC_000006 [ ENTREZ ]
RefSeq	NT_025741 [ SRS ]    NT_025741 [ ENTREZ ]
RefSeq	NW_001838990 [ SRS ]    NW_001838990 [ ENTREZ ]
RefSeq	NW_923184 [ SRS ]    NW_923184 [ ENTREZ ]
AceView	WISP3 AceView - NCBI
Unigene	Hs.558428 [ SRS ]    Hs.558428 [ NCBI ]     HS558428 [ spliceNest ]
Fast-db	16210 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	O95389 [ SRS]    O95389 [ EXPASY ]     O95389 [ INTERPRO ]     O95389 [ UNIPROT ]
Prosite	PS01185 CTCK_1 [ SRS ]    PS01185 CTCK_1 [ Expasy ]
Prosite	PS01225 CTCK_2 [ SRS ]    PS01225 CTCK_2 [ Expasy ]
Prosite	PS00222 IGFBP_N_1 [ SRS ]    PS00222 IGFBP_N_1 [ Expasy ]
Prosite	PS51323 IGFBP_N_2 [ SRS ]    PS51323 IGFBP_N_2 [ Expasy ]
Prosite	PS50092 TSP1 [ SRS ]    PS50092 TSP1 [ Expasy ]
Interpro	IPR006208 Cys_knot [ SRS ]    IPR006208 Cys_knot [ EBI ]
Interpro	IPR006207 Cys_knot_C [ SRS ]    IPR006207 Cys_knot_C [ EBI ]
Interpro	IPR012395 IGFBP_CNN [ SRS ]    IPR012395 IGFBP_CNN [ EBI ]
Interpro	IPR000867 IGFBP_like [ SRS ]    IPR000867 IGFBP_like [ EBI ]
Interpro	IPR000884 TSP1 [ SRS ]    IPR000884 TSP1 [ EBI ]
CluSTr	O95389
Pfam	PF00007 Cys_knot [ SRS ]    PF00007 Cys_knot [ Sanger ]    pfam00007 [ NCBI-CDD ]
Pfam	PF00219 IGFBP [ SRS ]    PF00219 IGFBP [ Sanger ]    pfam00219 [ NCBI-CDD ]
Pfam	PF00090 TSP_1 [ SRS ]    PF00090 TSP_1 [ Sanger ]    pfam00090 [ NCBI-CDD ]
Smart	SM00041 CT [EMBL]
Smart	SM00121 IB [EMBL]
Smart	SM00209 TSP1 [EMBL]
Blocks	O95389
HPRD	04550
	Protein Interaction databases
DIP	O95389
IntAct	O95389
	Polymorphism : SNP, mutations, diseases
OMIM	208230;603400    [ map ]
GENECLINICS	208230;603400
SNP	WISP3 [dbSNP-NCBI]
SNP	NM_003880 [SNP-NCI]
SNP	NM_130396 [SNP-NCI]
SNP	NM_198239 [SNP-NCI]
SNP	WISP3 [GeneSNPs - Utah]  WISP3] [HGBASE - SRS]
HAPMAP	WISP3 [HAPMAP]
HGMD	WISP3
	General knowledge
Family Browser	WISP3 [UCSC Family Browser]
SOURCE	NM_003880
SOURCE	NM_130396
SOURCE	NM_198239
SMD	Hs.558428
SAGE	Hs.558428
GO	regulation of cell growth [Amigo]  regulation of cell growth
GO	insulin-like growth factor binding [Amigo]  insulin-like growth factor binding
GO	extracellular region [Amigo]  extracellular region
GO	soluble fraction [Amigo]  soluble fraction
GO	signal transduction [Amigo]  signal transduction
GO	cell-cell signaling [Amigo]  cell-cell signaling
GO	growth factor activity [Amigo]  growth factor activity
PubGene	WISP3
TreeFam	WISP3
CTD	8838 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	WISP3 Related clones (RZPD - Berlin)
	PubMed
PubMed	19 Pubmed reference(s) in LocusLink

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

Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia.

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

Nature genetics. 1999 ; 23 (1) : 94-98.

PMID 10471507

A novel putative low-affinity insulin-like growth factor-binding protein, LIBC (lost in inflammatory breast cancer), and RhoC GTPase correlate with the inflammatory breast cancer phenotype.

van Golen KL, Davies S, Wu ZF, Wang Y, Bucana CD, Root H, Chandrasekharappa S, Strawderman M, Ethier SP, Merajver SD

Clinical cancer research : an official journal of the American Association for Cancer Research. 1999 ; 5 (9) : 2511-2519.

PMID 10499627

WNT1 inducible signaling pathway protein 3, WISP-3, a novel target gene in colorectal carcinomas with microsatellite instability.

Thorstensen L, Diep CB, Meling GI, Aagesen TH, Ahrens CH, Rognum TO, Lothe RA

Gastroenterology. 2001 ; 121 (6) : 1275-1280.

PMID 11729105

WISP3 is a novel tumor suppressor gene of inflammatory breast cancer.

Kleer CG, Zhang Y, Pan Q, van Golen KL, Wu ZF, Livant D, Merajver SD

Oncogene. 2002 ; 21 (20) : 3172-3180.

PMID 12082632

Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.

Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Mammalian Gene Collection Program Team, Marra MA

Proceedings of the National Academy of Sciences of the United States of America. 2002 ; 99 (26) : 16899-16903.

PMID 12477932

Variant WISPs as targets for gastrointestinal carcinomas.

Tanaka S, Sugimachi K, Shimada M, Maehara Y, Sugimachi K

Gastroenterology. 2002 ; 123 (1) : 392-393.

PMID 12105881

The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A

Genome research. 2003 ; 13 (10) : 2265-2270.

PMID 12975309

WISP3 (CCN6) is a secreted tumor-suppressor protein that modulates IGF signaling in inflammatory breast cancer.

Kleer CG, Zhang Y, Pan Q, Merajver SD

Neoplasia (New York, N.Y.). 2004 ; 6 (2) : 179-185.

PMID 15140407

WISP3-dependent regulation of type II collagen and aggrecan production in chondrocytes.

Sen M, Cheng YH, Goldring MB, Lotz MK, Carson DA

Arthritis and rheumatism. 2004 ; 50 (2) : 488-497.

PMID 14872491

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	03-2005	Celina G Kleer, Lei Ding
		Department of Pathology, 2G332 University Hospital, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0054, USA

Citation

This paper should be referenced as such :

Kleer CG, Ding L . WISP3 (WNT-1 inducible signaling pathway protein 3). Atlas Genet Cytogenet Oncol Haematol. March 2005 . URL : http://AtlasGeneticsOncology.org/Genes/WISP3ID469ch6q22.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:18:28 2008