Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

WFDC1 (WAP four-disulfide core domain 1)

Written2003-03Raphael Saffroy, Antoinette Lemoine, Brigitte Debuire
Service de Biochimie et Biologie moleculaire, Hopital Paul Brousse, Faculte de Medecine Paris Sud, 94 800 Villejuif, France
Updated2005-06Raphael Saffroy, Antoinette Lemoine, Brigitte Debuire
Service de Biochimie et Biologie moleculaire, Hopital Paul Brousse, Faculte de Medecine Paris Sud, 94 800 Villejuif, France

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)PS20
HGNC (Hugo) WFDC1
LocusID (NCBI) 58189
Atlas_Id 424
Location 16q24.1  [Link to chromosome band 16q24]
Location_base_pair Starts at 84328312 and ends at 84363457 bp from pter ( according to hg19-Feb_2009)  [Mapping WFDC1.png]

DNA/RNA

Description The gene encompasses 35 kb of DNA; 7 exons.
Transcription 1366 nucleotides mRNA; 660 bp open reading frame.

Protein

 
  Representation of the position of the conserved cysteines for the category of "four-disulfide core" domain and the location of the signature pattern for such a domain in the human WFDC1 amino acid sequence.
Description 220 amino acids; 24 kDa protein. Like rat ps20, human ps20 protein contains a WAP signature domain.
Expression Widely expressed, absent in thymus.
Function The rat homologue of ps20 was originally identified as a secreted growth inhibitor. These growth regulatory effects and the cell phenotypic properties in vitro, suggest that ps20 may function as a mediator of stromal-epithelial interactions and contribute to the maintenance of tissue homeostasis. The ps20 protein is assumed to function as a protease inhibitor. In vitro studies indicate that exogeneous addition of ps20 protein stimulates endothelial cell migration, and promotes angiogenesis and tumour growth in a xenograft model of prostate cancer.
Homology The human WFDC1 protein shares approximately 86% and 88% identity with the rat and mouse proteins, respectively. WFDC1 is related to a family of human proteins that also have homology with WAP. The WFDC1 gene organization presents similarities with that of the KAL gene, which extends on 210 kb of DNA, includes 14 exons and is the largest gene in the WAP signature domain family.

Mutations

Note Although WFDC1 was mapped to human chromosome 16q24, an area of frequent loss of heterozygosity (LOH) in prostate and hepatocellular carcinomas, no tumour-associated mutations were identified in the coding region of WFDC1 in these cancer types. Mutations in WFDC1 gene resulting in Gly9Asp, Pro211Ser and Lys217Arg substitutions have been found at low frequency in the stroma of breast carcinomas. One mutation resulting in a Pro167Ser substitution has been identified in the epithelium of breast carcinoma.

Implicated in

Note
Disease Prostate cancer
Oncogenesis WFDC1 is significantly down-regulated in prostate cancer making it a candidate tumour suppressor gene. However, WFDC1 seems predominantly expressed in the stroma of normal prostate. In tumors, decreased stromal WFDC1 expression has been associated with increased epithelial WFDC1 expression. This correlate with shorter recurrence-free survival times and may indicate progression to a more aggressive epithelial phenotype and an epithelial mesenchymal transition process.
  

Bibliography

Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas.
Kurose K, Gilley K, Matsumoto S, Watson PH, Zhou XP, Eng C
Nature genetics. 2002 ; 32 (3) : 355-357.
PMID 12379854
 
The WFDC1 gene encoding ps20 localizes to 16q24, a region of LOH in multiple cancers.
Larsen M, Ressler SJ, Gerdes MJ, Lu B, Byron M, Lawrence JB, Rowley DR
Mammalian genome : official journal of the International Mammalian Genome Society. 2000 ; 11 (9) : 767-773.
PMID 10967136
 
Decreased stromal expression and increased epithelial expression of WFDC1/ps20 in prostate cancer is associated with reduced recurrence-free survival.
McAlhany SJ, Ayala GE, Frolov A, Ressler SJ, Wheeler TM, Watson JE, Collins C, Rowley DR
The Prostate. 2004 ; 61 (2) : 182-191.
PMID 15305341
 
Characterization of a fetal urogenital sinus mesenchymal cell line U4F: secretion of a negative growth regulatory activity.
Rowley DR
In vitro cellular & developmental biology : journal of the Tissue Culture Association. 1992 ; 28A (1) : 29-38.
PMID 1730568
 
Purification of a novel protein (ps20) from urogenital sinus mesenchymal cells with growth inhibitory properties in vitro.
Rowley DR, Dang TD, Larsen M, Gerdes MJ, McBride L, Lu B
The Journal of biological chemistry. 1995 ; 270 (37) : 22058-22065.
PMID 7665628
 
Responses of NBT-II bladder carcinoma cells to conditioned medium from normal fetal urogenital sinus.
Rowley DR, Tindall DJ
Cancer research. 1987 ; 47 (11) : 2955-2960.
PMID 3567912
 
Analysis of alterations of WFDC1, a new putative tumour suppressor gene, in hepatocellular carcinoma.
Saffroy R, Riou P, Soler G, Azoulay D, Emile JF, Debuire B, Lemoine A
European journal of human genetics : EJHG. 2002 ; 10 (4) : 239-244.
PMID 12032731
 
Integration of high-resolution array comparative genomic hybridization analysis of chromosome 16q with expression array data refines common regions of loss at 16q23-qter and identifies underlying candidate tumor suppressor genes in prostate cancer.
Watson JE, Doggett NA, Albertson DG, Andaya A, Chinnaiyan A, van Dekken H, Ginzinger D, Haqq C, James K, Kamkar S, Kowbel D, Pinkel D, Schmitt L, Simko JP, Volik S, Weinberg VK, Paris PL, Collins C
Oncogene. 2004 ; 23 (19) : 3487-3494.
PMID 15007382
 
Molecular analysis of WFDC1/ps20 gene in prostate cancer.
Watson JE, Kamkar S, James K, Kowbel D, Andaya A, Paris PL, Simko J, Carroll P, McAlhany S, Rowley D, Collins C
The Prostate. 2004 ; 61 (2) : 192-199.
PMID 15305342
 

Citation

This paper should be referenced as such :
Saffroy, R ; Lemoine, A ; Debuire, B
WFDC1 (WAP four-disulfide core domain 1)
Atlas Genet Cytogenet Oncol Haematol. 2005;9(4):282-283.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/WFDC1ID424.html
History of this paper:
Saffroy, R ; Lemoine, A ; Debuire, B. WFDC1 (WAP four-disulfide core domain 1). Atlas Genet Cytogenet Oncol Haematol. 2003;7(2):102-103.
http://documents.irevues.inist.fr/bitstream/handle/2042/37957/03-2003-WFDC1ID424.pdf


External links

Nomenclature
HGNC (Hugo)WFDC1   15466
Cards
AtlasWFDC1ID424
Entrez_Gene (NCBI)WFDC1  58189  WAP four-disulfide core domain 1
AliasesPS20
GeneCards (Weizmann)WFDC1
Ensembl hg19 (Hinxton)ENSG00000103175 [Gene_View]  chr16:84328312-84363457 [Contig_View]  WFDC1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000103175 [Gene_View]  chr16:84328312-84363457 [Contig_View]  WFDC1 [Vega]
ICGC DataPortalENSG00000103175
TCGA cBioPortalWFDC1
AceView (NCBI)WFDC1
Genatlas (Paris)WFDC1
WikiGenes58189
SOURCE (Princeton)WFDC1
Genetics Home Reference (NIH)WFDC1
Genomic and cartography
GoldenPath hg19 (UCSC)WFDC1  -     chr16:84328312-84363457 +  16q24.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)WFDC1  -     16q24.1   [Description]    (hg38-Dec_2013)
EnsemblWFDC1 - 16q24.1 [CytoView hg19]  WFDC1 - 16q24.1 [CytoView hg38]
Mapping of homologs : NCBIWFDC1 [Mapview hg19]  WFDC1 [Mapview hg38]
OMIM605322   
Gene and transcription
Genbank (Entrez)AF169631 AF302109 AK075061 AL713785 BC029159
RefSeq transcript (Entrez)NM_001282466 NM_001282467 NM_021197
RefSeq genomic (Entrez)NC_000016 NC_018927 NT_010498 NW_004929402
Consensus coding sequences : CCDS (NCBI)WFDC1
Cluster EST : UnigeneHs.36688 [ NCBI ]
CGAP (NCI)Hs.36688
Alternative Splicing GalleryENSG00000103175
Gene ExpressionWFDC1 [ NCBI-GEO ]   WFDC1 [ EBI - ARRAY_EXPRESS ]   WFDC1 [ SEEK ]   WFDC1 [ MEM ]
Gene Expression Viewer (FireBrowse)WFDC1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)58189
GTEX Portal (Tissue expression)WFDC1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9HC57   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9HC57  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9HC57
Splice isoforms : SwissVarQ9HC57
PhosPhoSitePlusQ9HC57
Domaine pattern : Prosite (Expaxy)WAP (PS51390)   
Domains : Interpro (EBI)WAP_dom   
Domain families : Pfam (Sanger)WAP (PF00095)   
Domain families : Pfam (NCBI)pfam00095   
Domain families : Smart (EMBL)WAP (SM00217)  
Conserved Domain (NCBI)WFDC1
DMDM Disease mutations58189
Blocks (Seattle)WFDC1
SuperfamilyQ9HC57
Human Protein AtlasENSG00000103175
Peptide AtlasQ9HC57
HPRD05614
IPIIPI00008997   
Protein Interaction databases
DIP (DOE-UCLA)Q9HC57
IntAct (EBI)Q9HC57
FunCoupENSG00000103175
BioGRIDWFDC1
STRING (EMBL)WFDC1
ZODIACWFDC1
Ontologies - Pathways
QuickGOQ9HC57
Ontology : AmiGOregulation of cell growth  molecular_function  serine-type endopeptidase inhibitor activity  extracellular space  extracellular space  negative regulation of endopeptidase activity  negative regulation of cell growth  response to estradiol  response to drug  negative regulation of epithelial cell proliferation  negative regulation of inflammatory response  negative regulation of wound healing  
Ontology : EGO-EBIregulation of cell growth  molecular_function  serine-type endopeptidase inhibitor activity  extracellular space  extracellular space  negative regulation of endopeptidase activity  negative regulation of cell growth  response to estradiol  response to drug  negative regulation of epithelial cell proliferation  negative regulation of inflammatory response  negative regulation of wound healing  
NDEx NetworkWFDC1
Atlas of Cancer Signalling NetworkWFDC1
Wikipedia pathwaysWFDC1
Orthology - Evolution
OrthoDB58189
GeneTree (enSembl)ENSG00000103175
Phylogenetic Trees/Animal Genes : TreeFamWFDC1
HOVERGENQ9HC57
HOGENOMQ9HC57
Homologs : HomoloGeneWFDC1
Homology/Alignments : Family Browser (UCSC)WFDC1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerWFDC1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)WFDC1
dbVarWFDC1
ClinVarWFDC1
1000_GenomesWFDC1 
Exome Variant ServerWFDC1
ExAC (Exome Aggregation Consortium)WFDC1 (select the gene name)
Genetic variants : HAPMAP58189
Genomic Variants (DGV)WFDC1 [DGVbeta]
DECIPHER (Syndromes)16:84328312-84363457  ENSG00000103175
CONAN: Copy Number AnalysisWFDC1 
Mutations
ICGC Data PortalWFDC1 
TCGA Data PortalWFDC1 
Broad Tumor PortalWFDC1
OASIS PortalWFDC1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICWFDC1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDWFDC1
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
BioMutasearch WFDC1
DgiDB (Drug Gene Interaction Database)WFDC1
DoCM (Curated mutations)WFDC1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)WFDC1 (select a term)
intoGenWFDC1
NCG5 (London)WFDC1
Cancer3DWFDC1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM605322   
Orphanet
MedgenWFDC1
Genetic Testing Registry WFDC1
NextProtQ9HC57 [Medical]
TSGene58189
GENETestsWFDC1
Huge Navigator WFDC1 [HugePedia]
snp3D : Map Gene to Disease58189
BioCentury BCIQWFDC1
ClinGenWFDC1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD58189
Chemical/Pharm GKB GenePA37963
Clinical trialWFDC1
Miscellaneous
canSAR (ICR)WFDC1 (select the gene name)
Probes
Litterature
PubMed22 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineWFDC1
EVEXWFDC1
GoPubMedWFDC1
iHOPWFDC1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Jan 12 11:36:26 CET 2017

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.