WFDC1 (WAP four-disulfide core domain 1)

2005-06-01   Raphael Saffroy , Antoinette Lemoine , Brigitte Debuire 

Service de Biochimie et Biologie moleculaire, Hopital Paul Brousse, Faculte de Medecine Paris Sud, 94 800 Villejuif, France

Identity

HGNC
LOCATION
16q24.1
LOCUSID
ALIAS
PS20

DNA/RNA

Description

The gene encompasses 35 kb of DNA; 7 exons.

Transcription

1366 nucleotides mRNA; 660 bp open reading frame.

Proteins

Atlas Image
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

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

Pubmed IDLast YearTitleAuthors
123798542002Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas.Kurose K et al
109671362000The WFDC1 gene encoding ps20 localizes to 16q24, a region of LOH in multiple cancers.Larsen M et al
153053412004Decreased stromal expression and increased epithelial expression of WFDC1/ps20 in prostate cancer is associated with reduced recurrence-free survival.McAlhany SJ et al
17305681992Characterization of a fetal urogenital sinus mesenchymal cell line U4F: secretion of a negative growth regulatory activity.Rowley DR et al
76656281995Purification of a novel protein (ps20) from urogenital sinus mesenchymal cells with growth inhibitory properties in vitro.Rowley DR et al
35679121987Responses of NBT-II bladder carcinoma cells to conditioned medium from normal fetal urogenital sinus.Rowley DR et al
120327312002Analysis of alterations of WFDC1, a new putative tumour suppressor gene, in hepatocellular carcinoma.Saffroy R et al
150073822004Integration 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 et al
153053422004Molecular analysis of WFDC1/ps20 gene in prostate cancer.Watson JE et al

Other Information

Locus ID:

NCBI: 58189
MIM: 605322
HGNC: 15466
Ensembl: ENSG00000103175

Variants:

dbSNP: 58189
ClinVar: 58189
TCGA: ENSG00000103175
COSMIC: WFDC1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000103175ENST00000219454Q9HC57
ENSG00000103175ENST00000568638Q9HC57
ENSG00000103175ENST00000613603A0A087WY77

Expression (GTEx)

0
50
100
150

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
188426792009Modulated expression of WFDC1 during carcinogenesis and cellular senescence.35
188426792009Modulated expression of WFDC1 during carcinogenesis and cellular senescence.35
179425342008WFDC1/ps20 is a novel innate immunomodulatory signature protein of human immunodeficiency virus (HIV)-permissive CD4+ CD45RO+ memory T cells that promotes infection by upregulating CD54 integrin expression and is elevated in HIV type 1 infection.11
200907712010Supervised machine learning and logistic regression identifies novel epistatic risk factors with PTPN22 for rheumatoid arthritis.9
194888302009Expression and functional analysis of the WAP four disulfide core domain 1 gene in human melanoma.7
153053422004Molecular analysis of WFDC1/ps20 gene in prostate cancer.5
120327312002Analysis of alterations of WFDC1, a new putative tumour suppressor gene, in hepatocellular carcinoma.2
271154702016Expression of two WFDC1/ps20 isoforms in prostate stromal cells induces paracrine apoptosis through regulation of PTGS2/COX-2.2
304233852019Phylogenetic, molecular evolution and structural analyses of the WFDC1/prostate stromal protein 20 (ps20).1
215457472011WFDC1 expression identifies memory CD4 T-lymphocytes rendered vulnerable to cell-cell HIV-1 transfer by promoting intercellular adhesive junctions.0

Citation

Raphael Saffroy ; Antoinette Lemoine ; Brigitte Debuire

WFDC1 (WAP four-disulfide core domain 1)

Atlas Genet Cytogenet Oncol Haematol. 2005-06-01

Online version: http://atlasgeneticsoncology.org/gene/424/wfdc1

Historical Card

2003-03-01 WFDC1 (WAP four-disulfide core domain 1) by  Raphael Saffroy,Antoinette Lemoine,Brigitte Debuire 

Service de Biochimie et Biologie moleculaire, Hopital Paul Brousse, Faculte de Medecine Paris Sud, 94 800 Villejuif, France