WFDC1 (WAP four-disulfide core domain 1)
2005-06-01 Raphael Saffroy  , Antoinette Lemoine  , Brigitte Debuire   AffiliationService de Biochimie et Biologie moleculaire, Hopital Paul Brousse, Faculte de Medecine Paris Sud, 94 800 Villejuif, France
DNA/RNA
Description
The gene encompasses 35 kb of DNA; 7 exons.
Transcription
1366 nucleotides mRNA; 660 bp open reading frame.
Proteins

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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12379854 | 2002 | Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. | Kurose K et al |
| 10967136 | 2000 | The WFDC1 gene encoding ps20 localizes to 16q24, a region of LOH in multiple cancers. | Larsen M et al |
| 15305341 | 2004 | Decreased stromal expression and increased epithelial expression of WFDC1/ps20 in prostate cancer is associated with reduced recurrence-free survival. | McAlhany SJ et al |
| 1730568 | 1992 | Characterization of a fetal urogenital sinus mesenchymal cell line U4F: secretion of a negative growth regulatory activity. | Rowley DR et al |
| 7665628 | 1995 | Purification of a novel protein (ps20) from urogenital sinus mesenchymal cells with growth inhibitory properties in vitro. | Rowley DR et al |
| 3567912 | 1987 | Responses of NBT-II bladder carcinoma cells to conditioned medium from normal fetal urogenital sinus. | Rowley DR et al |
| 12032731 | 2002 | Analysis of alterations of WFDC1, a new putative tumour suppressor gene, in hepatocellular carcinoma. | Saffroy R et al |
| 15007382 | 2004 | 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 et al |
| 15305342 | 2004 | Molecular 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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000103175 | ENST00000219454 | Q9HC57 |
| ENSG00000103175 | ENST00000568638 | Q9HC57 |
| ENSG00000103175 | ENST00000613603 | A0A087WY77 |
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 33615507 | 2021 | Molecular structure, gene expression and functional role of WFDC1 in angiogenesis and cancer. | 6 |
| 33615507 | 2021 | Molecular structure, gene expression and functional role of WFDC1 in angiogenesis and cancer. | 6 |
| 30423385 | 2019 | Phylogenetic, molecular evolution and structural analyses of the WFDC1/prostate stromal protein 20 (ps20). | 2 |
| 30423385 | 2019 | Phylogenetic, molecular evolution and structural analyses of the WFDC1/prostate stromal protein 20 (ps20). | 2 |
| 27115470 | 2016 | Expression of two WFDC1/ps20 isoforms in prostate stromal cells induces paracrine apoptosis through regulation of PTGS2/COX-2. | 4 |
| 27115470 | 2016 | Expression of two WFDC1/ps20 isoforms in prostate stromal cells induces paracrine apoptosis through regulation of PTGS2/COX-2. | 4 |
| 21545747 | 2011 | WFDC1 expression identifies memory CD4 T-lymphocytes rendered vulnerable to cell-cell HIV-1 transfer by promoting intercellular adhesive junctions. | 1 |
| 21545747 | 2011 | WFDC1 expression identifies memory CD4 T-lymphocytes rendered vulnerable to cell-cell HIV-1 transfer by promoting intercellular adhesive junctions. | 1 |
| 20090771 | 2010 | Supervised machine learning and logistic regression identifies novel epistatic risk factors with PTPN22 for rheumatoid arthritis. | 15 |
| 20090771 | 2010 | Supervised machine learning and logistic regression identifies novel epistatic risk factors with PTPN22 for rheumatoid arthritis. | 15 |
| 18842679 | 2009 | Modulated expression of WFDC1 during carcinogenesis and cellular senescence. | 48 |
| 18842679 | 2009 | Modulated expression of WFDC1 during carcinogenesis and cellular senescence. | 48 |
| 19488830 | 2009 | Expression and functional analysis of the WAP four disulfide core domain 1 gene in human melanoma. | 10 |
| 18842679 | 2009 | Modulated expression of WFDC1 during carcinogenesis and cellular senescence. | 48 |
| 18842679 | 2009 | Modulated expression of WFDC1 during carcinogenesis and cellular senescence. | 48 |
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  Affiliation
Service de Biochimie et Biologie moleculaire, Hopital Paul Brousse, Faculte de Medecine Paris Sud, 94 800 Villejuif, France
