WFDC2 explained

WAP four-disulfide core domain protein 2 - also known as Human Epididymis Protein 4^[1] (HE4) - is a protein that in humans is encoded by the WFDC2 gene.^{[2] [3] [4]}

HE4 is a tumor marker of ovarian cancer, with 80% sensitivity at a cut-off of 150 pmol/L.^[5]

Function

This gene encodes a protein that is a member of the WFDC domain family. The WFDC domain, or WAP Signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor in many family members. This gene is expressed in pulmonary epithelial cells among other tissues, and was also found to be expressed in some ovarian cancers.^[1] The encoded protein is a small secretory protein, which may be involved in sperm maturation.

Further reading

• Kirchhoff C . Molecular characterization of epididymal proteins . Rev. Reprod. . 3 . 2 . 86–95 . 1998 . 9685187 . 10.1530/ror.0.0030086 . free .
• Kirchhoff C, Osterhoff C, Habben I, Ivell R, Kirchloff C . Cloning and analysis of mRNAs expressed specifically in the human epididymis . Int. J. Androl. . 13 . 2 . 155–67 . 1990 . 1693137 . 10.1111/j.1365-2605.1990.tb00972.x . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Bingle L, Singleton V, Bingle CD . The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms . Oncogene . 21 . 17 . 2768–73 . 2002 . 11965550 . 10.1038/sj.onc.1205363 . 33406517 . free .
• Clauss A, Lilja H, Lundwall A . A locus on human chromosome 20 contains several genes expressing protease inhibitor domains with homology to whey acidic protein . Biochem. J. . 368 . Pt 1 . 233–42 . 2002 . 12206714 . 1222987 . 10.1042/BJ20020869 .
• Hellström I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M, Drescher C, Urban N, Hellström KE . The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma . Cancer Res. . 63 . 13 . 3695–700 . 2003 . 12839961 .
• Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR, Hecht JL . Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas . Cancer Res. . 65 . 6 . 2162–9 . 2005 . 15781627 . 10.1158/0008-5472.CAN-04-3924 . free .
• Clauss A, Lilja H, Lundwall A . The evolution of a genetic locus encoding small serine proteinase inhibitors . Biochem. Biophys. Res. Commun. . 333 . 2 . 383–9 . 2005 . 15950183 . 1939935 . 10.1016/j.bbrc.2005.05.125 .
• Bingle L, Cross SS, High AS, Wallace WA, Rassl D, Yuan G, Hellstrom I, Campos MA, Bingle CD . WFDC2 (HE4): A potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung . Respir. Res. . 7 . 1 . 61 . 2006 . 16600032 . 1459147 . 10.1186/1465-9921-7-61 . free .
• Ramachandran P, Boontheung P, Xie Y, Sondej M, Wong DT, Loo JA . Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry . J. Proteome Res. . 5 . 6 . 1493–503 . 2006 . 16740002 . 10.1021/pr050492k .

Notes and References

1. Hellström I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M, Drescher C, Urban N, Hellström KE . The HE4 (WFDC2) Protein Is a Biomarker for Ovarian Carcinoma . Cancer Research . 63 . 13 . 3695–3700 . 2003-07-01 . 12839961 . 2012-11-28 .
2. Kirchhoff C, Habben I, Ivell R, Krull N . A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors . Biol Reprod . 45 . 2 . 350–7 . Mar 1992 . 1686187 . 10.1095/biolreprod45.2.350 .
3. Schummer M, Ng WV, Bumgarner RE, Nelson PS, Schummer B, Bednarski DW, Hassell L, Baldwin RL, Karlan BY, Hood L . Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas . Gene . 238 . 2 . 375–85 . Dec 1999 . 10570965 . 10.1016/S0378-1119(99)00342-X .
4. Web site: Entrez Gene: WFDC2 WAP four-disulfide core domain 2.
5. Molina R, Escudero JM, Augé JM, Filella X, Foj L, Torné A, Lejarcegui J, Pahisa J . HE4 a novel tumour marker for ovarian cancer: Comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases . Tumor Biology . 32 . 6 . 1087–95 . 2011 . 21863264 . 3195682 . 10.1007/s13277-011-0204-3 .