WFDC2

"HE4" redirects here. For the isotope of helium (He-4 or ⁴He), see Helium-4.

"WAP5" redirects here. For the Indian railway locomotive, see Indian locomotive class WAP-5.

WFDC2
Identifiers
Aliases	WFDC2 , EDDM4, HE4, WAP5, dJ461P17.6, WAP four-disulfide core domain 2
External IDs	OMIM: 617548; MGI: 1914951; HomoloGene: 4450; GeneCards: WFDC2; OMA:WFDC2 - orthologs
Gene location (Human) Chr. Chromosome 20 (human) [1] Band 20q13.12 Start 45,469,753 bp [1] End 45,481,532 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2|2 H3 Start 164,404,333 bp [2] End 164,410,430 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in olfactory zone of nasal mucosa nasal epithelium right uterine tube epithelium of bronchus bronchial epithelial cell right lobe of thyroid gland left lobe of thyroid gland palpebral conjunctiva corpus epididymis trachea Top expressed in right lung lobe transitional epithelium of urinary bladder left lung left colon cervix olfactory epithelium left lung lobe medullary collecting duct right kidney embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function aspartic-type endopeptidase inhibitor activity peptidase inhibitor activity endopeptidase inhibitor activity serine-type endopeptidase inhibitor activity cysteine-type endopeptidase inhibitor activity Cellular component extracellular region extracellular exosome extracellular space Biological process negative regulation of peptidase activity proteolysis spermatogenesis negative regulation of endopeptidase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10406 67701 Ensembl ENSG00000101443 ENSMUSG00000017723 UniProt Q14508 Q9DAU7 RefSeq (mRNA) NM_006103 NM_080733 NM_080734 NM_080735 NM_080736 NM_026323 NM_001374655 RefSeq (protein) NP_006094 NP_080599 NP_001361584 Location (UCSC) Chr 20: 45.47 – 45.48 Mb Chr 2: 164.4 – 164.41 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

WAP four-disulfide core domain protein 2 - also known as Human Epididymis Protein 4 ^[5] (HE4) - is a protein that in humans is encoded by the WFDC2 gene. ^{[6] [7] [8]}

HE4 is a tumor marker of ovarian cancer, with 80% sensitivity at a cut-off of 150 pmol/L. ^[9]

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. ^[5] The encoded protein is a small secretory protein, which may be involved in sperm maturation. ^[8]

References

1. GRCh38: Ensembl release 89: ENSG00000101443 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000017723 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Hellström I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M, Drescher C, Urban N, Hellström KE (2003-07-01). "The HE4 (WFDC2) Protein Is a Biomarker for Ovarian Carcinoma". Cancer Research. 63 (13): 3695–3700. PMID   12839961 . Retrieved 2012-11-28.
6. Kirchhoff C, Habben I, Ivell R, Krull N (Mar 1992). "A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors". Biol Reprod. 45 (2): 350–7. doi:10.1095/biolreprod45.2.350. PMID   1686187.
7. Schummer M, Ng WV, Bumgarner RE, Nelson PS, Schummer B, Bednarski DW, Hassell L, Baldwin RL, Karlan BY, Hood L (Dec 1999). "Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas". Gene. 238 (2): 375–85. doi:10.1016/S0378-1119(99)00342-X. PMID   10570965.
8. "Entrez Gene: WFDC2 WAP four-disulfide core domain 2".
9. Molina R, Escudero JM, Augé JM, Filella X, Foj L, Torné A, Lejarcegui J, Pahisa J (2011). "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. doi:10.1007/s13277-011-0204-3. PMC   3195682 . PMID   21863264.

Further reading

• Kirchhoff C (1998). "Molecular characterization of epididymal proteins". Rev. Reprod. 3 (2): 86–95. doi: 10.1530/ror.0.0030086 . PMID   9685187.
• Kirchhoff C, Osterhoff C, Habben I, Ivell R, Kirchloff C (1990). "Cloning and analysis of mRNAs expressed specifically in the human epididymis". Int. J. Androl. 13 (2): 155–67. doi: 10.1111/j.1365-2605.1990.tb00972.x . PMID   1693137.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID   9373149.
• Bingle L, Singleton V, Bingle CD (2002). "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. doi: 10.1038/sj.onc.1205363 . PMID   11965550. S2CID   33406517.
• Clauss A, Lilja H, Lundwall A (2002). "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. doi:10.1042/BJ20020869. PMC   1222987 . PMID   12206714.
• Hellström I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M, Drescher C, Urban N, Hellström KE (2003). "The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma". Cancer Res. 63 (13): 3695–700. PMID   12839961.
• Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR, Hecht JL (2005). "Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas". Cancer Res. 65 (6): 2162–9. doi: 10.1158/0008-5472.CAN-04-3924 . PMID   15781627.
• Clauss A, Lilja H, Lundwall A (2005). "The evolution of a genetic locus encoding small serine proteinase inhibitors". Biochem. Biophys. Res. Commun. 333 (2): 383–9. doi:10.1016/j.bbrc.2005.05.125. PMC   1939935 . PMID   15950183.
• Bingle L, Cross SS, High AS, Wallace WA, Rassl D, Yuan G, Hellstrom I, Campos MA, Bingle CD (2006). "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. doi: 10.1186/1465-9921-7-61 . PMC   1459147 . PMID   16600032.
• Ramachandran P, Boontheung P, Xie Y, Sondej M, Wong DT, Loo JA (2006). "Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry". J. Proteome Res. 5 (6): 1493–503. doi:10.1021/pr050492k. PMID   16740002.