Reviewed, UniProtKB/Swiss-Prot Q14508 (WFDC2_HUMAN)

Names and origin

Protein names

Recommended name:
    WAP four-disulfide core domain protein 2
Alternative name(s):
    Major epididymis-specific protein E4
    Epididymal secretory protein E4
    Putative protease inhibitor WAP5

Gene names

Name:	WFDC2
Synonyms:	HE4, WAP5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	124 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Subcellular location	Secreted. Ref.7
Tissue specificity	Expressed in a number of normal tissues, including male reproductive system, regions of the respiratory tract and nasopharynx. Highly expressed in a number of tumors cells lines, such ovarian, colon, breast, lung and renal cells lines. Initially described as being exclusively transcribed in the epididymis. Ref.7
Sequence similarities	Contains 2 WAP domains.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	proteolysis Ref.1 Traceable author statement. Source: ProtInc spermatogenesis Ref.1 Traceable author statement. Source: ProtInc
Cellular component	extracellular space Ref.1 Traceable author statement. Source: ProtInc
Molecular function	serine-type endopeptidase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q14508-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q14508-2)

Also known as: HE4-V3;

The sequence of this isoform differs from the canonical sequence as follows:
     2-23: PACRLGPLAAALLLSLLLFGFT → LQVQVNLPVSPLPTYPYSFFYP
     24-74: Missing.

Isoform 3 (identifier: Q14508-3)

Also known as: HE4-V2;

The sequence of this isoform differs from the canonical sequence as follows:
     27-74: Missing.

Isoform 4 (identifier: Q14508-4)

Also known as: HE4-V1;

The sequence of this isoform differs from the canonical sequence as follows:
     71-79: SLPNDKEGS → LLCPNGQLAE
     80-124: Missing.

Isoform 5 (identifier: Q14508-5)

Also known as: HE4-V4;

The sequence of this isoform differs from the canonical sequence as follows:
     75-102: DKEGSCPQVNINFPQLGLCRDQCQVDSQ → ALFHWHLKTRRLWEISGPRPRRPTWDSS
     103-124: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 30	30	Potential
	Chain	31 – 124	94	WAP four-disulfide core domain protein 2		PRO_0000041370
Regions
	Domain	31 – 73	43	WAP 1
	Domain	74 – 123	50	WAP 2
Amino acid modifications
	Glycosylation	44	1	N-linked (GlcNAc...) Ref.8
	Disulfide bond	36 ↔ 62		By similarity
	Disulfide bond	45 ↔ 66		By similarity
	Disulfide bond	49 ↔ 61		By similarity
	Disulfide bond	55 ↔ 70		By similarity
	Disulfide bond	80 ↔ 110		By similarity
	Disulfide bond	93 ↔ 114		By similarity
	Disulfide bond	97 ↔ 109		By similarity
	Disulfide bond	103 ↔ 119		By similarity
Natural variations
	Alternative sequence	2 – 23	22	PACRL…LFGFT → LQVQVNLPVSPLPTYPYSFF YP in isoform 2.		VSP_007666
	Alternative sequence	24 – 74	51	Missing in isoform 2.		VSP_007667
	Alternative sequence	27 – 74	48	Missing in isoform 3.		VSP_007668
	Alternative sequence	71 – 79	9	SLPNDKEGS → LLCPNGQLAE in isoform 4.		VSP_007669
	Alternative sequence	75 – 102	28	DKEGS…QVDSQ → ALFHWHLKTRRLWEISGPRP RRPTWDSS in isoform 5.		VSP_007670
	Alternative sequence	80 – 124	45	Missing in isoform 4.		VSP_007671
	Alternative sequence	103 – 124	22	Missing in isoform 5.		VSP_007672
Experimental info
	Sequence conflict	71 – 72	2	SL → LLC in CAA44869. Ref.1
	Sequence conflict	71 – 72	2	SL → LLC in AAL37485. Ref.2
	Sequence conflict	101	1	S → T in CAA44869. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2002. Version 2. Checksum: 9536B00B385259AD	FASTA	124	12,993
	10 20 30 40 50 60 MPACRLGPLA AALLLSLLLF GFTLVSGTGA EKTGVCPELQ ADQNCTQECV SDSECADNLK 70 80 90 100 110 120 CCSAGCATFC SLPNDKEGSC PQVNINFPQL GLCRDQCQVD SQCPGQMKCC RNGCGKVSCV TPNF
	Isoform 2 (HE4-V3). Checksum: BDCFEECFA4FE8D59	FASTA	73	8,120
	10 20 30 40 50 60 MLQVQVNLPV SPLPTYPYSF FYPDKEGSCP QVNINFPQLG LCRDQCQVDS QCPGQMKCCR 70 NGCGKVSCVT PNF
	Isoform 3 (HE4-V2). Checksum: A93BE754FDAC93C2	FASTA	76	8,108
	10 20 30 40 50 60 MPACRLGPLA AALLLSLLLF GFTLVSDKEG SCPQVNINFP QLGLCRDQCQ VDSQCPGQMK 70 CCRNGCGKVS CVTPNF
	Isoform 4 (HE4-V1). Checksum: 75505D4E8301C895	FASTA	80	8,202
	10 20 30 40 50 60 MPACRLGPLA AALLLSLLLF GFTLVSGTGA EKTGVCPELQ ADQNCTQECV SDSECADNLK 70 80 CCSAGCATFC LLCPNGQLAE
	Isoform 5 (HE4-V4). Checksum: 36C13D09AAD2E15B	FASTA	102	11,043
	10 20 30 40 50 60 MPACRLGPLA AALLLSLLLF GFTLVSGTGA EKTGVCPELQ ADQNCTQECV SDSECADNLK 70 80 90 100 CCSAGCATFC SLPNALFHWH LKTRRLWEIS GPRPRRPTWD SS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors." Kirchhoff C., Habben L., Ivell R., Krull N. Biol. Reprod. 45:350-357(1991) [PubMed: 1686187] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Epididymis.
[2]	"The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms." Bingle L., Singleton V., Bingle C.D. Oncogene 21:2768-2773(2002) [PubMed: 11965550] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5).
[3]	"The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma." Hellstrom I., Raycraft J., Hayden-Ledbetter M., Ledbetter J.A., Schummer M., McIntosh M., Drescher C., Urban N., Hellstrom K.E. Cancer Res. 63:3695-3700(2003) [PubMed: 12839961] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon.
[7]	"Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas." Drapkin R., von Horsten H.H., Lin Y., Mok S.C., Crum C.P., Welch W.R., Hecht J.L. Cancer Res. 65:2162-2169(2005) [PubMed: 15781627] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]	"Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry." Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A. J. Proteome Res. 5:1493-1503(2006) [PubMed: 16740002] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-44, MASS SPECTROMETRY. Tissue: Saliva.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X63187 mRNA. Translation: CAA44869.1. AF330259 mRNA. Translation: AAL37485.1. AF330260 mRNA. Translation: AAL37486.1. AF330261 mRNA. Translation: AAL37487.1. AF330262 mRNA. Translation: AAL37488.1. AY212888 mRNA. Translation: AAO52683.1. CR456977 mRNA. Translation: CAG33258.1. AL031663 Genomic DNA. Translation: CAB37641.1. BC046106 mRNA. Translation: AAH46106.1.
IPI	IPI00103633. IPI00103636. IPI00103639. IPI00183629. IPI00291488.
PIR	S25454.
RefSeq	NP_006094.3.
UniGene	Hs.2719
3D structure databases
HSSP	HSSP built from PDB template 1TWP based on UniProtKB Q9N0L8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q14508. 1 interaction.
Proteomic databases
PeptideAtlas	Q14508.
PRIDE	Q14508.
Genome annotation databases
Ensembl	ENSG00000101443. Homo sapiens. [Contig view]
GeneID	10406.
KEGG	hsa:10406.
Organism-specific databases
GeneCards	GC20P043532.
HGNC	HGNC:15939. WFDC2.
PharmGKB	PA38059.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q14508.
OMA	Q14508. ECASDSE.
Gene expression databases
ArrayExpress	Q14508.
Bgee	Q14508.
CleanEx	HS_WFDC2.
GermOnline	ENSG00000101443. Homo sapiens.
Family and domain databases
InterPro	IPR015874. 4-disulphide_core. IPR018069. Whey_acidic_4-diS_core_CS. IPR008197. Whey_acidic_protein_4-diS_core. [Graphical view]
Gene3D	G3DSA:4.10.75.10. Whey_acidic_protein_4-diS_core. 2 hits.
Pfam	PF00095. WAP. 2 hits. [Graphical view]
PRINTS	PR00003. 4DISULPHCORE.
ProDom	PD001224. Prot_inh_I17. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00217. WAP. 2 hits. [Graphical view]
PROSITE	PS51390. WAP. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	39431.

Entry information

Entry name

WFDC2_HUMAN

Accession

Primary (citable) accession number: Q14508
Secondary accession number(s): Q6IB27 , Q8WXV9, Q8WXW0, Q8WXW1, Q8WXW2, Q96KJ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 23, 2002
Last modified:	June 16, 2009
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)