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Reviewed, UniProtKB/Swiss-Prot Q14508 (WFDC2_HUMAN)

Last modified June 16, 2009. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length124 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 componentSecreted
   Coding sequence diversityAlternative splicing
   DomainRepeat
Signal
   Molecular functionProtease inhibitor
Serine protease inhibitor
   PTMDisulfide bond
Glycoprotein
Gene Ontology (GO)
   Biological processproteolysis Ref.1

Traceable author statement. Source: ProtInc

spermatogenesis Ref.1

Traceable author statement. Source: ProtInc

   Cellular componentextracellular space Ref.1

Traceable author statement. Source: ProtInc

   Molecular functionserine-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3030 Potential
Chain31 – 12494WAP four-disulfide core domain protein 2
PRO_0000041370

Regions

Domain31 – 7343WAP 1
Domain74 – 12350WAP 2

Amino acid modifications

Glycosylation441N-linked (GlcNAc...) Ref.8
Disulfide bond36 ↔ 62 By similarity
Disulfide bond45 ↔ 66 By similarity
Disulfide bond49 ↔ 61 By similarity
Disulfide bond55 ↔ 70 By similarity
Disulfide bond80 ↔ 110 By similarity
Disulfide bond93 ↔ 114 By similarity
Disulfide bond97 ↔ 109 By similarity
Disulfide bond103 ↔ 119 By similarity

Natural variations

Alternative sequence2 – 2322PACRL…LFGFT → LQVQVNLPVSPLPTYPYSFF YP in isoform 2.
VSP_007666
Alternative sequence24 – 7451Missing in isoform 2.
VSP_007667
Alternative sequence27 – 7448Missing in isoform 3.
VSP_007668
Alternative sequence71 – 799SLPNDKEGS → LLCPNGQLAE in isoform 4.
VSP_007669
Alternative sequence75 – 10228DKEGS…QVDSQ → ALFHWHLKTRRLWEISGPRP RRPTWDSS in isoform 5.
VSP_007670
Alternative sequence80 – 12445Missing in isoform 4.
VSP_007671
Alternative sequence103 – 12422Missing in isoform 5.
VSP_007672

Experimental info

Sequence conflict71 – 722SL → LLC in CAA44869. Ref.1
Sequence conflict71 – 722SL → LLC in AAL37485. Ref.2
Sequence conflict1011S → T in CAA44869. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2002. Version 2.
Checksum: 9536B00B385259AD

FASTA12412,993
        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 

« Hide

Isoform 2 (HE4-V3).

Checksum: BDCFEECFA4FE8D59
Show »

FASTA738,120
Isoform 3 (HE4-V2).

Checksum: A93BE754FDAC93C2
Show »

FASTA768,108
Isoform 4 (HE4-V1).

Checksum: 75505D4E8301C895
Show »

FASTA808,202
Isoform 5 (HE4-V4).

Checksum: 36C13D09AAD2E15B
Show »

FASTA10211,043

References

« Hide '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. expand/collapse author list , 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

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.
IPIIPI00103633.
IPI00103636.
IPI00103639.
IPI00183629.
IPI00291488.
PIRS25454.
RefSeqNP_006094.3.
UniGeneHs.2719

3D structure databases

HSSPHSSP built from PDB template 1TWP based on UniProtKB Q9N0L8.
ModBaseSearch...

Protein-protein interaction databases

IntActQ14508. 1 interaction.

Proteomic databases

PeptideAtlasQ14508.
PRIDEQ14508.

Genome annotation databases

EnsemblENSG00000101443. Homo sapiens. [Contig view]
GeneID10406.
KEGGhsa:10406.

Organism-specific databases

GeneCardsGC20P043532.
HGNCHGNC:15939. WFDC2.
PharmGKBPA38059.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ14508.
OMAQ14508. ECASDSE.

Gene expression databases

ArrayExpressQ14508.
BgeeQ14508.
CleanExHS_WFDC2.
GermOnlineENSG00000101443. Homo sapiens.

Family and domain databases

InterProIPR015874. 4-disulphide_core.
IPR018069. Whey_acidic_4-diS_core_CS.
IPR008197. Whey_acidic_protein_4-diS_core.
[Graphical view]
Gene3DG3DSA:4.10.75.10. Whey_acidic_protein_4-diS_core. 2 hits.
PfamPF00095. WAP. 2 hits.
[Graphical view]
PRINTSPR00003. 4DISULPHCORE.
ProDomPD001224. Prot_inh_I17. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00217. WAP. 2 hits.
[Graphical view]
PROSITEPS51390. WAP. 2 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio39431.

Entry information

Entry nameWFDC2_HUMAN
AccessionPrimary (citable) accession number: Q14508
Secondary accession number(s): Q6IB27 expand/collapse secondary AC list , 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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents