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Q14508 (WFDC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
WAP four-disulfide core domain protein 2
Alternative name(s):
Epididymal secretory protein E4
Major epididymis-specific protein E4
Putative protease inhibitor WAP5
Gene names
Name:WFDC2
Synonyms:HE4, WAP5
OrganismHomo sapiens (Human) [Reference proteome]
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)

Function

Broad range protease inhibitor. Ref.10

Subunit structure

Homotrimer; disulfide-linked. Ref.10

Subcellular location

Secreted Ref.8 Ref.10.

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.8

Sequence similarities

Contains 2 WAP domains.

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.9 Ref.10
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) [UniParc].

Checksum: BDCFEECFA4FE8D59
Show »

FASTA738,120
Isoform 3 (HE4-V2) [UniParc].

Checksum: A93BE754FDAC93C2
Show »

FASTA768,108
Isoform 4 (HE4-V1) [UniParc].

Checksum: 75505D4E8301C895
Show »

FASTA808,202
Isoform 5 (HE4-V4) [UniParc].

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon.
[8]"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] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]"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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-44.
Tissue: Saliva.
[10]"Human epididymis protein-4 (HE-4): a novel cross-class protease inhibitor."
Chhikara N., Saraswat M., Tomar A.K., Dey S., Singh S., Yadav S.
PLoS ONE 7:E47672-E47672(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, GLYCOSYLATION AT ASN-44, SUBCELLULAR LOCATION.
Tissue: Seminal plasma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
AL031663 Genomic DNA. Translation: CAM28246.1.
AL031663 Genomic DNA. Translation: CAM28247.1.
AL031663 Genomic DNA. Translation: CAO03535.1.
CH471077 Genomic DNA. Translation: EAW75836.1.
CH471077 Genomic DNA. Translation: EAW75837.1.
CH471077 Genomic DNA. Translation: EAW75839.1.
BC046106 mRNA. Translation: AAH46106.1.
CCDSCCDS35501.1. [Q14508-1]
PIRS25454.
RefSeqNP_006094.3. NM_006103.3. [Q14508-1]
UniGeneHs.2719.

3D structure databases

ProteinModelPortalQ14508.
SMRQ14508. Positions 74-122.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115677. 2 interactions.
IntActQ14508. 2 interactions.
MINTMINT-1429295.

Polymorphism databases

DMDM20141958.

Proteomic databases

MaxQBQ14508.
PaxDbQ14508.
PeptideAtlasQ14508.
PRIDEQ14508.

Protocols and materials databases

DNASU10406.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000217425; ENSP00000217425; ENSG00000101443. [Q14508-5]
ENST00000339946; ENSP00000340215; ENSG00000101443. [Q14508-3]
ENST00000342873; ENSP00000342890; ENSG00000101443. [Q14508-2]
ENST00000372676; ENSP00000361761; ENSG00000101443. [Q14508-1]
GeneID10406.
KEGGhsa:10406.
UCSCuc002xoo.3. human. [Q14508-1]
uc002xop.3. human. [Q14508-3]
uc002xor.3. human. [Q14508-2]

Organism-specific databases

CTD10406.
GeneCardsGC20P044098.
HGNCHGNC:15939. WFDC2.
HPAHPA042302.
neXtProtNX_Q14508.
PharmGKBPA38059.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG27860.
HOVERGENHBG018073.
InParanoidQ14508.
OMALNGCGKV.
OrthoDBEOG7S7SG9.
PhylomeDBQ14508.

Gene expression databases

ArrayExpressQ14508.
BgeeQ14508.
CleanExHS_WFDC2.
GenevestigatorQ14508.

Family and domain databases

Gene3D4.10.75.10. 2 hits.
InterProIPR008197. WAP-type_4-diS_core.
[Graphical view]
PfamPF00095. WAP. 2 hits.
[Graphical view]
PRINTSPR00003. 4DISULPHCORE.
SMARTSM00217. WAP. 2 hits.
[Graphical view]
SUPFAMSSF57256. SSF57256. 2 hits.
PROSITEPS51390. WAP. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiWFDC2.
GenomeRNAi10406.
NextBio39431.
PROQ14508.

Entry information

Entry nameWFDC2_HUMAN
AccessionPrimary (citable) accession number: Q14508
Secondary accession number(s): A2A2A5 expand/collapse secondary AC list , A2A2A6, A6PVD5, Q6IB27, Q8WXV9, Q8WXW0, Q8WXW1, Q8WXW2, Q96KJ1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 23, 2002
Last modified: July 9, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human chromosome 20

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