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Q14508

- WFDC2_HUMAN

UniProt

Q14508 - WFDC2_HUMAN

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Protein

WAP four-disulfide core domain protein 2

Gene
WFDC2, HE4, WAP5
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Broad range protease inhibitor.1 Publication

GO - Molecular functioni

  1. aspartic-type endopeptidase inhibitor activity Source: UniProtKB-KW
  2. cysteine-type endopeptidase inhibitor activity Source: UniProtKB-KW
  3. endopeptidase inhibitor activity Source: ProtInc
  4. serine-type endopeptidase inhibitor activity Source: UniProtKB-KW

GO - Biological processi

  1. negative regulation of endopeptidase activity Source: GOC
  2. proteolysis Source: ProtInc
  3. spermatogenesis Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Aspartic protease inhibitor, Protease inhibitor, Serine protease inhibitor, Thiol protease inhibitor

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:WFDC2
Synonyms:HE4, WAP5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 20

Organism-specific databases

HGNCiHGNC:15939. WFDC2.

Subcellular locationi

Secreted 2 Publications

GO - Cellular componenti

  1. extracellular space Source: ProtInc
  2. extracellular vesicular exosome Source: UniProt
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA38059.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3030 Reviewed predictionAdd
BLAST
Chaini31 – 12494WAP four-disulfide core domain protein 2PRO_0000041370Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi36 ↔ 62 By similarity
Glycosylationi44 – 441N-linked (GlcNAc...)2 Publications
Disulfide bondi45 ↔ 66 By similarity
Disulfide bondi49 ↔ 61 By similarity
Disulfide bondi55 ↔ 70 By similarity
Disulfide bondi80 ↔ 110 By similarity
Disulfide bondi93 ↔ 114 By similarity
Disulfide bondi97 ↔ 109 By similarity
Disulfide bondi103 ↔ 119 By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ14508.
PaxDbiQ14508.
PeptideAtlasiQ14508.
PRIDEiQ14508.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

ArrayExpressiQ14508.
BgeeiQ14508.
CleanExiHS_WFDC2.
GenevestigatoriQ14508.

Organism-specific databases

HPAiHPA042302.

Interactioni

Subunit structurei

Homotrimer; disulfide-linked.1 Publication

Protein-protein interaction databases

BioGridi115677. 2 interactions.
IntActiQ14508. 2 interactions.
MINTiMINT-1429295.

Structurei

3D structure databases

ProteinModelPortaliQ14508.
SMRiQ14508. Positions 74-122.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini31 – 7343WAP 1Add
BLAST
Domaini74 – 12350WAP 2Add
BLAST

Sequence similaritiesi

Contains 2 WAP domains.

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG27860.
HOVERGENiHBG018073.
InParanoidiQ14508.
OMAiLNGCGKV.
OrthoDBiEOG7S7SG9.
PhylomeDBiQ14508.

Family and domain databases

Gene3Di4.10.75.10. 2 hits.
InterProiIPR008197. WAP.
[Graphical view]
PfamiPF00095. WAP. 2 hits.
[Graphical view]
PRINTSiPR00003. 4DISULPHCORE.
SMARTiSM00217. WAP. 2 hits.
[Graphical view]
SUPFAMiSSF57256. SSF57256. 2 hits.
PROSITEiPS51390. WAP. 2 hits.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. Align

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q14508-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MPACRLGPLA AALLLSLLLF GFTLVSGTGA EKTGVCPELQ ADQNCTQECV    50
SDSECADNLK CCSAGCATFC SLPNDKEGSC PQVNINFPQL GLCRDQCQVD 100
SQCPGQMKCC RNGCGKVSCV TPNF 124
Length:124
Mass (Da):12,993
Last modified:January 23, 2002 - v2
Checksum:i9536B00B385259AD
GO
Isoform 2 (identifier: Q14508-2) [UniParc]FASTAAdd to Basket

Also known as: HE4-V3

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

Show »
Length:73
Mass (Da):8,120
Checksum:iBDCFEECFA4FE8D59
GO
Isoform 3 (identifier: Q14508-3) [UniParc]FASTAAdd to Basket

Also known as: HE4-V2

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

Show »
Length:76
Mass (Da):8,108
Checksum:iA93BE754FDAC93C2
GO
Isoform 4 (identifier: Q14508-4) [UniParc]FASTAAdd to Basket

Also known as: HE4-V1

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

Show »
Length:80
Mass (Da):8,202
Checksum:i75505D4E8301C895
GO
Isoform 5 (identifier: Q14508-5) [UniParc]FASTAAdd to Basket

Also known as: HE4-V4

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

Show »
Length:102
Mass (Da):11,043
Checksum:i36C13D09AAD2E15B
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei2 – 2322PACRL…LFGFT → LQVQVNLPVSPLPTYPYSFF YP in isoform 2. VSP_007666Add
BLAST
Alternative sequencei24 – 7451Missing in isoform 2. VSP_007667Add
BLAST
Alternative sequencei27 – 7448Missing in isoform 3. VSP_007668Add
BLAST
Alternative sequencei71 – 799SLPNDKEGS → LLCPNGQLAE in isoform 4. VSP_007669
Alternative sequencei75 – 10228DKEGS…QVDSQ → ALFHWHLKTRRLWEISGPRP RRPTWDSS in isoform 5. VSP_007670Add
BLAST
Alternative sequencei80 – 12445Missing in isoform 4. VSP_007671Add
BLAST
Alternative sequencei103 – 12422Missing in isoform 5. VSP_007672Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti71 – 722SL → LLC in CAA44869. 1 Publication
Sequence conflicti71 – 722SL → LLC in AAL37485. 1 Publication
Sequence conflicti101 – 1011S → T in CAA44869. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS35501.1. [Q14508-1]
PIRiS25454.
RefSeqiNP_006094.3. NM_006103.3. [Q14508-1]
UniGeneiHs.2719.

Genome annotation databases

EnsembliENST00000217425; ENSP00000217425; ENSG00000101443. [Q14508-5]
ENST00000339946; ENSP00000340215; ENSG00000101443. [Q14508-3]
ENST00000342873; ENSP00000342890; ENSG00000101443. [Q14508-2]
ENST00000372676; ENSP00000361761; ENSG00000101443. [Q14508-1]
GeneIDi10406.
KEGGihsa:10406.
UCSCiuc002xoo.3. human. [Q14508-1]
uc002xop.3. human. [Q14508-3]
uc002xor.3. human. [Q14508-2]

Polymorphism databases

DMDMi20141958.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS35501.1. [Q14508-1 ]
PIRi S25454.
RefSeqi NP_006094.3. NM_006103.3. [Q14508-1 ]
UniGenei Hs.2719.

3D structure databases

ProteinModelPortali Q14508.
SMRi Q14508. Positions 74-122.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 115677. 2 interactions.
IntActi Q14508. 2 interactions.
MINTi MINT-1429295.

Polymorphism databases

DMDMi 20141958.

Proteomic databases

MaxQBi Q14508.
PaxDbi Q14508.
PeptideAtlasi Q14508.
PRIDEi Q14508.

Protocols and materials databases

DNASUi 10406.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000217425 ; ENSP00000217425 ; ENSG00000101443 . [Q14508-5 ]
ENST00000339946 ; ENSP00000340215 ; ENSG00000101443 . [Q14508-3 ]
ENST00000342873 ; ENSP00000342890 ; ENSG00000101443 . [Q14508-2 ]
ENST00000372676 ; ENSP00000361761 ; ENSG00000101443 . [Q14508-1 ]
GeneIDi 10406.
KEGGi hsa:10406.
UCSCi uc002xoo.3. human. [Q14508-1 ]
uc002xop.3. human. [Q14508-3 ]
uc002xor.3. human. [Q14508-2 ]

Organism-specific databases

CTDi 10406.
GeneCardsi GC20P044098.
HGNCi HGNC:15939. WFDC2.
HPAi HPA042302.
neXtProti NX_Q14508.
PharmGKBi PA38059.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG27860.
HOVERGENi HBG018073.
InParanoidi Q14508.
OMAi LNGCGKV.
OrthoDBi EOG7S7SG9.
PhylomeDBi Q14508.

Miscellaneous databases

GeneWikii WFDC2.
GenomeRNAii 10406.
NextBioi 39431.
PROi Q14508.

Gene expression databases

ArrayExpressi Q14508.
Bgeei Q14508.
CleanExi HS_WFDC2.
Genevestigatori Q14508.

Family and domain databases

Gene3Di 4.10.75.10. 2 hits.
InterProi IPR008197. WAP.
[Graphical view ]
Pfami PF00095. WAP. 2 hits.
[Graphical view ]
PRINTSi PR00003. 4DISULPHCORE.
SMARTi SM00217. WAP. 2 hits.
[Graphical view ]
SUPFAMi SSF57256. SSF57256. 2 hits.
PROSITEi PS51390. WAP. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

Entry informationi

Entry nameiWFDC2_HUMAN
AccessioniPrimary (citable) accession number: Q14508
Secondary accession number(s): A2A2A5
, A2A2A6, A6PVD5, Q6IB27, Q8WXV9, Q8WXW0, Q8WXW1, Q8WXW2, Q96KJ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 23, 2002
Last modified: September 3, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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