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Q14508

- WFDC2_HUMAN

UniProt

Q14508 - WFDC2_HUMAN

Protein

WAP four-disulfide core domain protein 2

Gene

WFDC2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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

    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

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA38059.

    PTM / Processingi

    Molecule processing

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

    Amino acid modifications

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

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini31 – 7343WAP 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini74 – 12350WAP 2PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 2 WAP domains.PROSITE-ProRule annotation

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti71 – 722SL → LLC in CAA44869. (PubMed:1686187)Curated
    Sequence conflicti71 – 722SL → LLC in AAL37485. (PubMed:11965550)Curated
    Sequence conflicti101 – 1011S → T in CAA44869. (PubMed:1686187)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei2 – 2322PACRL…LFGFT → LQVQVNLPVSPLPTYPYSFF YP in isoform 2. 1 PublicationVSP_007666Add
    BLAST
    Alternative sequencei24 – 7451Missing in isoform 2. 1 PublicationVSP_007667Add
    BLAST
    Alternative sequencei27 – 7448Missing in isoform 3. 1 PublicationVSP_007668Add
    BLAST
    Alternative sequencei71 – 799SLPNDKEGS → LLCPNGQLAE in isoform 4. 1 PublicationVSP_007669
    Alternative sequencei75 – 10228DKEGS…QVDSQ → ALFHWHLKTRRLWEISGPRP RRPTWDSS in isoform 5. 1 PublicationVSP_007670Add
    BLAST
    Alternative sequencei80 – 12445Missing in isoform 4. 1 PublicationVSP_007671Add
    BLAST
    Alternative sequencei103 – 12422Missing in isoform 5. 1 PublicationVSP_007672Add
    BLAST

    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

    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: October 1, 2014
    This is version 137 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