ID   WFDC2_HUMAN             Reviewed;         124 AA.
AC   Q14508; Q6IB27; Q8WXV9; Q8WXW0; Q8WXW1; Q8WXW2; Q96KJ1;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2002, sequence version 2.
DT   22-JUL-2008, entry version 85.
DE   RecName: Full=WAP four-disulfide core domain protein 2;
DE   AltName: Full=Major epididymis-specific protein E4;
DE   AltName: Full=Epididymal secretory protein E4;
DE   AltName: Full=Putative protease inhibitor WAP5;
DE   Flags: Precursor;
GN   Name=WFDC2; Synonyms=HE4, WAP5;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Epididymis;
RX   MEDLINE=92153963; PubMed=1686187;
RA   Kirchhoff C., Habben L., Ivell R., Krull N.;
RT   "A major human epididymis-specific cDNA encodes a protein with
RT   sequence homology to extracellular proteinase inhibitors.";
RL   Biol. Reprod. 45:350-357(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5).
RX   MEDLINE=21962329; PubMed=11965550; DOI=10.1038/sj.onc.1205363;
RA   Bingle L., Singleton V., Bingle C.D.;
RT   "The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in
RT   normal tissues and undergoes complex alternative splicing to yield
RT   multiple protein isoforms.";
RL   Oncogene 21:2768-2773(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=12839961;
RA   Hellstrom I., Raycraft J., Hayden-Ledbetter M., Ledbetter J.A.,
RA   Schummer M., McIntosh M., Drescher C., Urban N., Hellstrom K.E.;
RT   "The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma.";
RL   Cancer Res. 63:3695-3700(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   MEDLINE=21638749; PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA   Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA   Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA   Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA   Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA   Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA   Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA   Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA   Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA   Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA   Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA   Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA   Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Colon;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=15781627; DOI=10.1158/0008-5472.CAN-04-3924;
RA   Drapkin R., von Horsten H.H., Lin Y., Mok S.C., Crum C.P., Welch W.R.,
RA   Hecht J.L.;
RT   "Human epididymis protein 4 (HE4) is a secreted glycoprotein that is
RT   overexpressed by serous and endometrioid ovarian carcinomas.";
RL   Cancer Res. 65:2162-2169(2005).
RN   [8]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-44, AND MASS SPECTROMETRY.
RC   TISSUE=Saliva;
RX   PubMed=16740002; DOI=10.1021/pr050492k;
RA   Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T.,
RA   Loo J.A.;
RT   "Identification of N-linked glycoproteins in human saliva by
RT   glycoprotein capture and mass spectrometry.";
RL   J. Proteome Res. 5:1493-1503(2006).
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC         Comment=Additional isoforms seem to exist;
CC       Name=1;
CC         IsoId=Q14508-1; Sequence=Displayed;
CC       Name=2; Synonyms=HE4-V3;
CC         IsoId=Q14508-2; Sequence=VSP_007666, VSP_007667;
CC       Name=3; Synonyms=HE4-V2;
CC         IsoId=Q14508-3; Sequence=VSP_007668;
CC       Name=4; Synonyms=HE4-V1;
CC         IsoId=Q14508-4; Sequence=VSP_007669, VSP_007671;
CC       Name=5; Synonyms=HE4-V4;
CC         IsoId=Q14508-5; Sequence=VSP_007670, VSP_007672;
CC   -!- TISSUE SPECIFICITY: Expressed in a number of normal tissues,
CC       including male reproductive system, regions of the respiratory
CC       tract and nasopharynx. Highly expressed in a number of tumors
CC       cells lines, such ovarian, colon, breast, lung and renal cells
CC       lines. Initially described as being exclusively transcribed in the
CC       epididymis.
CC   -!- SIMILARITY: Contains 2 WAP domains.
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DR   EMBL; X63187; CAA44869.1; -; mRNA.
DR   EMBL; AF330259; AAL37485.1; -; mRNA.
DR   EMBL; AF330260; AAL37486.1; -; mRNA.
DR   EMBL; AF330261; AAL37487.1; -; mRNA.
DR   EMBL; AF330262; AAL37488.1; -; mRNA.
DR   EMBL; AY212888; AAO52683.1; -; mRNA.
DR   EMBL; CR456977; CAG33258.1; -; mRNA.
DR   EMBL; AL031663; CAB37641.1; -; Genomic_DNA.
DR   EMBL; BC046106; AAH46106.1; -; mRNA.
DR   PIR; S25454; S25454.
DR   RefSeq; NP_006094.3; -.
DR   UniGene; Hs.2719; -.
DR   HSSP; Q9N0L8; 1TWP.
DR   PeptideAtlas; Q14508; -.
DR   Ensembl; ENSG00000101443; Homo sapiens.
DR   GeneID; 10406; -.
DR   KEGG; hsa:10406; -.
DR   HGNC; HGNC:15939; WFDC2.
DR   PharmGKB; PA38059; -.
DR   HOVERGEN; Q14508; -.
DR   ArrayExpress; Q14508; -.
DR   CleanEx; HS_WFDC2; -.
DR   GermOnline; ENSG00000101443; Homo sapiens.
DR   GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR   GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc.
DR   GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR   GO; GO:0007283; P:spermatogenesis; TAS:ProtInc.
DR   InterPro; IPR015874; 4-disulphide_core.
DR   InterPro; IPR008197; Whey_acidic_protein_4-diS_core.
DR   Gene3D; G3DSA:4.10.75.10; Whey_acidic_protein_4-diS_core; 2.
DR   Pfam; PF00095; WAP; 2.
DR   PRINTS; PR00003; 4DISULPHCORE.
DR   ProDom; PD001224; Prot_inh_I17; 1.
DR   SMART; SM00217; WAP; 2.
DR   PROSITE; PS00317; 4_DISULFIDE_CORE; 2.
PE   1: Evidence at protein level;
KW   Alternative splicing; Glycoprotein; Protease inhibitor; Repeat;
KW   Secreted; Serine protease inhibitor; Signal.
FT   SIGNAL        1     30       Potential.
FT   CHAIN        31    124       WAP four-disulfide core domain protein 2.
FT                                /FTId=PRO_0000041370.
FT   DOMAIN       32     74       WAP 1.
FT   DOMAIN       76    124       WAP 2.
FT   CARBOHYD     44     44       N-linked (GlcNAc...).
FT   DISULFID     36     62       By similarity.
FT   DISULFID     45     66       By similarity.
FT   DISULFID     49     61       By similarity.
FT   DISULFID     55     70       By similarity.
FT   DISULFID     80    110       By similarity.
FT   DISULFID     93    114       By similarity.
FT   DISULFID     97    109       By similarity.
FT   DISULFID    103    119       By similarity.
FT   VAR_SEQ       2     23       PACRLGPLAAALLLSLLLFGFT -> LQVQVNLPVSPLPTY
FT                                PYSFFYP (in isoform 2).
FT                                /FTId=VSP_007666.
FT   VAR_SEQ      24     74       Missing (in isoform 2).
FT                                /FTId=VSP_007667.
FT   VAR_SEQ      27     74       Missing (in isoform 3).
FT                                /FTId=VSP_007668.
FT   VAR_SEQ      71     79       SLPNDKEGS -> LLCPNGQLAE (in isoform 4).
FT                                /FTId=VSP_007669.
FT   VAR_SEQ      75    102       DKEGSCPQVNINFPQLGLCRDQCQVDSQ -> ALFHWHLKT
FT                                RRLWEISGPRPRRPTWDSS (in isoform 5).
FT                                /FTId=VSP_007670.
FT   VAR_SEQ      80    124       Missing (in isoform 4).
FT                                /FTId=VSP_007671.
FT   VAR_SEQ     103    124       Missing (in isoform 5).
FT                                /FTId=VSP_007672.
FT   CONFLICT     71     72       SL -> LLC (in Ref. 1; CAA44869 and 2;
FT                                AAL37485).
FT   CONFLICT    101    101       S -> T (in Ref. 1; CAA44869).
SQ   SEQUENCE   124 AA;  12993 MW;  9536B00B385259AD CRC64;
     MPACRLGPLA AALLLSLLLF GFTLVSGTGA EKTGVCPELQ ADQNCTQECV SDSECADNLK
     CCSAGCATFC SLPNDKEGSC PQVNINFPQL GLCRDQCQVD SQCPGQMKCC RNGCGKVSCV
     TPNF
//