ID   WFDC2_HUMAN    STANDARD;      PRT;   124 AA.
AC   Q14508; Q8WXV9; Q8WXW0; Q8WXW1; Q8WXW2; Q96KJ1;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2002, sequence version 2.
DT   21-MAR-2006, entry version 58.
DE   WAP four-disulfide core domain protein 2 precursor (Major epididymis-
DE   specific protein E4) (Epididymal secretory protein E4) (Putative
DE   protease inhibitor WAP5).
GN   Name=WFDC2; Synonyms=HE4, WAP5;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae;
OC   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 (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 (ISOFORM 1).
RA   Hellstrom I., Raycraft J., Ledbetter M., Ledbetter J.A., Schummer M.,
RA   McIntosh M., Drescher C., Urban N., Hellstrom K.E.;
RT   "The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma.";
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Colon;
RX   MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899;
RA   Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA   Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA   Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA   Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA   Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA   Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA   Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA   Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA   Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA   Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA   Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA   Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA   Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA   Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA   Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA   Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA   Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT   "Generation and initial analysis of more than 15,000 full-length human
RT   and mouse cDNA sequences.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
CC   -!- SUBCELLULAR LOCATION: Secreted protein (Potential).
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 transcripted in
CC       the epididymis.
CC   -!- SIMILARITY: Contains 2 WAP domains.
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DR   EMBL; X63187; CAA44869.1; -; mRNA.
DR   EMBL; A18924; CAA01433.1; -; Unassigned_RNA.
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; AL031663; CAB37641.1; -; Genomic_DNA.
DR   EMBL; BC046106; AAH46106.1; -; mRNA.
DR   PIR; S25454; S25454.
DR   HSSP; Q9N0L8; 1TWP.
DR   Ensembl; ENSG00000101443; Homo sapiens.
DR   HGNC; HGNC:15939; WFDC2.
DR   GO; GO:0005615; C:extracellular space; TAS.
DR   GO; GO:0004866; F:endopeptidase inhibitor activity; TAS.
DR   GO; GO:0006508; P:proteolysis; TAS.
DR   GO; GO:0007283; P:spermatogenesis; TAS.
DR   InterPro; IPR008197; WAP.
DR   Pfam; PF00095; WAP; 2.
DR   PRINTS; PR00003; 4DISULPHCORE.
DR   SMART; SM00217; WAP; 2.
DR   PROSITE; PS00317; 4_DISULFIDE_CORE; 2.
KW   Alternative splicing; Glycoprotein; Protease inhibitor; Repeat;
KW   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...) (Potential).
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   VARSPLIC      2     23       PACRLGPLAAALLLSLLLFGFT -> LQVQVNLPVSPLPTY
FT                                PYSFFYP (in isoform 2).
FT                                /FTId=VSP_007666.
FT   VARSPLIC     24     74       Missing (in isoform 2).
FT                                /FTId=VSP_007667.
FT   VARSPLIC     27     74       Missing (in isoform 3).
FT                                /FTId=VSP_007668.
FT   VARSPLIC     71     79       SLPNDKEGS -> LLCPNGQLAE (in isoform 4).
FT                                /FTId=VSP_007669.
FT   VARSPLIC     75    102       DKEGSCPQVNINFPQLGLCRDQCQVDSQ -> ALFHWHLKT
FT                                RRLWEISGPRPRRPTWDSS (in isoform 5).
FT                                /FTId=VSP_007670.
FT   VARSPLIC     80    124       Missing (in isoform 4).
FT                                /FTId=VSP_007671.
FT   VARSPLIC    103    124       Missing (in isoform 5).
FT                                /FTId=VSP_007672.
FT   CONFLICT     71     72       SL -> LLC (in Ref. 1 and 2; AAL37485).
FT   CONFLICT    101    101       S -> T (in Ref. 1).
SQ   SEQUENCE   124 AA;  12993 MW;  9536B00B385259AD CRC64;
     MPACRLGPLA AALLLSLLLF GFTLVSGTGA EKTGVCPELQ ADQNCTQECV SDSECADNLK
     CCSAGCATFC SLPNDKEGSC PQVNINFPQL GLCRDQCQVD SQCPGQMKCC RNGCGKVSCV
     TPNF
//