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WAP four-disulfide core domain protein 2 (Epididymal secretory protein E4) (Major epididymis-specific protein E4) (Putative protease inhibitor WAP5)

 WFDC2_HUMAN             Reviewed;         124 AA.
Q14508; A2A2A5; A2A2A6; A6PVD5; Q6IB27; Q8WXV9; Q8WXW0; Q8WXW1;
Q8WXW2; Q96KJ1;
15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
23-JAN-2002, sequence version 2.
25-APR-2018, entry version 163.
RecName: Full=WAP four-disulfide core domain protein 2;
AltName: Full=Epididymal secretory protein E4;
AltName: Full=Major epididymis-specific protein E4;
AltName: Full=Putative protease inhibitor WAP5;
Flags: Precursor;
Name=WFDC2; Synonyms=HE4, WAP5;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Epididymis;
PubMed=1686187; DOI=10.1095/biolreprod45.2.350;
Kirchhoff C., Habben L., Ivell R., Krull N.;
"A major human epididymis-specific cDNA encodes a protein with
sequence homology to extracellular proteinase inhibitors.";
Biol. Reprod. 45:350-357(1991).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5).
PubMed=11965550; DOI=10.1038/sj.onc.1205363;
Bingle L., Singleton V., Bingle C.D.;
"The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in
normal tissues and undergoes complex alternative splicing to yield
multiple protein isoforms.";
Oncogene 21:2768-2773(2002).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=12839961;
Hellstrom I., Raycraft J., Hayden-Ledbetter M., Ledbetter J.A.,
Schummer M., McIntosh M., Drescher C., Urban N., Hellstrom K.E.;
"The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma.";
Cancer Res. 63:3695-3700(2003).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
"Cloning of human full open reading frames in Gateway(TM) system entry
vector (pDONR201).";
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=11780052; DOI=10.1038/414865a;
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.;
"The DNA sequence and comparative analysis of human chromosome 20.";
Nature 414:865-871(2001).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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., 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.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Colon;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
PubMed=15781627; DOI=10.1158/0008-5472.CAN-04-3924;
Drapkin R., von Horsten H.H., Lin Y., Mok S.C., Crum C.P., Welch W.R.,
Hecht J.L.;
"Human epididymis protein 4 (HE4) is a secreted glycoprotein that is
overexpressed by serous and endometrioid ovarian carcinomas.";
Cancer Res. 65:2162-2169(2005).
[9]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-44.
TISSUE=Saliva;
PubMed=16740002; DOI=10.1021/pr050492k;
Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T.,
Loo J.A.;
"Identification of N-linked glycoproteins in human saliva by
glycoprotein capture and mass spectrometry.";
J. Proteome Res. 5:1493-1503(2006).
[10]
FUNCTION, SUBUNIT, GLYCOSYLATION AT ASN-44, AND SUBCELLULAR LOCATION.
TISSUE=Seminal plasma;
PubMed=23139753; DOI=10.1371/journal.pone.0047672;
Chhikara N., Saraswat M., Tomar A.K., Dey S., Singh S., Yadav S.;
"Human epididymis protein-4 (HE-4): a novel cross-class protease
inhibitor.";
PLoS ONE 7:E47672-E47672(2012).
-!- FUNCTION: Broad range protease inhibitor.
{ECO:0000269|PubMed:23139753}.
-!- SUBUNIT: Homotrimer; disulfide-linked.
{ECO:0000269|PubMed:23139753}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15781627,
ECO:0000269|PubMed:23139753}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=5;
Comment=Additional isoforms seem to exist.;
Name=1;
IsoId=Q14508-1; Sequence=Displayed;
Name=2; Synonyms=HE4-V3;
IsoId=Q14508-2; Sequence=VSP_007666, VSP_007667;
Name=3; Synonyms=HE4-V2;
IsoId=Q14508-3; Sequence=VSP_007668;
Name=4; Synonyms=HE4-V1;
IsoId=Q14508-4; Sequence=VSP_007669, VSP_007671;
Name=5; Synonyms=HE4-V4;
IsoId=Q14508-5; Sequence=VSP_007670, VSP_007672;
-!- 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. {ECO:0000269|PubMed:15781627}.
-----------------------------------------------------------------------
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EMBL; X63187; CAA44869.1; -; mRNA.
EMBL; AF330259; AAL37485.1; -; mRNA.
EMBL; AF330260; AAL37486.1; -; mRNA.
EMBL; AF330261; AAL37487.1; -; mRNA.
EMBL; AF330262; AAL37488.1; -; mRNA.
EMBL; AY212888; AAO52683.1; -; mRNA.
EMBL; CR456977; CAG33258.1; -; mRNA.
EMBL; AL031663; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471077; EAW75836.1; -; Genomic_DNA.
EMBL; CH471077; EAW75837.1; -; Genomic_DNA.
EMBL; CH471077; EAW75839.1; -; Genomic_DNA.
EMBL; BC046106; AAH46106.1; -; mRNA.
CCDS; CCDS35501.1; -. [Q14508-1]
PIR; S25454; S25454.
RefSeq; NP_006094.3; NM_006103.3. [Q14508-1]
UniGene; Hs.2719; -.
ProteinModelPortal; Q14508; -.
SMR; Q14508; -.
BioGrid; 115677; 14.
IntAct; Q14508; 2.
STRING; 9606.ENSP00000361761; -.
MEROPS; I17.004; -.
iPTMnet; Q14508; -.
BioMuta; WFDC2; -.
DMDM; 20141958; -.
MaxQB; Q14508; -.
PaxDb; Q14508; -.
PeptideAtlas; Q14508; -.
PRIDE; Q14508; -.
DNASU; 10406; -.
Ensembl; ENST00000217425; ENSP00000217425; ENSG00000101443. [Q14508-5]
Ensembl; ENST00000339946; ENSP00000340215; ENSG00000101443. [Q14508-3]
Ensembl; ENST00000342873; ENSP00000342890; ENSG00000101443. [Q14508-2]
Ensembl; ENST00000372676; ENSP00000361761; ENSG00000101443. [Q14508-1]
GeneID; 10406; -.
KEGG; hsa:10406; -.
UCSC; uc002xoo.4; human. [Q14508-1]
CTD; 10406; -.
DisGeNET; 10406; -.
EuPathDB; HostDB:ENSG00000101443.17; -.
GeneCards; WFDC2; -.
HGNC; HGNC:15939; WFDC2.
HPA; HPA042302; -.
MIM; 617548; gene.
neXtProt; NX_Q14508; -.
OpenTargets; ENSG00000101443; -.
PharmGKB; PA38059; -.
eggNOG; ENOG410J36N; Eukaryota.
eggNOG; ENOG41125F3; LUCA.
GeneTree; ENSGT00730000111410; -.
HOVERGEN; HBG018073; -.
InParanoid; Q14508; -.
OMA; DLNCTQE; -.
OrthoDB; EOG091G0UW4; -.
PhylomeDB; Q14508; -.
ChiTaRS; WFDC2; human.
GeneWiki; WFDC2; -.
GenomeRNAi; 10406; -.
PRO; PR:Q14508; -.
Proteomes; UP000005640; Chromosome 20.
Bgee; ENSG00000101443; -.
CleanEx; HS_WFDC2; -.
ExpressionAtlas; Q14508; baseline and differential.
Genevisible; Q14508; HS.
GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
GO; GO:0005615; C:extracellular space; TAS:ProtInc.
GO; GO:0019828; F:aspartic-type endopeptidase inhibitor activity; IDA:CACAO.
GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc.
GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:CACAO.
GO; GO:0006508; P:proteolysis; TAS:ProtInc.
GO; GO:0007283; P:spermatogenesis; TAS:ProtInc.
Gene3D; 4.10.75.10; -; 2.
InterPro; IPR036645; Elafin-like_sf.
InterPro; IPR008197; WAP_dom.
Pfam; PF00095; WAP; 2.
PRINTS; PR00003; 4DISULPHCORE.
SMART; SM00217; WAP; 2.
SUPFAM; SSF57256; SSF57256; 2.
PROSITE; PS51390; WAP; 2.
1: Evidence at protein level;
Alternative splicing; Aspartic protease inhibitor; Complete proteome;
Disulfide bond; Glycoprotein; Protease inhibitor; Reference proteome;
Repeat; Secreted; Serine protease inhibitor; Signal;
Thiol protease inhibitor.
SIGNAL 1 30 {ECO:0000255}.
CHAIN 31 124 WAP four-disulfide core domain protein 2.
/FTId=PRO_0000041370.
DOMAIN 31 73 WAP 1. {ECO:0000255|PROSITE-
ProRule:PRU00722}.
DOMAIN 74 123 WAP 2. {ECO:0000255|PROSITE-
ProRule:PRU00722}.
CARBOHYD 44 44 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16740002,
ECO:0000269|PubMed:23139753}.
DISULFID 36 62 {ECO:0000255|PROSITE-ProRule:PRU00722}.
DISULFID 45 66 {ECO:0000255|PROSITE-ProRule:PRU00722}.
DISULFID 49 61 {ECO:0000255|PROSITE-ProRule:PRU00722}.
DISULFID 55 70 {ECO:0000255|PROSITE-ProRule:PRU00722}.
DISULFID 80 110 {ECO:0000255|PROSITE-ProRule:PRU00722}.
DISULFID 93 114 {ECO:0000255|PROSITE-ProRule:PRU00722}.
DISULFID 97 109 {ECO:0000255|PROSITE-ProRule:PRU00722}.
DISULFID 103 119 {ECO:0000255|PROSITE-ProRule:PRU00722}.
VAR_SEQ 2 23 PACRLGPLAAALLLSLLLFGFT -> LQVQVNLPVSPLPTY
PYSFFYP (in isoform 2).
{ECO:0000303|PubMed:11965550}.
/FTId=VSP_007666.
VAR_SEQ 24 74 Missing (in isoform 2).
{ECO:0000303|PubMed:11965550}.
/FTId=VSP_007667.
VAR_SEQ 27 74 Missing (in isoform 3).
{ECO:0000303|PubMed:11965550}.
/FTId=VSP_007668.
VAR_SEQ 71 79 SLPNDKEGS -> LLCPNGQLAE (in isoform 4).
{ECO:0000303|PubMed:11965550}.
/FTId=VSP_007669.
VAR_SEQ 75 102 DKEGSCPQVNINFPQLGLCRDQCQVDSQ -> ALFHWHLKT
RRLWEISGPRPRRPTWDSS (in isoform 5).
{ECO:0000303|PubMed:11965550}.
/FTId=VSP_007670.
VAR_SEQ 80 124 Missing (in isoform 4).
{ECO:0000303|PubMed:11965550}.
/FTId=VSP_007671.
VAR_SEQ 103 124 Missing (in isoform 5).
{ECO:0000303|PubMed:11965550}.
/FTId=VSP_007672.
CONFLICT 71 72 SL -> LLC (in Ref. 1; CAA44869 and 2;
AAL37485). {ECO:0000305}.
CONFLICT 101 101 S -> T (in Ref. 1; CAA44869).
{ECO:0000305}.
SEQUENCE 124 AA; 12993 MW; 9536B00B385259AD CRC64;
MPACRLGPLA AALLLSLLLF GFTLVSGTGA EKTGVCPELQ ADQNCTQECV SDSECADNLK
CCSAGCATFC SLPNDKEGSC PQVNINFPQL GLCRDQCQVD SQCPGQMKCC RNGCGKVSCV
TPNF


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