ID EPPI_HUMAN Reviewed; 133 AA. AC O95925; A6PVD6; Q86TP9; Q96SD7; Q9HD30; DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 13-FEB-2019, entry version 160. DE RecName: Full=Eppin; DE AltName: Full=Cancer/testis antigen 71; DE Short=CT71; DE AltName: Full=Epididymal protease inhibitor; DE AltName: Full=Protease inhibitor WAP7; DE AltName: Full=Serine protease inhibitor-like with Kunitz and WAP domains 1; DE AltName: Full=WAP four-disulfide core domain protein 7; DE Flags: Precursor; GN Name=EPPIN; Synonyms=SPINLW1, WAP7, WFDC7; 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] (ISOFORMS 1 AND 2), SUBUNIT, AND TISSUE RP SPECIFICITY. RC TISSUE=Epididymis, and Testis; RX PubMed=11404006; DOI=10.1016/S0378-1119(01)00462-0; RA Richardson R.T., Sivashanmugam P., Hall S.H., Hamil K.G., Moore P.A., RA Ruben S.M., French F.S., O'Rand M.G.; RT "Cloning and sequencing of human eppin: a novel family of protease RT inhibitors expressed in the epididymis and testis."; RL Gene 270:93-102(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Stavrides G.S., Huckle E.J., Deloukas P.; RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX 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=Brain; 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 [6] RP FUNCTION. RX PubMed=15229136; DOI=10.1095/biolreprod.104.031567; RA Yenugu S., Richardson R.T., Sivashanmugam P., Wang Z., O'rand M.G., RA French F.S., Hall S.H.; RT "Antimicrobial activity of human EPPIN, an androgen-regulated, sperm- RT bound protein with a whey acidic protein motif."; RL Biol. Reprod. 71:1484-1490(2004). RN [7] RP INTERACTION WITH SEMG1, SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=15590901; DOI=10.1095/biolreprod.104.036483; RA Wang Z., Widgren E.E., Sivashanmugam P., O'Rand M.G., Richardson R.T.; RT "Association of eppin with semenogelin on human spermatozoa."; RL Biol. Reprod. 72:1064-1070(2005). RN [8] RP IDENTIFICATION IN A COMPLEX WITH LTF AND CLU, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RX PubMed=17567961; DOI=10.1095/biolreprod.107.060194; RA Wang Z., Widgren E.E., Richardson R.T., O'Rand M.G.; RT "Characterization of an eppin protein complex from human semen and RT spermatozoa."; RL Biol. Reprod. 77:476-484(2007). RN [9] RP FUNCTION ON KLK3 ACTIVITY, AND MUTAGENESIS OF LEU-87. RX PubMed=17644992; RA Wang Z., Widgren E.E., Richardson R.T., Orand M.G.; RT "Eppin: a molecular strategy for male contraception."; RL Soc. Reprod. Fertil. Suppl. 65:535-542(2007). RN [10] RP DOMAIN. RX PubMed=18331357; DOI=10.1111/j.1742-4658.2008.06333.x; RA McCrudden M.T., Dafforn T.R., Houston D.F., Turkington P.T., RA Timson D.J.; RT "Functional domains of the human epididymal protease inhibitor, RT eppin."; RL FEBS J. 275:1742-1750(2008). RN [11] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=21461566; DOI=10.3892/mmr.2010.403; RA Long Y., Gu A., Yang H., Ji G., Han X., Song L., Wang S., Wang X.; RT "Distribution of Eppin in mouse and human testis."; RL Mol. Med. Report. 4:71-75(2011). RN [12] RP INTERACTION WITH LTF AND SEMG1, MUTAGENESIS OF CYS-102; TYR-107; RP CYS-110; PHE-117; CYS-123 AND CYS-127, AND PUTATIVE CONTRACEPTIVE RP TARGET. RX PubMed=22699487; DOI=10.1095/biolreprod.112.101832; RA Silva E.J., Hamil K.G., Richardson R.T., O'Rand M.G.; RT "Characterization of EPPIN's semenogelin I binding Site: a RT contraceptive drug target."; RL Biol. Reprod. 87:56-56(2012). CC -!- FUNCTION: Serine protease inhibitor that plays an essential role CC in male reproduction and fertility. Modulates the hydrolysis of CC SEMG1 by KLK3/PSA (a serine protease), provides antimicrobial CC protection for spermatozoa in the ejaculate coagulum, and binds CC SEMG1 thereby inhibiting sperm motility. CC {ECO:0000269|PubMed:15229136, ECO:0000269|PubMed:17644992}. CC -!- SUBUNIT: Monomer. Homodimer. Homomultimers. Interacts with SEMG1 CC (via 164-283 AA). Interacts with LTF. Found in a complex with LTF, CC CLU, EPPIN and SEMG1. {ECO:0000269|PubMed:11404006, CC ECO:0000269|PubMed:15590901, ECO:0000269|PubMed:17567961, CC ECO:0000269|PubMed:22699487}. CC -!- SUBCELLULAR LOCATION: Isoform 1: Secreted. Cell surface. CC Note=Bound to the surface of testicular and on the head and tail CC of ejaculate spermatozoa. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O95925-1; Sequence=Displayed; CC Name=2; Synonyms=Eppin-2; CC IsoId=O95925-2; Sequence=VSP_006755; CC Note=Lacks a cleavable signal sequence.; CC Name=3; CC IsoId=O95925-3; Sequence=VSP_043679; CC Note=Based on a readthrough transcript which may produce a CC EPPIN-WFDC6 fusion protein. No experimental confirmation CC available.; CC -!- TISSUE SPECIFICITY: In testis, expressed and secreted by Sertoli CC cells, appearing on the surface of testicular and ejaculate CC spermatozoa. Expressed in the spermatogonia and the earliest CC preleptotene spermatocytes. In the epididymis, is expressed and CC secreted by epithelial cells and covers the surface of epididymal CC spermatozoa and ciliated epithelial cells (at protein level). CC Expressed specifically in epididymis and testis. Isoform 2 is CC expressed only in the epididymis. Weak expression is detected in CC myoid cells as well as spermatogenic cells. CC {ECO:0000269|PubMed:11404006, ECO:0000269|PubMed:21461566}. CC -!- DOMAIN: The BPTI/Kunitz inhibitor domain is required for elastase CC inhibitory activity. BPTI/Kunitz inhibitor and WAP domains are CC involved in the protein antibacterial activity. CC {ECO:0000269|PubMed:18331357}. CC -!- MISCELLANEOUS: Might be used as a target for male contraception. CC {ECO:0000305|PubMed:22699487}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF286368; AAG00546.1; -; mRNA. DR EMBL; AF286369; AAG00547.1; -; mRNA. DR EMBL; AF286370; AAG00548.1; -; mRNA. DR EMBL; AL118493; CAB56343.1; -; mRNA. DR EMBL; AK301937; BAG63357.1; -; mRNA. DR EMBL; AL031663; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC044829; AAH44829.2; -; mRNA. DR EMBL; BC053369; AAH53369.1; -; mRNA. DR CCDS; CCDS13359.1; -. [O95925-1] DR RefSeq; NP_001185915.1; NM_001198986.1. [O95925-3] DR RefSeq; NP_001289790.1; NM_001302861.1. DR RefSeq; NP_065131.1; NM_020398.3. [O95925-1] DR UniGene; Hs.121084; -. DR UniGene; Hs.274876; -. DR ProteinModelPortal; O95925; -. DR SMR; O95925; -. DR BioGrid; 121383; 4. DR IntAct; O95925; 1. DR STRING; 9606.ENSP00000452085; -. DR MEROPS; I02.058; -. DR BioMuta; EPPIN; -. DR PaxDb; O95925; -. DR PeptideAtlas; O95925; -. DR PRIDE; O95925; -. DR ProteomicsDB; 51127; -. DR ProteomicsDB; 51128; -. [O95925-2] DR ProteomicsDB; 51129; -. [O95925-3] DR DNASU; 57119; -. DR Ensembl; ENST00000336443; ENSP00000338114; ENSG00000101448. [O95925-2] DR Ensembl; ENST00000354280; ENSP00000361746; ENSG00000101448. [O95925-1] DR Ensembl; ENST00000504988; ENSP00000424176; ENSG00000249139. [O95925-3] DR GeneID; 100526773; -. DR GeneID; 57119; -. DR KEGG; hsa:100526773; -. DR KEGG; hsa:57119; -. DR UCSC; uc002xou.4; human. [O95925-1] DR CTD; 100526773; -. DR CTD; 57119; -. DR DisGeNET; 57119; -. DR EuPathDB; HostDB:ENSG00000101448.13; -. DR EuPathDB; HostDB:ENSG00000249139.1; -. DR GeneCards; EPPIN; -. DR GeneCards; EPPIN-WFDC6; -. DR HGNC; HGNC:15932; EPPIN. DR HGNC; HGNC:38825; EPPIN-WFDC6. DR MIM; 609031; gene. DR neXtProt; NX_O95925; -. DR OpenTargets; ENSG00000101448; -. DR OpenTargets; ENSG00000249139; -. DR PharmGKB; PA38054; -. DR eggNOG; KOG4295; Eukaryota. DR eggNOG; ENOG410XQNP; LUCA. DR GeneTree; ENSGT00940000156753; -. DR HOGENOM; HOG000115819; -. DR HOVERGEN; HBG004024; -. DR InParanoid; O95925; -. DR OMA; CCVFNCG; -. DR OrthoDB; 1474897at2759; -. DR PhylomeDB; O95925; -. DR TreeFam; TF342459; -. DR Reactome; R-HSA-6803157; Antimicrobial peptides. DR GeneWiki; SPINLW1; -. DR PRO; PR:O95925; -. DR Proteomes; UP000005640; Chromosome 20. DR Bgee; ENSG00000101448; Expressed in 67 organ(s), highest expression level in corpus epididymis. DR ExpressionAtlas; O95925; baseline and differential. DR Genevisible; O95925; HS. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0097524; C:sperm plasma membrane; TAS:Reactome. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0019730; P:antimicrobial humoral response; TAS:Reactome. DR GO; GO:0042742; P:defense response to bacterium; IDA:UniProtKB. DR GO; GO:0090281; P:negative regulation of calcium ion import; IMP:UniProtKB. DR GO; GO:1901318; P:negative regulation of flagellated sperm motility; IMP:UniProtKB. DR GO; GO:0010466; P:negative regulation of peptidase activity; IDA:UniProtKB. DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB. DR CDD; cd00109; KU; 1. DR Gene3D; 4.10.410.10; -; 1. DR Gene3D; 4.10.75.10; -; 1. DR InterPro; IPR036645; Elafin-like_sf. DR InterPro; IPR002223; Kunitz_BPTI. DR InterPro; IPR036880; Kunitz_BPTI_sf. DR InterPro; IPR020901; Prtase_inh_Kunz-CS. DR InterPro; IPR008197; WAP_dom. DR Pfam; PF00014; Kunitz_BPTI; 1. DR Pfam; PF00095; WAP; 1. DR PRINTS; PR00759; BASICPTASE. DR SMART; SM00131; KU; 1. DR SMART; SM00217; WAP; 1. DR SUPFAM; SSF57256; SSF57256; 1. DR SUPFAM; SSF57362; SSF57362; 1. DR PROSITE; PS00280; BPTI_KUNITZ_1; 1. DR PROSITE; PS50279; BPTI_KUNITZ_2; 1. DR PROSITE; PS51390; WAP; 1. PE 1: Evidence at protein level; KW Alternative splicing; Antimicrobial; Complete proteome; KW Disulfide bond; Polymorphism; Protease inhibitor; Reference proteome; KW Secreted; Serine protease inhibitor; Signal. FT SIGNAL 1 21 {ECO:0000255}. FT CHAIN 22 133 Eppin. FT /FTId=PRO_0000041378. FT DOMAIN 26 73 WAP. {ECO:0000255|PROSITE- FT ProRule:PRU00722}. FT DOMAIN 77 127 BPTI/Kunitz inhibitor. FT {ECO:0000255|PROSITE-ProRule:PRU00031}. FT REGION 102 133 Interaction with SEMG1. FT REGION 117 133 Interaction with LTF. FT {ECO:0000269|PubMed:22699487}. FT DISULFID 33 61 {ECO:0000250}. FT DISULFID 40 65 {ECO:0000250}. FT DISULFID 48 60 {ECO:0000250}. FT DISULFID 54 69 {ECO:0000250}. FT DISULFID 77 127 {ECO:0000250}. FT DISULFID 86 110 {ECO:0000250}. FT DISULFID 102 123 {ECO:0000250}. FT VAR_SEQ 1 31 MGSSGLLSLLVLFVLLANVQGPGLTDWLFPR -> MLSKAH FT GCKTALSLG (in isoform 2). FT {ECO:0000303|PubMed:11404006}. FT /FTId=VSP_006755. FT VAR_SEQ 131 133 RFP -> QPCPKIKVECEVEEIDQCTKPRDCPENMKCCPFS FT RGKKCLDFRKASLST (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_043679. FT VARIANT 92 92 H -> R (in dbSNP:rs2231838). FT /FTId=VAR_024696. FT VARIANT 128 128 K -> T (in dbSNP:rs2231839). FT /FTId=VAR_052950. FT MUTAGEN 87 87 L->G: Loss of effect on KLK3 activity. FT {ECO:0000269|PubMed:17644992}. FT MUTAGEN 102 102 C->A: Reduces the binding to SEMG1 by FT 45%. {ECO:0000269|PubMed:22699487}. FT MUTAGEN 107 107 Y->A: Reduces the binding to SEMG1 by FT 68%. {ECO:0000269|PubMed:22699487}. FT MUTAGEN 110 110 C->A: Does not affect the binding of FT SEMG1 or LTF. Does not affect the binding FT of SEMG1; when associated with A-123 and FT A-127. {ECO:0000269|PubMed:22699487}. FT MUTAGEN 117 117 F->A: Reduces the binding to SEMG1 by 68% FT and to LTF by 73%. FT {ECO:0000269|PubMed:22699487}. FT MUTAGEN 123 123 C->A: Does not affect the binding of FT SEMG1 or LTF. Does not affect the binding FT of SEMG1; when associated with A-110 and FT A-127. {ECO:0000269|PubMed:22699487}. FT MUTAGEN 127 127 C->A: Does not affect the binding of FT SEMG1 or LTF. Does not affect the binding FT of SEMG1; when associated with A-110 and FT A-123. {ECO:0000269|PubMed:22699487}. SQ SEQUENCE 133 AA; 15284 MW; F7831B203366D9DC CRC64; MGSSGLLSLL VLFVLLANVQ GPGLTDWLFP RRCPKIREEC EFQERDVCTK DRQCQDNKKC CVFSCGKKCL DLKQDVCEMP KETGPCLAYF LHWWYDKKDN TCSMFVYGGC QGNNNNFQSK ANCLNTCKNK RFP //