ID EPPI_MOUSE Reviewed; 134 AA.
AC Q9DA01; A2A5G9;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 04-MAY-2001, sequence version 1.
DT 24-JAN-2024, entry version 150.
DE RecName: Full=Eppin;
DE AltName: Full=Epididymal protease inhibitor;
DE AltName: Full=Serine protease inhibitor-like with Kunitz and WAP domains 1;
DE Flags: Precursor;
GN Name=Eppin; Synonyms=Spinlw1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC STRAIN=BALB/cJ; TISSUE=Epididymis, and Testis;
RX PubMed=12909348; DOI=10.1016/s0378-1119(03)00608-5;
RA Sivashanmugam P., Hall S.H., Hamil K.G., French F.S., O'Rand M.G.,
RA Richardson R.T.;
RT "Characterization of mouse Eppin and a gene cluster of similar protease
RT inhibitors on mouse chromosome 2.";
RL Gene 312:125-134(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INDUCTION.
RX PubMed=16166195; DOI=10.1210/me.2005-0113;
RA Denolet E., De Gendt K., Allemeersch J., Engelen K., Marchal K.,
RA Van Hummelen P., Tan K.A., Sharpe R.M., Saunders P.T., Swinnen J.V.,
RA Verhoeven G.;
RT "The effect of a sertoli cell-selective knockout of the androgen receptor
RT on testicular gene expression in prepubertal mice.";
RL Mol. Endocrinol. 20:321-334(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
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).
CC -!- FUNCTION: Serine protease inhibitor that plays an essential role in
CC male reproduction and fertility. Modulates the hydrolysis of SEMG1 by
CC KLK3/PSA (a serine protease), provides antimicrobial protection for
CC spermatozoa in the ejaculate coagulum, and binds SEMG1 thereby
CC inhibiting sperm motility (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Homodimer. Homomultimers. Interacts (via C-terminus)
CC with SEMG1 (via 164-283 AA). Interacts with LTF. Found in a complex
CC with LTF, CLU, EPPIN and SEMG1. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted. Cell surface. Note=Present on the
CC surface of spermatozoa both before and after capacitation.
CC -!- TISSUE SPECIFICITY: Expressed in differentiated spermatogonia in
CC testis. Expressed in spermatogonia cell lines GC-1 spg and GC-2spd(ts)
CC as well as in the Leydig tumor cell line MLTC-1 (at protein level).
CC Expressed specifically in epididymis and testis. Expressed
CC predominantly on the postacrosomal region of mouse spermatozoa, in
CC Sertoli cells, Leydig cells, and round spermatids in the testis, and in
CC the principal cells of the cauda epididymidis epithelium.
CC {ECO:0000269|PubMed:12909348, ECO:0000269|PubMed:21461566}.
CC -!- INDUCTION: Androgen dependent. Down-regulated in Sertoli cell-selective
CC androgen receptor knockout mice. {ECO:0000269|PubMed:16166195}.
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DR EMBL; AF346413; AAK31335.1; -; mRNA.
DR EMBL; AK006296; BAB24514.1; -; mRNA.
DR EMBL; AL591478; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466551; EDL06403.1; -; Genomic_DNA.
DR EMBL; BC048637; AAH48637.1; -; mRNA.
DR CCDS; CCDS17043.1; -.
DR RefSeq; NP_083601.1; NM_029325.2.
DR AlphaFoldDB; Q9DA01; -.
DR SMR; Q9DA01; -.
DR STRING; 10090.ENSMUSP00000099389; -.
DR MEROPS; I02.956; -.
DR MEROPS; I17.953; -.
DR PaxDb; 10090-ENSMUSP00000099389; -.
DR ProteomicsDB; 275763; -.
DR DNASU; 75526; -.
DR Ensembl; ENSMUST00000103100.2; ENSMUSP00000099389.2; ENSMUSG00000017733.5.
DR GeneID; 75526; -.
DR KEGG; mmu:75526; -.
DR UCSC; uc008nvh.1; mouse.
DR AGR; MGI:1922776; -.
DR CTD; 57119; -.
DR MGI; MGI:1922776; Eppin.
DR VEuPathDB; HostDB:ENSMUSG00000017733; -.
DR eggNOG; KOG4295; Eukaryota.
DR GeneTree; ENSGT00940000156753; -.
DR HOGENOM; CLU_127181_0_0_1; -.
DR InParanoid; Q9DA01; -.
DR OMA; CCVFNCG; -.
DR OrthoDB; 3558236at2759; -.
DR PhylomeDB; Q9DA01; -.
DR TreeFam; TF342459; -.
DR Reactome; R-MMU-6803157; Antimicrobial peptides.
DR BioGRID-ORCS; 75526; 4 hits in 76 CRISPR screens.
DR PRO; PR:Q9DA01; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9DA01; Protein.
DR Bgee; ENSMUSG00000017733; Expressed in seminiferous tubule of testis and 14 other cell types or tissues.
DR Genevisible; Q9DA01; MM.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0090281; P:negative regulation of calcium ion import; IEA:Ensembl.
DR GO; GO:1901318; P:negative regulation of flagellated sperm motility; IEA:Ensembl.
DR GO; GO:0010466; P:negative regulation of peptidase activity; ISS:UniProtKB.
DR CDD; cd22611; Kunitz_eppin; 1.
DR Gene3D; 4.10.75.10; Elafin-like; 1.
DR Gene3D; 4.10.410.10; Pancreatic trypsin inhibitor Kunitz domain; 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 PANTHER; PTHR46751; EPPIN; 1.
DR PANTHER; PTHR46751:SF2; EPPIN; 1.
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; SSF57362; BPTI-like; 1.
DR SUPFAM; SSF57256; Elafin-like; 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 Antimicrobial; Disulfide bond; Protease inhibitor; Reference proteome;
KW Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..134
FT /note="Eppin"
FT /id="PRO_0000041380"
FT DOMAIN 26..73
FT /note="WAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DOMAIN 77..127
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT REGION 102..133
FT /note="Interaction with SEMG1"
FT /evidence="ECO:0000250"
FT REGION 117..133
FT /note="Interaction with LTF"
FT /evidence="ECO:0000250"
FT DISULFID 33..61
FT /evidence="ECO:0000250"
FT DISULFID 40..65
FT /evidence="ECO:0000250"
FT DISULFID 48..60
FT /evidence="ECO:0000250"
FT DISULFID 54..69
FT /evidence="ECO:0000250"
FT DISULFID 77..127
FT /evidence="ECO:0000250"
FT DISULFID 86..110
FT /evidence="ECO:0000250"
FT DISULFID 102..123
FT /evidence="ECO:0000250"
SQ SEQUENCE 134 AA; 15470 MW; DFFEB63D4D4C427F CRC64;
MKLSGFVSIL VLFGLLARVQ GPSLADLLFP RRCPRFREEC EHQERDLCTR DRDCPKKEKC
CVFNCGKKCL NPQQDICSLP KDSGYCMAYF RRWWFNKENS TCQVFIYGGC QGNNNNFQSQ
SICQNACEKK SSLT
//
