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O95925 (EPPI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Eppin
Alternative name(s):
Cancer/testis antigen 71
Short name=CT71
Epididymal protease inhibitor
Protease inhibitor WAP7
Serine protease inhibitor-like with Kunitz and WAP domains 1
WAP four-disulfide core domain protein 7
Gene names
Name:EPPIN
Synonyms:SPINLW1, WAP7, WFDC7
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length133 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine protease inhibitor that plays an essential role in male reproduction and fertility. Modulates the hydrolysis of SEMG1 by KLK3/PSA (a serine protease), provides antimicrobial protection for spermatozoa in the ejaculate coagulum, and binds SEMG1 thereby inhibiting sperm motility. Ref.6 Ref.9

Subunit structure

Monomer. Homodimer. Homomultimers. Interacts with SEMG1 (via 164-283 AA). Interacts with LTF. Found in a complex with LTF, CLU, EPPIN and SEMG1. Ref.1 Ref.7 Ref.8 Ref.12

Subcellular location

Isoform 1: Secreted. Cell surface. Note: Bound to the surface of testicular and on the head and tail of ejaculate spermatozoa. Ref.7 Ref.11

Tissue specificity

In testis, expressed and secreted by Sertoli cells, appearing on the surface of testicular and ejaculate spermatozoa. Expressed in the spermatogonia and the earliest preleptotene spermatocytes. In the epididymis, is expressed and secreted by epithelial cells and covers the surface of epididymal spermatozoa and ciliated epithelial cells (at protein level). Expressed specifically in epididymis and testis. Isoform 2 is expressed only in the epididymis. Weak expression is detected in myoid cells as well as spermatogenic cells. Ref.1 Ref.11

Domain

The BPTI/Kunitz inhibitor domain is required for elastase inhibitory activity. BPTI/Kunitz inhibitor and WAP domains are involved in the protein antibacterial activity. Ref.10

Miscellaneous

Might be used as a target for male contraception (Ref.12).

Sequence similarities

Contains 1 BPTI/Kunitz inhibitor domain.

Contains 1 WAP domain.

Ontologies

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95925-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O95925-2)

Also known as: Eppin-2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-31: MGSSGLLSLLVLFVLLANVQGPGLTDWLFPR → MLSKAHGCKTALSLG
Note: Lacks a cleavable signal sequence.
Isoform 3 (identifier: O95925-3)

The sequence of this isoform differs from the canonical sequence as follows:
     131-133: RFP → QPCPKIKVECEVEEIDQCTKPRDCPENMKCCPFSRGKKCLDFRKASLST
Note: Based on a readthrough transcript which may produce a EPPIN-WFDC6 fusion protein. No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 133112Eppin
PRO_0000041378

Regions

Domain26 – 7348WAP
Domain77 – 12751BPTI/Kunitz inhibitor
Region102 – 13332Interaction with SEMG1
Region117 – 13317Interaction with LTF

Amino acid modifications

Disulfide bond33 ↔ 61 By similarity
Disulfide bond40 ↔ 65 By similarity
Disulfide bond48 ↔ 60 By similarity
Disulfide bond54 ↔ 69 By similarity
Disulfide bond77 ↔ 127 By similarity
Disulfide bond86 ↔ 110 By similarity
Disulfide bond102 ↔ 123 By similarity

Natural variations

Alternative sequence1 – 3131MGSSG…WLFPR → MLSKAHGCKTALSLG in isoform 2.
VSP_006755
Alternative sequence131 – 1333RFP → QPCPKIKVECEVEEIDQCTK PRDCPENMKCCPFSRGKKCL DFRKASLST in isoform 3.
VSP_043679
Natural variant921H → R.
Corresponds to variant rs2231838 [ dbSNP | Ensembl ].
VAR_024696
Natural variant1281K → T.
Corresponds to variant rs2231839 [ dbSNP | Ensembl ].
VAR_052950

Experimental info

Mutagenesis871L → G: Loss of effect on KLK3 activity. Ref.9
Mutagenesis1021C → A: Reduces the binding to SEMG1 by 45%. Ref.12
Mutagenesis1071Y → A: Reduces the binding to SEMG1 by 68%. Ref.12
Mutagenesis1101C → A: Does not affect the binding of SEMG1 or LTF. Does not affect the binding of SEMG1; when associated with A-123 and A-127. Ref.12
Mutagenesis1171F → A: Reduces the binding to SEMG1 by 68% and to LTF by 73%. Ref.12
Mutagenesis1231C → A: Does not affect the binding of SEMG1 or LTF. Does not affect the binding of SEMG1; when associated with A-110 and A-127. Ref.12
Mutagenesis1271C → A: Does not affect the binding of SEMG1 or LTF. Does not affect the binding of SEMG1; when associated with A-110 and A-123. Ref.12

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: F7831B203366D9DC

FASTA13315,284
        10         20         30         40         50         60 
MGSSGLLSLL VLFVLLANVQ GPGLTDWLFP RRCPKIREEC EFQERDVCTK DRQCQDNKKC 

        70         80         90        100        110        120 
CVFSCGKKCL DLKQDVCEMP KETGPCLAYF LHWWYDKKDN TCSMFVYGGC QGNNNNFQSK 

       130 
ANCLNTCKNK RFP 

« Hide

Isoform 2 (Eppin-2) [UniParc].

Checksum: 96161FAB3CFEDB47
Show »

FASTA11713,486
Isoform 3 [UniParc].

Checksum: AD2399D2093D0197
Show »

FASTA17920,486

References

« Hide 'large scale' references
[1]"Cloning and sequencing of human eppin: a novel family of protease inhibitors expressed in the epididymis and testis."
Richardson R.T., Sivashanmugam P., Hall S.H., Hamil K.G., Moore P.A., Ruben S.M., French F.S., O'Rand M.G.
Gene 270:93-102(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBUNIT, TISSUE SPECIFICITY.
Tissue: Epididymis and Testis.
[2]Stavrides G.S., Huckle E.J., Deloukas P.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Testis.
[4]"The DNA sequence and comparative analysis of human chromosome 20."
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. expand/collapse author list , 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.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[6]"Antimicrobial activity of human EPPIN, an androgen-regulated, sperm-bound protein with a whey acidic protein motif."
Yenugu S., Richardson R.T., Sivashanmugam P., Wang Z., O'rand M.G., French F.S., Hall S.H.
Biol. Reprod. 71:1484-1490(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Association of eppin with semenogelin on human spermatozoa."
Wang Z., Widgren E.E., Sivashanmugam P., O'Rand M.G., Richardson R.T.
Biol. Reprod. 72:1064-1070(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SEMG1, SUBCELLULAR LOCATION, SUBUNIT.
[8]"Characterization of an eppin protein complex from human semen and spermatozoa."
Wang Z., Widgren E.E., Richardson R.T., O'Rand M.G.
Biol. Reprod. 77:476-484(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH LTF AND CLU, IDENTIFICATION BY MASS SPECTROMETRY.
[9]"Eppin: a molecular strategy for male contraception."
Wang Z., Widgren E.E., Richardson R.T., Orand M.G.
Soc. Reprod. Fertil. Suppl. 65:535-542(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION ON KLK3 ACTIVITY, MUTAGENESIS OF LEU-87.
[10]"Functional domains of the human epididymal protease inhibitor, eppin."
McCrudden M.T., Dafforn T.R., Houston D.F., Turkington P.T., Timson D.J.
FEBS J. 275:1742-1750(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN.
[11]"Distribution of Eppin in mouse and human testis."
Long Y., Gu A., Yang H., Ji G., Han X., Song L., Wang S., Wang X.
Mol. Med. Report. 4:71-75(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[12]"Characterization of EPPIN's semenogelin I binding Site: a contraceptive drug target."
Silva E.J., Hamil K.G., Richardson R.T., O'Rand M.G.
Biol. Reprod. 87:56-56(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LTF AND SEMG1, MUTAGENESIS OF CYS-102; TYR-107; CYS-110; PHE-117; CYS-123 AND CYS-127, PUTATIVE CONTRACEPTIVE TARGET.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF286368 mRNA. Translation: AAG00546.1.
AF286369 mRNA. Translation: AAG00547.1.
AF286370 mRNA. Translation: AAG00548.1.
AL118493 mRNA. Translation: CAB56343.1.
AK301937 mRNA. Translation: BAG63357.1.
AL031663 Genomic DNA. Translation: CAB37635.1.
AL031663 Genomic DNA. Translation: CAO03536.1.
AL031663 Genomic DNA. Translation: CAC36265.1.
BC044829 mRNA. Translation: AAH44829.2.
BC053369 mRNA. Translation: AAH53369.1.
CCDSCCDS13359.1. [O95925-1]
RefSeqNP_001185915.1. NM_001198986.1. [O95925-3]
NP_065131.1. NM_020398.3. [O95925-1]
UniGeneHs.121084.
Hs.274876.

3D structure databases

ProteinModelPortalO95925.
SMRO95925. Positions 35-133.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO95925. 1 interaction.
STRING9606.ENSP00000361746.

Protein family/group databases

MEROPSI02.058.

Proteomic databases

PaxDbO95925.
PRIDEO95925.

Protocols and materials databases

DNASU57119.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000336443; ENSP00000338114; ENSG00000101448. [O95925-2]
ENST00000354280; ENSP00000361746; ENSG00000101448. [O95925-1]
ENST00000504988; ENSP00000424176; ENSG00000249139. [O95925-3]
ENST00000555685; ENSP00000452085; ENSG00000101448. [O95925-3]
GeneID100526773.
57119.
KEGGhsa:100526773.
hsa:57119.
UCSCuc002xou.3. human. [O95925-1]
uc010zxc.2. human. [O95925-3]

Organism-specific databases

CTD100526773.
57119.
GeneCardsGC20M044164.
GC20M044184.
HGNCHGNC:15932. EPPIN.
HGNC:38825. EPPIN-WFDC6.
MIM609031. gene.
neXtProtNX_O95925.
PharmGKBPA38054.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG314382.
HOGENOMHOG000115819.
HOVERGENHBG004024.
OMAFPRRCPK.
OrthoDBEOG754HSR.
PhylomeDBO95925.
TreeFamTF342459.

Gene expression databases

ArrayExpressO95925.
BgeeO95925.
CleanExHS_SPINLW1.
GenevestigatorO95925.

Family and domain databases

Gene3D4.10.410.10. 1 hit.
4.10.75.10. 1 hit.
InterProIPR002223. Prot_inh_Kunz-m.
IPR020901. Prtase_inh_Kunz-CS.
IPR008197. WAP-type_4-diS_core.
[Graphical view]
PfamPF00014. Kunitz_BPTI. 1 hit.
PF00095. WAP. 1 hit.
[Graphical view]
PRINTSPR00759. BASICPTASE.
SMARTSM00131. KU. 1 hit.
SM00217. WAP. 1 hit.
[Graphical view]
SUPFAMSSF57256. SSF57256. 1 hit.
SSF57362. SSF57362. 1 hit.
PROSITEPS00280. BPTI_KUNITZ_1. 1 hit.
PS50279. BPTI_KUNITZ_2. 1 hit.
PS51390. WAP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSPINLW1.
NextBio62993.
PROO95925.
SOURCESearch...

Entry information

Entry nameEPPI_HUMAN
AccessionPrimary (citable) accession number: O95925
Secondary accession number(s): A6PVD6 expand/collapse secondary AC list , Q86TP9, Q96SD7, Q9HD30
Entry history
Integrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: May 1, 1999
Last modified: July 9, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM