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Protein

Eppin

Gene

EPPIN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

GO - Biological processi

  • defense response to bacterium Source: UniProtKB
  • negative regulation of calcium ion import Source: UniProtKB
  • negative regulation of flagellated sperm motility Source: UniProtKB
  • negative regulation of peptidase activity Source: UniProtKB
  • protein oligomerization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Antimicrobial, Protease inhibitor, Serine protease inhibitor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101448-MONOMER.
ReactomeiR-HSA-6803157. Antimicrobial peptides.

Protein family/group databases

MEROPSiI17.953.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:EPPIN
Synonyms:SPINLW1, WAP7, WFDC7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:15932. EPPIN.
HGNC:38825. EPPIN-WFDC6.

Subcellular locationi

Isoform 1 :
  • Secreted
  • Cell surface

  • Note: Bound to the surface of testicular and on the head and tail of ejaculate spermatozoa.

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • extracellular space Source: UniProtKB
  • protein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi87L → G: Loss of effect on KLK3 activity. 1 Publication1
Mutagenesisi102C → A: Reduces the binding to SEMG1 by 45%. 1 Publication1
Mutagenesisi107Y → A: Reduces the binding to SEMG1 by 68%. 1 Publication1
Mutagenesisi110C → 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. 1 Publication1
Mutagenesisi117F → A: Reduces the binding to SEMG1 by 68% and to LTF by 73%. 1 Publication1
Mutagenesisi123C → 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. 1 Publication1
Mutagenesisi127C → 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. 1 Publication1

Organism-specific databases

DisGeNETi57119.
OpenTargetsiENSG00000101448.
ENSG00000249139.
PharmGKBiPA38054.

Polymorphism and mutation databases

BioMutaiEPPIN.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000004137822 – 133EppinAdd BLAST112

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi33 ↔ 61By similarity
Disulfide bondi40 ↔ 65By similarity
Disulfide bondi48 ↔ 60By similarity
Disulfide bondi54 ↔ 69By similarity
Disulfide bondi77 ↔ 127By similarity
Disulfide bondi86 ↔ 110By similarity
Disulfide bondi102 ↔ 123By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiO95925.
PeptideAtlasiO95925.
PRIDEiO95925.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiENSG00000101448.
CleanExiHS_SPINLW1.
ExpressionAtlasiO95925. baseline and differential.
GenevisibleiO95925. HS.

Interactioni

Subunit structurei

Monomer. Homodimer. Homomultimers. Interacts with SEMG1 (via 164-283 AA). Interacts with LTF. Found in a complex with LTF, CLU, EPPIN and SEMG1.4 Publications

Protein-protein interaction databases

BioGridi121383. 4 interactors.
IntActiO95925. 1 interactor.
STRINGi9606.ENSP00000452085.

Structurei

3D structure databases

ProteinModelPortaliO95925.
SMRiO95925.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 73WAPPROSITE-ProRule annotationAdd BLAST48
Domaini77 – 127BPTI/Kunitz inhibitorPROSITE-ProRule annotationAdd BLAST51

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni102 – 133Interaction with SEMG1Add BLAST32
Regioni117 – 133Interaction with LTF1 PublicationAdd BLAST17

Domaini

The BPTI/Kunitz inhibitor domain is required for elastase inhibitory activity. BPTI/Kunitz inhibitor and WAP domains are involved in the protein antibacterial activity.1 Publication

Sequence similaritiesi

Contains 1 BPTI/Kunitz inhibitor domain.PROSITE-ProRule annotation
Contains 1 WAP domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4295. Eukaryota.
ENOG410XQNP. LUCA.
GeneTreeiENSGT00730000110932.
HOGENOMiHOG000115819.
HOVERGENiHBG004024.
InParanoidiO95925.
OMAiANVQGPG.
OrthoDBiEOG091G09P2.
PhylomeDBiO95925.
TreeFamiTF342459.

Family and domain databases

Gene3Di4.10.410.10. 1 hit.
4.10.75.10. 1 hit.
InterProiIPR002223. Kunitz_BPTI.
IPR020901. Prtase_inh_Kunz-CS.
IPR008197. WAP_dom.
[Graphical view]
PfamiPF00014. Kunitz_BPTI. 1 hit.
PF00095. WAP. 1 hit.
[Graphical view]
PRINTSiPR00759. BASICPTASE.
SMARTiSM00131. KU. 1 hit.
SM00217. WAP. 1 hit.
[Graphical view]
SUPFAMiSSF57256. SSF57256. 1 hit.
SSF57362. SSF57362. 1 hit.
PROSITEiPS00280. BPTI_KUNITZ_1. 1 hit.
PS50279. BPTI_KUNITZ_2. 1 hit.
PS51390. WAP. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95925-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGSSGLLSLL VLFVLLANVQ GPGLTDWLFP RRCPKIREEC EFQERDVCTK
60 70 80 90 100
DRQCQDNKKC CVFSCGKKCL DLKQDVCEMP KETGPCLAYF LHWWYDKKDN
110 120 130
TCSMFVYGGC QGNNNNFQSK ANCLNTCKNK RFP
Length:133
Mass (Da):15,284
Last modified:May 1, 1999 - v1
Checksum:iF7831B203366D9DC
GO
Isoform 2 (identifier: O95925-2) [UniParc]FASTAAdd to basket
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.
Show »
Length:117
Mass (Da):13,486
Checksum:i96161FAB3CFEDB47
GO
Isoform 3 (identifier: O95925-3) [UniParc]FASTAAdd to basket

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.
Show »
Length:179
Mass (Da):20,486
Checksum:iAD2399D2093D0197
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02469692H → R.Corresponds to variant rs2231838dbSNPEnsembl.1
Natural variantiVAR_052950128K → T.Corresponds to variant rs2231839dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0067551 – 31MGSSG…WLFPR → MLSKAHGCKTALSLG in isoform 2. 1 PublicationAdd BLAST31
Alternative sequenceiVSP_043679131 – 133RFP → QPCPKIKVECEVEEIDQCTK PRDCPENMKCCPFSRGKKCL DFRKASLST in isoform 3. 1 Publication3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13359.1. [O95925-1]
RefSeqiNP_001185915.1. NM_001198986.1. [O95925-3]
NP_001289790.1. NM_001302861.1.
NP_065131.1. NM_020398.3. [O95925-1]
UniGeneiHs.121084.
Hs.274876.

Genome annotation databases

EnsembliENST00000336443; ENSP00000338114; ENSG00000101448. [O95925-2]
ENST00000354280; ENSP00000361746; ENSG00000101448. [O95925-1]
ENST00000504988; ENSP00000424176; ENSG00000249139. [O95925-3]
GeneIDi100526773.
57119.
KEGGihsa:100526773.
hsa:57119.
UCSCiuc002xou.4. human. [O95925-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13359.1. [O95925-1]
RefSeqiNP_001185915.1. NM_001198986.1. [O95925-3]
NP_001289790.1. NM_001302861.1.
NP_065131.1. NM_020398.3. [O95925-1]
UniGeneiHs.121084.
Hs.274876.

3D structure databases

ProteinModelPortaliO95925.
SMRiO95925.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121383. 4 interactors.
IntActiO95925. 1 interactor.
STRINGi9606.ENSP00000452085.

Protein family/group databases

MEROPSiI17.953.

Polymorphism and mutation databases

BioMutaiEPPIN.

Proteomic databases

PaxDbiO95925.
PeptideAtlasiO95925.
PRIDEiO95925.

Protocols and materials databases

DNASUi57119.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336443; ENSP00000338114; ENSG00000101448. [O95925-2]
ENST00000354280; ENSP00000361746; ENSG00000101448. [O95925-1]
ENST00000504988; ENSP00000424176; ENSG00000249139. [O95925-3]
GeneIDi100526773.
57119.
KEGGihsa:100526773.
hsa:57119.
UCSCiuc002xou.4. human. [O95925-1]

Organism-specific databases

CTDi100526773.
57119.
DisGeNETi57119.
GeneCardsiEPPIN.
EPPIN-WFDC6.
HGNCiHGNC:15932. EPPIN.
HGNC:38825. EPPIN-WFDC6.
MIMi609031. gene.
neXtProtiNX_O95925.
OpenTargetsiENSG00000101448.
ENSG00000249139.
PharmGKBiPA38054.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4295. Eukaryota.
ENOG410XQNP. LUCA.
GeneTreeiENSGT00730000110932.
HOGENOMiHOG000115819.
HOVERGENiHBG004024.
InParanoidiO95925.
OMAiANVQGPG.
OrthoDBiEOG091G09P2.
PhylomeDBiO95925.
TreeFamiTF342459.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101448-MONOMER.
ReactomeiR-HSA-6803157. Antimicrobial peptides.

Miscellaneous databases

GeneWikiiSPINLW1.
PROiO95925.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101448.
CleanExiHS_SPINLW1.
ExpressionAtlasiO95925. baseline and differential.
GenevisibleiO95925. HS.

Family and domain databases

Gene3Di4.10.410.10. 1 hit.
4.10.75.10. 1 hit.
InterProiIPR002223. Kunitz_BPTI.
IPR020901. Prtase_inh_Kunz-CS.
IPR008197. WAP_dom.
[Graphical view]
PfamiPF00014. Kunitz_BPTI. 1 hit.
PF00095. WAP. 1 hit.
[Graphical view]
PRINTSiPR00759. BASICPTASE.
SMARTiSM00131. KU. 1 hit.
SM00217. WAP. 1 hit.
[Graphical view]
SUPFAMiSSF57256. SSF57256. 1 hit.
SSF57362. SSF57362. 1 hit.
PROSITEiPS00280. BPTI_KUNITZ_1. 1 hit.
PS50279. BPTI_KUNITZ_2. 1 hit.
PS51390. WAP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEPPI_HUMAN
AccessioniPrimary (citable) accession number: O95925
Secondary accession number(s): A6PVD6
, Q86TP9, Q96SD7, Q9HD30
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: May 1, 1999
Last modified: November 30, 2016
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

Might be used as a target for male contraception.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.