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EPPIN Gene

protein-coding   GIFtS: 37
GCID: GC20M044186

Epididymal Peptidase Inhibitor

(Previous names: serine protease inhibitor-like, with Kunitz and WAP domains...)
(Previous symbol: SPINLW1)
  See EPPIN-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Epididymal Peptidase Inhibitor1 2     CT712 3
SPINLW11 2 3 5     WFDC72 3
Epididymal Protease Inhibitor1 2 3     WAP Four-Disulfide Core Domain Protein 72 3
WAP72 3 5     Serine Protease Inhibitor-Like, With Kunitz And WAP Domains 1 (Eppin)1
Serine Peptidase Inhibitor-Like, With Kunitz And WAP Domains 1 (Eppin)1 2     CT722
Cancer/Testis Antigen 721 2     dJ461P17.22
Cancer/Testis Antigen 712 3     eppin2
Protease Inhibitor WAP72 3     Serine Protease Inhibitor-Like With Kunitz And WAP Domains 13

External Ids:    HGNC: 159321   Entrez Gene: 571192   Ensembl: ENSG000001014487   OMIM: 6090315   UniProtKB: O959253   

Export aliases for EPPIN gene to outside databases

Previous GC identifers: GC20M044176 GC20M044184


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for EPPIN Gene:
This gene encodes an epididymal protease inhibitor, which contains both kunitz-type and WAP-type four-disulfide
core (WFDC) protease inhibitor consensus sequences. Most WFDC genes are localized to chromosome 20q12-q13 in two
clusters: centromeric and telomeric. This gene is a member of the WFDC gene family and belongs to the telomeric
cluster. The protein can inhibit human sperm motility, and polymorphisms in this gene are associated with male
infertility. Read-through transcription also exists between this gene and the downstream WFDC6 (WAP
four-disulfide core domain 6) gene. (provided by RefSeq, Nov 2010)

GeneCards Summary for EPPIN Gene:
EPPIN (epididymal peptidase inhibitor) is a protein-coding gene. Diseases associated with EPPIN include male infertility, and infertility. GO annotations related to this gene include serine-type endopeptidase inhibitor activity. An important paralog of this gene is WFDC6.

UniProtKB/Swiss-Prot: EPPI_HUMAN, O95925
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

Gene Wiki entry for EPPIN (SPINLW1) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000020.10  NC_018931.2  NT_011362.11  
Regulatory elements:
   Search for regulatory transcription factor binding sites for EPPIN
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidEPPIN promoter sequence
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Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat EPPIN


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20q13.12   Ensembl cytogenetic band:  20q13.12   HGNC cytogenetic band: 20q13.12

EPPIN Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
EPPIN gene location

GeneLoc information about chromosome 20         GeneLoc Exon Structure

GeneLoc location for GC20M044186:  view genomic region     (about GC identifiers)

Start:
44,165,625 bp from pter      End:
44,176,391 bp from pter
Size:
10,767 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: EPPI_HUMAN, O95925 (See protein sequence)
Recommended Name: Eppin precursor  
Size: 133 amino acids; 15284 Da
Subunit: Monomer. Homodimer. Homomultimers. Interacts with SEMG1 (via 164-283 AA). Interacts with LTF. Found in a
complex with LTF, CLU, EPPIN and SEMG1
Miscellaneous: Might be used as a target for male contraception (PubMed:22699487)
Secondary accessions: A6PVD6 Q86TP9 Q96SD7 Q9HD30
Alternative splicing: 3 isoforms:  O95925-1   O95925-2   O95925-3   (Based on a readthrough transcript which may produce a EPPIN-WFDC6 fusion protein. No experimental confirmation available)

Explore the universe of human proteins at neXtProt for EPPIN: NX_O95925

Explore proteomics data for EPPIN at MOPED


See EPPIN Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_065131.1  
ENSEMBL proteins: 
 ENSP00000361746   ENSP00000387153   ENSP00000338114   ENSP00000452085  

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antibodies-online proteins for EPPIN (7 products) 

 
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antibodies-online antibodies for EPPIN (19 products) 

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:
WFDC: WAP four-disulfide core domain containing

3 InterPro protein domains:
 IPR002223 Prot_inh_Kunz-m
 IPR008197 WAP-type_4-diS_core
 IPR020901 Prtase_inh_Kunz-CS

Graphical View of Domain Structure for InterPro Entry O95925

ProtoNet protein and cluster: O95925

2 Blocks protein domains:
IPB002223 Pancreatic trypsin inhibitor (Kunitz)
IPB008197 4-disulphide core signature


UniProtKB/Swiss-Prot: EPPI_HUMAN, O95925
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
Similarity: Contains 1 BPTI/Kunitz inhibitor domain
Similarity: Contains 1 WAP domain


Find genes that share domains with EPPIN           About GenesLikeMe


(According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

     UniProtKB/Swiss-Prot Summary: EPPI_HUMAN, O95925
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

     Gene Ontology (GO): 3 molecular function terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0004867serine-type endopeptidase inhibitor activity IEA--
GO:0005515protein binding IPI15590901
GO:0030414peptidase inhibitor activity ----
     
Find genes that share ontologies with EPPIN           About GenesLikeMe


Animal Models:
   genOway: Develop your customized and physiologically relevant rodent model for EPPIN

miRNA
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miRTarBase miRNAs that target EPPIN:
hsa-mir-26b-5p (MIRT029867)

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(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot
EPPI_HUMAN, O95925: Isoform 1: Secreted. Cell surface. Note=Bound to the surface of testicular and on the head
and tail of ejaculate spermatozoa

Gene Ontology (GO): 2 cellular component terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0005576extracellular region IEA--
GO:0009986cell surface IEA--

Find genes that share ontologies with EPPIN           About GenesLikeMe


(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for EPPIN
Interactions:

    Search GeneGlobe Interaction Network for EPPIN

Gene Ontology (GO): 2 biological process terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0010466negative regulation of peptidase activity IDA18331357
GO:0042742defense response to bacterium IDA18331357

Find genes that share ontologies with EPPIN           About GenesLikeMe



(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore
   Browse drugs & compounds from Enzo Life Sciences
  Browse compounds at ApexBio 

Browse Tocris compounds for EPPIN (EPPI)

3 Novoseek inferred chemical compound relationships for EPPIN gene    About this table
Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
whey 67 4 17044815 (1), 15229136 (1), 16423450 (1)
cysteine 21.3 3 15590901 (2)
serine 4.6 6 17644992 (1), 17566290 (1)



Find genes that share compounds with EPPIN           About GenesLikeMe



(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for EPPIN gene (2 alternative transcripts): 
NM_020398.3  NM_181502.1  

Unigene Cluster for EPPIN:

Epididymal peptidase inhibitor
Hs.121084  [show with all ESTs]
Unigene Representative Sequence: NM_020398
5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
ENST00000354280(uc002xou.3) ENST00000409554 ENST00000336443 ENST00000496898(uc002xov.2)
ENST00000555685
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  QuantiFast Probe-based Assays in human, mouse, rat EPPIN

Additional mRNA sequence: 

AF286368.1 AF286369.1 AF286370.2 AK311906.1 AL118493.1 BC003675.1 BC044829.1 BC053369.1 

6 DOTS entries:

DT.100743157  DT.107690  DT.95366079  DT.95090034  DT.100739455  DT.120812006 

Selected AceView cDNA sequences (see all 54):

NM_020398 NM_080827 AF286368 NM_181502 AF286369 AF286370 AK126022 AL118493 
AF411861 AI633364 BC044829 AI039400 AI648695 AX810710 AI023486 AA719397 
AI222418 AW449129 AL449632 BC053369 AL449631 BX094264 AA451856 AI374968 

GeneLoc Exon Structure


(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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EPPIN expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>2/3
CGAP TAG: --
EPPIN Expression
About this image


EPPIN expression in embryonic tissues and stem cells    About this table
Data from LifeMap, the Embryonic Development and Stem Cells Database
 selected tissues (see all 3) fully expand
 
 Testis (Reproductive System)    fully expand to see all 3 entries
         XY Germ Cells Testis Cord
         Seminiferous Tubules
 
 Ovary (Reproductive System)    fully expand to see all 2 entries
         Pre-Granulosa Cells Primordial Follicle
 
 Gonad
         XY Germ Cells Testis Cord
EPPIN Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

EPPIN Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.121084

UniProtKB/Swiss-Prot: EPPI_HUMAN, O95925
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

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(Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for EPPIN gene from Selected species (see all 9)    About this table
Organism Taxonomic
classification
Gene Description Human
Similarity
Orthology
Type
Details
mouse
(Mus musculus)
Mammalia Eppin5
Wfdc6a1
serine protease inhibitor-like, with Kunitz and WAP more5
WAP four-disulfide core domain 6A1
66.67(n)1
52.17(a)1
  2 (85.21 cM)5
2093511  NM_001177848.11  NP_001171319.11 
 1645883435 
lizard
(Anolis carolinensis)
Reptilia --
--
Uncharacterized protein
28(a)
26(a)
many ↔ many
many ↔ many
GL344854.1(11157-16565)
GL344356.1(47896-55721)
fruit fly
(Drosophila melanogaster)
Insecta CG36046
--
27(a)
1 → many
2L(3697242-3697872)
worm
(Caenorhabditis elegans)
Secernentea R12A1.36
Protein R12A1.3 (R12A1.3) mRNA, complete cds
18(a)
1 → many
V(1422796-1425717) WBGene00020017


ENSEMBL Gene Tree for EPPIN (if available)
TreeFam Gene Tree for EPPIN (if available)

(Paralogs according to 1HomoloGene,
2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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Paralogs for EPPIN gene
WFDC62  WFDC82  EPPIN-WFDC62  
13 SIMAP similar genes for EPPIN using alignment to 2 protein entries:     EPPI_HUMAN (see all proteins):
SPINLW1    COL6A3    DKFZp686D23123    WFDC6    SPINT2    TFPI2
SPINT3    APP    APLP2    WFIKKN2    WFDC3    TFPI
WFDC8

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(SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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2 SNPs for EPPIN    About this table                                 

Genomic DataTranscription Related DataAllele Frequencies
SNP IDValidClinical
significance
Chr 20 posSequence#AA
Chg
TypeMore#Allele
freq
PopTotal
sample
More
----------
rs22318391,2,4
----see VAR_0529502 mis40--------
rs22318381,2,4
----see VAR_0246962 mis40--------

HapMap Linkage Disequilibrium report for EPPIN (44165625 - 44176391 bp)

Structural Variations
      Database of Genomic Variants (DGV) variations for EPPIN: --
Site Specific Mutation Identification with PCR Assays
SeqTarget long-range PCR primers for resequencing EPPIN
DNA2.0 Custom Variant and Variant Library Synthesis for EPPIN

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 609031    OMIM disorders: --

2 diseases for EPPIN:    
About MalaCards
male infertility    infertility


Find genes that share disorders with EPPIN           About GenesLikeMe

1 Novoseek inferred disease relationship for EPPIN gene    About this table

Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
infertility 39.6 3 18466682 (1), 17345778 (1), 20158997 (1)


Export disorders for EPPIN gene to outside databases

(in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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PubMed articles for EPPIN gene, integrated from 10 sources (see all 38):
(articles sorted by number of sources associating them with EPPIN)
    Utopia: connect your pdf to the dynamic
world of online information

  1. Cloning and sequencing of human eppin: a novel family of protease inhibitors expressed in the epididymis and testis. (PubMed id 11404006)1, 2, 3, 9 Richardson R.T.... O'Rand M.G. (Gene 2001)
  2. Association of eppin with semenogelin on human spermatozoa. (PubMed id 15590901)1, 2, 9 Wang Z.... Richardson R.T. (Biol. Reprod. 2005)
  3. Eppin: a molecular strategy for male contraception. (PubMed id 17644992)1, 2, 9 Wang Z.... Orand M.G. (Soc. Reprod. Fertil. Suppl. 2007)
  4. Antimicrobial activity of human EPPIN, an androgen-regulated, sperm- bound protein with a whey acidic protein motif. (PubMed id 15229136)1, 2, 9 Yenugu S.... Hall S.H. (Biol. Reprod. 2004)
  5. Functional domains of the human epididymal protease inhibitor, eppin. (PubMed id 18331357)1, 2, 9 McCrudden M.T....Timson D.J. (FEBS J. 2008)
  6. Characterization of an eppin protein complex from human semen and spermatozoa. (PubMed id 17567961)1, 2, 9 Wang Z.... O'Rand M.G. (Biol. Reprod. 2007)
  7. A locus on human chromosome 20 contains several genes expressing protease inhibitor domains with homology to whey acidic protein. (PubMed id 12206714)1, 3, 9 Clauss A.... Lundwall A. (Biochem. J. 2002)
  8. Characterization of EPPIN's semenogelin I binding Site: a contraceptive drug target. (PubMed id 22699487)1, 2 Silva E.J.... O'Rand M.G. (Biol. Reprod. 2012)
  9. Distribution of Eppin in mouse and human testis. (PubMed id 21461566)1, 2 Long Y.... Wang X. (Mol. Med. Report. 2011)
  10. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)

(in PubMed, OMIM, and NCBI Bookshelf)
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 ANDOR
Aliases
Disorders
Free Text  

  Query String
PubMed
OMIM
NCBI Bookshelf
  (Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 57119 HGNC: 15932 AceView: SPINLW1andWFDC6 Ensembl:ENSG00000101448 euGenes: HUgn57119
ECgene: EPPIN H-InvDB: EPPIN

(According to HUGE)
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  --

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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PharmGKB entry for EPPIN Pharmacogenomics, SNPs, Pathways

(Patent information from GeneIP,
Licensable technologies from WIS Yeda, Salk, Tufts,
IP news from LifeMap Sciences, Inc.)
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Patent Information for EPPIN gene:
Search GeneIP for patents involving EPPIN

GeneCards and IP:
Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from genOway)
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 EMD Millipore genomic analysis products

  
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