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ZP4 Gene

protein-coding   GIFtS: 53
GCID: GC01M238045

Zona Pellucida Glycoprotein 4

  See ZP4-related disease
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
Zona Pellucida Glycoprotein 41 2 3     ZBP2
ZPB2 3 5     ZP12
Zona Pellucida Protein B2 3     Zona Pellucida B Protein2
Zp-42 3     Zona Pellucida Sperm-Binding Protein 42

External Ids:    HGNC: 157701   Entrez Gene: 578292   Ensembl: ENSG000001169967   OMIM: 6135145   UniProtKB: Q128363   

Export aliases for ZP4 gene to outside databases

Previous GC identifers: GC01M236178 GC01M233499 GC01M234342 GC01M235086 GC01M234371 GC01M236112 GC01M208497


(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 ZP4 Gene:
The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed primarily
of three or four glycoproteins with various functions during fertilization and preimplantation development. The
nascent protein contains a N-terminal signal peptide sequence, a conserved ZP domain, a consensus furin cleavage
site, and a C-terminal transmembrane domain. It is hypothesized that furin cleavage results in release of the
mature protein from the plasma membrane for subsequent incorporation into the zona pellucida matrix. However, the
requirement for furin cleavage in this process remains controversial based on mouse studies. Previously, this
gene has been referred to as ZP1 or ZPB and thought to have similar functions as mouse Zp1. However, a human gene
with higher similarity and chromosomal synteny to mouse Zp1 has been assigned the symbol ZP1 and this gene has
been assigned the symbol ZP4. (provided by RefSeq, Jul 2008)

GeneCards Summary for ZP4 Gene:
ZP4 (zona pellucida glycoprotein 4) is a protein-coding gene. Diseases associated with ZP4 include oophoritis. GO annotations related to this gene include acrosin binding and signal transducer activity. An important paralog of this gene is ZP1.

UniProtKB/Swiss-Prot: ZP4_HUMAN, Q12836
Function: The mammalian zona pellucida, which mediates species-specific sperm binding, induction of the acrosome
reaction and prevents post-fertilization polyspermy, is composed of three to four glycoproteins, ZP1, ZP2, ZP3,
and ZP4. ZP4 may act as a sperm receptor

Gene Wiki entry for ZP4 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_000001.10  NC_018912.2  NT_167186.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the ZP4 gene promoter:
         c-Fos   AP-1   NRSF form 1   HTF   FOXD1   NRSF form 2   LCR-F1   CREB   Zic1   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidZP4 promoter sequence
   Search Chromatin IP Primers for ZP4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ZP4


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

Entrez Gene cytogenetic band: 1q43   Ensembl cytogenetic band:  1q43   HGNC cytogenetic band: 1q43

ZP4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ZP4 gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01M238045:  view genomic region     (about GC identifiers)

Start:
238,041,164 bp from pter      End:
238,054,222 bp from pter
Size:
13,059 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., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: ZP4_HUMAN, Q12836 (See protein sequence)
Recommended Name: Zona pellucida sperm-binding protein 4 precursor  
Size: 540 amino acids; 59400 Da
Secondary accessions: B2RAE1

Explore the universe of human proteins at neXtProt for ZP4: NX_Q12836

Explore proteomics data for ZP4 at MOPED

Post-translational modifications: 

  • Proteolytically cleaved before the transmembrane segment to yield the secreted ectodomain incorporated in the zona
    pellucida1
  • Glycosylation2 at Asn69, Asn202, Asn219, Asn267, Thr302, Asn470, Asn474
  • Modification sites at PhosphoSitePlus

  • See ZP4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_067009.1  
    ENSEMBL proteins: 
     ENSP00000355529  
    Reactome Protein details: Q12836

    ZP4 Human Recombinant Protein 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:
    ZP: Zona pellucida glycoproteins

    4 InterPro protein domains:
     IPR017977 ZP_dom_CS
     IPR000519 P_trefoil
     IPR017957 P_trefoil_CS
     IPR001507 ZP_dom

    Graphical View of Domain Structure for InterPro Entry Q12836

    ProtoNet protein and cluster: Q12836

    2 Blocks protein domains:
    IPB000519 P-type trefoil domain
    IPB001507 Endoglin/CD105 antigen


    UniProtKB/Swiss-Prot: ZP4_HUMAN, Q12836
    Domain: The ZP domain is involved in the polymerization of the ZP proteins to form the zona pellucida
    Similarity: Belongs to the ZP domain family. ZPB subfamily
    Similarity: Contains 1 P-type (trefoil) domain
    Similarity: Contains 1 ZP domain


    Find genes that share domains with ZP4           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, 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: ZP4_HUMAN, Q12836
    Function: The mammalian zona pellucida, which mediates species-specific sperm binding, induction of the acrosome
    reaction and prevents post-fertilization polyspermy, is composed of three to four glycoproteins, ZP1, ZP2, ZP3,
    and ZP4. ZP4 may act as a sperm receptor

         Gene Ontology (GO): 2 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004871signal transducer activity IMP18667750
    GO:0032190acrosin binding IPI15950651
         
    Find genes that share ontologies with ZP4           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for ZP4:
     Decreased viability with pacli 

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for ZP4
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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
    ZP4_HUMAN, Q12836: Processed zona pellucida sperm-binding protein 4: Secreted, extracellular space,
    extracellular matrix. Note=The glycoproteinaceous translucent extracellular matrix that surrounds the mammalian
    oocyte is called zona pellucida
    ZP4_HUMAN, Q12836: Cell membrane; Single-pass type I membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5
    plasma membrane5
    endoplasmic reticulum1
    golgi apparatus1

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region TAS--
    GO:0005578proteinaceous extracellular matrix IEA--
    GO:0005886plasma membrane IEA--
    GO:0016021integral component of membrane IEA--

    Find genes that share ontologies with ZP4           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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    SuperPaths for ZP4 About    
    See pathways by source

    SuperPathContained pathways About
    1Reproduction
    Reproduction1.00
    Interaction With The Zona Pellucida0.00
    Fertilization1.00


    Find genes that share SuperPaths with ZP4           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    1 Reactome Pathway for ZP4
        Interaction With The Zona Pellucida


        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for ZP4
    Interactions:

        Search GeneGlobe Interaction Network for ZP4

    STRING Interaction Network Preview (showing 1 interactants - click image to see more details)

    1 Interacting protein for ZP4 (Q128363 ENSP000003555294) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    FURINP099583, ENSP000002681714I2D: score=1 STRING: ENSP00000268171
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002922positive regulation of humoral immune response IDA19004505
    GO:0007338single fertilization TAS--
    GO:0007339binding of sperm to zona pellucida TAS--
    GO:0010737protein kinase A signaling IDA18667750
    GO:0032504multicellular organism reproduction TAS--

    Find genes that share ontologies with ZP4           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 ZP4



    (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 ZP4 gene: 
    NM_021186.3  

    Unigene Cluster for ZP4:

    Zona pellucida glycoprotein 4
    Hs.136241  [show with all ESTs]
    Unigene Representative Sequence: NM_021186
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000366570(uc001hym.3)
    miRNA
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    hsa-miR-607 hsa-miR-29b-1*
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    Inhib. RNA
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      QuantiFast Probe-based Assays in human, mouse, rat ZP4

    Additional mRNA sequence: 

    AK314151.1 BC069521.1 

    1 DOTS entry:

    DT.91924499 

    6 AceView cDNA sequences:

    NM_021186 BC069521 CB126151 CB126325 AA169152 AA169775 

    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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    ZP4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ATTCTACTCC
    ZP4 Expression
    About this image

    ZP4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ZP4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.136241

    UniProtKB/Swiss-Prot: ZP4_HUMAN, Q12836
    Tissue specificity: Oocytes

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    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ZP4

    (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 chordates.

    Orthologs for ZP4 gene from Selected species (see all 9)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Zp4-ps5 zona pellucida glycoprotein 4, pseudogene   --   13 (4.37 cM) 11522052 
    chicken
    (Gallus gallus)
    Aves ZP41 zona pellucida glycoprotein 4 63.62(n)
    53.75(a)
      395692  NM_204879.1  NP_990210.1 
    lizard
    (Anolis carolinensis)
    Reptilia --
    Uncharacterized protein
    14(a)
    many ↔ many
    2(68672297-68707627)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia zp41 zona pellucida glycoprotein 4 53.83(n)
    46.39(a)
      394445  NM_203523.1  NP_988854.1 
    zebrafish
    (Danio rerio)
    Actinopterygii BM037412.12   -- 71.36(n)    BM037412.1 


    ENSEMBL Gene Tree for ZP4 (if available)
    TreeFam Gene Tree for ZP4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for ZP4 gene
    ZP12  ZP22  
    2 SIMAP similar genes for ZP4 using alignment to 1 protein entry:     ZP4_HUMAN:
    ZP1    ZP2

    Find genes that share paralogs with ZP4           About GenesLikeMe



    (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 ZP4    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs343702531,2,4
    ----see VAR_0529972 mis40--------
    rs348119801,2,4
    ----see VAR_0529982 mis40--------

    HapMap Linkage Disequilibrium report for ZP4 (238041164 - 238054222 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for ZP4:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2725729CNV Deletion23290073
    nsv873342CNV Gain21882294
    esv34468CNV Gain17911159
    dgv193e1CNV Complex17122850

    Site Specific Mutation Identification with PCR Assays
    Search QIAGEN SeqTarget long-range PCR primers for resequencing ZP4
    DNA2.0 Custom Variant and Variant Library Synthesis for ZP4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 613514    OMIM disorders: --

    1 disease for ZP4:    
    About MalaCards
    oophoritis

    2 diseases from the University of Copenhagen DISEASES database for ZP4:
    Oophoritis     Infertility

    Find genes that share disorders with ZP4           About GenesLikeMe

    Genetic Association Database (GAD): ZP4
    Human Genome Epidemiology (HuGE) Navigator: ZP4 (3 documents)

    Export disorders for ZP4 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 ZP4 gene, integrated from 10 sources (see all 44):
    (articles sorted by number of sources associating them with ZP4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Cloning and characterization of zona pellucida genes and cDNAs from a variety of mammalian species: the ZPA, ZPB and ZPC gene families. (PubMed id 7841460)1, 2, 3, 9 Harris J.D....Sacco A.G. (DNA Seq. 1994)
    2. Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease. (PubMed id 20708005)1, 4 Chalasani N....Rotter J.I. (Gastroenterology 2010)
    3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)1, 4 Rose J.E....Uhl G.R. (Mol. Med. 2010)
    4. Follow-up examination of linkage and association to chromosome 1q43 in multiple sclerosis. (PubMed id 19626040)1, 4 McCauley J.L....Haines J.L. (Genes Immun. 2009)
    5. Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population. (PubMed id 19625618)1, 4 Nakano M....Tashiro K. (Proc. Natl. Acad. Sci. U.S.A. 2009)
    6. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. (PubMed id 17554300)1, 4 (Nature 2007)
    7. The DNA sequence and biological annotation of human chromosome 1. (PubMed id 16710414)1, 2 Gregory S.G.... Bentley D.R. (Nature 2006)
    8. 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)
    9. DNA vaccine encoding chimeric protein encompassing epitopes of human ZP3 and ZP4: immunogenicity and characterization of antibodies. (PubMed id 19004505)1, 9 Choudhury S....Gupta S.K. (J. Reprod. Immunol. 2009)
    10. Effects of native human zona pellucida glycoproteins 3 and 4 on acrosome reaction and zona pellucida binding of human spermatozoa. (PubMed id 18667750)1, 9 Chiu P.C....Yeung W.S. (Biol. Reprod. 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    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: 57829 HGNC: 15770 AceView: ZP4 Ensembl:ENSG00000116996 euGenes: HUgn57829
    ECgene: ZP4 H-InvDB: ZP4

    (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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    NameDescription
    PharmGKB entry for ZP4 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 ZP4 gene:
    Search GeneIP for patents involving ZP4

    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, LSBio, eBioscience, 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 inGenious Targeting Laboratory, genOway)
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