The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed of three glycoproteins with various functions during fertilization and preimplantation development. The glycosylated mature peptide is one of the structural components of the zona pellucida and functions in secondary binding and penetration of acrosome-reacted spermatozoa. F... See more...

Aliases for ZP2 Gene

Aliases for ZP2 Gene

  • Zona Pellucida Glycoprotein 2 2 3 4 5
  • ZPA 2 3 4
  • Zona Pellucida Glycoprotein 2 (Sperm Receptor) 2 3
  • Zona Pellucida Sperm-Binding Protein 2 3 4
  • Zona Pellucida Protein A 3 4
  • Zp-2 3 4
  • Zona Pellucida Glycoprotein ZP2 3
  • OOMD6 3
  • ZP2 5

External Ids for ZP2 Gene

Previous GeneCards Identifiers for ZP2 Gene

  • GC16M020617
  • GC16M021217
  • GC16M021175
  • GC16M021116
  • GC16M019743
  • GC16M021208

Summaries for ZP2 Gene

Entrez Gene Summary for ZP2 Gene

  • The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed of three glycoproteins with various functions during fertilization and preimplantation development. The glycosylated mature peptide is one of the structural components of the zona pellucida and functions in secondary binding and penetration of acrosome-reacted spermatozoa. Female mice lacking this gene do not form a stable zona matrix and are sterile. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

GeneCards Summary for ZP2 Gene

ZP2 (Zona Pellucida Glycoprotein 2) is a Protein Coding gene. Diseases associated with ZP2 include Oocyte Maturation Defect 6 and Female Infertility Due To Zona Pellucida Defect. Among its related pathways are Fertilization and Ovarian Infertility Genes. Gene Ontology (GO) annotations related to this gene include coreceptor activity and acrosin binding. An important paralog of this gene is ZP4.

UniProtKB/Swiss-Prot Summary for ZP2 Gene

  • Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy (PubMed:29895852). The zona pellucida is composed of 3 to 4 glycoproteins, ZP1, ZP2, ZP3, and ZP4. ZP2 may act as a secondary sperm receptor (PubMed:29895852).

Gene Wiki entry for ZP2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ZP2 Gene

Genomics for ZP2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ZP2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH16J021211 Promoter 0.3 EPDnew 607.9 +2.9 2915 0.1 ZP2 lnc-CRYM-2 DNAH3
GH16J021279 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 10.9 -63.8 -63790 1.4 SP1 HNRNPL GATAD2A CTCF TEAD4 PRDM10 ZNF512 IKZF1 KDM1A RCOR2 CRYM DNAH3 TMEM159 ZP2 ENSG00000260306 lnc-ZP2-4 lnc-ZP2-3 ANKS4B
GH16J021260 Enhancer 1.4 Ensembl ENCODE CraniofacialAtlas 10.5 -48.4 -48391 5.8 GATAD2A PRDM10 REST TFE3 LEF1 SOX13 IKZF1 NFKBIZ RCOR2 JUND lnc-ZP2-3 CRYM SMG1P4 SMG1P3 ANKS4B EEF2K TMEM159 DNAH3 ZP2 NPIPB4
GH16J021222 Enhancer 0.8 Ensembl ENCODE 0.4 -8.5 -8490 2.4 GATAD2A SOX13 ZSCAN29 ZSCAN5C FOXA2 ZNF205 WT1 KLF17 TAL1 KLF1 TMEM159 DNAH3 CRYM DCUN1D3 ZP2 piR-38051-113 ANKS4B lnc-CRYM-1
GH16J021187 Enhancer 1 ENCODE 0.3 +26.1 26095 1.2 GATAD2A CTCF ZNF629 TFE3 LEF1 IKZF1 RCOR2 JUND ZNF143 ZIC2 TMEM159 DNAH3 ENSG00000262983 ZP2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ZP2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ZP2

Genomic Locations for ZP2 Gene

Genomic Locations for ZP2 Gene
chr16:21,197,450-21,214,510
(GRCh38/hg38)
Size:
17,061 bases
Orientation:
Minus strand
chr16:21,208,773-21,225,831
(GRCh37/hg19)
Size:
17,059 bases
Orientation:
Minus strand

Genomic View for ZP2 Gene

Genes around ZP2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ZP2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ZP2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ZP2 Gene

Proteins for ZP2 Gene

  • Protein details for ZP2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q05996-ZP2_HUMAN
    Recommended name:
    Zona pellucida sperm-binding protein 2
    Protein Accession:
    Q05996
    Secondary Accessions:
    • B2R7J2
    • Q4VAN9
    • Q4VAP0
    • Q4VAP1

    Protein attributes for ZP2 Gene

    Size:
    745 amino acids
    Molecular mass:
    82357 Da
    Quaternary structure:
    • Can form homopolymers that assemble into long fibers (in vitro). Polymers of ZP2 and ZP3 organized into long filaments cross-linked by ZP1 homodimers (By similarity). Interacts with ZP3 (PubMed:28886344).

    Alternative splice isoforms for ZP2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ZP2 Gene

Post-translational modifications for ZP2 Gene

  • Proteolytically cleaved before the transmembrane segment to yield the secreted ectodomain incorporated in the zona pellucida.
  • Proteolytically cleaved in the N-terminal part by the metalloendopeptidase ASTL exocytosed from cortical granules after fertilization, yielding a N-terminal peptide of about 30 kDa which remains covalently attached to the C-terminal peptide via disulfide bond(s). This cleavage may play an important role in the post-fertilization block to polyspermy. Additional proteolytically cleavage of the N-terminal peptide of 30 kDa occurs in one-cell and two-cell embryos.
  • N-glycosylated.
  • O-glycosylated; contains sulfate-substituted glycans.
  • Glycosylation at Asn105, Asn122, and Thr462
  • Modification sites at PhosphoSitePlus

Other Protein References for ZP2 Gene

No data available for DME Specific Peptides for ZP2 Gene

Domains & Families for ZP2 Gene

Gene Families for ZP2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for ZP2 Gene

InterPro:
Blocks:
  • Endoglin/CD105 antigen
ProtoNet:

Suggested Antigen Peptide Sequences for ZP2 Gene

GenScript: Design optimal peptide antigens:
  • ZP2 protein (Q4VAP1_HUMAN)
  • Zona pellucida protein A (ZP2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q05996

UniProtKB/Swiss-Prot:

ZP2_HUMAN :
  • The ZP domain is involved in the polymerization of the ZP proteins to form the zona pellucida.
Domain:
  • The ZP domain is involved in the polymerization of the ZP proteins to form the zona pellucida.
  • Belongs to the ZP domain family. ZPA subfamily.
genes like me logo Genes that share domains with ZP2: view

Function for ZP2 Gene

Molecular function for ZP2 Gene

UniProtKB/Swiss-Prot Function:
Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy (PubMed:29895852). The zona pellucida is composed of 3 to 4 glycoproteins, ZP1, ZP2, ZP3, and ZP4. ZP2 may act as a secondary sperm receptor (PubMed:29895852).
GENATLAS Biochemistry:
zona pellucida glycoprotein 2 (sperm receptor)

Phenotypes From GWAS Catalog for ZP2 Gene

Gene Ontology (GO) - Molecular Function for ZP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 15950651
GO:0015026 coreceptor activity TAS 8385033
GO:0032190 acrosin binding IPI 15950651
GO:0035804 structural constituent of egg coat IMP 29895852
GO:0042802 identical protein binding IPI 26879157
genes like me logo Genes that share ontologies with ZP2: view
genes like me logo Genes that share phenotypes with ZP2: view

Human Phenotype Ontology for ZP2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ZP2 Gene

MGI Knock Outs for ZP2:
  • Zp2 Zp2<tm1Dean>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ZP2

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targets and HOMER Transcription for ZP2 Gene

Localization for ZP2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ZP2 Gene

[Processed zona pellucida sperm-binding protein 2]: Secreted, extracellular space, extracellular matrix. Note=Located in oocyte zona pellucida. {ECO:0000250 UniProtKB:P20239, ECO:0000269 PubMed:29895852}.
Cell membrane. Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ZP2 gene
Compartment Confidence
plasma membrane 4
extracellular 4
endoplasmic reticulum 4
endosome 4
nucleus 3
cytoskeleton 2
mitochondrion 1
cytosol 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for ZP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005771 multivesicular body IEA,ISS --
GO:0005783 endoplasmic reticulum IEA,ISS --
GO:0005886 plasma membrane ISS --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with ZP2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for ZP2 Gene

Pathways & Interactions for ZP2 Gene

PathCards logo

SuperPathways for ZP2 Gene

genes like me logo Genes that share pathways with ZP2: view

Pathways by source for ZP2 Gene

1 BioSystems pathway for ZP2 Gene

Gene Ontology (GO) - Biological Process for ZP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007338 single fertilization IEA --
GO:0007339 binding of sperm to zona pellucida IEA,TAS --
GO:0060046 NOT regulation of acrosome reaction IDA 11751269
GO:0060468 prevention of polyspermy ISS 22472438
genes like me logo Genes that share ontologies with ZP2: view

No data available for SIGNOR curated interactions for ZP2 Gene

Drugs & Compounds for ZP2 Gene

No Compound Related Data Available

Transcripts for ZP2 Gene

mRNA/cDNA for ZP2 Gene

5 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ZP2

Alternative Splicing Database (ASD) splice patterns (SP) for ZP2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19
SP1: -
SP2: - -
SP3:

Relevant External Links for ZP2 Gene

GeneLoc Exon Structure for
ZP2

Expression for ZP2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ZP2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ZP2 Gene

This gene is overexpressed in Brain - Cerebellar Hemisphere (x25.9) and Brain - Cerebellum (x25.7).

Protein differential expression in normal tissues from HIPED for ZP2 Gene

This gene is overexpressed in Monocytes (32.7), Tlymphocyte (16.7), and Blymphocyte (15.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for ZP2 Gene



Protein tissue co-expression partners for ZP2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ZP2

SOURCE GeneReport for Unigene cluster for ZP2 Gene:

Hs.73982

mRNA Expression by UniProt/SwissProt for ZP2 Gene:

Q05996-ZP2_HUMAN
Tissue specificity: Expressed in occytes(at protein level).

Evidence on tissue expression from TISSUES for ZP2 Gene

  • Nervous system(4.5)
  • Muscle(2.2)
  • Heart(2)
genes like me logo Genes that share expression patterns with ZP2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for ZP2 Gene

Orthologs for ZP2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for ZP2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ZP2 30 31
  • 99.51 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia ZP2 30 31
  • 80.62 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia ZP2 30 31
  • 80.17 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Zp2 30
  • 73.06 (n)
Mouse
(Mus musculus)
Mammalia Zp2 30 17 31
  • 72.71 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 50 (a)
OneToMany
-- 31
  • 44 (a)
OneToMany
Oppossum
(Monodelphis domestica)
Mammalia ZP2 31
  • 49 (a)
OneToOne
Chicken
(Gallus gallus)
Aves ZP2 30 31
  • 56.51 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 48 (a)
OneToMany
-- 31
  • 47 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia zp2 30
  • 50.25 (n)
African clawed frog
(Xenopus laevis)
Amphibia xlZPA 30
Zebrafish
(Danio rerio)
Actinopterygii si:ch211-223m11.2 31
  • 14 (a)
ManyToMany
Species where no ortholog for ZP2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for ZP2 Gene

ENSEMBL:
Gene Tree for ZP2 (if available)
TreeFam:
Gene Tree for ZP2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ZP2: view image

Paralogs for ZP2 Gene

Paralogs for ZP2 Gene

(2) SIMAP similar genes for ZP2 Gene using alignment to 2 proteins:

  • ZP2_HUMAN
  • Q4VAP1_HUMAN
genes like me logo Genes that share paralogs with ZP2: view

Variants for ZP2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ZP2 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
689402 Pathogenic: OOCYTE MATURATION DEFECT 6 21,202,276(-) C/G MISSENSE_VARIANT
708592 Benign: not provided 21,198,771(-) G/A INTRON_VARIANT
710348 Benign: not provided 21,205,764(-) T/G NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
714693 Benign: not provided 21,206,861(-) T/C MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
776993 Benign: not provided 21,201,527(-) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for ZP2 Gene

Structural Variations from Database of Genomic Variants (DGV) for ZP2 Gene

Variant ID Type Subtype PubMed ID
esv3638164 CNV gain 21293372
esv3638165 CNV gain 21293372
nsv1762 CNV insertion 18451855
nsv436835 CNV insertion 17901297
nsv509605 CNV insertion 20534489
nsv524978 CNV loss 19592680
nsv571623 CNV gain 21841781
nsv833166 CNV gain+loss 17160897

Variation tolerance for ZP2 Gene

Residual Variation Intolerance Score: 23.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.02; 80.13% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ZP2 Gene

Human Gene Mutation Database (HGMD)
ZP2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ZP2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ZP2 Gene

Disorders for ZP2 Gene

MalaCards: The human disease database

(17) MalaCards diseases for ZP2 Gene - From: OMIM, ClinVar, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search ZP2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

ZP2_HUMAN
  • Oocyte maturation defect 6 (OOMD6) [MIM:618353]: An autosomal recessive infertility disorder characterized by oocyte fertilization failure, due to defective sperm-binding to an abnormally thin zona pellucida in patient oocytes. {ECO:0000269 PubMed:29895852}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for ZP2

genes like me logo Genes that share disorders with ZP2: view

No data available for Genatlas for ZP2 Gene

Publications for ZP2 Gene

  1. Conservation of mammalian secondary sperm receptor genes enables the promoter of the human gene to function in mouse oocytes. (PMID: 8385033) Liang LF … Dean J (Developmental biology 1993) 2 3 4 23
  2. ZP2 pathogenic variants cause in vitro fertilization failure and female infertility. (PMID: 29895852) Dai C … Lin G (Genetics in medicine : official journal of the American College of Medical Genetics 2019) 3 4
  3. A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility. (PMID: 28886344) Chen T … Chen ZJ (American journal of human genetics 2017) 3 4
  4. Detection of zona pellucida proteins during human folliculogenesis. (PMID: 18033806) Gook DA … Martic M (Human reproduction (Oxford, England) 2008) 3 23
  5. Biological effects of recombinant human zona pellucida proteins on sperm function. (PMID: 16407501) Caballero-Campo P … Gerton GL (Biology of reproduction 2006) 3 23

Products for ZP2 Gene

  • Signalway ELISA kits for ZP2

Sources for ZP2 Gene