Seroatlas · Human Serome Atlas

ZP3

Zona pellucida sperm-binding protein 3

Also known as: ZP3_HUMAN, ZP3-372, ZP3-424, ZP3A, ZP3B, ZPC

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P21754
Gene
ZP3
Ensembl
ENSG00000188372
Chromosome
7
Canonical length
424 aa
Protein class
Disease related genes, Human disease related genes, Predicted membrane proteins, Predicted secreted proteins
Secretome location
Secreted in female reproductive system
Quaternary structure
Homodimer

OverviewNCBI 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 protein encoded by this gene is a structural component of the zona pellucida and functions in primary binding and induction of the sperm acrosome reaction. The nascent protein contains a N-terminal signal peptide sequence, a conserved ZP domain, a C-terminal consensus furin cleavage site, and a 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. A variation in the last exon of this gene has previously served as the basis for an additional ZP3 locus; however, sequence and literature review reveals that there is only one full-length ZP3 locus in the human genome. Another locus encoding a bipartite transcript designated POMZP3 contains a duplication of the last four exons of ZP3, including the above described variation, and maps closely to this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

424 residues, UniProt reviewed canonical sequence.

>P21754|ZP3
     1  MELSYRLFIC LLLWGSTELC YPQPLWLLQG GASHPETSVQ PVLVECQEAT LMVMVSKDLF
    61  GTGKLIRAAD LTLGPEACEP LVSMDTEDVV RFEVGLHECG NSMQVTDDAL VYSTFLLHDP
   121  RPVGNLSIVR TNRAEIPIEC RYPRQGNVSS QAILPTWLPF RTTVFSEEKL TFSLRLMEEN
   181  WNAEKRSPTF HLGDAAHLQA EIHTGSHVPL RLFVDHCVAT PTPDQNASPY HTIVDFHGCL
   241  VDGLTDASSA FKVPRPGPDT LQFTVDVFHF ANDSRNMIYI TCHLKVTLAE QDPDELNKAC
   301  SFSKPSNSWF PVEGSADICQ CCNKGDCGTP SHSRRQPHVM SQWSRSASRN RRHVTEEADV
   361  TVGPLIFLDR RGDHEVEQWA LPSDTSVVLL GVGLAVVVSL TLTAVILVLT RRCRTASHPV
   421  SASE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ZP3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
1
Mean surface accessibility (rSASA)
0.42
Highest tissue expression
19 nTPM

Expression across tissuesHPA

Tissue

  • ovary: 19 nTPM
  • choroid plexus: 6.3 nTPM
  • basal ganglia: 4.3 nTPM
  • esophagus: 4 nTPM
  • pancreas: 3.9 nTPM
  • skin: 3.9 nTPM

Single-cell type

  • oocytes: 2,910 nCPM
  • late spermatids: 95 nCPM
  • epicardial cells: 66 nCPM
  • late primary spermatocytes: 45 nCPM
  • esophageal apical cells: 28 nCPM
  • early spermatids: 25 nCPM

Immune cell

  • myeloid DC: 9.5 nTPM
  • classical monocyte: 9.4 nTPM
  • non-classical monocyte: 4.6 nTPM
  • naive CD4 T-cell: 4.5 nTPM
  • intermediate monocyte: 3.9 nTPM
  • naive CD8 T-cell: 3.1 nTPM

Brain region

  • basal ganglia: 5.1 nTPM
  • choroid plexus: 4.9 nTPM
  • cerebral cortex: 3.8 nTPM
  • thalamus: 3.8 nTPM
  • white matter: 3.8 nTPM
  • cerebellum: 3.7 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ZP3.

Disease | AllUniProt

Conditions ZP3 is implicated in, by any mechanism.

  • Oocyte/zygote/embryo maturation arrest 3 (OZEMA3) MIM:617712

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 122 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

ReferencesPubMed · IEDB

Publications for ZP3 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

4 publications

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.95
gnomAD pLI
0
gnomAD missense Z
-0.02
DepMap mean gene effect
-0.08
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ZP3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ZP3 as an antibody target. Whether an autoantibody or antibody against ZP3 could matter depends on whether native ZP3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ZP3 is annotated at the cell surface, where native ZP3 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label ZP3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/ZP3. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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