Seroatlas · Human Serome Atlas

ZP4

Zona pellucida sperm-binding protein 4

Also known as: ZP1B, ZP4_HUMAN, ZPB, ZPB2

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

Protein identityUniProt · HPA

UniProt accession: Q12836
Gene: ZP4
Ensembl: ENSG00000116996
Chromosome: 1
Canonical length: 540 aa
Protein class: Predicted membrane proteins, Predicted secreted proteins
Secretome location: Secreted in female reproductive system

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 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]

Canonical amino-acid sequenceUniProt

540 residues, UniProt reviewed canonical sequence.

>Q12836|ZP4
     1  MWLLRCVLLC VSLSLAVSGQ HKPEAPDYSS VLHCGPWSFQ FAVNLNQEAT SPPVLIAWDN
    61  QGLLHELQND SDCGTWIRKG PGSSVVLEAT YSSCYVTEWD SHYIMPVGVE GAGAAEHKVV
   121  TERKLLKCPM DLLARDAPDT DWCDSIPARD RLPCAPSPIS RGDCEGLGCC YSSEEVNSCY
   181  YGNTVTLHCT REGHFSIAVS RNVTSPPLLL DSVRLALRND SACNPVMATQ AFVLFQFPFT
   241  SCGTTRQITG DRAVYENELV ATRDVKNGSR GSVTRDSIFR LHVSCSYSVS SNSLPINVQV
   301  FTLPPPFPET QPGPLTLELQ IAKDKNYGSY YGVGDYPVVK LLRDPIYVEV SILHRTDPYL
   361  GLLLQQCWAT PSTDPLSQPQ WPILVKGCPY IGDNYQTQLI PVQKALDLPF PSHHQRFSIF
   421  TFSFVNPTVE KQALRGPVHL HCSVSVCQPA ETPSCVVTCP DLSRRRNFDN SSQNTTASVS
   481  SKGPMILLQA TKDPPEKLRV PVDSKVLWVA GLSGTLILGA LLVSYLAVKK QKSCPDQMCQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ZP4 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): 0.39
Highest tissue expression: 3.6 nTPM

Expression across tissuesHPA

Tissue

ovary: 3.6 nTPM
tonsil: 0.2 nTPM
placenta: 0.1 nTPM
thymus: 0.1 nTPM
adipose tissue: 0 nTPM
adrenal gland: 0 nTPM

Single-cell type

oocytes: 92 nCPM
foveolar cells: 1.7 nCPM
esophageal apical cells: 0.9 nCPM
granulosa cells: 0.8 nCPM
submucosal glandular cells: 0.7 nCPM
ovarian stromal cells: 0.6 nCPM

Immune cell

basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM
intermediate monocyte: 0 nTPM
MAIT T-cell: 0 nTPM

Brain region

medulla oblongata: 0.1 nTPM
amygdala: 0 nTPM
basal ganglia: 0 nTPM
cerebellum: 0 nTPM
cerebral cortex: 0 nTPM
choroid plexus: 0 nTPM

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): 1.31
gnomAD pLI: 0
gnomAD missense Z: -1.24
DepMap mean gene effect: 0.03
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% 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

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ZP4 as an antibody target. Whether an autoantibody or antibody against ZP4 could matter depends on whether native ZP4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ZP4 is annotated at the cell surface, where native ZP4 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 ZP4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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