Search by BoMiProt ID - Bomi10821

Primary Information

BoMiProt ID Bomi10821
Protein Name Zona pellucida sperm-binding protein 4
Organism Bos taurus
Uniprot IDQ9BH11
Milk FractionMFGM
Ref Sequence ID NP_776400.1
Aminoacid Length 534
Molecular Weight 59200
FASTA Sequence Download
Gene Name ZP4
Gene ID 280965
Protein Existence Status Reviewed

Secondary Information

Protein Function Component of extracellular matrix sheltering mammalian oocytes and embryos which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy.
Biochemical Properties ZP4 primarily bind to the capacitated acrosome-intact human spermatozoa.The human ZP4 gene has 13 exons and encodes a 540 aa long polypeptide with 18 aa long signal peptide, ‘trefoil-domain’ corresponding to 141–183 aa residues, ‘ZP domain’ corresponding to 188–460 aa residues and CFCS, SRRR, from 463 to 465 aa residues.Trefoil domain’ has a characteristic pattern of 6 conserved cysteine in a trefoil-like arrangement and is found in a family of small peptides called the Trefoil family.ZP domain consists of approximately 260 aa including 8 conserved cysteine residues and is predicted to have high β-strand content with additional conservation of hydrophobicity, polarity, and turn-forming tendency.It has a bipartite structure with ZP-N and ZP-C subdomains separated by a protease-sensitive region. ‘ZP domain’ plays an important role in the polymerization of human zona proteins into filaments.Immediately after ‘ZP domain’ have CFCS. Proteolytic cleavage at CFCS by proprotein convertase enzyme is critical for the secretion and assembly.Downstream of CFCS, hydrophobic transmembrane-like domain (TMD) and short cytoplasmic tail is present. 
PTMs N-linked glycosylation,proteolytic cleavage
Site(s) of PTM(s)

N-glycosylation, O-glycosylation,
Predicted Disorder Regions NA
DisProt Annotation
TM Helix Prediction 1TMH; (508-530)
Significance of PTMs Proteolytically cleaved before the transmembrane segment to yield the secreted ectodomain incorporated in the zona pellucida. N-linked glycosylation occupies ∼18% of the molecular mass of ZP4.Baculovirus-expressed recombinant human ZP3 and ZP4 deficient in N-linked glycosylation showed significant reduction in their ability to induce acrosome reaction, whereas removal of O-linked glycosylation (by alkali treatment) has no adverse effect on their ability to induce acrosme reaction.Also removal of N-linked glycosylation by N-glycosidase-F from native ZP3 and ZP4 purified from human eggs also significantly inhibited their ability to induce AR in capacitated human sperm as compared to untreated ZP3 and ZP4.
Additional Comments ZP4 may have a role in sperm-egg binding. In rabbits, recombinant ZP4 binds to the acrosome of rabbit sperm
Linking IDs
Bibliography Gupta SK. Human Zona Pellucida Glycoproteins: Binding Characteristics With Human Spermatozoa and Induction of Acrosome Reaction. Front Cell Dev Biol. 2021 Feb 11;9:619868. doi: 10.3389/fcell.2021.619868. PMID: 33681199; PMCID: PMC7928326.