ZP3 is one of the four glycoproteins (ZP1-ZP4) that build the zona pellucida, the thick extracellular coat surrounding mammalian oocytes and pre-implantation embryos. It is made by growing oocytes as a type I membrane precursor and is proteolytically cleaved just before its transmembrane segment, so the mature, heavily N- and O-glycosylated ectodomain is released and incorporated into the coat. Through its ZP domain, ZP3 polymerizes with ZP2 into long filaments that ZP1 cross-links, giving the zona its structure; human variants that disrupt this yield oocytes with no zona pellucida and female infertility. At fertilization ZP3 is the principal sperm-binding component of the coat and the physiological inducer of the acrosome reaction, binding the anterior head of capacitated sperm and triggering calcium-dependent acrosomal exocytosis in a manner that depends on its glycans; it also binds proacrosin/acrosin. ZP3 is widely used as an immunogen in contraceptive-vaccine and autoimmune-oophoritis models, which is the origin of several immune-process annotations rather than a function of the protein.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001809 positive regulation of type IV hypersensitivity | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Immune-response term transferred by similarity from rodent ZP3 immunization studies. Reason: These terms derive from experiments in which ZP3 peptides are used as immunogens in contraceptive-vaccine and autoimmune-oophoritis models: ZP3 is the antigen, not a participant in the immune process. The native protein is an oocyte egg-coat structural glycoprotein. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Component of the zona pellucida, an extracellular matrix PMID:19004505 The immune sera significantly inhibited (p<0.005) the binding of |
| GO:0001825 blastocyst formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Blastocyst formation transferred by similarity from mouse Zp3. Reason: The zona pellucida encloses the pre-implantation embryo and ZP3 is needed to build it, so the term is defensible, but ZP3 performs no step of blastocyst morphogenesis. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Component of the zona pellucida, an extracellular matrix |
| GO:0002455 humoral immune response mediated by circulating immunoglobulin | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Immune-response term transferred by similarity from rodent ZP3 immunization studies. Reason: These terms derive from experiments in which ZP3 peptides are used as immunogens in contraceptive-vaccine and autoimmune-oophoritis models: ZP3 is the antigen, not a participant in the immune process. The native protein is an oocyte egg-coat structural glycoprotein. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Component of the zona pellucida, an extracellular matrix PMID:19004505 The immune sera significantly inhibited (p<0.005) the binding of |
| GO:0002687 positive regulation of leukocyte migration | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Immune-response term transferred by similarity from rodent ZP3 immunization studies. Reason: These terms derive from experiments in which ZP3 peptides are used as immunogens in contraceptive-vaccine and autoimmune-oophoritis models: ZP3 is the antigen, not a participant in the immune process. The native protein is an oocyte egg-coat structural glycoprotein. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Component of the zona pellucida, an extracellular matrix PMID:19004505 The immune sera significantly inhibited (p<0.005) the binding of |
| GO:0002922 positive regulation of humoral immune response | IDA PMID:19004505 DNA vaccine encoding chimeric protein encompassing epitopes ... | MARK AS OVER ANNOTATED | Summary: IDA from a ZP3/ZP4 epitope DNA-vaccine study in mice. Reason: The antibody response is raised against ZP3 as an immunogen; this is antigenicity, not a function of ZP3 in humoral immunity. Supporting Evidence: PMID:19004505 The immune sera significantly inhibited (p<0.005) the binding of |
| GO:0005201 extracellular matrix structural constituent | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | MODIFY | Summary: ZP3 is a structural constituent of the zona pellucida extracellular matrix. Reason: Correct but general: the specific supported term is structural constituent of egg coat (GO:0035804), which the gene already carries; detection in a bone-marrow matrix proteome does not establish a role in other matrices. Proposed replacements: structural constituent of egg coat Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Polymers of ZP2 and ZP3 organized into long filaments cross- file:human/ZP3/ZP3-uniprot.txt abnormal oocytes that lack the zona pellucida, and oocytes |
| GO:0005515 protein binding | IPI PMID:15950651 Binding of recombinant human proacrosin/acrosin to zona pell... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19945174 Identification of human sperm proteins that interact with hu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19945174 Identification of human sperm proteins that interact with hu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19945174 Identification of human sperm proteins that interact with hu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19945174 Identification of human sperm proteins that interact with hu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19945174 Identification of human sperm proteins that interact with hu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19945174 Identification of human sperm proteins that interact with hu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23355646 Identification of sperm head proteins involved in zona pellu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23355646 Identification of sperm head proteins involved in zona pellu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23355646 Identification of sperm head proteins involved in zona pellu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23355646 Identification of sperm head proteins involved in zona pellu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23355646 Identification of sperm head proteins involved in zona pellu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23355646 Identification of sperm head proteins involved in zona pellu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23355646 Identification of sperm head proteins involved in zona pellu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23355646 Identification of sperm head proteins involved in zona pellu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23355646 Identification of sperm head proteins involved in zona pellu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23355646 Identification of sperm head proteins involved in zona pellu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23355646 Identification of sperm head proteins involved in zona pellu... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28886344 A Recurrent Missense Mutation in ZP3 Causes Empty Follicle S... | REMOVE | Summary: Bare protein binding from an interaction assay. Reason: Generic protein binding is uninformative under the protein-binding policy; the reported interactions are not disputed, but no more specific molecular function is established by this row. Supporting Evidence: |
| GO:0005576 extracellular region | IMP PMID:19246320 Functional activity of human ZP3 primary sperm receptor resi... | MODIFY | Summary: Secreted ZP3 ectodomain is extracellular. Reason: Correct but general; the supported specific location is the egg coat (zona pellucida), which the gene already carries. Proposed replacements: egg coat Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Zona pellucida {ECO:0000269|PubMed:29895852} file:human/ZP3/ZP3-uniprot.txt Proteolytically cleaved before the transmembrane segment to yield |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1297338 | MODIFY | Summary: Reactome places ZP3 in the extracellular region. Reason: Correct but general; the egg coat (zona pellucida) is the specific supported location. Proposed replacements: egg coat Supporting Evidence: Reactome:R-HSA-1297338 file:human/ZP3/ZP3-uniprot.txt Zona pellucida {ECO:0000269|PubMed:29895852} |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: ZP3 is synthesized as a type I membrane precursor at the oocyte plasma membrane before cleavage. Reason: Retained as a precursor/trafficking location: the nascent protein carries a transmembrane segment and is cleaved before it to release the ectodomain into the zona pellucida, so the functional pool is extracellular, not membrane-anchored. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Single-pass type I membrane protein file:human/ZP3/ZP3-uniprot.txt Proteolytically cleaved before the transmembrane segment to yield |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ZP3 is synthesized as a type I membrane precursor at the oocyte plasma membrane before cleavage. Reason: Retained as a precursor/trafficking location: the nascent protein carries a transmembrane segment and is cleaved before it to release the ectodomain into the zona pellucida, so the functional pool is extracellular, not membrane-anchored. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Single-pass type I membrane protein file:human/ZP3/ZP3-uniprot.txt Proteolytically cleaved before the transmembrane segment to yield |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ZP3 is synthesized as a type I membrane precursor at the oocyte plasma membrane before cleavage. Reason: Retained as a precursor/trafficking location: the nascent protein carries a transmembrane segment and is cleaved before it to release the ectodomain into the zona pellucida, so the functional pool is extracellular, not membrane-anchored. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Single-pass type I membrane protein file:human/ZP3/ZP3-uniprot.txt Proteolytically cleaved before the transmembrane segment to yield |
| GO:0007165 signal transduction | IEA GO_REF:0000108 | MODIFY | Summary: Electronic mapping to signal transduction. Reason: ZP3 does not transduce a signal itself; it acts as the extracellular ligand that triggers the sperm acrosome reaction, which is better captured by positive regulation of the acrosome reaction. Proposed replacements: positive regulation of acrosome reaction Supporting Evidence: PMID:20394732 being ZP3 the physiological inductor of the AR PMID:18667750 They induced acrosome reaction and inhibited spermatozoa-ZP binding time- and dose-dependently to different extents. |
| GO:0007339 binding of sperm to zona pellucida | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of sperm binding to the zona pellucida for the ZP3/ZPC subfamily. Reason: Matches direct human evidence; the ancestral node is well placed for an egg-coat sperm receptor. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt ZP3 is essential for sperm binding and zona matrix formation. PMID:19700799 A higher percentage of baculovirus-expressed recombinant human ZP3 coated beads showed significant (P<0.05) binding of capacitated human sperm as compared to beads coated with fetuin. |
| GO:0007339 binding of sperm to zona pellucida | IDA PMID:19246320 Functional activity of human ZP3 primary sperm receptor resi... | ACCEPT | Summary: ZP3 mediates binding of sperm to the zona pellucida. Reason: Core function: recombinant human ZP3 on beads binds capacitated human sperm, anti-ZP3 antibodies block that binding, and human ZP3 supports a functional zona in rescue mice. Supporting Evidence: PMID:19246320 revealed binding to the anterior head of capacitated human spermatozoa |
| GO:0007339 binding of sperm to zona pellucida | IDA PMID:19700799 Binding characteristics of sperm with recombinant human zona... | ACCEPT | Summary: ZP3 mediates binding of sperm to the zona pellucida. Reason: Core function: recombinant human ZP3 on beads binds capacitated human sperm, anti-ZP3 antibodies block that binding, and human ZP3 supports a functional zona in rescue mice. Supporting Evidence: PMID:19700799 A higher percentage of baculovirus-expressed recombinant human ZP3 coated beads showed significant (P<0.05) binding of capacitated human sperm as compared to beads coated with fetuin. |
| GO:0007339 binding of sperm to zona pellucida | IGI PMID:9609824 Human ZP3 restores fertility in Zp3 null mice without affect... | ACCEPT | Summary: ZP3 mediates binding of sperm to the zona pellucida. Reason: Core function: recombinant human ZP3 on beads binds capacitated human sperm, anti-ZP3 antibodies block that binding, and human ZP3 supports a functional zona in rescue mice. Supporting Evidence: PMID:9609824 notwithstanding the absence of mouse ZP3, mouse sperm bound to ovulated eggs in vitro and fertility was restored in vivo |
| GO:0007339 binding of sperm to zona pellucida | IMP PMID:19004505 DNA vaccine encoding chimeric protein encompassing epitopes ... | ACCEPT | Summary: ZP3 mediates binding of sperm to the zona pellucida. Reason: Core function: recombinant human ZP3 on beads binds capacitated human sperm, anti-ZP3 antibodies block that binding, and human ZP3 supports a functional zona in rescue mice. Supporting Evidence: PMID:19004505 The immune sera significantly inhibited (p<0.005) the binding of |
| GO:0030246 carbohydrate binding | IDA PMID:19246320 Functional activity of human ZP3 primary sperm receptor resi... | ACCEPT | Summary: ZP3 binds sperm in a glycan-dependent manner. Reason: Carbohydrate binding here describes the ZP3 glycans being recognized rather than ZP3 acting as a lectin; the row is nevertheless supported in the sense that ZP3 sperm-binding and acrosome-inducing activity depends on its N- and O-linked glycans. Kept, with that caveat noted. Supporting Evidence: PMID:18667750 These biological activities of human ZP3 and ZP4 depended partly on their glycosylation, with N-linked glycosylation contributing much more significantly than O-linked glycosylation. PMID:19246320 revealed binding to the anterior head of capacitated human spermatozoa |
| GO:0031012 extracellular matrix | HDA PMID:28344315 Proteomic characterization of human multiple myeloma bone ma... | MODIFY | Summary: High-throughput proteomic detection in an extracellular matrix preparation. Reason: Correct but general; the physiological matrix for ZP3 is the egg coat. Proposed replacements: egg coat Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Zona pellucida {ECO:0000269|PubMed:29895852} |
| GO:0031012 extracellular matrix | IDA PMID:19246320 Functional activity of human ZP3 primary sperm receptor resi... | MODIFY | Summary: ZP3 is a component of an extracellular matrix. Reason: Correct but general; the egg coat (zona pellucida) is the specific supported location. Proposed replacements: egg coat Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Zona pellucida {ECO:0000269|PubMed:29895852} file:human/ZP3/ZP3-uniprot.txt Polymers of ZP2 and ZP3 organized into long filaments cross- |
| GO:0032190 acrosin binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of acrosin binding for the ZP3 subfamily. Reason: Consistent with direct binding of recombinant proacrosin/acrosin to human ZP3 (rec-hZPC). Supporting Evidence: PMID:15950651 saturable high affinity binding of Rec-40 to ZP components was |
| GO:0032190 acrosin binding | IPI PMID:15950651 Binding of recombinant human proacrosin/acrosin to zona pell... | ACCEPT | Summary: Recombinant proacrosin/acrosin binds human ZP3. Reason: Direct in vitro binding assay; an informative, specific binding function. Supporting Evidence: PMID:15950651 saturable high affinity binding of Rec-40 to ZP components was |
| GO:0032729 positive regulation of type II interferon production | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Immune-response term transferred by similarity from rodent ZP3 immunization studies. Reason: These terms derive from experiments in which ZP3 peptides are used as immunogens in contraceptive-vaccine and autoimmune-oophoritis models: ZP3 is the antigen, not a participant in the immune process. The native protein is an oocyte egg-coat structural glycoprotein. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Component of the zona pellucida, an extracellular matrix PMID:19004505 The immune sera significantly inhibited (p<0.005) the binding of |
| GO:0032753 positive regulation of interleukin-4 production | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Immune-response term transferred by similarity from rodent ZP3 immunization studies. Reason: These terms derive from experiments in which ZP3 peptides are used as immunogens in contraceptive-vaccine and autoimmune-oophoritis models: ZP3 is the antigen, not a participant in the immune process. The native protein is an oocyte egg-coat structural glycoprotein. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Component of the zona pellucida, an extracellular matrix PMID:19004505 The immune sera significantly inhibited (p<0.005) the binding of |
| GO:0035803 egg coat formation | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of egg coat formation. Reason: Core process: ZP3 polymerizes into the zona pellucida and its loss leaves oocytes without one. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Polymers of ZP2 and ZP3 organized into long filaments cross- file:human/ZP3/ZP3-uniprot.txt abnormal oocytes that lack the zona pellucida, and oocytes |
| GO:0035803 egg coat formation | ISS GO_REF:0000024 | ACCEPT | Summary: Egg coat formation by similarity. Reason: Consistent with human disease genetics and with the ZP-domain polymerization mechanism. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt abnormal oocytes that lack the zona pellucida, and oocytes file:human/ZP3/ZP3-uniprot.txt The ZP domain is involved in the polymerization of the ZP |
| GO:0035804 structural constituent of egg coat | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of structural constituent of egg coat. Reason: Core molecular function of ZP3. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Polymers of ZP2 and ZP3 organized into long filaments cross- file:human/ZP3/ZP3-uniprot.txt The ZP domain is involved in the polymerization of the ZP |
| GO:0035804 structural constituent of egg coat | ISS GO_REF:0000024 | ACCEPT | Summary: Structural constituent of egg coat by similarity. Reason: Core molecular function, supported by ZP-domain polymerization and the zona-less oocyte phenotype. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt The ZP domain is involved in the polymerization of the ZP file:human/ZP3/ZP3-uniprot.txt abnormal oocytes that lack the zona pellucida, and oocytes |
| GO:0035805 egg coat | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference that ZP3 acts in the egg coat. Reason: Correct functional location. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Zona pellucida {ECO:0000269|PubMed:29895852} file:human/ZP3/ZP3-uniprot.txt Polymers of ZP2 and ZP3 organized into long filaments cross- |
| GO:0035805 egg coat | IDA PMID:29895852 ZP2 pathogenic variants cause in vitro fertilization failure... | ACCEPT | Summary: ZP3 protein detected in the human zona pellucida. Reason: Core location of the mature, cleaved ectodomain. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Zona pellucida {ECO:0000269|PubMed:29895852} |
| GO:0035805 egg coat | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic mapping to egg coat. Reason: Consistent with direct evidence. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Zona pellucida {ECO:0000269|PubMed:29895852} |
| GO:0042102 positive regulation of T cell proliferation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Immune-response term transferred by similarity from rodent ZP3 immunization studies. Reason: These terms derive from experiments in which ZP3 peptides are used as immunogens in contraceptive-vaccine and autoimmune-oophoritis models: ZP3 is the antigen, not a participant in the immune process. The native protein is an oocyte egg-coat structural glycoprotein. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Component of the zona pellucida, an extracellular matrix PMID:19004505 The immune sera significantly inhibited (p<0.005) the binding of |
| GO:0042802 identical protein binding | IPI PMID:26879157 A common 'aggregation-prone' interface possibly participates... | ACCEPT | Summary: ZP3 self-associates: ZP-domain peptides from ZP2, ZP3 and ZP4 self-assemble into filaments. Reason: Informative binding function underlying coat assembly, consistent with the ZP-domain polymerization mechanism. Supporting Evidence: PMID:26879157 ZP proteins form heterodimers, which are incorporated into filaments through a common bipartite polymerizing component, designated as the ZP domain. file:human/ZP3/ZP3-uniprot.txt The ZP domain is involved in the polymerization of the ZP |
| GO:0045892 negative regulation of DNA-templated transcription | ISS GO_REF:0000024 | REMOVE | Summary: Negative regulation of DNA-templated transcription (ISS), inferred from mouse Zp3, from a study in which ZP3 was used as a vaccine antigen (PMID:18667753). Reason: The row is inferred from mouse Zp3, where the term was annotated from a study of immunization with a recombinant cytomegalovirus expressing ZP3 (PMID:18667753). In that work ZP3 is the vaccine antigen: the immune response against it destroys ovarian follicles, and the diminished expression of genes of follicle development such as Nobox, Gdf9 and Gja1 follows from the loss of follicles. The experiment does not show that the ZP3 protein regulates transcription, and nothing else suggests that a secreted structural glycoprotein of the egg coat does so. The claim is unsupported at its source and at odds with the biology of the protein, so the row is removed. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Component of the zona pellucida, an extracellular matrix file:human/ZP3/ZP3-uniprot.txt Proteolytically cleaved before the transmembrane segment to yield |
| GO:0045893 positive regulation of DNA-templated transcription | ISS GO_REF:0000024 | REMOVE | Summary: Positive regulation of DNA-templated transcription (ISS), inferred from mouse Zp3, from a study in which ZP3 was used as a vaccine antigen (PMID:18667753). Reason: The row is inferred from mouse Zp3, where the term was annotated from a study of immunization with a recombinant cytomegalovirus expressing ZP3 (PMID:18667753). In that work ZP3 is the vaccine antigen, and the changes in gene expression in the ovary accompany autoimmune destruction of follicles and infiltration by inflammatory cells; they are not an effect of the ZP3 protein on transcription. Nothing else suggests that a secreted structural glycoprotein of the egg coat regulates transcription. The claim is unsupported at its source and at odds with the biology of the protein, so the row is removed. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Component of the zona pellucida, an extracellular matrix file:human/ZP3/ZP3-uniprot.txt Proteolytically cleaved before the transmembrane segment to yield |
| GO:0048018 receptor ligand activity | ISS GO_REF:0000024 | ACCEPT | Summary: ZP3 acts as the extracellular ligand that activates sperm receptors. Reason: Supported: ZP3 binds the anterior sperm head and triggers receptor-dependent signaling culminating in the acrosome reaction. Supporting Evidence: PMID:19246320 revealed binding to the anterior head of capacitated human spermatozoa PMID:20394732 being ZP3 the physiological inductor of the AR |
| GO:0048599 oocyte development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Oocyte development by similarity. Reason: ZP3 is made by growing oocytes and its loss gives degenerating, zona-less oocytes, so the association is real, but ZP3 builds the coat rather than executing oocyte differentiation. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt abnormal oocytes that lack the zona pellucida, and oocytes |
| GO:0050729 positive regulation of inflammatory response | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Immune-response term transferred by similarity from rodent ZP3 immunization studies. Reason: These terms derive from experiments in which ZP3 peptides are used as immunogens in contraceptive-vaccine and autoimmune-oophoritis models: ZP3 is the antigen, not a participant in the immune process. The native protein is an oocyte egg-coat structural glycoprotein. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Component of the zona pellucida, an extracellular matrix PMID:19004505 The immune sera significantly inhibited (p<0.005) the binding of |
| GO:0140149 non-collagenous component of interstitial matrix | TAS PMID:36399478 MatrisomeDB 2.0: 2023 updates to the ECM-protein knowledge d... | MODIFY | Summary: MatrisomeDB classifies ZP3 as a non-collagenous matrix component. Reason: Correct in kind but mis-specific: ZP3 is not a component of interstitial matrix; it is a component of the egg coat, a specialized extracellular matrix. Proposed replacements: egg coat Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Zona pellucida {ECO:0000269|PubMed:29895852} |
| GO:2000344 positive regulation of acrosome reaction | IBA GO_REF:0000033 | ACCEPT | Summary: ZP3 induces the sperm acrosome reaction. Reason: Core function: native and recombinant human ZP3 trigger acrosomal exocytosis in capacitated human sperm in a glycosylation-dependent, calcium-channel-dependent manner. Supporting Evidence: PMID:18667750 They induced acrosome reaction and inhibited spermatozoa-ZP binding time- and dose-dependently to different extents. PMID:20394732 being ZP3 the physiological inductor of the AR |
| GO:2000344 positive regulation of acrosome reaction | IDA PMID:11751269 A role for the human sperm glycine receptor/Cl(-) channel in... | ACCEPT | Summary: ZP3 induces the sperm acrosome reaction. Reason: Core function: native and recombinant human ZP3 trigger acrosomal exocytosis in capacitated human sperm in a glycosylation-dependent, calcium-channel-dependent manner. Supporting Evidence: PMID:20394732 being ZP3 the physiological inductor of the AR |
| GO:2000344 positive regulation of acrosome reaction | IDA PMID:18667750 Effects of native human zona pellucida glycoproteins 3 and 4... | ACCEPT | Summary: ZP3 induces the sperm acrosome reaction. Reason: Core function: native and recombinant human ZP3 trigger acrosomal exocytosis in capacitated human sperm in a glycosylation-dependent, calcium-channel-dependent manner. Supporting Evidence: PMID:18667750 They induced acrosome reaction and inhibited spermatozoa-ZP binding time- and dose-dependently to different extents. PMID:18667750 These biological activities of human ZP3 and ZP4 depended partly on their glycosylation, with N-linked glycosylation contributing much more significantly than O-linked glycosylation. |
| GO:2000344 positive regulation of acrosome reaction | IDA PMID:20394732 Recombinant human ZP3-induced sperm acrosome reaction: evide... | ACCEPT | Summary: ZP3 induces the sperm acrosome reaction. Reason: Core function: native and recombinant human ZP3 trigger acrosomal exocytosis in capacitated human sperm in a glycosylation-dependent, calcium-channel-dependent manner. Supporting Evidence: PMID:20394732 being ZP3 the physiological inductor of the AR |
| GO:2000360 negative regulation of binding of sperm to zona pellucida | IDA PMID:18667750 Effects of native human zona pellucida glycoproteins 3 and 4... | KEEP AS NON CORE | Summary: Purified native ZP3 inhibits sperm-zona binding in a competition assay. Reason: Soluble purified ZP3 competes with the intact zona for sperm, so the inhibition observed is the expected behaviour of the sperm-binding ligand in a competition assay rather than a physiological inhibitory role. Kept, but peripheral. Supporting Evidence: PMID:18667750 They induced acrosome reaction and inhibited spermatozoa-ZP binding time- and dose-dependently to different extents. |
| GO:2000368 positive regulation of acrosomal vesicle exocytosis | IDA PMID:19246320 Functional activity of human ZP3 primary sperm receptor resi... | ACCEPT | Summary: ZP3 triggers acrosomal exocytosis in capacitated human sperm. Reason: Core function, demonstrated with recombinant ZP3 fragments. Supporting Evidence: PMID:19246320 Significant induction of acrosomal exocytosis was observed when capacitated sperm were incubated with PMID:19246320 revealed binding to the anterior head of capacitated human spermatozoa |
| GO:2000368 positive regulation of acrosomal vesicle exocytosis | IMP PMID:19004505 DNA vaccine encoding chimeric protein encompassing epitopes ... | ACCEPT | Summary: Antibodies raised against a ZP3 epitope block ZP3-induced acrosomal exocytosis. Reason: Supports ZP3 as the inducer of acrosomal exocytosis. Supporting Evidence: PMID:19004505 The immune sera significantly inhibited (p<0.005) the binding of PMID:20394732 being ZP3 the physiological inductor of the AR |
| GO:2000386 positive regulation of ovarian follicle development | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Positive regulation of ovarian follicle development by similarity. Reason: Derived from rodent immunization models in which anti-ZP3 responses disturb folliculogenesis; ZP3 itself is a structural coat protein, not a regulator of follicle development. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Component of the zona pellucida, an extracellular matrix PMID:19004505 The immune sera significantly inhibited (p<0.005) the binding of |
| GO:2000388 positive regulation of antral ovarian follicle growth | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Positive regulation of antral follicle growth by similarity. Reason: Same basis as the preceding row; not a function of the ZP3 protein. Supporting Evidence: file:human/ZP3/ZP3-uniprot.txt Component of the zona pellucida, an extracellular matrix PMID:19004505 The immune sera significantly inhibited (p<0.005) the binding of |
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Download this section (compressed HTML)Q: Which sperm-surface receptor(s) does human ZP3 engage, and does species-specific sperm binding reside in ZP3 glycans, in ZP2, or in the supramolecular arrangement of the coat?
Q: Is any uncleaved, membrane-anchored ZP3 present at the oocyte surface, and does it have a role distinct from the secreted ectodomain?
Experiment: Cross-link and identify sperm-surface partners of defined, correctly glycosylated human ZP3 ectodomain preparations, with ZP2/ZP4 controls, to identify the receptor responsible for acrosome-reaction induction.
Experiment: Use oocyte-specific tagging and surface labelling of non-permeabilized human or humanized-mouse oocytes to quantify membrane-anchored versus coat-incorporated ZP3.
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