WIPI2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0034045 phagophore assembly site membrane	IBA GO_REF:0000033	MODIFY	Summary: Localization to the phagophore membrane is supported. Reason: Live QuickGO checked on 2026-09-20 marks GO:0034045 obsolete and provides the current GO:7770114 phagophore membrane. The demonstrated peripheral membrane localization should be retained with the current membrane term; a new term proposal is no longer necessary. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000132136 · PTN000132136 SUPPORTS TRANSFER The PAINT ancestral localization is supported, including target experimental evidence. The change updates the obsolete destination term, without rejecting the inherited membrane association. Proposed replacements: phagophore membrane Supporting Evidence: PMID:20505359 WIPI2 is recruited to early autophagosomal structures along with Atg16L and ULK1 and is required for the formation of LC3-positive autophagosomes.
GO:0032266 phosphatidylinositol-3-phosphate binding	IBA GO_REF:0000033	ACCEPT	Summary: Phosphatidylinositol-3-phosphate binding, the ligand-recognition half of the adaptor. Reason: WIPI2 is a seven-bladed PROPPIN beta-propeller with two PtdIns3P sites built around the conserved FRRG motif, and it is a bona fide mammalian PtdIns3P effector. This binding is what localizes it to omegasome and phagophore membranes. Supported by two IDA experiments as well as by IBA across the family. Core. Supporting Evidence: PMID:20505359 We show that WIPI2 is a mammalian effector of PtdIns3P and is ubiquitously expressed in a variety of cell lines. PMID:24954904 All known members have two PtdIns(3)P binding sites formed around a conserved FRRG motif and a hydrophobic loop that is predicted to insert into the membrane
GO:0000422 autophagy of mitochondrion	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Autophagy of mitochondrion, a selective-autophagy subtype that follows from the core role. Reason: Mitophagy in mammalian cells uses the same PtdIns3P-to-ATG16L1 relay that WIPI2 provides for bulk autophagy, so the claim is biologically defensible, but it is a consequence of the core adaptor function rather than a dedicated mitochondrial activity. Non-core.
GO:0000425 pexophagy	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: WIPI2 participates in experimentally demonstrated human pexophagy. Reason: Full PMID:37621214 Fig. EV3B measures peroxisome-targeted Keima-SKL in wild-type and WIPI2-knockout HeLa cells after phenanthroline treatment and finds blocked pexophagy in the knockout. Combined with the demonstrated WIPI2 adaptor function in recruiting autophagic conjugation machinery, this supports execution of peroxisome clearance rather than cargo-substrate necessity. It corroborates the inherited PROPPIN assertion independently of donor count. Retain this stimulus-specific role as noncore without claiming every pexophagy route requires WIPI2. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000132136 · PTN000132136 SUPPORTS TRANSFER The ancestral PROPPIN pexophagy IBD now has corroborating target-specific human WIPI2 knockout evidence in PMID:37621214 Fig. EV3B. WIPI2 performs adaptor/conjugation-machinery work, not merely cargo recognition. Supporting Evidence: PMID:37621214 finding a complete block of pexophagy in WIPI2 KO cells (Fig EV3B ).
GO:0030674 protein-macromolecule adaptor activity	IBA GO_REF:0000033	ACCEPT	Summary: Protein-macromolecule adaptor activity. This is WIPI2's defining molecular function: it couples a lipid signal to a protein complex. Reason: WIPI2 has no catalytic activity. What it does is read PtdIns3P through its FRRG-centred binding sites and, from that membrane vantage point, bind ATG16L1 and so deliver the ATG12-ATG5-ATG16L1 conjugation machinery to the phagophore. The two halves are separable: an FRRG-to-FTTG mutant that cannot bind PtdIns3P still binds ATG16L1, showing the lipid-reading and the cargo-holding are distinct surfaces of one adaptor. Core. Supporting Evidence: PMID:24954904 Inhibition of PtdIns(3)P binding through mutation of the PtdIns(3)P binding motif FRRG to FTTG (GFP-WIPI2b FTTG) had no significant effect on the ability of WIPI2b to bind Atg16L1
GO:0044804 nucleophagy	IBA GO_REF:0000033	UNDECIDED	Summary: The inherited nucleophagy contribution remains unresolved, not disproven. Reason: PTN000132136 places this selective-autophagy process in the ancestral PROPPIN family, with descendant evidence from SGD:S000001917, SGD:S000003455 and SGD:S000006021. WIPI2 performs membrane-localized adaptor work that recruits ATG16L1 and enables ATG8 lipidation, so a shared execution role can count as participation without providing cargo selectivity. The term is not rejected merely because a different receptor recognizes cargo. Nucleophagy is not limited by definition to yeast piecemeal microautophagy. The exact conservation or division of these functions among WIPI paralogs requires focused evidence adjudication. The completed OpenScientist report recommends retaining selective-process IBAs as non-core on a shared-machinery model. Its statement that every canonical selective autophagosome necessarily requires WIPI2 is stronger than the cited target assays, and it also identifies unresolved paralog-specific dependence. The report is incorporated as an explicit alternative interpretation, with a second opinion still required on process-specific conservation; no duplicate report is needed. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000132136 · PTN000132136 UNRESOLVED The IBD is a genuine ancestral PROPPIN assertion supported by SGD:S000001917, SGD:S000003455 and SGD:S000006021. No target-specific loss has been established. Shared machinery versus cargo recognition does not itself invalidate process participation; the relevant target/ortholog experiments remain to be adjudicated.
GO:0061723 glycophagy	IBA GO_REF:0000033	UNDECIDED	Summary: The inherited glycophagy contribution remains unresolved, not disproven. Reason: PTN000132136 places this selective-autophagy process in the ancestral PROPPIN family, with descendant evidence from FB:FBgn0035850. WIPI2 performs membrane-localized adaptor work that recruits ATG16L1 and enables ATG8 lipidation, so a shared execution role can count as participation without providing cargo selectivity. The term is not rejected merely because a different receptor recognizes cargo. Glycophagy is glycogen degradation by macroautophagy; STBD1-dependent cargo recruitment and WIPI2-dependent membrane assembly would perform different steps, so lack of glycogen binding is not evidence against participation. The exact conservation or division of these functions among WIPI paralogs requires focused evidence adjudication. The completed OpenScientist report recommends retaining selective-process IBAs as non-core on a shared-machinery model. Its statement that every canonical selective autophagosome necessarily requires WIPI2 is stronger than the cited target assays, and it also identifies unresolved paralog-specific dependence. The report is incorporated as an explicit alternative interpretation, with a second opinion still required on process-specific conservation; no duplicate report is needed. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000132136 · PTN000132136 UNRESOLVED The IBD is a genuine ancestral PROPPIN assertion supported by FB:FBgn0035850. No target-specific loss has been established. Shared machinery versus cargo recognition does not itself invalidate process participation; the relevant target/ortholog experiments remain to be adjudicated.
GO:0034497 protein localization to phagophore assembly site	IBA GO_REF:0000033	ACCEPT	Summary: Protein localization to phagophore assembly site. This is what WIPI2 does, stated as a process. Reason: Once activated by PtdIns3P, WIPI2 recruits the ATG12-ATG5-ATG16L1 complex to the phagophore assembly site; ATG16L1 mutants that cannot bind WIPI2 fail to bring LC3 to the phagophore. The process counterpart of the accepted GO:0030674 adaptor activity, supported by IMP as well as IBA. Core. Supporting Evidence: PMID:24954904 Significantly less LC3 was recruited to p62-positive Salmonella in cells expressing the WIPI2-binding mutant compared to WT Atg16L1
GO:0080025 phosphatidylinositol-3,5-bisphosphate binding	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phosphatidylinositol-3,5-bisphosphate binding, a second PROPPIN ligand that is not the autophagy-relevant one. Reason: PtdIns(3,5)P2 binding is a supported secondary lipid-binding activity of WIPI2/PROPPIN proteins. PI3P is the ligand established for recruitment of WIPI2 during canonical autophagosome formation; the physiological contexts that specifically use the other ligand are less well resolved.
GO:0006950 response to stress	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: The broad stress-response annotation is compatible with WIPI2-dependent autophagy. Reason: WIPI2 executes adaptor-mediated membrane assembly during starvation-induced autophagy, a documented stress response. The broad term does not exceed that evidence or assert involvement in every form of stress. Retain it as contextual rather than treating generic scope as a biological error. Supporting Evidence: PMID:20505359 is required for the formation of LC3-positive autophagosomes.
GO:0032266 phosphatidylinositol-3-phosphate binding	IEA GO_REF:0000117	ACCEPT	Summary: Phosphatidylinositol-3-phosphate binding, the ligand-recognition half of the adaptor. Reason: WIPI2 is a seven-bladed PROPPIN beta-propeller with two PtdIns3P sites built around the conserved FRRG motif, and it is a bona fide mammalian PtdIns3P effector. This binding is what localizes it to omegasome and phagophore membranes. Supported by two IDA experiments as well as by IBA across the family. Core. Supporting Evidence: PMID:20505359 We show that WIPI2 is a mammalian effector of PtdIns3P and is ubiquitously expressed in a variety of cell lines. PMID:24954904 All known members have two PtdIns(3)P binding sites formed around a conserved FRRG motif and a hydrophobic loop that is predicted to insert into the membrane
GO:0034045 phagophore assembly site membrane	IEA GO_REF:0000120	MODIFY	Summary: Localization to the phagophore membrane is supported. Reason: Live QuickGO checked on 2026-09-20 marks GO:0034045 obsolete and provides the current GO:7770114 phagophore membrane. The demonstrated peripheral membrane localization should be retained with the current membrane term; a new term proposal is no longer necessary. Proposed replacements: phagophore membrane Supporting Evidence: PMID:20505359 WIPI2 is recruited to early autophagosomal structures along with Atg16L and ULK1 and is required for the formation of LC3-positive autophagosomes.
GO:0034497 protein localization to phagophore assembly site	IEA GO_REF:0000117	ACCEPT	Summary: Protein localization to phagophore assembly site. This is what WIPI2 does, stated as a process. Reason: Once activated by PtdIns3P, WIPI2 recruits the ATG12-ATG5-ATG16L1 complex to the phagophore assembly site; ATG16L1 mutants that cannot bind WIPI2 fail to bring LC3 to the phagophore. The process counterpart of the accepted GO:0030674 adaptor activity, supported by IMP as well as IBA. Core. Supporting Evidence: PMID:24954904 Significantly less LC3 was recruited to p62-positive Salmonella in cells expressing the WIPI2-binding mutant compared to WT Atg16L1
GO:0005515 protein binding	IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi...	REMOVE	Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor.
GO:0005515 protein binding	IPI PMID:39284914 ER-phagy restrains inflammatory responses through its recept...	REMOVE	Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor.
GO:0000421 autophagosome membrane	IDA PMID:31006538 Intrinsically Disordered Protein TEX264 Mediates ER-phagy.	KEEP AS NON CORE	Summary: Autophagosome membrane. Defensible only in the phagophore sense, and in tension with the NOT autophagosome annotation on this same gene. Reason: WIPI2 marks the growing phagophore and leaves before the autophagosome matures, which is exactly what the NOT\|colocalizes_with GO:0005776 annotation from PMID:20505359 records. Reading GO:0000421 as the phagophore membrane makes the two consistent; reading it as the membrane of a completed autophagosome makes them contradictory. Retained as non-core rather than removed, because the source full text is not available here and the curator may have used the term in the phagophore sense that GO's autophagy branch has long conflated. This ambiguity is the same one that motivates the proposed phagophore membrane term below.
GO:0034045 phagophore assembly site membrane	EXP PMID:23916833 Inhibition of LRRK2 kinase activity stimulates macroautophag...	MODIFY	Summary: Localization to the phagophore membrane is supported. Reason: Live QuickGO checked on 2026-09-20 marks GO:0034045 obsolete and provides the current GO:7770114 phagophore membrane. The demonstrated peripheral membrane localization should be retained with the current membrane term; a new term proposal is no longer necessary. Proposed replacements: phagophore membrane Supporting Evidence: PMID:20505359 WIPI2 is recruited to early autophagosomal structures along with Atg16L and ULK1 and is required for the formation of LC3-positive autophagosomes.
GO:0034045 phagophore assembly site membrane	EXP PMID:28561066 WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC...	MODIFY	Summary: Localization to the phagophore membrane is supported. Reason: Live QuickGO checked on 2026-09-20 marks GO:0034045 obsolete and provides the current GO:7770114 phagophore membrane. The demonstrated peripheral membrane localization should be retained with the current membrane term; a new term proposal is no longer necessary. Proposed replacements: phagophore membrane Supporting Evidence: PMID:20505359 WIPI2 is recruited to early autophagosomal structures along with Atg16L and ULK1 and is required for the formation of LC3-positive autophagosomes.
GO:0034045 phagophore assembly site membrane	EXP PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates ...	MODIFY	Summary: Localization to the phagophore membrane is supported. Reason: Live QuickGO checked on 2026-09-20 marks GO:0034045 obsolete and provides the current GO:7770114 phagophore membrane. The demonstrated peripheral membrane localization should be retained with the current membrane term; a new term proposal is no longer necessary. Proposed replacements: phagophore membrane Supporting Evidence: PMID:20505359 WIPI2 is recruited to early autophagosomal structures along with Atg16L and ULK1 and is required for the formation of LC3-positive autophagosomes.
GO:0034045 phagophore assembly site membrane	EXP PMID:33499712 Mammalian BCAS3 and C16orf70 associate with the phagophore a...	MODIFY	Summary: Localization to the phagophore membrane is supported. Reason: Live QuickGO checked on 2026-09-20 marks GO:0034045 obsolete and provides the current GO:7770114 phagophore membrane. The demonstrated peripheral membrane localization should be retained with the current membrane term; a new term proposal is no longer necessary. Proposed replacements: phagophore membrane Supporting Evidence: PMID:20505359 WIPI2 is recruited to early autophagosomal structures along with Atg16L and ULK1 and is required for the formation of LC3-positive autophagosomes.
GO:0000407 phagophore assembly site	IDA PMID:33499712 Mammalian BCAS3 and C16orf70 associate with the phagophore a...	ACCEPT	Summary: Phagophore assembly site, observed directly in three independent studies. Reason: Direct microscopy places WIPI2 at early autophagic structures where its PI3P-binding and ATG16L1-recruiting activities support phagophore assembly. This functional site is compatible with its more specific membrane and diffuse cytosolic pools.
GO:0000045 autophagosome assembly	IDA PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates ...	ACCEPT	Summary: Autophagosome assembly, WIPI2's core biological process. Reason: WIPI2 is required for the formation of LC3-positive autophagosomes: it binds PtdIns3P generated on the omegasome and recruits the ATG12-ATG5-ATG16L1 complex that drives LC3 lipidation and membrane elongation. Depleting it stalls the pathway at the omegasome stage. Supported independently by IDA and by two IMP experiments. Supporting Evidence: PMID:20505359 WIPI2 is recruited to early autophagosomal structures along with Atg16L and ULK1 and is required for the formation of LC3-positive autophagosomes.
GO:0005515 protein binding	IPI PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates ...	REMOVE	Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor.
GO:0005515 protein binding	IPI PMID:28561066 WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC...	REMOVE	Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor.
GO:0034497 protein localization to phagophore assembly site	IMP PMID:28561066 WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC...	ACCEPT	Summary: Protein localization to phagophore assembly site. This is what WIPI2 does, stated as a process. Reason: Once activated by PtdIns3P, WIPI2 recruits the ATG12-ATG5-ATG16L1 complex to the phagophore assembly site; ATG16L1 mutants that cannot bind WIPI2 fail to bring LC3 to the phagophore. The process counterpart of the accepted GO:0030674 adaptor activity, supported by IMP as well as IBA. Core. Supporting Evidence: PMID:24954904 Significantly less LC3 was recruited to p62-positive Salmonella in cells expressing the WIPI2-binding mutant compared to WT Atg16L1
GO:0000045 autophagosome assembly	IMP PMID:28561066 WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC...	ACCEPT	Summary: Autophagosome assembly, WIPI2's core biological process. Reason: WIPI2 is required for the formation of LC3-positive autophagosomes: it binds PtdIns3P generated on the omegasome and recruits the ATG12-ATG5-ATG16L1 complex that drives LC3 lipidation and membrane elongation. Depleting it stalls the pathway at the omegasome stage. Supported independently by IDA and by two IMP experiments. Supporting Evidence: PMID:20505359 WIPI2 is recruited to early autophagosomal structures along with Atg16L and ULK1 and is required for the formation of LC3-positive autophagosomes.
GO:0000407 phagophore assembly site	IDA PMID:28561066 WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC...	ACCEPT	Summary: Phagophore assembly site, observed directly in three independent studies. Reason: Direct microscopy places WIPI2 at early autophagic structures where its PI3P-binding and ATG16L1-recruiting activities support phagophore assembly. This functional site is compatible with its more specific membrane and diffuse cytosolic pools.
GO:0009267 cellular response to starvation	IDA PMID:28561066 WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC...	KEEP AS NON CORE	Summary: Cellular response to starvation, the physiological trigger for WIPI2 recruitment. Reason: Amino-acid starvation activates ULK1 and the class III PI3K, generating the PtdIns3P that recruits WIPI2, so this is a genuine and directly observed response. It is the upstream context in which the core adaptor function is deployed rather than the function itself, so non-core.
GO:0032266 phosphatidylinositol-3-phosphate binding	IDA PMID:28561066 WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC...	ACCEPT	Summary: Phosphatidylinositol-3-phosphate binding, the ligand-recognition half of the adaptor. Reason: WIPI2 is a seven-bladed PROPPIN beta-propeller with two PtdIns3P sites built around the conserved FRRG motif, and it is a bona fide mammalian PtdIns3P effector. This binding is what localizes it to omegasome and phagophore membranes. Supported by two IDA experiments as well as by IBA across the family. Core. Supporting Evidence: PMID:20505359 We show that WIPI2 is a mammalian effector of PtdIns3P and is ubiquitously expressed in a variety of cell lines. PMID:24954904 All known members have two PtdIns(3)P binding sites formed around a conserved FRRG motif and a hydrophobic loop that is predicted to insert into the membrane
GO:0080025 phosphatidylinositol-3,5-bisphosphate binding	IDA PMID:28561066 WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC...	KEEP AS NON CORE	Summary: Phosphatidylinositol-3,5-bisphosphate binding, a second PROPPIN ligand that is not the autophagy-relevant one. Reason: PtdIns(3,5)P2 binding is a supported secondary lipid-binding activity of WIPI2/PROPPIN proteins. PI3P is the ligand established for recruitment of WIPI2 during canonical autophagosome formation; the physiological contexts that specifically use the other ligand are less well resolved.
GO:0016020 membrane	IDA PMID:25578879 PI(5)P regulates autophagosome biogenesis.	ACCEPT	Summary: WIPI2 associates with autophagic membranes. Reason: PI3P binding recruits WIPI2 to the cytoplasmic face of phagophore membranes. The broad membrane location is correct and complements the specific phagophore terms; breadth alone is not evidence of over-annotation. Supporting Evidence: PMID:20505359 WIPI2 is recruited to early autophagosomal structures along with Atg16L and ULK1 and is required for the formation of LC3-positive autophagosomes.
GO:0005829 cytosol	TAS Reactome:R-HSA-5676229	ACCEPT	Summary: WIPI2 cycles between the cytosol and PI3P-containing autophagic membranes. Reason: The target has an independent curated IDA cytosol annotation from PMID:20505359, also recorded in UniProt. Defer to that curator-read experiment while the local paper cache is abstract-only; the abstract establishes recruitment to early autophagosomal structures but is not itself a cytosolic-localization assay. The soluble pool and conditional membrane engagement are compatible parts of the adaptor mechanism. Supporting Evidence: UniProt:Q9Y4P8 DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
GO:0005829 cytosol	TAS Reactome:R-HSA-5678490	ACCEPT	Summary: WIPI2 cycles between the cytosol and PI3P-containing autophagic membranes. Reason: The target has an independent curated IDA cytosol annotation from PMID:20505359, also recorded in UniProt. Defer to that curator-read experiment while the local paper cache is abstract-only; the abstract establishes recruitment to early autophagosomal structures but is not itself a cytosolic-localization assay. The soluble pool and conditional membrane engagement are compatible parts of the adaptor mechanism. Supporting Evidence: UniProt:Q9Y4P8 DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
GO:0005829 cytosol	TAS Reactome:R-HSA-5679255	ACCEPT	Summary: WIPI2 cycles between the cytosol and PI3P-containing autophagic membranes. Reason: The target has an independent curated IDA cytosol annotation from PMID:20505359, also recorded in UniProt. Defer to that curator-read experiment while the local paper cache is abstract-only; the abstract establishes recruitment to early autophagosomal structures but is not itself a cytosolic-localization assay. The soluble pool and conditional membrane engagement are compatible parts of the adaptor mechanism. Supporting Evidence: UniProt:Q9Y4P8 DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
GO:0000407 phagophore assembly site	IDA PMID:22456507 Dynamic and transient interactions of Atg9 with autophagosom...	ACCEPT	Summary: Phagophore assembly site, observed directly in three independent studies. Reason: Direct microscopy places WIPI2 at early autophagic structures where its PI3P-binding and ATG16L1-recruiting activities support phagophore assembly. This functional site is compatible with its more specific membrane and diffuse cytosolic pools.
GO:0005515 protein binding	IPI PMID:21575909 A Tecpr1-dependent selective autophagy pathway targets bacte...	REMOVE	Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor.
GO:0000045 autophagosome assembly	IMP PMID:20505359 Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phag...	ACCEPT	Summary: Autophagosome assembly, WIPI2's core biological process. Reason: WIPI2 is required for the formation of LC3-positive autophagosomes: it binds PtdIns3P generated on the omegasome and recruits the ATG12-ATG5-ATG16L1 complex that drives LC3 lipidation and membrane elongation. Depleting it stalls the pathway at the omegasome stage. Supported independently by IDA and by two IMP experiments. Supporting Evidence: PMID:20505359 WIPI2 is recruited to early autophagosomal structures along with Atg16L and ULK1 and is required for the formation of LC3-positive autophagosomes.
GO:0005776 autophagosome	IDA NOT PMID:20505359 Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phag...	ACCEPT	Summary: NOT autophagosome. A deliberate negative annotation: WIPI2 marks the phagophore and is not retained on the completed autophagosome. Reason: Negative annotations of this kind are scarce and valuable, and this one carries real information about the pathway - it places WIPI2 upstream of closure and distinguishes it from ATG8-family proteins that persist on the mature organelle. Consistent with the companion NOT\|involved_in GO:0097352 autophagosome maturation from the same study. Retained as stated.
GO:0005829 cytosol	IDA PMID:20505359 Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phag...	ACCEPT	Summary: WIPI2 cycles between the cytosol and PI3P-containing autophagic membranes. Reason: The target has an independent curated IDA cytosol annotation from PMID:20505359, also recorded in UniProt. Defer to that curator-read experiment while the local paper cache is abstract-only; the abstract establishes recruitment to early autophagosomal structures but is not itself a cytosolic-localization assay. The soluble pool and conditional membrane engagement are compatible parts of the adaptor mechanism. Supporting Evidence: UniProt:Q9Y4P8 DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
GO:0032266 phosphatidylinositol-3-phosphate binding	IDA PMID:20505359 Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phag...	ACCEPT	Summary: Phosphatidylinositol-3-phosphate binding, the ligand-recognition half of the adaptor. Reason: WIPI2 is a seven-bladed PROPPIN beta-propeller with two PtdIns3P sites built around the conserved FRRG motif, and it is a bona fide mammalian PtdIns3P effector. This binding is what localizes it to omegasome and phagophore membranes. Supported by two IDA experiments as well as by IBA across the family. Core. Supporting Evidence: PMID:20505359 We show that WIPI2 is a mammalian effector of PtdIns3P and is ubiquitously expressed in a variety of cell lines. PMID:24954904 All known members have two PtdIns(3)P binding sites formed around a conserved FRRG motif and a hydrophobic loop that is predicted to insert into the membrane
GO:0034045 phagophore assembly site membrane	IDA PMID:20505359 Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phag...	MODIFY	Summary: Localization to the phagophore membrane is supported. Reason: Live QuickGO checked on 2026-09-20 marks GO:0034045 obsolete and provides the current GO:7770114 phagophore membrane. The demonstrated peripheral membrane localization should be retained with the current membrane term; a new term proposal is no longer necessary. Proposed replacements: phagophore membrane Supporting Evidence: PMID:20505359 WIPI2 is recruited to early autophagosomal structures along with Atg16L and ULK1 and is required for the formation of LC3-positive autophagosomes.
GO:0080025 phosphatidylinositol-3,5-bisphosphate binding	IDA PMID:20505359 Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phag...	KEEP AS NON CORE	Summary: Phosphatidylinositol-3,5-bisphosphate binding, a second PROPPIN ligand that is not the autophagy-relevant one. Reason: PtdIns(3,5)P2 binding is a supported secondary lipid-binding activity of WIPI2/PROPPIN proteins. PI3P is the ligand established for recruitment of WIPI2 during canonical autophagosome formation; the physiological contexts that specifically use the other ligand are less well resolved.
GO:0097352 autophagosome maturation	IMP NOT PMID:20505359 Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phag...	ACCEPT	Summary: NOT autophagosome maturation. WIPI2 depletion does not block maturation; it blocks an earlier step. Reason: The companion negative to NOT GO:0005776. Together they place WIPI2's requirement at omegasome-to-phagophore progression and explicitly exclude the downstream maturation step, which is a sharper functional statement than either positive annotation on its own. Depleting WIPI2 causes omegasomes to accumulate rather than autophagosomes to stall. Retained as stated. Supporting Evidence: PMID:20505359 Furthermore, when WIPI2 is depleted, we observe a remarkable accumulation of omegasomes, ER-localized PtdIns3P-containing structures labeled by DFCP1 (double FYVE domain-containing protein 1), which are thought to act as platforms for autophagosome formation.
GO:0032991 protein-containing complex	IDA GO_REF:0000054	KEEP AS NON CORE	Summary: An experimentally reported protein-containing assembly is retained at its stated broad scope. Reason: This high-throughput IDA assertion does not identify a specific stable complex. Its limited specificity is not evidence that assembly membership is false. Retain the generic observation as noncore without converting transient ATG16L1 recruitment or ULK1 association into untested permanent complex membership.

Gene Description

Existing Annotations Review

Core Functions

Reads the PtdIns3P signal generated on omegasome and phagophore membranes by the ULK1-activated class III PI3-kinase, and from that membrane position recruits the ATG12-ATG5-ATG16L1 conjugation complex, coupling the initiating lipid mark to ATG8-family lipidation and phagophore expansion.

Binds phosphatidylinositol 3-phosphate through two pockets built around the conserved FRRG motif of its beta-propeller, the ligand-recognition half of the adaptor and the activity that localizes WIPI2 to autophagic membranes.

References

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📚 Additional Documentation

Notes

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