ANKFY1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0010008 endosome membrane	IBA GO_REF:0000033	ACCEPT	Summary: Endosome membrane localization/activity is well supported for ANKFY1/Rabankyrin-5. Reason: ANKFY1 is a FYVE-domain Rab5 effector that binds PI3P and localizes on early/endosomal membranes; this location is central to its endosomal trafficking and ATG2A-bridging roles. Supporting Evidence: PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:15328530 Rabankyrin-5 binds most strongly to PI(3)P PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0031267 small GTPase binding	IBA GO_REF:0000033	ACCEPT	Summary: Small GTPase binding is directly supported by Rab5 and RhoD/RAB-family interaction evidence. Reason: Rabankyrin-5 was identified as a GTP-dependent Rab5 effector, and additional disease/trafficking work supports interaction with RAB5-regulatory machinery; this is a core molecular function. Supporting Evidence: PMID:15328530 Rabankyrin-5 binds to Rab5 specifically, directly, and GTP dependently PMID:24102721 RhoD binds to the Rab5 effector Rabankyrin-5 PMID:29959197 GAPVD1 and ANKFY1 interact with the endosomal regulator RAB5
GO:0042147 retrograde transport, endosome to Golgi	IBA GO_REF:0000033	ACCEPT	Summary: Endosome-to-Golgi retrograde transport is supported by Rank-5/retromer evidence. Reason: Rank-5 interacts and colocalizes with retromer cargo-recognition components, and Rank-5 depletion impairs mannose 6-phosphate receptor retrieval from endosomes to the Golgi. Supporting Evidence: PMID:22284051 Rank-5 colocalizes and interacts with components of the retromer complex such as vacuolar protein sorting 26 (Vps26) PMID:22284051 depletion of Rank-5 causes mislocalization of Vps26 and affects both the retrieval of mannose 6-phosphate receptor transport to the Golgi from endosomes and biosynthetic transport
GO:0090160 Golgi to lysosome transport	IBA GO_REF:0000033	ACCEPT	Summary: Golgi-to-lysosome/biosynthetic transport is supported as part of the Rank-5 retromer-trafficking phenotype. Reason: The same Rank-5 depletion experiments that disrupt retromer distribution also affect biosynthetic transport, consistent with a role in endosome/Golgi/lysosome trafficking. Supporting Evidence: PMID:22284051 depletion of Rank-5 causes mislocalization of Vps26 and affects both the retrieval of mannose 6-phosphate receptor transport to the Golgi from endosomes and biosynthetic transport
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Cytoplasmic localization is supported but is less informative than endosome-membrane localization. Reason: ANKFY1 was initially described as a cytoplasmic protein and is present in soluble fractions, but the biologically informative location is its recruitment to PI3P/Rab5-positive endosomal membranes. Supporting Evidence: PMID:10940552 Ankhzn protein is ubiquitously expressed in a spatiotemporal-specific manner and is located on endosomes PMID:10940552 present in both membrane and soluble fractions obtained on subcellular fractionation PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity
GO:0005768 endosome	IEA GO_REF:0000117	ACCEPT	Summary: Endosome localization is supported and relevant to ANKFY1 function. Reason: The original ANKHZN paper and later Rabankyrin-5 studies place the protein on endosomes, where it binds Rab5/PI3P and coordinates endocytic trafficking. Supporting Evidence: PMID:10940552 Ankhzn protein is ubiquitously expressed in a spatiotemporal-specific manner and is located on endosomes PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity
GO:0005769 early endosome	IEA GO_REF:0000044	ACCEPT	Summary: Early endosome localization is supported by Rabankyrin-5 colocalization with Rab5/EEA1-positive compartments and later functional studies. Reason: ANKFY1/Rabankyrin-5 localizes to early endosomes and its endosomal localization is required for endosomal fusion, retromer-related trafficking, and ATG2A recruitment during autophagy stimulation. Supporting Evidence: PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:22284051 Rank-5 colocalizes and interacts with components of the retromer complex such as vacuolar protein sorting 26 (Vps26) PMID:29959197 GAPVD1 and ANKFY1 interact with the endosomal regulator RAB5 PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0005829 cytosol	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Cytosol localization is supported as a source pool but is not the main functional location. Reason: ANKFY1 occurs in soluble and membrane-associated fractions; the reviewed functional evidence points to membrane recruitment at PI3P/Rab5-positive endosomes. Supporting Evidence: PMID:10940552 present in both membrane and soluble fractions obtained on subcellular fractionation PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity
GO:0010008 endosome membrane	IEA GO_REF:0000120	ACCEPT	Summary: Endosome membrane localization/activity is well supported for ANKFY1/Rabankyrin-5. Reason: ANKFY1 is a FYVE-domain Rab5 effector that binds PI3P and localizes on early/endosomal membranes; this location is central to its endosomal trafficking and ATG2A-bridging roles. Supporting Evidence: PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:15328530 Rabankyrin-5 binds most strongly to PI(3)P PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0016020 membrane	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Generic membrane localization is supported but too broad to represent the core location. Reason: Membrane association is real, but the more informative annotation is endosome membrane/early endosome, where ANKFY1 binds PI3P and functions with Rab5 and ATG2A. Supporting Evidence: PMID:10940552 present in both membrane and soluble fractions obtained on subcellular fractionation PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0046872 metal ion binding	IEA GO_REF:0000002	MODIFY	Summary: Metal ion binding is a broad domain-derived proxy for the FYVE zinc finger and should be replaced by the directly demonstrated lipid-binding activity. Reason: The FYVE domain is biologically important because it binds PI3P-containing membranes; direct lipid-binding experiments support phosphatidylinositol phosphate binding, while generic metal ion binding is not informative for ANKFY1 function. Proposed replacements: phosphatidylinositol phosphate binding Supporting Evidence: PMID:15328530 Rabankyrin-5 binds most strongly to PI(3)P PMID:38622126 enhanced ATG2A-mediated lipid transfer between PI3P-containing liposomes
GO:0005515 protein binding	IPI PMID:15328530 The Rab5 effector Rabankyrin-5 regulates and coordinates dif...	MODIFY	Summary: The generic protein-binding row reflects Rab5 interaction and should be replaced by small GTPase binding. Reason: The publication demonstrates specific, direct, GTP-dependent Rab5 binding; GO:0031267 captures the molecular function better than generic protein binding. Proposed replacements: small GTPase binding Supporting Evidence: PMID:15328530 Rabankyrin-5 binds to Rab5 specifically, directly, and GTP dependently
GO:0005515 protein binding	IPI PMID:20562859 Network organization of the human autophagy system.	MODIFY	Summary: The generic protein-binding row reflects ATG8/GABARAP-family association in a high-throughput autophagy network. Reason: The evidence is a proteomic autophagy-network interaction, so the more specific molecular-function replacement is ubiquitin-like protein binding; it should be treated as non-core relative to Rab5/PI3P/endosomal trafficking. Proposed replacements: ubiquitin-like protein binding Supporting Evidence: PMID:20562859 The six ATG8 orthologues in humans (MAP1LC3/GABARAP proteins) interact with a cohort of 67 proteins PMID:20562859 FYVE domain-containing proteins FYCO1 and ANKFY1
GO:0005515 protein binding	IPI PMID:22284051 Rabankyrin-5 interacts with EHD1 and Vps26 to regulate endoc...	MODIFY	Summary: The generic protein-binding row reflects Rank-5 binding to the EHD1 EH domain. Reason: Rank-5 contains an NPFED motif that binds the EHD1 EH domain; GO:1990175 EH domain binding captures this interaction better than generic protein binding. Proposed replacements: EH domain binding Supporting Evidence: PMID:22284051 binding occurs between the EH domain of EHD1 and the NPFED motif of Rank-5
GO:0005515 protein binding	IPI PMID:27189942 EHD3 Protein Is Required for Tubular Recycling Endosome Stab...	UNDECIDED	Summary: The local cached article does not provide ANKFY1-specific text for this generic EHD1/Q9H4M9 interaction row. Reason: The abstract supports EHD paralog binding to NPF-containing partners generally, but the cached text available locally does not document the ANKFY1/Rabankyrin-5 interaction with EHD1 specifically. A replacement such as EH domain binding may be appropriate if full interaction evidence is checked, but this row should remain undecided until the specific evidence is accessible. Supporting Evidence: PMID:27189942 EHD proteins have an EH domain that interacts with proteins containing an NPF motif PMID:22284051 binding occurs between the EH domain of EHD1 and the NPFED motif of Rank-5
GO:0005515 protein binding	IPI PMID:27189942 EHD3 Protein Is Required for Tubular Recycling Endosome Stab...	UNDECIDED	Summary: The local cached article does not provide ANKFY1-specific text for this generic EHD3/Q9NZN3 interaction row. Reason: The GOA includes a distinct PMID:27189942 IPI row for EHD3/Q9NZN3. The cached abstract supports EHD-family EH-domain recognition of NPF-containing partners and distinguishes EHD1 from EHD3, but it does not expose ANKFY1/Rabankyrin-5-specific interaction evidence for this partner. This row should remain undecided until the specific IntAct/full-text evidence is accessible. Supporting Evidence: PMID:27189942 EHD proteins have an EH domain that interacts with proteins containing an NPF motif PMID:27189942 EHD1 and EHD3 have 86% amino acid identity; they homo- and heterodimerize and partially co-localize to TRE
GO:0005768 endosome	IDA GO_REF:0000052	ACCEPT	Summary: Endosome localization is supported and relevant to ANKFY1 function. Reason: The original ANKHZN paper and later Rabankyrin-5 studies place the protein on endosomes, where it binds Rab5/PI3P and coordinates endocytic trafficking. Supporting Evidence: PMID:10940552 Ankhzn protein is ubiquitously expressed in a spatiotemporal-specific manner and is located on endosomes PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity
GO:0005737 cytoplasm	EXP PMID:10940552 Characterization and chromosomal mapping of a novel human ge...	KEEP AS NON CORE	Summary: Cytoplasmic localization is supported but is less informative than endosome-membrane localization. Reason: ANKFY1 was initially described as a cytoplasmic protein and is present in soluble fractions, but the biologically informative location is its recruitment to PI3P/Rab5-positive endosomal membranes. Supporting Evidence: PMID:10940552 Ankhzn protein is ubiquitously expressed in a spatiotemporal-specific manner and is located on endosomes PMID:10940552 present in both membrane and soluble fractions obtained on subcellular fractionation PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity
GO:0005769 early endosome	EXP PMID:22284051 Rabankyrin-5 interacts with EHD1 and Vps26 to regulate endoc...	ACCEPT	Summary: Early endosome localization is supported by Rabankyrin-5 colocalization with Rab5/EEA1-positive compartments and later functional studies. Reason: ANKFY1/Rabankyrin-5 localizes to early endosomes and its endosomal localization is required for endosomal fusion, retromer-related trafficking, and ATG2A recruitment during autophagy stimulation. Supporting Evidence: PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:22284051 Rank-5 colocalizes and interacts with components of the retromer complex such as vacuolar protein sorting 26 (Vps26) PMID:29959197 GAPVD1 and ANKFY1 interact with the endosomal regulator RAB5 PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0005769 early endosome	EXP PMID:29959197 GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nep...	ACCEPT	Summary: Early endosome localization is supported by Rabankyrin-5 colocalization with Rab5/EEA1-positive compartments and later functional studies. Reason: ANKFY1/Rabankyrin-5 localizes to early endosomes and its endosomal localization is required for endosomal fusion, retromer-related trafficking, and ATG2A recruitment during autophagy stimulation. Supporting Evidence: PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:22284051 Rank-5 colocalizes and interacts with components of the retromer complex such as vacuolar protein sorting 26 (Vps26) PMID:29959197 GAPVD1 and ANKFY1 interact with the endosomal regulator RAB5 PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0010008 endosome membrane	EXP PMID:10940552 Characterization and chromosomal mapping of a novel human ge...	ACCEPT	Summary: Endosome membrane localization/activity is well supported for ANKFY1/Rabankyrin-5. Reason: ANKFY1 is a FYVE-domain Rab5 effector that binds PI3P and localizes on early/endosomal membranes; this location is central to its endosomal trafficking and ATG2A-bridging roles. Supporting Evidence: PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:15328530 Rabankyrin-5 binds most strongly to PI(3)P PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0010008 endosome membrane	TAS Reactome:R-HSA-9013438	ACCEPT	Summary: Endosome membrane localization/activity is well supported for ANKFY1/Rabankyrin-5. Reason: ANKFY1 is a FYVE-domain Rab5 effector that binds PI3P and localizes on early/endosomal membranes; this location is central to its endosomal trafficking and ATG2A-bridging roles. Supporting Evidence: PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:15328530 Rabankyrin-5 binds most strongly to PI(3)P PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0070062 extracellular exosome	HDA PMID:18570454 Proteomic analysis of exosomes from human neural stem cells ...	KEEP AS NON CORE	Summary: Extracellular exosome detection comes from high-throughput proteomics and is not central to ANKFY1 function. Reason: The exosome rows may reflect proteomic detection, but they do not explain the core Rab5/PI3P/endosomal trafficking and ATG2A autophagosome-assembly roles. Supporting Evidence: PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:20562859 depletion of ANKFY1 also led to increased autophagosomal number without blocking flux PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0016197 endosomal transport	IMP PMID:24102721 RhoD binds the Rab5 effector Rabankyrin-5 and has a role in ...	ACCEPT	Summary: Endosomal transport is supported by RhoD/PDGFR trafficking and the broader Rabankyrin-5 endosomal phenotype. Reason: RhoD and Rabankyrin-5 coordinate Rab/Rho activities during internalization and trafficking of activated receptor cargo; this is consistent with the core endosomal transport function. Supporting Evidence: PMID:24102721 coordinating RhoD and Rab activities during internalization and trafficking of activated tyrosine kinase receptors PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:22284051 depletion of Rank-5 causes mislocalization of Vps26 and affects both the retrieval of mannose 6-phosphate receptor transport to the Golgi from endosomes and biosynthetic transport
GO:0030904 retromer complex	IDA PMID:22284051 Rabankyrin-5 interacts with EHD1 and Vps26 to regulate endoc...	KEEP AS NON CORE	Summary: Retromer complex colocalization is supported, but ANKFY1 is not established as a retromer complex subunit. Reason: The qualifier is colocalizes_with, and the evidence shows interaction/colocalization with VPS26 and retromer distribution defects rather than stable retromer-complex membership. Supporting Evidence: PMID:22284051 Rank-5 colocalizes and interacts with components of the retromer complex such as vacuolar protein sorting 26 (Vps26) PMID:22284051 depletion of Rank-5 causes mislocalization of Vps26 and affects both the retrieval of mannose 6-phosphate receptor transport to the Golgi from endosomes and biosynthetic transport
GO:0042147 retrograde transport, endosome to Golgi	IMP PMID:22284051 Rabankyrin-5 interacts with EHD1 and Vps26 to regulate endoc...	ACCEPT	Summary: Endosome-to-Golgi retrograde transport is supported by Rank-5/retromer evidence. Reason: Rank-5 interacts and colocalizes with retromer cargo-recognition components, and Rank-5 depletion impairs mannose 6-phosphate receptor retrieval from endosomes to the Golgi. Supporting Evidence: PMID:22284051 Rank-5 colocalizes and interacts with components of the retromer complex such as vacuolar protein sorting 26 (Vps26) PMID:22284051 depletion of Rank-5 causes mislocalization of Vps26 and affects both the retrieval of mannose 6-phosphate receptor transport to the Golgi from endosomes and biosynthetic transport
GO:0090160 Golgi to lysosome transport	IMP PMID:22284051 Rabankyrin-5 interacts with EHD1 and Vps26 to regulate endoc...	ACCEPT	Summary: Golgi-to-lysosome/biosynthetic transport is supported as part of the Rank-5 retromer-trafficking phenotype. Reason: The same Rank-5 depletion experiments that disrupt retromer distribution also affect biosynthetic transport, consistent with a role in endosome/Golgi/lysosome trafficking. Supporting Evidence: PMID:22284051 depletion of Rank-5 causes mislocalization of Vps26 and affects both the retrieval of mannose 6-phosphate receptor transport to the Golgi from endosomes and biosynthetic transport
GO:0005769 early endosome	IDA PMID:15328530 The Rab5 effector Rabankyrin-5 regulates and coordinates dif...	ACCEPT	Summary: Early endosome localization is supported by Rabankyrin-5 colocalization with Rab5/EEA1-positive compartments and later functional studies. Reason: ANKFY1/Rabankyrin-5 localizes to early endosomes and its endosomal localization is required for endosomal fusion, retromer-related trafficking, and ATG2A recruitment during autophagy stimulation. Supporting Evidence: PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:22284051 Rank-5 colocalizes and interacts with components of the retromer complex such as vacuolar protein sorting 26 (Vps26) PMID:29959197 GAPVD1 and ANKFY1 interact with the endosomal regulator RAB5 PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0031267 small GTPase binding	IDA PMID:15328530 The Rab5 effector Rabankyrin-5 regulates and coordinates dif...	ACCEPT	Summary: Small GTPase binding is directly supported by Rab5 and RhoD/RAB-family interaction evidence. Reason: Rabankyrin-5 was identified as a GTP-dependent Rab5 effector, and additional disease/trafficking work supports interaction with RAB5-regulatory machinery; this is a core molecular function. Supporting Evidence: PMID:15328530 Rabankyrin-5 binds to Rab5 specifically, directly, and GTP dependently PMID:24102721 RhoD binds to the Rab5 effector Rabankyrin-5 PMID:29959197 GAPVD1 and ANKFY1 interact with the endosomal regulator RAB5
GO:0034058 endosomal vesicle fusion	IDA PMID:15328530 The Rab5 effector Rabankyrin-5 regulates and coordinates dif...	ACCEPT	Summary: Endosomal vesicle fusion is directly supported by the original Rabankyrin-5 functional study. Reason: Rabankyrin-5 is a Rab5/PI3P effector that stimulates early-endosome fusion and affects endosomal vesicle dynamics. Supporting Evidence: PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:15328530 Rabankyrin-5 is a Rab5 effector required for the formation of macropinosomes
GO:0044354 macropinosome	IDA PMID:15328530 The Rab5 effector Rabankyrin-5 regulates and coordinates dif...	ACCEPT	Summary: Macropinosome localization is directly supported and relevant to the pinocytosis phenotype. Reason: Rabankyrin-5 localizes to macropinosomes and its perturbation changes fluid-phase uptake. Supporting Evidence: PMID:15328530 Overexpression of Rabankyrin-5 increases the number of macropinosomes and stimulates fluid-phase uptake, whereas its downregulation inhibits these processes
GO:0048549 positive regulation of pinocytosis	IDA PMID:15328530 The Rab5 effector Rabankyrin-5 regulates and coordinates dif...	ACCEPT	Summary: Positive regulation of pinocytosis is directly supported. Reason: Overexpression and depletion experiments show that Rabankyrin-5 promotes fluid-phase/macropinocytic uptake, including apical non-clathrin-mediated uptake in polarized cells. Supporting Evidence: PMID:15328530 Overexpression of Rabankyrin-5 increases the number of macropinosomes and stimulates fluid-phase uptake, whereas its downregulation inhibits these processes PMID:15328530 specifically stimulates apical, non-clathrin-mediated fluid-phase endocytosis
GO:1901981 phosphatidylinositol phosphate binding	IDA PMID:15328530 The Rab5 effector Rabankyrin-5 regulates and coordinates dif...	ACCEPT	Summary: Phosphatidylinositol phosphate binding is a core ANKFY1 molecular function. Reason: ANKFY1/Rabankyrin-5 binds PI3P via its FYVE domain; this lipid-binding activity explains endosomal recruitment and is required for ATG2A-mediated lipid-transfer enhancement. Supporting Evidence: PMID:15328530 Rabankyrin-5 binds most strongly to PI(3)P PMID:38622126 enhanced ATG2A-mediated lipid transfer between PI3P-containing liposomes
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: Extracellular exosome detection comes from high-throughput proteomics and is not central to ANKFY1 function. Reason: The exosome rows may reflect proteomic detection, but they do not explain the core Rab5/PI3P/endosomal trafficking and ATG2A autophagosome-assembly roles. Supporting Evidence: PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:20562859 depletion of ANKFY1 also led to increased autophagosomal number without blocking flux PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0005765 lysosomal membrane	HDA PMID:17897319 Integral and associated lysosomal membrane proteins.	KEEP AS NON CORE	Summary: Lysosomal membrane detection is plausible but high-throughput and not core. Reason: The dominant evidence places ANKFY1 on early/endosomal membranes; lysosomal-membrane proteomic detection is peripheral and should not drive the core function summary. Supporting Evidence: PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0016020 membrane	IDA PMID:10940552 Characterization and chromosomal mapping of a novel human ge...	KEEP AS NON CORE	Summary: Generic membrane localization is supported but too broad to represent the core location. Reason: Membrane association is real, but the more informative annotation is endosome membrane/early endosome, where ANKFY1 binds PI3P and functions with Rab5 and ATG2A. Supporting Evidence: PMID:10940552 present in both membrane and soluble fractions obtained on subcellular fractionation PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0010008 endosome membrane	ISS GO_REF:0000024	ACCEPT	Summary: Endosome membrane localization/activity is well supported for ANKFY1/Rabankyrin-5. Reason: ANKFY1 is a FYVE-domain Rab5 effector that binds PI3P and localizes on early/endosomal membranes; this location is central to its endosomal trafficking and ATG2A-bridging roles. Supporting Evidence: PMID:15328530 novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity PMID:15328530 Rabankyrin-5 binds most strongly to PI(3)P PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores
GO:0000045 autophagosome assembly	IMP PMID:38622126 ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes ...	NEW	Summary: ANKFY1 should be added to autophagosome assembly for its ATG2A-dependent endosome-to-phagophore lipid-transfer role. Reason: ANKFY1 depletion impairs autophagosome growth, reduces autophagy flux, and phenocopies ATG2A/B depletion; in vitro ANKFY1 enhances ATG2A-mediated lipid transfer between PI3P-containing membranes. GO:0000045 is the conservative process term for this phagophore-growth/autophagosome-completion role. Supporting Evidence: PMID:38622126 identified a new ATG2A-binding protein, ANKFY1 PMID:38622126 Depletion of this endosome-localized protein led to the impaired autophagosome growth and the reduced autophagy flux PMID:38622126 enhanced ATG2A-mediated lipid transfer between PI3P-containing liposomes PMID:38622126 ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores file:human/ANKFY1/ANKFY1-deep-research-falcon.md A 2024 study identified ANKFY1 as an ATG2A-binding endosomal factor that bridges endosomes and phagophores, promoting ATG2A-mediated lipid transfer for phagophore growth

Gene Description

Existing Annotations Review

Core Functions

ANKFY1 is a Rab5/PI3P-positive endosomal effector that coordinates early endosome fusion, macropinocytosis, endosomal transport, and retromer-associated endosome-to-Golgi and Golgi-to-lysosome trafficking.

ANKFY1 binds PI3P-rich endosomal membranes through its FYVE domain and promotes ATG2A-mediated lipid transfer from endosomes to phagophores, supporting autophagosome growth and completion during autophagy induction.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

📚 Additional Documentation

Notes

Pn Notes

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