{"gene":"ANKFY1","run_date":"2026-06-09T22:02:43","timeline":{"discoveries":[{"year":1999,"finding":"ANKFY1 (Ankhzn) protein localizes to endosomal membranes, as determined by immunoelectron microscopy. The protein contains 17 ankyrin repeats hooked to a zinc finger (FYVE) motif, and was confirmed at ~130 kDa by in vitro transcription/translation and antibody detection on SDS-PAGE.","method":"Immunoelectron microscopy, in vitro transcription/translation, SDS-PAGE/Western blot","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct subcellular localization by immunoelectron microscopy with protein confirmation, single lab","pmids":["10092534"],"is_preprint":false},{"year":2000,"finding":"Human ANKFY1 (ANKHZN) protein is present in both membrane and soluble fractions on subcellular fractionation, confirming partial membrane association. The gene maps to chromosome 17p13.","method":"Subcellular fractionation, Western blot, radiation hybrid panel, FISH","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct fractionation experiment with Western blot confirmation, single lab","pmids":["10940552"],"is_preprint":false},{"year":2003,"finding":"ANKFY1 (Ankhzn) co-localizes with phagocytosed dextran particles and transferrin-labeled endocytotic structures in macrophages, and its immunoreactivity is markedly increased in serum-starved cells, suggesting involvement in endocytosis and autophagy vesicle formation.","method":"Immunohistochemistry, immunofluorescence co-localization with transferrin and dextran, serum starvation assay","journal":"Kaibogaku zasshi. Journal of anatomy","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization by immunostaining only, single lab, single method, no functional genetic manipulation","pmids":["12833855"],"is_preprint":false},{"year":2017,"finding":"ANKFY1 acts as a BTB-domain adaptor protein for the CUL3 E3 ubiquitin ligase complex and is required for early endosomal localization of integrin β1 on the cell surface of endothelial cells. CUL3 physically interacts with ANKFY1 and is required for ANKFY1's early endosomal localization. Depletion of either CUL3 or ANKFY1 by siRNA reduces surface integrin β1 levels and impairs angiogenesis.","method":"siRNA knockdown, co-immunoprecipitation, immunofluorescence/confocal localization, flow cytometry for surface integrin β1, siRNA screen of 175 BTBPs","journal":"Biology open","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, siRNA knockdown with cellular phenotype, multiple orthogonal methods in single lab","pmids":["29038302"],"is_preprint":false},{"year":2018,"finding":"ANKFY1 physically interacts with GAPVD1 (co-immunoprecipitation) and both proteins co-localize in HEK293T cells. Both proteins interact with active RAB5 (GTP-bound form). Patient-derived missense mutations in ANKFY1 alter binding affinity for active RAB5 and reduce ability to rescue knockout-induced podocyte migration defects, implicating ANKFY1 in RAB5-dependent endosomal regulation in podocytes.","method":"Co-immunoprecipitation, co-localization in HEK293T, siRNA silencing, podocyte migration assay, ectopic expression of patient-derived mutant proteins, Drosophila nephrocyte endocytosis assay","journal":"Journal of the American Society of Nephrology : JASN","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, multiple functional assays, patient mutations tested, cross-species validation in Drosophila","pmids":["29959197"],"is_preprint":false},{"year":2020,"finding":"ANKFY1 knockdown in human retinal microvascular endothelial cells (HRMECs) reduces cell-surface VEGFR2 protein levels (without affecting VEGFR2 mRNA) and attenuates downstream Akt/eNOS signaling, thereby impairing VEGF-dependent and -independent endothelial cell proliferation and migration.","method":"siRNA knockdown, Western blot for surface VEGFR2 and Akt/eNOS phosphorylation, qRT-PCR, cell proliferation and migration assays","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined molecular phenotype (surface receptor and signaling pathway), single lab, multiple methods","pmids":["33092793"],"is_preprint":false},{"year":2021,"finding":"Ankfy1 knockout mice develop normally but at 9 months show progressive loss of cerebellar Purkinje cells (with other cerebellar cell types largely unaffected) and defective motor function, establishing a cell-type-specific role for ANKFY1 in Purkinje cell maintenance in vivo.","method":"Whole-body knockout mouse model, histology, immunofluorescence, motor behavior tests","journal":"Frontiers in cellular neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined cell-type-specific in vivo KO phenotype, single lab","pmids":["33796010"],"is_preprint":false},{"year":2024,"finding":"ANKFY1 is an endosome-localized protein that binds PI3P through its FYVE domain, directly interacts with ATG2A, and promotes ATG2A-mediated lipid transfer from PI3P-containing liposomes. A pool of ANKFY1 co-localizes with ATG2A between endosomes and phagophores. Depletion of ANKFY1 impairs autophagosome growth and reduces autophagy flux, phenocopying ATG2A/B depletion. Depletion of UVRAG, ANKFY1, or ATG2A/B reduces PI3P on phagophores, placing ANKFY1 in the UVRAG–PI3P–ATG2A lipid transfer pathway from endosomes to phagophores.","method":"Co-immunoprecipitation/pulldown, in vitro lipid transfer assay with purified recombinant proteins and PI3P-containing liposomes, siRNA/shRNA depletion, autophagy flux assays, confocal co-localization, genetic epistasis (UVRAG/ANKFY1/ATG2A/B depletion)","journal":"Cell discovery","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with purified proteins, lipid transfer assay, mutagenesis of FYVE domain, genetic epistasis, multiple orthogonal methods","pmids":["38622126"],"is_preprint":false},{"year":2016,"finding":"Ankfy1 is dispensable for neural stem/precursor cell development in mice with a mixed genetic background, but Ankfy1 knockout is lethal by embryonic day 11.5 in a pure C57BL/6 inbred background, indicating an essential but genetically background-dependent role in early embryonic development.","method":"Knockout mouse generation, immunofluorescence, in situ hybridization, genotyping by PCR","journal":"Neural regeneration research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo KO with defined developmental phenotype, single lab","pmids":["28123425"],"is_preprint":false},{"year":2024,"finding":"Compound heterozygous ANKFY1 variants (p.Ser918Ter and a splice-site deletion) found in a patient with proteinuria and movement disorder lead to reduced ANKFY1 protein expression in vitro, supporting a loss-of-function mechanism for bi-allelic ANKFY1 variants in a neuro-renal syndrome.","method":"Whole-exome sequencing, in vitro functional study (Western blot for protein expression of patient variants)","journal":"Clinical kidney journal","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single in vitro expression study, single lab, limited mechanistic follow-up","pmids":["38915441"],"is_preprint":false},{"year":2026,"finding":"ANKFY1 interacts with PDCoV nonstructural protein nsp8, recruits the E3 ubiquitin ligase Cullin3 to catalyze K63/K33-linked ubiquitination of nsp8 at lysine 58, and the ubiquitinated nsp8 is subsequently recognized by selective autophagy receptor p62 and delivered to autolysosomes for degradation, thereby suppressing viral replication.","method":"Co-immunoprecipitation, gain/loss-of-function (overexpression and siRNA depletion), ubiquitination assay with site-directed mutagenesis (K58 site), p62 interaction assay, viral replication and RNA synthesis quantification","journal":"Veterinary microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, ubiquitination assay with mutagenesis, loss-of-function with defined antiviral phenotype, single lab","pmids":["41763084"],"is_preprint":false},{"year":2023,"finding":"miR-760 directly targets the ANKFY1 3'UTR (validated by luciferase reporter assay) and suppresses ANKFY1 protein expression. ANKFY1 participates in APS-mediated promotion of osteogenic differentiation and proliferation of human bone marrow mesenchymal stem cells.","method":"Luciferase reporter assay, Western blot, qRT-PCR, miR-760 overexpression/knockdown, osteogenic differentiation assays","journal":"Bone & joint research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — luciferase reporter for miRNA-mRNA targeting, pathway placement indirect, single lab","pmids":["37532241"],"is_preprint":false}],"current_model":"ANKFY1 (Rabankyrin-5/Ankhzn) is an endosome-localized protein with ankyrin repeats and a PI3P-binding FYVE domain that (1) acts as a CUL3 E3 ligase adaptor to regulate endosomal trafficking of cell-surface receptors (integrin β1, VEGFR2); (2) binds active RAB5 and interacts with GAPVD1 to support endocytic trafficking and podocyte function; (3) bridges ATG2A-mediated lipid transfer from PI3P-enriched endosomes to phagophores during autophagosome biogenesis; and (4) recruits CUL3 to ubiquitinate substrates (e.g., viral nsp8) for p62-dependent selective autophagic degradation, with loss-of-function causing defects in podocyte migration, retinal endothelial signaling, and Purkinje cell maintenance in vivo."},"narrative":{"mechanistic_narrative":"ANKFY1 (Rabankyrin-5/Ankhzn) is an endosome-associated protein that integrates phosphoinositide-dependent membrane recognition with ubiquitin signaling and lipid transfer to control endosomal trafficking, receptor surface display, and autophagosome biogenesis [PMID:10092534, PMID:38622126]. It localizes to endosomal membranes via a FYVE domain that binds PI3P and is found in both membrane and soluble pools [PMID:10092534, PMID:10940552, PMID:38622126]. ANKFY1 functions as a BTB/adaptor for the CUL3 E3 ubiquitin ligase, with CUL3 required for its early endosomal localization; this CUL3–ANKFY1 module sustains cell-surface levels of integrin β1 and supports angiogenesis [PMID:29038302], and ANKFY1 likewise maintains surface VEGFR2 and downstream Akt/eNOS signaling in endothelial cells without affecting receptor transcription [PMID:33092793]. In a parallel trafficking role, ANKFY1 binds active GTP-bound RAB5 and interacts with GAPVD1 to govern RAB5-dependent endosomal regulation in podocytes [PMID:29959197]. Beyond receptor trafficking, ANKFY1 directly interacts with ATG2A and promotes ATG2A-mediated lipid transfer from PI3P-containing membranes, operating within a UVRAG–PI3P–ATG2A pathway that delivers lipid from endosomes to growing phagophores; its loss impairs autophagosome growth and autophagy flux [PMID:38622126]. ANKFY1 can also recruit CUL3 to ubiquitinate a viral substrate (PDCoV nsp8) for p62-dependent selective autophagic degradation, restricting viral replication [PMID:41763084]. In vivo, loss of ANKFY1 causes background-dependent embryonic lethality, progressive cerebellar Purkinje cell degeneration with motor defects, and bi-allelic loss-of-function variants are associated with a neuro-renal syndrome of proteinuria and movement disorder [PMID:33796010, PMID:28123425, PMID:38915441].","teleology":[{"year":1999,"claim":"Established the basic identity and subcellular home of ANKFY1, defining it as an endosomal ankyrin-repeat/FYVE protein and setting the structural basis for membrane recognition.","evidence":"Immunoelectron microscopy and in vitro transcription/translation with antibody detection","pmids":["10092534"],"confidence":"Medium","gaps":["FYVE-PI3P binding not yet functionally demonstrated","no molecular partners or activity defined"]},{"year":2000,"claim":"Refined biochemical distribution and genomic mapping, showing ANKFY1 partitions between membrane and soluble fractions consistent with dynamic membrane association.","evidence":"Subcellular fractionation/Western blot and radiation hybrid/FISH mapping to 17p13","pmids":["10940552"],"confidence":"Medium","gaps":["determinants of membrane vs soluble partitioning unknown","no functional role assigned"]},{"year":2003,"claim":"Linked ANKFY1 to endocytic and starvation-responsive vesicular compartments, hinting at roles in endocytosis and autophagy.","evidence":"Immunofluorescence co-localization with transferrin and dextran plus serum-starvation in macrophages","pmids":["12833855"],"confidence":"Low","gaps":["localization-only, no genetic manipulation","autophagy involvement not mechanistically tested"]},{"year":2017,"claim":"Identified ANKFY1 as a CUL3 E3 ligase adaptor controlling surface receptor trafficking, providing the first mechanistic activity and a physiological angiogenesis output.","evidence":"BTBP siRNA screen, reciprocal Co-IP, surface integrin β1 flow cytometry in endothelial cells","pmids":["29038302"],"confidence":"High","gaps":["ubiquitination substrates in this pathway not identified","how CUL3 directs endosomal localization unresolved"]},{"year":2018,"claim":"Connected ANKFY1 to RAB5/GAPVD1-dependent endosomal regulation and to human disease, showing patient mutations impair RAB5 binding and podocyte function.","evidence":"Co-IP, co-localization, podocyte migration rescue with patient mutants, Drosophila nephrocyte assay","pmids":["29959197"],"confidence":"High","gaps":["structural basis of active-RAB5 recognition not resolved","relationship between RAB5 and CUL3 functions unclear"]},{"year":2020,"claim":"Extended the receptor-trafficking role to VEGFR2, showing ANKFY1 maintains surface receptor levels and downstream Akt/eNOS signaling post-transcriptionally.","evidence":"siRNA knockdown with surface VEGFR2 Western blot, signaling and migration/proliferation assays in HRMECs","pmids":["33092793"],"confidence":"Medium","gaps":["whether CUL3 ubiquitination drives VEGFR2 trafficking untested","trafficking step affected (recycling vs degradation) undefined"]},{"year":2021,"claim":"Demonstrated a cell-type-specific in vivo requirement, with Purkinje cell loss and motor defects upon ANKFY1 knockout.","evidence":"Whole-body knockout mouse histology, immunofluorescence, motor behavior","pmids":["33796010"],"confidence":"Medium","gaps":["molecular cause of Purkinje cell vulnerability unknown","endosomal vs autophagy contribution to phenotype not separated"]},{"year":2016,"claim":"Revealed an essential but genetic-background-dependent role in early embryogenesis, complicating interpretation of organismal requirement.","evidence":"Knockout mice in mixed vs pure C57BL/6 backgrounds with developmental analysis","pmids":["28123425"],"confidence":"Medium","gaps":["modifier loci explaining background dependence unidentified","molecular pathway underlying lethality unknown"]},{"year":2024,"claim":"Defined a direct biochemical mechanism in autophagy: ANKFY1 binds PI3P and ATG2A and promotes ATG2A-mediated lipid transfer from endosomes to phagophores.","evidence":"In vitro lipid transfer with purified proteins and PI3P liposomes, FYVE mutagenesis, autophagy flux assays, UVRAG/ANKFY1/ATG2A epistasis","pmids":["38622126"],"confidence":"High","gaps":["how ANKFY1 tethers ATG2A to phagophores structurally undefined","relationship between autophagy and CUL3/RAB5 roles unresolved"]},{"year":2024,"claim":"Strengthened the human disease link by associating bi-allelic loss-of-function ANKFY1 variants with a neuro-renal syndrome.","evidence":"Whole-exome sequencing with in vitro protein-expression assay of patient variants","pmids":["38915441"],"confidence":"Low","gaps":["single in vitro expression readout, no rescue or animal model","genotype-phenotype causality not formally established"]},{"year":2026,"claim":"Showed ANKFY1 couples CUL3-mediated ubiquitination to selective autophagy of a substrate, recruiting CUL3 to ubiquitinate viral nsp8 for p62-dependent degradation.","evidence":"Co-IP, ubiquitination assay with K58 mutagenesis, p62 interaction, viral replication quantification","pmids":["41763084"],"confidence":"Medium","gaps":["endogenous (non-viral) ubiquitination substrates not identified","generality of CUL3-to-p62 axis beyond this pathogen untested"]},{"year":null,"claim":"How ANKFY1's distinct activities — CUL3 adaptor, RAB5/GAPVD1 endosomal regulator, and ATG2A lipid-transfer cofactor — are coordinated on a single endosomal platform, and which is responsible for each in vivo phenotype, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["no integrated model linking trafficking, ubiquitination, and lipid transfer","endogenous ubiquitination substrates unknown","structural basis of multivalent partner engagement undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[7]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,7]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[3,10]}],"localization":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0,3,7]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[2,3]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[3,4,5]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[7,10]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[3,10]}],"complexes":["CUL3 E3 ubiquitin ligase complex"],"partners":["CUL3","GAPVD1","RAB5","ATG2A","UVRAG","SQSTM1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9P2R3","full_name":"Ankyrin repeat and FYVE domain-containing protein 1","aliases":["Ankyrin repeats hooked to a zinc finger motif","Rab5-binding and ankyrin repeats-containing protein","Rabankyrin-5","Rank-5"],"length_aa":1169,"mass_kda":128.4,"function":"Proposed effector of Rab5 (PubMed:15328530). Binds to phosphatidylinositol 3-phosphate (PI[3]P) (PubMed:15328530). Involved in homotypic early endosome fusion and to a lesser extent in heterotypic fusion of clathrin-coated vesicles with early endosomes (PubMed:15328530). Involved in macropinocytosis; the function is dependent on Rab5-GTP (PubMed:15328530). Required for correct endosomal localization (PubMed:15328530). Involved in the internalization and trafficking of activated tyrosine kinase receptors such as PDGFRB (PubMed:24102721). Regulates the subcellular localization of the retromer complex in a EHD1-dependent manner (PubMed:22284051). Involved in endosome-to-Golgi transport and biosynthetic transport to late endosomes and lysosomes indicative for a regulation of retromer complex-mediated retrograde transport (PubMed:22284051). Required for podocyte migration (PubMed:29959197)","subcellular_location":"Cytoplasm; Endosome membrane; Early endosome","url":"https://www.uniprot.org/uniprotkb/Q9P2R3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ANKFY1","classification":"Not Classified","n_dependent_lines":19,"n_total_lines":1208,"dependency_fraction":0.015728476821192054},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ANKFY1","total_profiled":1310},"omim":[{"mim_id":"621535","title":"SPINOCEREBELLAR ATAXIA 52; SCA52","url":"https://www.omim.org/entry/621535"},{"mim_id":"621004","title":"AUTOIMMUNE DISEASE, MULTISYSTEM, INFANTILE-ONSET, 4; ADMIO4","url":"https://www.omim.org/entry/621004"},{"mim_id":"611714","title":"GTPase-ACTIVATING PROTEIN AND VPS9 DOMAINS 1; GAPVD1","url":"https://www.omim.org/entry/611714"},{"mim_id":"611302","title":"SPASTIC ATAXIA 2, AUTOSOMAL RECESSIVE; SPAX2","url":"https://www.omim.org/entry/611302"},{"mim_id":"607927","title":"ANKYRIN REPEATS- AND FYVE DOMAIN-CONTAINING PROTEIN 1; ANKFY1","url":"https://www.omim.org/entry/607927"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Endosomes","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ANKFY1"},"hgnc":{"alias_symbol":["ANKHZN","KIAA1255","ZFYVE14","BTBD23","RANK-5"],"prev_symbol":[]},"alphafold":{"accession":"Q9P2R3","domains":[{"cath_id":"3.30.710.10","chopping":"59-162","consensus_level":"high","plddt":83.5628,"start":59,"end":162},{"cath_id":"1.25.40.20","chopping":"451-523_543-615","consensus_level":"medium","plddt":89.1613,"start":451,"end":615},{"cath_id":"1.25.40.20","chopping":"616-709","consensus_level":"medium","plddt":93.4421,"start":616,"end":709},{"cath_id":"1.25.40.20","chopping":"725-760_768-835","consensus_level":"medium","plddt":95.7663,"start":725,"end":835},{"cath_id":"3.30.40.10","chopping":"1070-1166","consensus_level":"medium","plddt":88.0963,"start":1070,"end":1166},{"cath_id":"1.20.5","chopping":"2-32","consensus_level":"medium","plddt":69.689,"start":2,"end":32}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9P2R3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9P2R3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9P2R3-F1-predicted_aligned_error_v6.png","plddt_mean":86.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ANKFY1","jax_strain_url":"https://www.jax.org/strain/search?query=ANKFY1"},"sequence":{"accession":"Q9P2R3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9P2R3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9P2R3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9P2R3"}},"corpus_meta":[{"pmid":"29959197","id":"PMC_29959197","title":"GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome.","date":"2018","source":"Journal of the American Society of Nephrology : JASN","url":"https://pubmed.ncbi.nlm.nih.gov/29959197","citation_count":50,"is_preprint":false},{"pmid":"29038302","id":"PMC_29038302","title":"Cullin-3 and its adaptor protein ANKFY1 determine the surface level of integrin β1 in endothelial cells.","date":"2017","source":"Biology open","url":"https://pubmed.ncbi.nlm.nih.gov/29038302","citation_count":33,"is_preprint":false},{"pmid":"10092534","id":"PMC_10092534","title":"Molecular cloning of a novel 130-kDa cytoplasmic protein, Ankhzn, containing Ankyrin repeats hooked to a zinc finger motif.","date":"1999","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/10092534","citation_count":18,"is_preprint":false},{"pmid":"37532241","id":"PMC_37532241","title":"Astragalus polysaccharide promotes osteogenic differentiation of human bone marrow derived mesenchymal stem cells by facilitating ANKFY1 expression through miR-760 inhibition.","date":"2023","source":"Bone & joint research","url":"https://pubmed.ncbi.nlm.nih.gov/37532241","citation_count":12,"is_preprint":false},{"pmid":"38622126","id":"PMC_38622126","title":"ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores.","date":"2024","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/38622126","citation_count":10,"is_preprint":false},{"pmid":"10940552","id":"PMC_10940552","title":"Characterization and chromosomal mapping of a novel human gene, ANKHZN.","date":"2000","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/10940552","citation_count":8,"is_preprint":false},{"pmid":"33092793","id":"PMC_33092793","title":"ANKFY1 is essential for retinal endothelial cell proliferation and migration via VEGFR2/Akt/eNOS pathway.","date":"2020","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/33092793","citation_count":8,"is_preprint":false},{"pmid":"33796010","id":"PMC_33796010","title":"Ankfy1 Is Involved in the Maintenance of Cerebellar Purkinje Cells.","date":"2021","source":"Frontiers in cellular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/33796010","citation_count":7,"is_preprint":false},{"pmid":"28123425","id":"PMC_28123425","title":"Ankfy1 is dispensable for neural stem/precursor cell development.","date":"2016","source":"Neural regeneration research","url":"https://pubmed.ncbi.nlm.nih.gov/28123425","citation_count":5,"is_preprint":false},{"pmid":"35322905","id":"PMC_35322905","title":"The relationship of maternal rank, 5-HTTLPR genotype, and MAOA-LPR genotype to temperament in infant rhesus monkeys (Macaca mulatta).","date":"2022","source":"American journal of primatology","url":"https://pubmed.ncbi.nlm.nih.gov/35322905","citation_count":3,"is_preprint":false},{"pmid":"12833855","id":"PMC_12833855","title":"[Possible involvement of Ankhzn, a novel protein possessing FYVE domain, in cellular endocytosis and autophagocytosis in vitro].","date":"2003","source":"Kaibogaku zasshi. Journal of anatomy","url":"https://pubmed.ncbi.nlm.nih.gov/12833855","citation_count":1,"is_preprint":false},{"pmid":"40594855","id":"PMC_40594855","title":"Identification of spastic ataxia-related proteins via comparative proteomic analysis of the cerebellum of conditional Ankfy1 knockout mice.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40594855","citation_count":0,"is_preprint":false},{"pmid":"38915441","id":"PMC_38915441","title":"Compound heterozygous variants of ANKFY1 in a child with infantile-onset proteinuria and movement disorder.","date":"2024","source":"Clinical kidney journal","url":"https://pubmed.ncbi.nlm.nih.gov/38915441","citation_count":0,"is_preprint":false},{"pmid":"41763084","id":"PMC_41763084","title":"ANKFY1 suppresses PDCoV replication by degrading viral nsp8 protein via p62-dependent selective autophagy.","date":"2026","source":"Veterinary microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/41763084","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.03.31.25324887","title":"Comprehensive profiling of the mutational landscape of hidradenoma papilliferum validates key role of alterations in the PI3K/AKT pathway alterations","date":"2025-04-01","source":"bioRxiv","url":"https://doi.org/10.1101/2025.03.31.25324887","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9736,"output_tokens":3171,"usd":0.038386,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10563,"output_tokens":3637,"usd":0.07187,"stage2_stop_reason":"end_turn"},"total_usd":0.110256,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"ANKFY1 (Ankhzn) protein localizes to endosomal membranes, as determined by immunoelectron microscopy. The protein contains 17 ankyrin repeats hooked to a zinc finger (FYVE) motif, and was confirmed at ~130 kDa by in vitro transcription/translation and antibody detection on SDS-PAGE.\",\n      \"method\": \"Immunoelectron microscopy, in vitro transcription/translation, SDS-PAGE/Western blot\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct subcellular localization by immunoelectron microscopy with protein confirmation, single lab\",\n      \"pmids\": [\"10092534\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Human ANKFY1 (ANKHZN) protein is present in both membrane and soluble fractions on subcellular fractionation, confirming partial membrane association. The gene maps to chromosome 17p13.\",\n      \"method\": \"Subcellular fractionation, Western blot, radiation hybrid panel, FISH\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct fractionation experiment with Western blot confirmation, single lab\",\n      \"pmids\": [\"10940552\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"ANKFY1 (Ankhzn) co-localizes with phagocytosed dextran particles and transferrin-labeled endocytotic structures in macrophages, and its immunoreactivity is markedly increased in serum-starved cells, suggesting involvement in endocytosis and autophagy vesicle formation.\",\n      \"method\": \"Immunohistochemistry, immunofluorescence co-localization with transferrin and dextran, serum starvation assay\",\n      \"journal\": \"Kaibogaku zasshi. Journal of anatomy\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization by immunostaining only, single lab, single method, no functional genetic manipulation\",\n      \"pmids\": [\"12833855\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"ANKFY1 acts as a BTB-domain adaptor protein for the CUL3 E3 ubiquitin ligase complex and is required for early endosomal localization of integrin β1 on the cell surface of endothelial cells. CUL3 physically interacts with ANKFY1 and is required for ANKFY1's early endosomal localization. Depletion of either CUL3 or ANKFY1 by siRNA reduces surface integrin β1 levels and impairs angiogenesis.\",\n      \"method\": \"siRNA knockdown, co-immunoprecipitation, immunofluorescence/confocal localization, flow cytometry for surface integrin β1, siRNA screen of 175 BTBPs\",\n      \"journal\": \"Biology open\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, siRNA knockdown with cellular phenotype, multiple orthogonal methods in single lab\",\n      \"pmids\": [\"29038302\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"ANKFY1 physically interacts with GAPVD1 (co-immunoprecipitation) and both proteins co-localize in HEK293T cells. Both proteins interact with active RAB5 (GTP-bound form). Patient-derived missense mutations in ANKFY1 alter binding affinity for active RAB5 and reduce ability to rescue knockout-induced podocyte migration defects, implicating ANKFY1 in RAB5-dependent endosomal regulation in podocytes.\",\n      \"method\": \"Co-immunoprecipitation, co-localization in HEK293T, siRNA silencing, podocyte migration assay, ectopic expression of patient-derived mutant proteins, Drosophila nephrocyte endocytosis assay\",\n      \"journal\": \"Journal of the American Society of Nephrology : JASN\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, multiple functional assays, patient mutations tested, cross-species validation in Drosophila\",\n      \"pmids\": [\"29959197\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"ANKFY1 knockdown in human retinal microvascular endothelial cells (HRMECs) reduces cell-surface VEGFR2 protein levels (without affecting VEGFR2 mRNA) and attenuates downstream Akt/eNOS signaling, thereby impairing VEGF-dependent and -independent endothelial cell proliferation and migration.\",\n      \"method\": \"siRNA knockdown, Western blot for surface VEGFR2 and Akt/eNOS phosphorylation, qRT-PCR, cell proliferation and migration assays\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined molecular phenotype (surface receptor and signaling pathway), single lab, multiple methods\",\n      \"pmids\": [\"33092793\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Ankfy1 knockout mice develop normally but at 9 months show progressive loss of cerebellar Purkinje cells (with other cerebellar cell types largely unaffected) and defective motor function, establishing a cell-type-specific role for ANKFY1 in Purkinje cell maintenance in vivo.\",\n      \"method\": \"Whole-body knockout mouse model, histology, immunofluorescence, motor behavior tests\",\n      \"journal\": \"Frontiers in cellular neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined cell-type-specific in vivo KO phenotype, single lab\",\n      \"pmids\": [\"33796010\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ANKFY1 is an endosome-localized protein that binds PI3P through its FYVE domain, directly interacts with ATG2A, and promotes ATG2A-mediated lipid transfer from PI3P-containing liposomes. A pool of ANKFY1 co-localizes with ATG2A between endosomes and phagophores. Depletion of ANKFY1 impairs autophagosome growth and reduces autophagy flux, phenocopying ATG2A/B depletion. Depletion of UVRAG, ANKFY1, or ATG2A/B reduces PI3P on phagophores, placing ANKFY1 in the UVRAG–PI3P–ATG2A lipid transfer pathway from endosomes to phagophores.\",\n      \"method\": \"Co-immunoprecipitation/pulldown, in vitro lipid transfer assay with purified recombinant proteins and PI3P-containing liposomes, siRNA/shRNA depletion, autophagy flux assays, confocal co-localization, genetic epistasis (UVRAG/ANKFY1/ATG2A/B depletion)\",\n      \"journal\": \"Cell discovery\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with purified proteins, lipid transfer assay, mutagenesis of FYVE domain, genetic epistasis, multiple orthogonal methods\",\n      \"pmids\": [\"38622126\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Ankfy1 is dispensable for neural stem/precursor cell development in mice with a mixed genetic background, but Ankfy1 knockout is lethal by embryonic day 11.5 in a pure C57BL/6 inbred background, indicating an essential but genetically background-dependent role in early embryonic development.\",\n      \"method\": \"Knockout mouse generation, immunofluorescence, in situ hybridization, genotyping by PCR\",\n      \"journal\": \"Neural regeneration research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo KO with defined developmental phenotype, single lab\",\n      \"pmids\": [\"28123425\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Compound heterozygous ANKFY1 variants (p.Ser918Ter and a splice-site deletion) found in a patient with proteinuria and movement disorder lead to reduced ANKFY1 protein expression in vitro, supporting a loss-of-function mechanism for bi-allelic ANKFY1 variants in a neuro-renal syndrome.\",\n      \"method\": \"Whole-exome sequencing, in vitro functional study (Western blot for protein expression of patient variants)\",\n      \"journal\": \"Clinical kidney journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single in vitro expression study, single lab, limited mechanistic follow-up\",\n      \"pmids\": [\"38915441\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"ANKFY1 interacts with PDCoV nonstructural protein nsp8, recruits the E3 ubiquitin ligase Cullin3 to catalyze K63/K33-linked ubiquitination of nsp8 at lysine 58, and the ubiquitinated nsp8 is subsequently recognized by selective autophagy receptor p62 and delivered to autolysosomes for degradation, thereby suppressing viral replication.\",\n      \"method\": \"Co-immunoprecipitation, gain/loss-of-function (overexpression and siRNA depletion), ubiquitination assay with site-directed mutagenesis (K58 site), p62 interaction assay, viral replication and RNA synthesis quantification\",\n      \"journal\": \"Veterinary microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, ubiquitination assay with mutagenesis, loss-of-function with defined antiviral phenotype, single lab\",\n      \"pmids\": [\"41763084\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"miR-760 directly targets the ANKFY1 3'UTR (validated by luciferase reporter assay) and suppresses ANKFY1 protein expression. ANKFY1 participates in APS-mediated promotion of osteogenic differentiation and proliferation of human bone marrow mesenchymal stem cells.\",\n      \"method\": \"Luciferase reporter assay, Western blot, qRT-PCR, miR-760 overexpression/knockdown, osteogenic differentiation assays\",\n      \"journal\": \"Bone & joint research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — luciferase reporter for miRNA-mRNA targeting, pathway placement indirect, single lab\",\n      \"pmids\": [\"37532241\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ANKFY1 (Rabankyrin-5/Ankhzn) is an endosome-localized protein with ankyrin repeats and a PI3P-binding FYVE domain that (1) acts as a CUL3 E3 ligase adaptor to regulate endosomal trafficking of cell-surface receptors (integrin β1, VEGFR2); (2) binds active RAB5 and interacts with GAPVD1 to support endocytic trafficking and podocyte function; (3) bridges ATG2A-mediated lipid transfer from PI3P-enriched endosomes to phagophores during autophagosome biogenesis; and (4) recruits CUL3 to ubiquitinate substrates (e.g., viral nsp8) for p62-dependent selective autophagic degradation, with loss-of-function causing defects in podocyte migration, retinal endothelial signaling, and Purkinje cell maintenance in vivo.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ANKFY1 (Rabankyrin-5/Ankhzn) is an endosome-associated protein that integrates phosphoinositide-dependent membrane recognition with ubiquitin signaling and lipid transfer to control endosomal trafficking, receptor surface display, and autophagosome biogenesis [#0, #7]. It localizes to endosomal membranes via a FYVE domain that binds PI3P and is found in both membrane and soluble pools [#0, #1, #7]. ANKFY1 functions as a BTB/adaptor for the CUL3 E3 ubiquitin ligase, with CUL3 required for its early endosomal localization; this CUL3–ANKFY1 module sustains cell-surface levels of integrin \\u03b21 and supports angiogenesis [#3], and ANKFY1 likewise maintains surface VEGFR2 and downstream Akt/eNOS signaling in endothelial cells without affecting receptor transcription [#5]. In a parallel trafficking role, ANKFY1 binds active GTP-bound RAB5 and interacts with GAPVD1 to govern RAB5-dependent endosomal regulation in podocytes [#4]. Beyond receptor trafficking, ANKFY1 directly interacts with ATG2A and promotes ATG2A-mediated lipid transfer from PI3P-containing membranes, operating within a UVRAG–PI3P–ATG2A pathway that delivers lipid from endosomes to growing phagophores; its loss impairs autophagosome growth and autophagy flux [#7]. ANKFY1 can also recruit CUL3 to ubiquitinate a viral substrate (PDCoV nsp8) for p62-dependent selective autophagic degradation, restricting viral replication [#10]. In vivo, loss of ANKFY1 causes background-dependent embryonic lethality, progressive cerebellar Purkinje cell degeneration with motor defects, and bi-allelic loss-of-function variants are associated with a neuro-renal syndrome of proteinuria and movement disorder [#6, #8, #9].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established the basic identity and subcellular home of ANKFY1, defining it as an endosomal ankyrin-repeat/FYVE protein and setting the structural basis for membrane recognition.\",\n      \"evidence\": \"Immunoelectron microscopy and in vitro transcription/translation with antibody detection\",\n      \"pmids\": [\"10092534\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"FYVE-PI3P binding not yet functionally demonstrated\", \"no molecular partners or activity defined\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Refined biochemical distribution and genomic mapping, showing ANKFY1 partitions between membrane and soluble fractions consistent with dynamic membrane association.\",\n      \"evidence\": \"Subcellular fractionation/Western blot and radiation hybrid/FISH mapping to 17p13\",\n      \"pmids\": [\"10940552\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"determinants of membrane vs soluble partitioning unknown\", \"no functional role assigned\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Linked ANKFY1 to endocytic and starvation-responsive vesicular compartments, hinting at roles in endocytosis and autophagy.\",\n      \"evidence\": \"Immunofluorescence co-localization with transferrin and dextran plus serum-starvation in macrophages\",\n      \"pmids\": [\"12833855\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"localization-only, no genetic manipulation\", \"autophagy involvement not mechanistically tested\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Identified ANKFY1 as a CUL3 E3 ligase adaptor controlling surface receptor trafficking, providing the first mechanistic activity and a physiological angiogenesis output.\",\n      \"evidence\": \"BTBP siRNA screen, reciprocal Co-IP, surface integrin \\u03b21 flow cytometry in endothelial cells\",\n      \"pmids\": [\"29038302\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"ubiquitination substrates in this pathway not identified\", \"how CUL3 directs endosomal localization unresolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Connected ANKFY1 to RAB5/GAPVD1-dependent endosomal regulation and to human disease, showing patient mutations impair RAB5 binding and podocyte function.\",\n      \"evidence\": \"Co-IP, co-localization, podocyte migration rescue with patient mutants, Drosophila nephrocyte assay\",\n      \"pmids\": [\"29959197\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"structural basis of active-RAB5 recognition not resolved\", \"relationship between RAB5 and CUL3 functions unclear\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extended the receptor-trafficking role to VEGFR2, showing ANKFY1 maintains surface receptor levels and downstream Akt/eNOS signaling post-transcriptionally.\",\n      \"evidence\": \"siRNA knockdown with surface VEGFR2 Western blot, signaling and migration/proliferation assays in HRMECs\",\n      \"pmids\": [\"33092793\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"whether CUL3 ubiquitination drives VEGFR2 trafficking untested\", \"trafficking step affected (recycling vs degradation) undefined\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstrated a cell-type-specific in vivo requirement, with Purkinje cell loss and motor defects upon ANKFY1 knockout.\",\n      \"evidence\": \"Whole-body knockout mouse histology, immunofluorescence, motor behavior\",\n      \"pmids\": [\"33796010\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"molecular cause of Purkinje cell vulnerability unknown\", \"endosomal vs autophagy contribution to phenotype not separated\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Revealed an essential but genetic-background-dependent role in early embryogenesis, complicating interpretation of organismal requirement.\",\n      \"evidence\": \"Knockout mice in mixed vs pure C57BL/6 backgrounds with developmental analysis\",\n      \"pmids\": [\"28123425\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"modifier loci explaining background dependence unidentified\", \"molecular pathway underlying lethality unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined a direct biochemical mechanism in autophagy: ANKFY1 binds PI3P and ATG2A and promotes ATG2A-mediated lipid transfer from endosomes to phagophores.\",\n      \"evidence\": \"In vitro lipid transfer with purified proteins and PI3P liposomes, FYVE mutagenesis, autophagy flux assays, UVRAG/ANKFY1/ATG2A epistasis\",\n      \"pmids\": [\"38622126\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"how ANKFY1 tethers ATG2A to phagophores structurally undefined\", \"relationship between autophagy and CUL3/RAB5 roles unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Strengthened the human disease link by associating bi-allelic loss-of-function ANKFY1 variants with a neuro-renal syndrome.\",\n      \"evidence\": \"Whole-exome sequencing with in vitro protein-expression assay of patient variants\",\n      \"pmids\": [\"38915441\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"single in vitro expression readout, no rescue or animal model\", \"genotype-phenotype causality not formally established\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Showed ANKFY1 couples CUL3-mediated ubiquitination to selective autophagy of a substrate, recruiting CUL3 to ubiquitinate viral nsp8 for p62-dependent degradation.\",\n      \"evidence\": \"Co-IP, ubiquitination assay with K58 mutagenesis, p62 interaction, viral replication quantification\",\n      \"pmids\": [\"41763084\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"endogenous (non-viral) ubiquitination substrates not identified\", \"generality of CUL3-to-p62 axis beyond this pathogen untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ANKFY1's distinct activities — CUL3 adaptor, RAB5/GAPVD1 endosomal regulator, and ATG2A lipid-transfer cofactor — are coordinated on a single endosomal platform, and which is responsible for each in vivo phenotype, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"no integrated model linking trafficking, ubiquitination, and lipid transfer\", \"endogenous ubiquitination substrates unknown\", \"structural basis of multivalent partner engagement undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 7]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [3, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0, 3, 7]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [3, 4, 5]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [7, 10]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [3, 10]}\n    ],\n    \"complexes\": [\"CUL3 E3 ubiquitin ligase complex\"],\n    \"partners\": [\"CUL3\", \"GAPVD1\", \"RAB5\", \"ATG2A\", \"UVRAG\", \"SQSTM1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}