{"gene":"PEX13","run_date":"2026-04-29T11:37:58","timeline":{"discoveries":[{"year":1999,"finding":"PEX13 encodes a peroxisomal membrane protein with a cytoplasmically exposed SH3 domain that functions as a docking factor for the PTS1 receptor PEX5; missense mutations in the SH3 domain reduce PEX13 activity and impair peroxisomal matrix protein import","method":"Complementation of PBD patient fibroblasts by PEX13 expression, missense mutation analysis, analogous yeast mutation validation","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 2 — reciprocal complementation and mutation analysis replicated across two groups (PMID:10441568, PMID:10332040)","pmids":["10441568","10332040"],"is_preprint":false},{"year":1999,"finding":"PEX13 SH3 domain temperature-sensitive mutation I326T renders the protein unstable at 37°C but stable at 30°C, and a nonsense mutation W234ter causing loss of SH3 domain and transmembrane domain leads to severe Zellweger phenotype, demonstrating domain-function relationships","method":"Patient mutation analysis, temperature-sensitive rescue assay in PEX13-defective CHO cells expressing mutant PEX13 cDNA","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 1-2 — in vitro cell-based reconstitution with mutagenesis at defined temperatures","pmids":["10332040"],"is_preprint":false},{"year":2003,"finding":"Pex13 knockout mice lack morphologically intact peroxisomes and show deficient import of matrix proteins containing either PTS1 or PTS2 signals, with severe impairment of peroxisomal fatty acid oxidation and plasmalogen synthesis","method":"Conditional Cre-mediated knockout mouse, biochemical assays of peroxisomal fatty acid oxidation and plasmalogen synthesis, immunofluorescence for matrix protein import","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 — clean KO with multiple orthogonal biochemical readouts in vivo","pmids":["12897163"],"is_preprint":false},{"year":2005,"finding":"Yeast Pex13 directly binds Pex14 via two sites: its SH3 domain and a novel intraperoxisomal site; Pex5 also contributes to Pex13-Pex14 association; all three interactions together are required for full PTS1- and PTS2-dependent matrix protein import and association of Pex13 with the docking complex","method":"Genetic epistasis with double/triple mutant combinations, co-purification assays, growth on oleic acid, in vivo import assays","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 — multiple mutant combinations with direct biochemical interaction assays and functional import readouts","pmids":["15798189"],"is_preprint":false},{"year":2013,"finding":"Human PEX13 forms homooligomers at the peroxisomal membrane; the conserved W313 residue in the SH3 domain is required for self-association but not for PEX14 interaction; homooligomerization is necessary for PTS1 protein import; N-terminal half mediates peroxisomal localization which is prerequisite for homooligomerization","method":"Live-cell FRET microscopy, co-immunoprecipitation, truncation constructs, complementation rescue of import in W313G mutant cells","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (FRET, co-IP, complementation) in live cells","pmids":["23716570"],"is_preprint":false},{"year":2016,"finding":"PEX13 is required for selective autophagy (virophagy of Sindbis virus and mitophagy of damaged mitochondria); disease-associated PEX13 mutants I326T and W313G are specifically defective in mitophagy; this function is shared with PEX3 but not PEX14 or PEX19","method":"KO/knockdown cells with selective autophagy assays, disease-mutant expression, comparison across peroxin knockdowns","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 — clean KO with specific phenotypic readouts, but single lab study","pmids":["27827795"],"is_preprint":false},{"year":2018,"finding":"PEX13 adopts a Nout-Cin membrane topology, with its C-terminal SH3 domain exposed to the peroxisome matrix (intraperoxisomal), while PEX14 has Nin-Cout topology; this resolves the organization of the peroxisomal protein import machinery","method":"Protease-protection assays on proteoliposomes and purified rat liver peroxisomes, mass spectrometry, Edman degradation, western blotting with domain-specific antibodies","journal":"The FEBS journal","confidence":"High","confidence_rationale":"Tier 1 — reconstituted proteoliposomes with multiple orthogonal biochemical methods","pmids":["30414318"],"is_preprint":false},{"year":2023,"finding":"PEX13 prevents pexophagy of healthy peroxisomes; loss of PEX13 causes accumulation of ubiquitinated PEX5 on peroxisomes and increased peroxisome-derived ROS, together inducing pexophagy; PEX13 protein levels are downregulated during amino acid starvation to facilitate pexophagy","method":"CRISPR gene editing, quantitative fluorescence microscopy, zebrafish model, ubiquitination assays, ROS measurement","journal":"Autophagy","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods across cell and zebrafish models with defined molecular mechanism","pmids":["36541703"],"is_preprint":false},{"year":2024,"finding":"The C-terminal SH3 domain of PEX13 binds WxxxF/Y motifs in the import receptor PEX5; this is regulated by an intramolecular FxxxF motif proximal to the SH3 domain that competes with PEX5 binding; the FxxxF motif also mediates PEX14 binding; crystal structures reveal recognition through a non-canonical surface on the SH3 domain distinct from canonical PxxP-binding surface","method":"Biochemical binding assays, NMR, crystal structures, mutagenesis, functional import assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 — crystal structures combined with biochemical and mutagenesis validation","pmids":["38632234"],"is_preprint":false},{"year":2025,"finding":"ZBTB17/MIZ1 transcription factor directly regulates PEX13 expression to modulate peroxisomal matrix protein import; knockdown of ZBTB17 or PEX13 produces similar metabolic alterations including downregulated purine synthesis","method":"CRISPR/Cas9 ubiquitin ligase library screen, transcriptional reporter assays, siRNA knockdown, metabolomic profiling","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 — CRISPR screen with orthogonal metabolomic validation, single lab","pmids":["40243840"],"is_preprint":false},{"year":2025,"finding":"PEDV nonstructural protein NSP8 directly interacts with PEX13 (identified by mass spectrometry) and induces its degradation via the autophagy-lysosomal pathway, leading to ubiquitination of PEX5, NBR1 recruitment, and pexophagy, thereby suppressing MAVS-dependent IFN-III production","method":"Mass spectrometry interaction screen, co-immunoprecipitation, autophagy pathway inhibitors, IFN-III production assays","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2-3 — direct interaction by MS and co-IP, functional pexophagy and IFN signaling readouts, single lab","pmids":["41186416"],"is_preprint":false},{"year":2026,"finding":"PEX13 depletion-induced pexophagy is orchestrated by an ATM-PINK1-STUB1-ABCD3-SQSTM1 signaling cascade; PINK1 phosphorylates STUB1 to enhance its E3 ligase activity toward ABCD3, which recruits SQSTM1 for peroxisomal degradation","method":"siRNA screening, phosphorylation assays, ubiquitination assays, epistasis with ATM and PINK1 inhibitors/mutants","journal":"Cell death and differentiation","confidence":"Medium","confidence_rationale":"Tier 2 — siRNA screen with defined biochemical cascade, single lab","pmids":["41927977"],"is_preprint":false},{"year":2010,"finding":"Brain-restricted PEX13 deficiency in mice leads to impaired cerebellar development, defective granule cell migration, and Purkinje cell layer development; cultured PEX13-null cerebellar neurons exhibit elevated reactive oxygen species, increased mitochondrial SOD2, enhanced apoptosis, and mitochondrial dysfunction","method":"Conditional brain-specific Cex13 knockout mouse, ROS measurements, mitochondrial function assays, histology","journal":"Disease models & mechanisms","confidence":"High","confidence_rationale":"Tier 2 — conditional KO with multiple biochemical and cellular phenotypic readouts","pmids":["20959636"],"is_preprint":false},{"year":2020,"finding":"Hepatocyte-specific deletion of Pex13 reduces hepatic hepcidin expression through increased SMAD7 signaling and ER stress, disrupting systemic iron homeostasis","method":"Conditional hepatocyte Pex13 KO mouse, siRNA knockdown in HepG2/C3A cells, hepcidin and SMAD7 expression analysis","journal":"Biochimica et biophysica acta. Molecular basis of disease","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo KO confirmed by cell-based knockdown with defined signaling pathway, single lab","pmids":["32565019"],"is_preprint":false}],"current_model":"PEX13 is an integral peroxisomal membrane protein (Nout-Cin topology) whose cytoplasmic N-terminus anchors it in the membrane while its SH3 domain faces the peroxisome matrix; the SH3 domain binds WxxxF/Y motifs in the PTS1 receptor PEX5 (regulated by an intramolecular FxxxF motif) and PEX14 via a non-canonical surface, forming a docking complex essential for import of both PTS1- and PTS2-targeted matrix proteins; PEX13 homooligomerization is additionally required for PTS1 import; beyond import, PEX13 prevents pexophagy of healthy peroxisomes by limiting ubiquitinated PEX5 accumulation and peroxisomal ROS, and is required for selective autophagy of damaged mitochondria and viruses, linking peroxisome biogenesis to organelle quality control and innate immune signaling."},"narrative":{"teleology":[{"year":1999,"claim":"Identification of PEX13 as the gene mutated in a Zellweger spectrum complementation group established it as a peroxisomal membrane docking factor for PEX5, linking SH3 domain integrity to peroxisomal matrix protein import and human disease.","evidence":"Complementation cloning from PBD patient fibroblasts, missense/nonsense mutation analysis, temperature-sensitive rescue in CHO cells","pmids":["10441568","10332040"],"confidence":"High","gaps":["Precise stoichiometry and architecture of the docking complex unknown","Whether PEX13 has import-independent functions not addressed"]},{"year":2003,"claim":"A knockout mouse model demonstrated that PEX13 is essential for both PTS1- and PTS2-dependent import in vivo, and that its loss abolishes peroxisomal fatty acid oxidation and plasmalogen synthesis, confirming it as non-redundant in the import machinery.","evidence":"Cre-mediated Pex13 knockout mouse with biochemical assays and immunofluorescence","pmids":["12897163"],"confidence":"High","gaps":["Tissue-specific consequences not yet dissected","Contribution of individual PEX13 interaction interfaces to in vivo import not tested"]},{"year":2005,"claim":"Dissection of yeast Pex13–Pex14 interactions revealed two binding sites (SH3 domain and intraperoxisomal region) plus a Pex5-dependent contribution, showing that multiple simultaneous contacts are required for full docking complex assembly and import.","evidence":"Double/triple yeast mutant combinations with co-purification and oleic acid growth assays","pmids":["15798189"],"confidence":"High","gaps":["Structural basis of the intraperoxisomal binding site unresolved","Whether the same dual-site architecture applies in mammals not shown"]},{"year":2010,"claim":"Brain-specific PEX13 deletion revealed that peroxisomal dysfunction causes cerebellar developmental defects, elevated ROS, and secondary mitochondrial dysfunction, establishing a cell-autonomous link between peroxisomal import and neuronal survival.","evidence":"Conditional brain Pex13 KO mouse with ROS measurement, mitochondrial assays, and histology","pmids":["20959636"],"confidence":"High","gaps":["Which specific metabolites drive ROS elevation and mitochondrial damage not identified","Whether neuronal phenotype is import-dependent or involves PEX13's autophagy role unknown"]},{"year":2013,"claim":"Demonstration that PEX13 forms homooligomers at the peroxisomal membrane, mediated by the conserved W313 residue, and that this self-association is required for PTS1 import independently of PEX14 binding, revealed an additional layer of import regulation.","evidence":"Live-cell FRET, co-immunoprecipitation, W313G mutant complementation","pmids":["23716570"],"confidence":"High","gaps":["Oligomeric stoichiometry and whether oligomerization forms part of the translocation channel unknown","Whether homooligomerization also affects PTS2 import not tested"]},{"year":2016,"claim":"Discovery that PEX13 is required for selective autophagy (virophagy and mitophagy) independently of general peroxisomal import expanded its functional repertoire beyond peroxisome biogenesis to organelle quality control.","evidence":"PEX13 KO/knockdown with mitophagy and Sindbis virophagy assays; disease mutants I326T and W313G specifically defective in mitophagy","pmids":["27827795"],"confidence":"Medium","gaps":["Molecular mechanism by which PEX13 promotes mitophagy/virophagy undefined","Whether selective autophagy function is SH3-dependent or involves a distinct domain unknown","Single-lab finding not yet independently replicated"]},{"year":2018,"claim":"Determination of PEX13's Nout-Cin topology—with the SH3 domain facing the peroxisome matrix—resolved a longstanding controversy about import machinery organization and reframed how the docking complex is assembled across the membrane.","evidence":"Protease protection on reconstituted proteoliposomes and purified rat liver peroxisomes, mass spectrometry, Edman degradation","pmids":["30414318"],"confidence":"High","gaps":["How cytoplasmic PEX5 accesses the intraperoxisomal SH3 domain during import not mechanistically explained","No full-length PEX13 structure available"]},{"year":2023,"claim":"Establishing that PEX13 actively prevents pexophagy of healthy peroxisomes by limiting ubiquitinated PEX5 accumulation and peroxisomal ROS—and that starvation-induced PEX13 downregulation triggers pexophagy—defined PEX13 as a molecular switch between peroxisome maintenance and turnover.","evidence":"CRISPR KO, quantitative fluorescence microscopy, zebrafish model, ubiquitination and ROS assays","pmids":["36541703"],"confidence":"High","gaps":["Mechanism of starvation-induced PEX13 downregulation (transcriptional vs. post-translational) not fully resolved","Whether PEX13 directly deubiquitinates PEX5 or prevents ubiquitination upstream unknown"]},{"year":2024,"claim":"Crystal structures of the PEX13 SH3 domain revealed that PEX5 WxxxF/Y motifs bind a non-canonical surface distinct from classical PxxP recognition, and that an intramolecular FxxxF motif competes with PEX5 for this surface while also mediating PEX14 binding, providing a structural basis for regulated docking.","evidence":"X-ray crystallography, NMR, biochemical binding assays, mutagenesis, functional import assays","pmids":["38632234"],"confidence":"High","gaps":["No structure of a full-length PEX13 or PEX13–PEX14–PEX5 ternary complex","How FxxxF autoinhibition is relieved during active import not defined"]},{"year":2025,"claim":"Identification of ZBTB17/MIZ1 as a direct transcriptional regulator of PEX13 connected ubiquitin ligase-dependent transcriptional control to peroxisomal import capacity and downstream purine metabolism.","evidence":"CRISPR/Cas9 ubiquitin ligase library screen, transcriptional reporter assays, siRNA knockdown, metabolomics","pmids":["40243840"],"confidence":"Medium","gaps":["Whether ZBTB17 regulation of PEX13 is physiologically modulated in specific tissues unknown","Single-lab finding"]},{"year":2025,"claim":"PEDV NSP8 was shown to directly target PEX13 for autophagy-lysosomal degradation, triggering PEX5 ubiquitination and pexophagy that suppresses MAVS-dependent IFN-III signaling, revealing viral exploitation of PEX13's anti-pexophagy function for immune evasion.","evidence":"Mass spectrometry interaction screen, co-immunoprecipitation, autophagy inhibitors, IFN-III assays in PEDV-infected cells","pmids":["41186416"],"confidence":"Medium","gaps":["Whether other viruses use the same PEX13-degradation strategy not examined","Structural basis of NSP8–PEX13 interaction unknown","Single-lab finding"]},{"year":2026,"claim":"The signaling cascade downstream of PEX13 loss during pexophagy was elucidated as ATM–PINK1–STUB1–ABCD3–SQSTM1, where PINK1 phosphorylation activates STUB1 E3 ligase activity toward ABCD3 to recruit SQSTM1, providing a complete molecular pathway for pexophagy initiation.","evidence":"siRNA screening, phosphorylation and ubiquitination assays, epistasis with ATM/PINK1 inhibitors and mutants","pmids":["41927977"],"confidence":"Medium","gaps":["Whether this cascade operates in all cell types not tested","How ATM senses peroxisomal dysfunction upstream of PINK1 unclear","Single-lab finding"]},{"year":null,"claim":"Key open questions include the full-length structure of PEX13, the mechanism by which its intraperoxisomal SH3 domain engages cytoplasmic PEX5 during translocation, and the molecular basis of its import-independent role in selective autophagy.","evidence":"","pmids":[],"confidence":"High","gaps":["No full-length PEX13 structure or cryo-EM of the assembled import complex","Mechanism coupling FxxxF autoinhibition relief to cargo translocation unknown","Whether PEX13's autophagy function is separable from its import function at the domain level unresolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,3,4,6,8]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,3,8]}],"localization":[{"term_id":"GO:0043226","term_label":"organelle","supporting_discovery_ids":[0,2,4,6]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[5,7,10,11]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,2,4,6,8]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,2,3,8]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[2,13]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[0,1,12]}],"complexes":["Peroxisomal docking/import complex (PEX13–PEX14–PEX5)"],"partners":["PEX5","PEX14","PEX3","ZBTB17","SQSTM1","STUB1","PINK1"],"other_free_text":[]},"mechanistic_narrative":"PEX13 is an integral peroxisomal membrane protein that serves as a central docking factor for peroxisomal matrix protein import and as a gatekeeper of organelle quality control through regulation of pexophagy. Its SH3 domain, which faces the peroxisome matrix in a Nout-Cin topology, binds WxxxF/Y motifs in the PTS1 receptor PEX5 via a non-canonical surface and interacts with PEX14 through both the SH3 domain and an intraperoxisomal site; an intramolecular FxxxF motif regulates PEX5 binding by competing for the same SH3 surface, and PEX13 homooligomerization at the membrane is additionally required for PTS1 import [PMID:38632234, PMID:23716570, PMID:15798189, PMID:30414318]. Loss of PEX13 eliminates both PTS1- and PTS2-dependent import, abolishes peroxisomal fatty acid oxidation and plasmalogen synthesis, and causes Zellweger spectrum peroxisome biogenesis disorders; brain-specific deletion impairs cerebellar development with elevated ROS and mitochondrial dysfunction [PMID:12897163, PMID:10441568, PMID:20959636]. PEX13 also prevents pexophagy of healthy peroxisomes by limiting ubiquitinated PEX5 accumulation and peroxisomal ROS—its downregulation during amino acid starvation facilitates pexophagy through an ATM–PINK1–STUB1–ABCD3–SQSTM1 cascade—and is independently required for selective autophagy of damaged mitochondria and viruses [PMID:36541703, PMID:41927977, PMID:27827795]."},"prefetch_data":{"uniprot":{"accession":"Q92968","full_name":"Peroxisomal membrane protein PEX13","aliases":["Peroxin-13"],"length_aa":403,"mass_kda":44.1,"function":"Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor (PubMed:28765278, PubMed:8858165, PubMed:9653144). The PEX13-PEX14 docking complex forms a large import pore which can be opened to a diameter of about 9 nm (By similarity). Mechanistically, PEX5 receptor along with cargo proteins associates with the PEX14 subunit of the PEX13-PEX14 docking complex in the cytosol, leading to the insertion of the receptor into the organelle membrane with the concomitant translocation of the cargo into the peroxisome matrix (PubMed:28765278, PubMed:8858165, PubMed:9653144). Involved in the import of PTS1- and PTS2-type containing proteins (PubMed:8858165, PubMed:9653144)","subcellular_location":"Peroxisome membrane","url":"https://www.uniprot.org/uniprotkb/Q92968/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PEX13","classification":"Not Classified","n_dependent_lines":66,"n_total_lines":1208,"dependency_fraction":0.054635761589403975},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/PEX13","total_profiled":1310},"omim":[{"mim_id":"621410","title":"PEROXISOME BIOGENESIS FACTOR 39; PEX39","url":"https://www.omim.org/entry/621410"},{"mim_id":"614885","title":"PEROXISOME BIOGENESIS DISORDER 11B; PBD11B","url":"https://www.omim.org/entry/614885"},{"mim_id":"614883","title":"PEROXISOME BIOGENESIS DISORDER 11A (ZELLWEGER); PBD11A","url":"https://www.omim.org/entry/614883"},{"mim_id":"614870","title":"PEROXISOME BIOGENESIS DISORDER 6A (ZELLWEGER); PBD6A","url":"https://www.omim.org/entry/614870"},{"mim_id":"602859","title":"PEROXISOME BIOGENESIS FACTOR 10; PEX10","url":"https://www.omim.org/entry/602859"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Peroxisomes","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PEX13"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q92968","domains":[{"cath_id":"2.30.30.40","chopping":"266-350","consensus_level":"high","plddt":85.2149,"start":266,"end":350},{"cath_id":"1.20.5","chopping":"117-199","consensus_level":"medium","plddt":83.1688,"start":117,"end":199}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92968","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q92968-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q92968-F1-predicted_aligned_error_v6.png","plddt_mean":64.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PEX13","jax_strain_url":"https://www.jax.org/strain/search?query=PEX13"},"sequence":{"accession":"Q92968","fasta_url":"https://rest.uniprot.org/uniprotkb/Q92968.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q92968/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92968"}},"corpus_meta":[{"pmid":"12897163","id":"PMC_12897163","title":"Pex13 inactivation in the mouse disrupts peroxisome biogenesis and leads to a Zellweger syndrome phenotype.","date":"2003","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12897163","citation_count":92,"is_preprint":false},{"pmid":"10332040","id":"PMC_10332040","title":"Nonsense and temperature-sensitive mutations in PEX13 are the cause of complementation group H of peroxisome biogenesis disorders.","date":"1999","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/10332040","citation_count":70,"is_preprint":false},{"pmid":"16813573","id":"PMC_16813573","title":"The Arabidopsis pex12 and pex13 mutants are defective in both PTS1- and PTS2-dependent protein transport to peroxisomes.","date":"2006","source":"The Plant journal : for cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/16813573","citation_count":68,"is_preprint":false},{"pmid":"10441568","id":"PMC_10441568","title":"PEX13 is mutated in complementation group 13 of the peroxisome-biogenesis disorders.","date":"1999","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/10441568","citation_count":56,"is_preprint":false},{"pmid":"20959636","id":"PMC_20959636","title":"PEX13 deficiency in mouse brain as a model of Zellweger syndrome: abnormal cerebellum formation, reactive gliosis and oxidative stress.","date":"2010","source":"Disease models & mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/20959636","citation_count":54,"is_preprint":false},{"pmid":"36541703","id":"PMC_36541703","title":"PEX13 prevents pexophagy by regulating ubiquitinated PEX5 and peroxisomal ROS.","date":"2023","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/36541703","citation_count":49,"is_preprint":false},{"pmid":"15798189","id":"PMC_15798189","title":"Identification of a novel, intraperoxisomal pex14-binding site in pex13: association of pex13 with the docking complex is essential for peroxisomal matrix protein import.","date":"2005","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/15798189","citation_count":41,"is_preprint":false},{"pmid":"20192831","id":"PMC_20192831","title":"Peroxisome biogenesis factor PEX13 is required for appressorium-mediated plant infection by the anthracnose fungus Colletotrichum orbiculare.","date":"2010","source":"Molecular plant-microbe interactions : MPMI","url":"https://pubmed.ncbi.nlm.nih.gov/20192831","citation_count":41,"is_preprint":false},{"pmid":"27827795","id":"PMC_27827795","title":"Peroxisomal protein PEX13 functions in selective autophagy.","date":"2016","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/27827795","citation_count":40,"is_preprint":false},{"pmid":"17041890","id":"PMC_17041890","title":"Identification of novel mutations in PEX2, PEX6, PEX10, PEX12, and PEX13 in Zellweger spectrum patients.","date":"2006","source":"Human 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Molecular basis of disease","url":"https://pubmed.ncbi.nlm.nih.gov/32565019","citation_count":4,"is_preprint":false},{"pmid":"29187321","id":"PMC_29187321","title":"Impaired neurogenesis and associated gliosis in mouse brain with PEX13 deficiency.","date":"2017","source":"Molecular and cellular neurosciences","url":"https://pubmed.ncbi.nlm.nih.gov/29187321","citation_count":4,"is_preprint":false},{"pmid":"19422853","id":"PMC_19422853","title":"Quantitative genotyping of mouse brain-specific PEX13 gene disruption by real-time PCR.","date":"2009","source":"Journal of neuroscience methods","url":"https://pubmed.ncbi.nlm.nih.gov/19422853","citation_count":3,"is_preprint":false},{"pmid":"37962062","id":"PMC_37962062","title":"Severe Zellweger spectrum disorder due to a novel missense variant in the PEX13 gene: A case report and the literature review.","date":"2023","source":"Molecular genetics & genomic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/37962062","citation_count":1,"is_preprint":false},{"pmid":"40243840","id":"PMC_40243840","title":"ZBTB17/MIZ1 promotes peroxisome biogenesis by transcriptional regulation of PEX13.","date":"2025","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/40243840","citation_count":0,"is_preprint":false},{"pmid":"41186416","id":"PMC_41186416","title":"PEDV NSP8 inhibits IFN-III production induced by MAVS through downregulation of PEX13.","date":"2025","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/41186416","citation_count":0,"is_preprint":false},{"pmid":"41927977","id":"PMC_41927977","title":"PINK1 and STUB1 pathway orchestrates peroxisomal selective autophagy by PEX13 depletion.","date":"2026","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/41927977","citation_count":0,"is_preprint":false},{"pmid":"41860470","id":"PMC_41860470","title":"Loss of Peroxisomal Membrane Proteins PEX13 and PEX14 Disrupts Fatty Acid Oxidation and Drives Lipid Imbalance.","date":"2026","source":"Bioscience reports","url":"https://pubmed.ncbi.nlm.nih.gov/41860470","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.27.672480","title":"Global Profiling of Remodeled Subcellular Structures Due to Drug Treatment and Disease","date":"2025-08-31","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.27.672480","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.07.25.605214","title":"CRISPR screens reveal ZBTB17/MIZ1 as a peroxisome regulator","date":"2024-07-26","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.25.605214","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":17690,"output_tokens":3251,"usd":0.050917},"stage2":{"model":"claude-opus-4-6","input_tokens":6640,"output_tokens":3386,"usd":0.176775},"total_usd":0.227692,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"PEX13 encodes a peroxisomal membrane protein with a cytoplasmically exposed SH3 domain that functions as a docking factor for the PTS1 receptor PEX5; missense mutations in the SH3 domain reduce PEX13 activity and impair peroxisomal matrix protein import\",\n      \"method\": \"Complementation of PBD patient fibroblasts by PEX13 expression, missense mutation analysis, analogous yeast mutation validation\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal complementation and mutation analysis replicated across two groups (PMID:10441568, PMID:10332040)\",\n      \"pmids\": [\"10441568\", \"10332040\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"PEX13 SH3 domain temperature-sensitive mutation I326T renders the protein unstable at 37°C but stable at 30°C, and a nonsense mutation W234ter causing loss of SH3 domain and transmembrane domain leads to severe Zellweger phenotype, demonstrating domain-function relationships\",\n      \"method\": \"Patient mutation analysis, temperature-sensitive rescue assay in PEX13-defective CHO cells expressing mutant PEX13 cDNA\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — in vitro cell-based reconstitution with mutagenesis at defined temperatures\",\n      \"pmids\": [\"10332040\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Pex13 knockout mice lack morphologically intact peroxisomes and show deficient import of matrix proteins containing either PTS1 or PTS2 signals, with severe impairment of peroxisomal fatty acid oxidation and plasmalogen synthesis\",\n      \"method\": \"Conditional Cre-mediated knockout mouse, biochemical assays of peroxisomal fatty acid oxidation and plasmalogen synthesis, immunofluorescence for matrix protein import\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with multiple orthogonal biochemical readouts in vivo\",\n      \"pmids\": [\"12897163\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Yeast Pex13 directly binds Pex14 via two sites: its SH3 domain and a novel intraperoxisomal site; Pex5 also contributes to Pex13-Pex14 association; all three interactions together are required for full PTS1- and PTS2-dependent matrix protein import and association of Pex13 with the docking complex\",\n      \"method\": \"Genetic epistasis with double/triple mutant combinations, co-purification assays, growth on oleic acid, in vivo import assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple mutant combinations with direct biochemical interaction assays and functional import readouts\",\n      \"pmids\": [\"15798189\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Human PEX13 forms homooligomers at the peroxisomal membrane; the conserved W313 residue in the SH3 domain is required for self-association but not for PEX14 interaction; homooligomerization is necessary for PTS1 protein import; N-terminal half mediates peroxisomal localization which is prerequisite for homooligomerization\",\n      \"method\": \"Live-cell FRET microscopy, co-immunoprecipitation, truncation constructs, complementation rescue of import in W313G mutant cells\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (FRET, co-IP, complementation) in live cells\",\n      \"pmids\": [\"23716570\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"PEX13 is required for selective autophagy (virophagy of Sindbis virus and mitophagy of damaged mitochondria); disease-associated PEX13 mutants I326T and W313G are specifically defective in mitophagy; this function is shared with PEX3 but not PEX14 or PEX19\",\n      \"method\": \"KO/knockdown cells with selective autophagy assays, disease-mutant expression, comparison across peroxin knockdowns\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with specific phenotypic readouts, but single lab study\",\n      \"pmids\": [\"27827795\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PEX13 adopts a Nout-Cin membrane topology, with its C-terminal SH3 domain exposed to the peroxisome matrix (intraperoxisomal), while PEX14 has Nin-Cout topology; this resolves the organization of the peroxisomal protein import machinery\",\n      \"method\": \"Protease-protection assays on proteoliposomes and purified rat liver peroxisomes, mass spectrometry, Edman degradation, western blotting with domain-specific antibodies\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstituted proteoliposomes with multiple orthogonal biochemical methods\",\n      \"pmids\": [\"30414318\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PEX13 prevents pexophagy of healthy peroxisomes; loss of PEX13 causes accumulation of ubiquitinated PEX5 on peroxisomes and increased peroxisome-derived ROS, together inducing pexophagy; PEX13 protein levels are downregulated during amino acid starvation to facilitate pexophagy\",\n      \"method\": \"CRISPR gene editing, quantitative fluorescence microscopy, zebrafish model, ubiquitination assays, ROS measurement\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods across cell and zebrafish models with defined molecular mechanism\",\n      \"pmids\": [\"36541703\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The C-terminal SH3 domain of PEX13 binds WxxxF/Y motifs in the import receptor PEX5; this is regulated by an intramolecular FxxxF motif proximal to the SH3 domain that competes with PEX5 binding; the FxxxF motif also mediates PEX14 binding; crystal structures reveal recognition through a non-canonical surface on the SH3 domain distinct from canonical PxxP-binding surface\",\n      \"method\": \"Biochemical binding assays, NMR, crystal structures, mutagenesis, functional import assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structures combined with biochemical and mutagenesis validation\",\n      \"pmids\": [\"38632234\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ZBTB17/MIZ1 transcription factor directly regulates PEX13 expression to modulate peroxisomal matrix protein import; knockdown of ZBTB17 or PEX13 produces similar metabolic alterations including downregulated purine synthesis\",\n      \"method\": \"CRISPR/Cas9 ubiquitin ligase library screen, transcriptional reporter assays, siRNA knockdown, metabolomic profiling\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — CRISPR screen with orthogonal metabolomic validation, single lab\",\n      \"pmids\": [\"40243840\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PEDV nonstructural protein NSP8 directly interacts with PEX13 (identified by mass spectrometry) and induces its degradation via the autophagy-lysosomal pathway, leading to ubiquitination of PEX5, NBR1 recruitment, and pexophagy, thereby suppressing MAVS-dependent IFN-III production\",\n      \"method\": \"Mass spectrometry interaction screen, co-immunoprecipitation, autophagy pathway inhibitors, IFN-III production assays\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — direct interaction by MS and co-IP, functional pexophagy and IFN signaling readouts, single lab\",\n      \"pmids\": [\"41186416\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"PEX13 depletion-induced pexophagy is orchestrated by an ATM-PINK1-STUB1-ABCD3-SQSTM1 signaling cascade; PINK1 phosphorylates STUB1 to enhance its E3 ligase activity toward ABCD3, which recruits SQSTM1 for peroxisomal degradation\",\n      \"method\": \"siRNA screening, phosphorylation assays, ubiquitination assays, epistasis with ATM and PINK1 inhibitors/mutants\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — siRNA screen with defined biochemical cascade, single lab\",\n      \"pmids\": [\"41927977\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Brain-restricted PEX13 deficiency in mice leads to impaired cerebellar development, defective granule cell migration, and Purkinje cell layer development; cultured PEX13-null cerebellar neurons exhibit elevated reactive oxygen species, increased mitochondrial SOD2, enhanced apoptosis, and mitochondrial dysfunction\",\n      \"method\": \"Conditional brain-specific Cex13 knockout mouse, ROS measurements, mitochondrial function assays, histology\",\n      \"journal\": \"Disease models & mechanisms\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — conditional KO with multiple biochemical and cellular phenotypic readouts\",\n      \"pmids\": [\"20959636\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Hepatocyte-specific deletion of Pex13 reduces hepatic hepcidin expression through increased SMAD7 signaling and ER stress, disrupting systemic iron homeostasis\",\n      \"method\": \"Conditional hepatocyte Pex13 KO mouse, siRNA knockdown in HepG2/C3A cells, hepcidin and SMAD7 expression analysis\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular basis of disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo KO confirmed by cell-based knockdown with defined signaling pathway, single lab\",\n      \"pmids\": [\"32565019\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PEX13 is an integral peroxisomal membrane protein (Nout-Cin topology) whose cytoplasmic N-terminus anchors it in the membrane while its SH3 domain faces the peroxisome matrix; the SH3 domain binds WxxxF/Y motifs in the PTS1 receptor PEX5 (regulated by an intramolecular FxxxF motif) and PEX14 via a non-canonical surface, forming a docking complex essential for import of both PTS1- and PTS2-targeted matrix proteins; PEX13 homooligomerization is additionally required for PTS1 import; beyond import, PEX13 prevents pexophagy of healthy peroxisomes by limiting ubiquitinated PEX5 accumulation and peroxisomal ROS, and is required for selective autophagy of damaged mitochondria and viruses, linking peroxisome biogenesis to organelle quality control and innate immune signaling.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PEX13 is an integral peroxisomal membrane protein that serves as a central docking factor for peroxisomal matrix protein import and as a gatekeeper of organelle quality control through regulation of pexophagy. Its SH3 domain, which faces the peroxisome matrix in a Nout-Cin topology, binds WxxxF/Y motifs in the PTS1 receptor PEX5 via a non-canonical surface and interacts with PEX14 through both the SH3 domain and an intraperoxisomal site; an intramolecular FxxxF motif regulates PEX5 binding by competing for the same SH3 surface, and PEX13 homooligomerization at the membrane is additionally required for PTS1 import [PMID:38632234, PMID:23716570, PMID:15798189, PMID:30414318]. Loss of PEX13 eliminates both PTS1- and PTS2-dependent import, abolishes peroxisomal fatty acid oxidation and plasmalogen synthesis, and causes Zellweger spectrum peroxisome biogenesis disorders; brain-specific deletion impairs cerebellar development with elevated ROS and mitochondrial dysfunction [PMID:12897163, PMID:10441568, PMID:20959636]. PEX13 also prevents pexophagy of healthy peroxisomes by limiting ubiquitinated PEX5 accumulation and peroxisomal ROS—its downregulation during amino acid starvation facilitates pexophagy through an ATM–PINK1–STUB1–ABCD3–SQSTM1 cascade—and is independently required for selective autophagy of damaged mitochondria and viruses [PMID:36541703, PMID:41927977, PMID:27827795].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Identification of PEX13 as the gene mutated in a Zellweger spectrum complementation group established it as a peroxisomal membrane docking factor for PEX5, linking SH3 domain integrity to peroxisomal matrix protein import and human disease.\",\n      \"evidence\": \"Complementation cloning from PBD patient fibroblasts, missense/nonsense mutation analysis, temperature-sensitive rescue in CHO cells\",\n      \"pmids\": [\"10441568\", \"10332040\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Precise stoichiometry and architecture of the docking complex unknown\", \"Whether PEX13 has import-independent functions not addressed\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"A knockout mouse model demonstrated that PEX13 is essential for both PTS1- and PTS2-dependent import in vivo, and that its loss abolishes peroxisomal fatty acid oxidation and plasmalogen synthesis, confirming it as non-redundant in the import machinery.\",\n      \"evidence\": \"Cre-mediated Pex13 knockout mouse with biochemical assays and immunofluorescence\",\n      \"pmids\": [\"12897163\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Tissue-specific consequences not yet dissected\", \"Contribution of individual PEX13 interaction interfaces to in vivo import not tested\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Dissection of yeast Pex13–Pex14 interactions revealed two binding sites (SH3 domain and intraperoxisomal region) plus a Pex5-dependent contribution, showing that multiple simultaneous contacts are required for full docking complex assembly and import.\",\n      \"evidence\": \"Double/triple yeast mutant combinations with co-purification and oleic acid growth assays\",\n      \"pmids\": [\"15798189\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the intraperoxisomal binding site unresolved\", \"Whether the same dual-site architecture applies in mammals not shown\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Brain-specific PEX13 deletion revealed that peroxisomal dysfunction causes cerebellar developmental defects, elevated ROS, and secondary mitochondrial dysfunction, establishing a cell-autonomous link between peroxisomal import and neuronal survival.\",\n      \"evidence\": \"Conditional brain Pex13 KO mouse with ROS measurement, mitochondrial assays, and histology\",\n      \"pmids\": [\"20959636\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Which specific metabolites drive ROS elevation and mitochondrial damage not identified\", \"Whether neuronal phenotype is import-dependent or involves PEX13's autophagy role unknown\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Demonstration that PEX13 forms homooligomers at the peroxisomal membrane, mediated by the conserved W313 residue, and that this self-association is required for PTS1 import independently of PEX14 binding, revealed an additional layer of import regulation.\",\n      \"evidence\": \"Live-cell FRET, co-immunoprecipitation, W313G mutant complementation\",\n      \"pmids\": [\"23716570\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Oligomeric stoichiometry and whether oligomerization forms part of the translocation channel unknown\", \"Whether homooligomerization also affects PTS2 import not tested\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Discovery that PEX13 is required for selective autophagy (virophagy and mitophagy) independently of general peroxisomal import expanded its functional repertoire beyond peroxisome biogenesis to organelle quality control.\",\n      \"evidence\": \"PEX13 KO/knockdown with mitophagy and Sindbis virophagy assays; disease mutants I326T and W313G specifically defective in mitophagy\",\n      \"pmids\": [\"27827795\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism by which PEX13 promotes mitophagy/virophagy undefined\", \"Whether selective autophagy function is SH3-dependent or involves a distinct domain unknown\", \"Single-lab finding not yet independently replicated\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Determination of PEX13's Nout-Cin topology—with the SH3 domain facing the peroxisome matrix—resolved a longstanding controversy about import machinery organization and reframed how the docking complex is assembled across the membrane.\",\n      \"evidence\": \"Protease protection on reconstituted proteoliposomes and purified rat liver peroxisomes, mass spectrometry, Edman degradation\",\n      \"pmids\": [\"30414318\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How cytoplasmic PEX5 accesses the intraperoxisomal SH3 domain during import not mechanistically explained\", \"No full-length PEX13 structure available\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Establishing that PEX13 actively prevents pexophagy of healthy peroxisomes by limiting ubiquitinated PEX5 accumulation and peroxisomal ROS—and that starvation-induced PEX13 downregulation triggers pexophagy—defined PEX13 as a molecular switch between peroxisome maintenance and turnover.\",\n      \"evidence\": \"CRISPR KO, quantitative fluorescence microscopy, zebrafish model, ubiquitination and ROS assays\",\n      \"pmids\": [\"36541703\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of starvation-induced PEX13 downregulation (transcriptional vs. post-translational) not fully resolved\", \"Whether PEX13 directly deubiquitinates PEX5 or prevents ubiquitination upstream unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Crystal structures of the PEX13 SH3 domain revealed that PEX5 WxxxF/Y motifs bind a non-canonical surface distinct from classical PxxP recognition, and that an intramolecular FxxxF motif competes with PEX5 for this surface while also mediating PEX14 binding, providing a structural basis for regulated docking.\",\n      \"evidence\": \"X-ray crystallography, NMR, biochemical binding assays, mutagenesis, functional import assays\",\n      \"pmids\": [\"38632234\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structure of a full-length PEX13 or PEX13–PEX14–PEX5 ternary complex\", \"How FxxxF autoinhibition is relieved during active import not defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identification of ZBTB17/MIZ1 as a direct transcriptional regulator of PEX13 connected ubiquitin ligase-dependent transcriptional control to peroxisomal import capacity and downstream purine metabolism.\",\n      \"evidence\": \"CRISPR/Cas9 ubiquitin ligase library screen, transcriptional reporter assays, siRNA knockdown, metabolomics\",\n      \"pmids\": [\"40243840\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether ZBTB17 regulation of PEX13 is physiologically modulated in specific tissues unknown\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"PEDV NSP8 was shown to directly target PEX13 for autophagy-lysosomal degradation, triggering PEX5 ubiquitination and pexophagy that suppresses MAVS-dependent IFN-III signaling, revealing viral exploitation of PEX13's anti-pexophagy function for immune evasion.\",\n      \"evidence\": \"Mass spectrometry interaction screen, co-immunoprecipitation, autophagy inhibitors, IFN-III assays in PEDV-infected cells\",\n      \"pmids\": [\"41186416\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether other viruses use the same PEX13-degradation strategy not examined\", \"Structural basis of NSP8–PEX13 interaction unknown\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"The signaling cascade downstream of PEX13 loss during pexophagy was elucidated as ATM–PINK1–STUB1–ABCD3–SQSTM1, where PINK1 phosphorylation activates STUB1 E3 ligase activity toward ABCD3 to recruit SQSTM1, providing a complete molecular pathway for pexophagy initiation.\",\n      \"evidence\": \"siRNA screening, phosphorylation and ubiquitination assays, epistasis with ATM/PINK1 inhibitors and mutants\",\n      \"pmids\": [\"41927977\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether this cascade operates in all cell types not tested\", \"How ATM senses peroxisomal dysfunction upstream of PINK1 unclear\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key open questions include the full-length structure of PEX13, the mechanism by which its intraperoxisomal SH3 domain engages cytoplasmic PEX5 during translocation, and the molecular basis of its import-independent role in selective autophagy.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No full-length PEX13 structure or cryo-EM of the assembled import complex\", \"Mechanism coupling FxxxF autoinhibition relief to cargo translocation unknown\", \"Whether PEX13's autophagy function is separable from its import function at the domain level unresolved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 3, 4, 6, 8]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 3, 8]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0043226\", \"supporting_discovery_ids\": [0, 2, 4, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [5, 7, 10, 11]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 2, 4, 6, 8]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 2, 3, 8]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [2, 13]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [0, 1, 12]}\n    ],\n    \"complexes\": [\n      \"Peroxisomal docking/import complex (PEX13–PEX14–PEX5)\"\n    ],\n    \"partners\": [\n      \"PEX5\",\n      \"PEX14\",\n      \"PEX3\",\n      \"ZBTB17\",\n      \"SQSTM1\",\n      \"STUB1\",\n      \"PINK1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}