PEX13

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005778 peroxisomal membrane	IBA GO_REF:0000033	ACCEPT	Summary: PEX13 is a well-established integral peroxisomal membrane protein. UniProt annotates it as "Peroxisome membrane; Multi-pass membrane protein" with three predicted transmembrane helices (PMID:8858165, PMID:11390669). IBA annotation is fully consistent with extensive experimental data. Reason: Core localization supported by multiple IDA studies, UniProt annotation, and the deep research synthesis. PEX13 is an integral peroxisomal membrane protein by definition. Supporting Evidence: PMID:8858165 We have identified Pex13p, a novel integral peroxisomal membrane from both yeast and humans that binds the PTS1 receptor via a cytoplasmically oriented SH3 domain. PMID:9653144 Recombinant Pex14p was specifically recognized by the "import inhibiting" ab-MF3 and bound Pex5p and the Src homology 3 (SH3) domain of Pex13p in ligand blots.
GO:0016560 protein import into peroxisome matrix, docking	IBA GO_REF:0000033	ACCEPT	Summary: PEX13 is a core component of the docking/translocation module (DTM) for peroxisomal matrix protein import. The docking function is the primary biological process role of PEX13 and is supported by extensive evidence from yeast to humans (PMID:8858165, PMID:28765278). Reason: This is the core biological process annotation for PEX13. Loss of Pex13p eliminates import of PTS1 and PTS2 proteins and reduces peroxisome-associated Pex5p by ~40-fold (PMID:8858165). The DTM comprising PEX13 and PEX14 is the established docking complex. Supporting Evidence: PMID:8858165 loss of Pex13p further reduces the amount of peroxisome-associated Pex5p by approximately 40-fold. Furthermore, loss of Pex13p eliminates import of peroxisomal matrix proteins that contain either the type-1 or type-2 peroxisomal targeting signal PMID:28765278 the peroxisomal membrane docking/translocation module (DTM) comprising PEX13, PEX14, and the three “Really Interesting New Gene” (RING) finger peroxins PEX2, PEX10, and PEX12
GO:1990429 peroxisomal importomer complex	IBA GO_REF:0000033	ACCEPT	Summary: PEX13 is part of the peroxisomal importomer complex (docking/translocation module), which includes PEX13, PEX14, PEX2, PEX10, and PEX12 (PMID:28765278). IBA annotation is well-supported by biochemical co-purification and functional studies. Reason: PEX13 is a bona fide component of the importomer complex. Dias et al. (2017) describe the DTM as comprising PEX13, PEX14, and the RING peroxins. PEX14 complexes purified from human cells contain PEX13 (PMID:21525035). Supporting Evidence: PMID:28765278 the peroxisomal membrane docking/translocation module (DTM) comprising PEX13, PEX14, and the three “Really Interesting New Gene” (RING) finger peroxins PEX2, PEX10, and PEX12
GO:0005777 peroxisome	IEA GO_REF:0000120	ACCEPT	Summary: Automated annotation of PEX13 to peroxisome. This is correct but less specific than peroxisomal membrane (GO:0005778), which is more accurate for PEX13 as an integral membrane protein. Acceptable as a broader IEA annotation. Reason: PEX13 is indeed a peroxisomal protein. While peroxisomal membrane is more specific, the broader peroxisome term is not incorrect for an IEA. Multiple IDA annotations also support peroxisome localization.
GO:0005778 peroxisomal membrane	IEA GO_REF:0000120	ACCEPT	Summary: Automated annotation to peroxisomal membrane. Correct and consistent with extensive experimental evidence showing PEX13 is an integral peroxisomal membrane protein. Reason: Consistent with IBA and multiple IDA annotations for the same term.
GO:0015031 protein transport	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation from UniProt keyword mapping. PEX13 is involved in protein transport, specifically peroxisomal matrix protein import. This term is very broad but not incorrect. Reason: PEX13 is indeed involved in protein transport (specifically peroxisomal matrix protein import). This broad IEA is acceptable alongside the more specific docking term.
GO:0016020 membrane	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation from InterPro mapping. PEX13 is a membrane protein. Very generic but not wrong for an automated annotation. Reason: PEX13 is an integral membrane protein. This is a broad IEA that is subsumed by more specific peroxisomal membrane annotations but is not incorrect.
GO:0016560 protein import into peroxisome matrix, docking	IEA GO_REF:0000002	ACCEPT	Summary: IEA from InterPro mapping for the docking function. Correct and consistent with IBA and experimental annotations for the same term. Reason: Correctly maps the InterPro domain information to the core docking function.
GO:0005515 protein binding	IPI PMID:10704444 PEX19 binds multiple peroxisomal membrane proteins, is predo...	MARK AS OVER ANNOTATED	Summary: This IPI annotation comes from Sacksteder et al. (2000), which demonstrates PEX19 binds PEX13 (among many other PMPs) using dihybrid and blot overlay assays. The interaction is with PEX19, the peroxisomal membrane protein import receptor/chaperone. Reason: The generic "protein binding" term is uninformative. The actual interaction is PEX13 binding PEX19, which is part of the PMP targeting pathway. PEX19 binds the mPTS region of PEX13 to facilitate its insertion into the peroxisomal membrane. This is better captured by other existing annotations (peroxisomal membrane localization) rather than a vague protein binding annotation. Supporting Evidence: PMID:10704444 PEX19 binds a broad spectrum of PMPs, displays saturable PMP binding, and interacts with regions of PMPs required for their targeting to peroxisomes.
GO:0005515 protein binding	IPI PMID:20531392 The peroxisomal receptor Pex19p forms a helical mPTS recogni...	MARK AS OVER ANNOTATED	Summary: Schueller et al. (2010) characterized the Pex19p mPTS recognition domain structure. PEX13 is listed as a PEX19 binding partner. This is again generic "protein binding." Reason: Generic protein binding is uninformative. The paper primarily characterizes PEX19 structure and its mPTS recognition; PEX13 is one of many PMPs that bind PEX19. The interaction is part of the PMP targeting pathway rather than a specific functional interaction of PEX13. Supporting Evidence: PMID:20531392 The protein Pex19p functions as a receptor and chaperone of peroxisomal membrane proteins (PMPs). The crystal structure of the folded C-terminal part of the receptor reveals a globular domain that displays a bundle of three long helices in an antiparallel arrangement.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Luck et al. (2020) is a high-throughput binary protein interactome map. PEX13 was identified in a binary interaction. High-throughput Y2H data without specific functional context. Reason: High-throughput interactome study; generic protein binding is uninformative for PEX13 whose specific interaction partners (PEX5, PEX14, PEX19) are well characterized. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome.
GO:0005777 peroxisome	IDA GO_REF:0000052	ACCEPT	Summary: IDA from curation of immunofluorescence data showing PEX13 localizes to peroxisomes. Correct but less specific than peroxisomal membrane. Reason: Immunofluorescence data correctly places PEX13 at peroxisomes. This is consistent with all other localization evidence. The broader term is acceptable alongside the more specific peroxisomal membrane annotations.
GO:0005778 peroxisomal membrane	IDA PMID:37165185 Peroxisome biogenesis initiated by protein phase separation.	ACCEPT	Summary: Ravindran et al. (2023, Nature) demonstrated that Pex13 localizes to the peroxisomal membrane where it forms phase-separated condensates with Pex5-cargo. Although primary experiments were in yeast, the annotation to human PEX13 peroxisomal membrane is supported by conserved function and multiple other human-specific studies. Reason: PEX13 peroxisomal membrane localization is extremely well established. This study adds mechanistic insight about phase separation at the membrane. Supporting Evidence: PMID:37165185 the minimum transport machinery includes the membrane proteins Pex13 and Pex14 and the cargo-protein-binding transport receptor, Pex5
GO:0016560 protein import into peroxisome matrix, docking	NAS PMID:37165185 Peroxisome biogenesis initiated by protein phase separation.	ACCEPT	Summary: NAS annotation based on Ravindran et al. (2023) which showed Pex13 forms LLPS-based transport channels with Pex5 and Pex14 for peroxisomal protein import. The docking function is well supported. Reason: The paper provides strong evidence that Pex13 is central to the import process, forming transient protein transport channels. The docking step is well established. Supporting Evidence: PMID:37165185 Our findings lead us to suggest a model in which LLPS of Pex5-cargo with Pex13 and Pex14 results in transient protein transport channels
GO:0005778 peroxisomal membrane	IDA PMID:28765278 The peroxisomal matrix protein translocon is a large cavity-...	ACCEPT	Summary: Dias et al. (2017) characterized the DTM architecture and showed PEX13 is part of the peroxisomal membrane docking/translocation module in mammalian cells. Reason: Direct biochemical evidence from cell-free import assays using mammalian peroxisomes. Supporting Evidence: PMID:28765278 the peroxisomal membrane docking/translocation module (DTM) comprising PEX13, PEX14, and the three “Really Interesting New Gene” (RING) finger peroxins PEX2, PEX10, and PEX12
GO:0008320 protein transmembrane transporter activity	IDA PMID:28765278 The peroxisomal matrix protein translocon is a large cavity-...	ACCEPT	Summary: Dias et al. (2017) showed that PEX5 enters a large cavity formed by the DTM (PEX13, PEX14 and the RING peroxins PEX2/PEX10/PEX12) to release its cargo, i.e. the DTM is the peroxisomal matrix-protein translocon. PEX13 is not a peripheral subunit of that translocon: its N-terminal YG-rich intrinsically disordered region is the component now proposed to constitute the translocation conduit itself, forming a nucleoporin-FG-like selective phase that PEX5-cargo partitions into (PMID:37165185). UniProt correspondingly describes the PEX13-PEX14 docking complex as a translocon channel. Reason: An earlier draft of this review flagged the annotation as an over-annotation on the grounds that transport is an emergent property of the whole DTM. That reasoning does not survive the newer mechanistic work: Ravindran et al. (2023) show that Pex13 itself undergoes LLPS with Pex5-cargo, that import depends on the aromatic residues of the Pex13 IDR, and that cargo import coincides with transient Pex13/Pex14 focusing at the membrane - i.e. PEX13 is conduit-forming, not merely a scaffold. The activity is still exercised only in the context of a multi-subunit translocon, so it is recorded in core_functions as contributes_to_molecular_function rather than as an activity PEX13 has in isolation. Deferring to the UniProt curator's IDA call, which was made from the full Dias et al. text. Supporting Evidence: PMID:28765278 the DTM is best described as a large cavity-forming protein assembly into which cytosolic PEX5 can enter to release its cargo PMID:37165185 cargo import correlates with transient focusing of GFP-Pex13 and GFP-Pex14 on the peroxisome membrane file:human/PEX13/PEX13-deep-research-falcon.md A key mechanistic proposal is that PEX13’s YG domain forms a cohesive meshwork (selective phase) inside the membrane, and that PEX5 partitions into this phase using its aromatic WxxxF/Y motifs, bringing folded cargo across an aqueous conduit without conventional channel proteins.
GO:0016560 protein import into peroxisome matrix, docking	IDA PMID:28765278 The peroxisomal matrix protein translocon is a large cavity-...	ACCEPT	Summary: Dias et al. (2017) directly demonstrate PEX13 as part of the DTM docking machinery using cell-free import assays with truncated PEX5 molecules. Reason: Core function of PEX13, supported by direct biochemical evidence. Supporting Evidence: PMID:28765278 This import involves binding of newly synthesized proteins by cytosolic peroxisomal biogenesis factor 5 (PEX5) followed by insertion of the PEX5-cargo complex into the peroxisomal membrane at the docking/translocation module (DTM).
GO:0016561 protein import into peroxisome matrix, translocation	IDA PMID:28765278 The peroxisomal matrix protein translocon is a large cavity-...	ACCEPT	Summary: Dias et al. (2017) present evidence that the DTM (including PEX13) forms a cavity into which PEX5 enters to release cargo, supporting both docking and translocation roles. The YG-rich IDR of PEX13 has been proposed to form the selective phase conduit through which cargo crosses the membrane (PMID:37165185). Reason: Recent evidence supports PEX13 involvement in translocation, not just docking. The YG-rich IDR forms a phase-separated conduit analogous to nucleoporin FG repeats that enables cargo translocation. The DTM cavity model places PEX13 directly in the translocation process, and the deep-research synthesis independently converges on PEX13 as the conduit-forming component rather than a docking-only factor. Supporting Evidence: file:human/PEX13/PEX13-deep-research-falcon.md PEX13 contributes the core translocation conduit in the peroxisomal docking/translocation module (DTM) PMID:28765278 these results suggest that the DTM is best described as a large cavity-forming protein assembly into which cytosolic PEX5 can enter to release its cargo PMID:37165185 Pex13 undergoes liquid-liquid phase separation (LLPS) with Pex5-cargo. Intrinsically disordered regions in Pex13 and Pex5 resemble those found in nuclear pore complex proteins.
GO:0005778 peroxisomal membrane	IDA PMID:19197237 Structural basis for competitive interactions of Pex14 with ...	ACCEPT	Summary: Neufeld et al. (2009) studied the structural basis for PEX14 interactions with PEX5 and PEX19. PEX13 peroxisomal membrane localization is established context in this study. Reason: Consistent with all other evidence for PEX13 peroxisomal membrane localization. Supporting Evidence: PMID:19197237 Pex14 is a central component of the peroxisomal import machinery and binds the soluble receptors Pex5 and Pex19
GO:0034614 cellular response to reactive oxygen species	IDA PMID:26344566 ATM functions at the peroxisome to induce pexophagy in respo...	MARK AS OVER ANNOTATED	Summary: Zhang et al. (2015) demonstrated that ATM is localized to peroxisomes by PEX5 and activates pexophagy in response to ROS via PEX5 Ser141 phosphorylation, Lys209 monoubiquitination and p62 recognition. The peroxins assayed are PEX5, PEX1, PEX14 and the RING E3 peroxins PEX2/PEX10/PEX12; the readouts for pexophagy are PEX1 and PEX14 levels. PEX13 does not appear in the paper at all. Reason: The cached record for PMID:26344566 is full text (full_text_available: true), and a search of the whole body returns no occurrence of PEX13 - the ROS-responsive participants characterised are ATM, PEX5, the PEX2/PEX10/PEX12 E3 and p62. This is not a case of an abstract foregrounding another gene while the full text assays the target, so the usual caution about second-guessing an IDA does not apply here. Not using REMOVE because supplementary figures are outside the cache and because PEX13 loss is independently reported to raise peroxisomal ROS and trigger pexophagy, so the broad claim is plausible even though this reference does not establish it; flagged as an over-annotation of PEX13's role rather than deleted. Supporting Evidence: PMID:26344566 the PEX5 peroxisome import receptor binds ataxia-telangiectasia mutated (ATM) and localizes this kinase to the peroxisome. In response to ROS, ATM signalling activates ULK1 and inhibits mTORC1 to induce autophagy.
GO:0005829 cytosol	TAS Reactome:R-HSA-9603775	KEEP AS NON CORE	Summary: Reactome annotation for PEX3:PEX19:class I PMP dissociation reaction. PEX13 as a class I PMP would transiently be in the cytosol as a PEX19-bound intermediate before membrane insertion. This represents a transient biosynthetic intermediate state, not a steady-state localization. Reason: PEX13 is predominantly a peroxisomal membrane protein. The cytosol annotation reflects its transient state as a newly synthesized PMP bound to PEX19 before membrane insertion. This is a legitimate but non-core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-9603784	KEEP AS NON CORE	Summary: Reactome annotation for PEX19:class I PMP binding PEX3. Same as above; PEX13 transiently passes through cytosol as PEX19-bound intermediate. Reason: Transient biosynthetic intermediate state. PEX13 steady-state localization is peroxisomal membrane.
GO:0005829 cytosol	TAS Reactome:R-HSA-9603804	KEEP AS NON CORE	Summary: Reactome annotation for PEX19 binding class I PMPs. PEX13 transiently in cytosol as newly synthesized protein before PEX19-mediated targeting to peroxisomes. Reason: Same rationale as other cytosol annotations. Transient biosynthetic intermediate.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-8953917	ACCEPT	Summary: Reactome reaction where PEX2:PEX10:PEX12 binds PEX5 in the PEX5:PEX13:PEX14 complex. PEX13 is correctly placed at the peroxisomal membrane in this reaction. Reason: Consistent with PEX13 peroxisomal membrane localization during the import cycle.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-8953946	ACCEPT	Summary: Reactome reaction for PEX5 monoubiquitination. PEX13 at peroxisomal membrane as part of the DTM during the ubiquitination step. Reason: Consistent with core localization.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033235	ACCEPT	Summary: Reactome reaction for cargo translocation from cytosol to peroxisomal matrix. PEX13 at peroxisomal membrane. Reason: Consistent with core localization during the import cycle.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033236	ACCEPT	Summary: Reactome reaction for PEX5:Cargo binding the DTM (PEX13:PEX14:PEX2:PEX10:PEX12). PEX13 at peroxisomal membrane. Reason: Consistent with core localization.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033485	ACCEPT	Summary: Reactome reaction for PEX5L monoubiquitination. PEX13 at peroxisomal membrane. Reason: Consistent with core localization.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033499	ACCEPT	Summary: Reactome reaction for PEX1:PEX6 extracting PEX5L from the DTM. PEX13 at peroxisomal membrane as part of the complex from which PEX5 is extracted. Reason: Consistent with core localization.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033514	ACCEPT	Summary: Reactome reaction for PTS2 cargo translocation. PEX13 at peroxisomal membrane. Reason: Consistent with core localization.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033516	ACCEPT	Summary: Reactome reaction for DTM-REM complex assembly. PEX13 at peroxisomal membrane. Reason: Consistent with core localization.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033527	ACCEPT	Summary: Reactome reaction for E3 ligase binding PEX5L in the PTS2 pathway complex. PEX13 at peroxisomal membrane. Reason: Consistent with core localization.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033533	ACCEPT	Summary: Reactome reaction for Ub-PEX5:PEX13:PEX14 binding PEX1:PEX6:PEX26. PEX13 at peroxisomal membrane. Reason: Consistent with core localization.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9603775	ACCEPT	Summary: Reactome reaction for PEX3:PEX19:PMP dissociation. PEX13 as a class I PMP is inserted into the peroxisomal membrane in this step. Reason: Consistent with core localization. This reaction represents PEX13 arriving at its functional destination.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	ACCEPT	Summary: Ghosh et al. (2010) identified PEX13 in a membrane proteomics study of NK cells. The generic "membrane" term is very broad but correct. Reason: PEX13 is an integral membrane protein. Identification in a membrane proteome is consistent. This broad HDA annotation is acceptable. Supporting Evidence: PMID:19946888 The present study was initiated to define the composition of the membrane proteome of the Natural Killer (NK) like cell line YTS.
GO:0005778 peroxisomal membrane	HDA PMID:21525035 PEX14 is required for microtubule-based peroxisome motility ...	ACCEPT	Summary: Bharti et al. (2011) identified PEX13 as a constituent of PEX14 complexes purified from human cells using mass spectrometry, confirming its presence in the peroxisomal membrane import machinery. Reason: Direct identification of PEX13 in PEX14 complexes from human peroxisomal membranes supports peroxisomal membrane localization. Supporting Evidence: PMID:21525035 Using mass spectrometric analysis, almost all known human peroxins involved in protein import were identified as constituents of the PEX14 complexes.
GO:0005777 peroxisome	IDA PMID:17881773 Peroxisomes in human and mouse testis: differential expressi...	ACCEPT	Summary: Nenicu et al. (2007) characterized peroxisomal proteins in testis cell types, including PEX13 as a peroxisomal marker protein. PEX13 was detected in peroxisomes of various testicular cell types. Reason: Direct detection of PEX13 in peroxisomes by immunolocalization in testis tissue. Supporting Evidence: PMID:17881773 our results obtained by detection of different peroxisomal marker proteins show the presence of these organelles in most cell types in the testis
GO:0005778 peroxisomal membrane	IDA PMID:11402059 Multiple distinct targeting signals in integral peroxisomal ...	ACCEPT	Summary: Jones et al. (2001) showed PEX13 contains two independent peroxisomal targeting signals, confirming it as an integral peroxisomal membrane protein. PEX13-GFP constructs targeted to peroxisomes. Reason: Direct experimental evidence from GFP-fusion targeting experiments demonstrating PEX13 localizes to the peroxisomal membrane. Supporting Evidence: PMID:11402059 another integral PMP, the peroxin PEX13, also contains two independent sets of peroxisomal targeting information
GO:0005777 peroxisome	IDA PMID:11829486 Pex13, the mouse ortholog of the human peroxisome biogenesis...	ACCEPT	Summary: Bjorkman et al. (2002) localized mouse Pex13 protein to peroxisomes in mouse liver and showed the human PEX13 protein sorts to peroxisomes in human fibroblasts. Reason: Direct experimental localization of PEX13 to peroxisomes. Supporting Evidence: PMID:11829486 We have localized PEX13 protein to peroxisomes in mouse liver and show that this protein also sorts to peroxisomes in human skin fibroblasts.
GO:0001561 fatty acid alpha-oxidation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation transferred from mouse ortholog. PEX13 knockout mice likely show deficiency in fatty acid alpha-oxidation as a downstream consequence of failed peroxisomal matrix protein import, since alpha-oxidation enzymes are peroxisomal matrix proteins. This is a secondary consequence of loss of peroxisomal import, not a direct function of PEX13. Reason: Fatty acid alpha-oxidation is a peroxisomal metabolic process that would be disrupted when PEX13 is lost due to failure of matrix protein import. This is an indirect phenotypic consequence, not a direct molecular function. PEX13 does not catalyze alpha-oxidation; it enables import of the enzymes that do. Keep as non-core to indicate the indirect relationship.
GO:0001764 neuron migration	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation from mouse Pex13 knockout phenotype. PEX13-null mice show neurological defects consistent with Zellweger syndrome. Neuron migration defects are a pleiotropic downstream consequence of peroxisome dysfunction, not a direct function of PEX13. Reason: Neuron migration defects in Pex13 knockout mice reflect the broad developmental consequences of peroxisome biogenesis failure (Zellweger spectrum). PEX13 does not directly regulate neuron migration; this is several steps removed from its molecular function as a docking complex component.
GO:0001967 suckling behavior	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation from mouse Pex13 knockout phenotype. Suckling behavior defects in PEX13-null mice are a pleiotropic downstream consequence of peroxisome dysfunction affecting brain/neurological development. Reason: Highly pleiotropic phenotype far removed from PEX13 molecular function. Suckling behavior impairment is a clinical feature of Zellweger syndrome mouse models due to neurological dysfunction, not a direct role of PEX13.
GO:0007626 locomotory behavior	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation from mouse Pex13 knockout phenotype. Locomotory behavior defects in PEX13-null mice are a pleiotropic downstream consequence of Zellweger-like neurological dysfunction. Reason: Pleiotropic phenotype far removed from PEX13 molecular function. Locomotory defects arise from broad neurological and developmental impacts of peroxisome dysfunction.
GO:0021795 cerebral cortex cell migration	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation from mouse Pex13 knockout phenotype. Cerebral cortex cell migration defects are observed in Zellweger syndrome models due to peroxisome dysfunction affecting brain development. Reason: Pleiotropic developmental phenotype. PEX13 does not directly regulate cortical cell migration; defects arise from broad peroxisomal metabolic dysfunction affecting brain development in Zellweger spectrum disorders.
GO:0060152 microtubule-based peroxisome localization	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: ISS annotation transferred from mouse. Nguyen et al. (2006, PMID:16449325) showed that PEX13-null mouse cells exhibit loss of microtubule-based peroxisome distribution. However, this effect is secondary to reduced peroxisome abundance and size due to import failure, not a direct role of PEX13 in microtubule-peroxisome interactions. The direct mediator of microtubule-peroxisome interaction is PEX14 (PMID:21525035). Reason: The microtubule-peroxisome localization defect in PEX13-null cells is an indirect consequence of peroxisome dysfunction. Bharti et al. (2011) showed PEX14, not PEX13, directly binds tubulin and mediates peroxisome motility along microtubules. The PEX13 knockout phenotype reflects general peroxisome biogenesis failure rather than a specific role in microtubule-based localization. Supporting Evidence: PMID:16449325 remnant peroxisomes in fibroblasts from patients with PEX1-null Zellweger syndrome or D-BP deficiency exhibited clustering and loss of alignment along peripheral microtubules. Similar effects were observed for both cultured embryonic fibroblasts and brain neurons from a PEX13-null mouse PMID:21525035 human PEX14 is a multi-tasking protein that not only facilitates peroxisomal protein import but is also required for peroxisome motility by serving as membrane anchor for microtubules
GO:0005515 protein binding	IPI PMID:8858165 Pex13p is an SH3 protein of the peroxisome membrane and a do...	MODIFY	Summary: Gould et al. (1996) showed PEX13 binds PEX5 (PTS1 receptor) via its cytoplasmically oriented SH3 domain. Both GOA rows for this paper (WITH P50542-1 and P50542-2) record the same PEX5 isoform interaction. The interaction is specific and functionally critical, but "protein binding" conveys none of it. Reason: Per project curation guidelines, bare protein binding should be replaced by an informative MF term rather than merely flagged. The SH3 domain of PEX13 engages the WxxxF/Y diaromatic motifs of PEX5 and, through the same non-canonical surface plus the proximal FxxxF motif, also engages PEX14; PEX5 in turn bridges PEX13 to PEX14 in the docking complex. That simultaneous engagement of two partners to assemble a functional module is protein-macromolecule adaptor activity (GO:0030674), which is the MF recorded in core_functions. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:8858165 We have identified Pex13p, a novel integral peroxisomal membrane from both yeast and humans that binds the PTS1 receptor via a cytoplasmically oriented SH3 domain.
GO:0005778 peroxisomal membrane	IDA PMID:8858165 Pex13p is an SH3 protein of the peroxisome membrane and a do...	ACCEPT	Summary: Foundational paper by Gould et al. (1996) identifying PEX13 as an integral peroxisomal membrane protein with a cytoplasmically oriented SH3 domain. Reason: Primary discovery paper establishing PEX13 peroxisomal membrane localization. Supporting Evidence: PMID:8858165 We have identified Pex13p, a novel integral peroxisomal membrane from both yeast and humans that binds the PTS1 receptor via a cytoplasmically oriented SH3 domain.
GO:0016560 protein import into peroxisome matrix, docking	IMP PMID:8858165 Pex13p is an SH3 protein of the peroxisome membrane and a do...	ACCEPT	Summary: Gould et al. (1996) showed loss of Pex13p eliminates PTS1 and PTS2 protein import and reduces peroxisome-associated Pex5p ~40-fold, establishing PEX13 as a docking factor. Reason: Foundational IMP evidence for PEX13 docking function. Loss-of-function phenotype directly demonstrates requirement for matrix protein import docking. Supporting Evidence: PMID:8858165 loss of Pex13p further reduces the amount of peroxisome-associated Pex5p by approximately 40-fold. Furthermore, loss of Pex13p eliminates import of peroxisomal matrix proteins that contain either the type-1 or type-2 peroxisomal targeting signal but does not affect targeting and insertion of integral peroxisomal membrane proteins. We conclude that Pex13p functions as a docking factor for the predominantly cytoplasmic PTS1 receptor.
GO:0005515 protein binding	IPI PMID:9653144 Identification of a human PTS1 receptor docking protein dire...	MODIFY	Summary: Fransen et al. (1998) identified human PEX14 and showed in ligand blots that it binds both PEX5 and the SH3 domain of PEX13. The GOA row records the PEX13-PEX14 (O75381) interaction. Generic "protein binding" is uninformative. Reason: Same rationale as the PMID:8858165 row: the informative statement is that the PEX13 SH3 domain simultaneously engages PEX5 and PEX14 to assemble the docking complex, an adaptor/scaffolding activity rather than unqualified binding. Replaced with protein-macromolecule adaptor activity (GO:0030674), the MF carried in core_functions. Complex membership (GO:1990429) and the docking process terms capture the downstream consequences but not the molecular activity itself. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:9653144 Recombinant Pex14p was specifically recognized by the “import inhibiting” ab-MF3 and bound Pex5p and the Src homology 3 (SH3) domain of Pex13p in ligand blots.
GO:0005778 peroxisomal membrane	IDA PMID:16449325 Failure of microtubule-mediated peroxisome division and traf...	ACCEPT	Summary: Nguyen et al. (2006) studied peroxisome distribution defects in PEX13-null mouse cells, with PEX13 detected at the peroxisomal membrane in control cells. Reason: Consistent with all other localization evidence. PEX13 at peroxisomal membrane in cell biological studies. Supporting Evidence: PMID:16449325 Similar effects were observed for both cultured embryonic fibroblasts and brain neurons from a PEX13-null mouse with a Zellweger-syndrome-like phenotype
GO:0016560 protein import into peroxisome matrix, docking	TAS PMID:10704444 PEX19 binds multiple peroxisomal membrane proteins, is predo...	ACCEPT	Summary: Sacksteder et al. (2000) reference PEX13 as a known component of the peroxisomal protein import docking machinery in the context of studying PEX19 function. Reason: TAS annotation consistent with the established role of PEX13 in docking, referenced in the study context.
GO:0016558 protein import into peroxisome matrix	IMP PMID:8858165 Pex13p is an SH3 protein of the peroxisome membrane and a do...	NEW	Summary: PEX13 is required for import of both PTS1 and PTS2 matrix proteins into peroxisomes. Loss of PEX13 eliminates import of both types of cargo. This broader process term captures the full import role beyond just the docking step. Reason: GOA carries the two sub-steps (GO:0016560 docking and GO:0016561 translocation) but not their parent GO:0016558. Adding the parent makes the whole-cycle role explicit and matches the loss-of-function phenotype, which is failure of import per se rather than failure of one step: PEX13 loss abolishes import of both PTS1 and PTS2 cargo while leaving PMP targeting intact. GO:0016558 is also the term used in core_functions. Supporting Evidence: PMID:8858165 loss of Pex13p eliminates import of peroxisomal matrix proteins that contain either the type-1 or type-2 peroxisomal targeting signal but does not affect targeting and insertion of integral peroxisomal membrane proteins

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

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