PEX10

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0016558 protein import into peroxisome matrix	IBA GO_REF:0000033	ACCEPT	Summary: PEX10 is required for peroxisomal matrix protein import. Loss of PEX10 abolishes import of PTS1 and PTS2 matrix proteins (PMID:9683594, PMID:9700193). PEX10 functions within the PEX2-PEX10-PEX12 E3 ligase complex to ubiquitinate PEX5, which is essential for the import cycle (PMID:24662292). IBA annotation from phylogenetic analysis is well-supported and at the right level of specificity. Reason: Core function of PEX10. Phylogenetic inference is consistent with extensive experimental evidence showing PEX10 is required for peroxisomal matrix protein import across eukaryotes. PEX10-deficient cells fail to import matrix proteins (PMID:9683594). Supporting Evidence: PMID:9683594 PEX10-deficient PBD100 cells contain many peroxisomes and import peroxisomal membrane proteins but do not import peroxisomal matrix proteins, indicating that loss of PEX10 has its most pronounced effect on peroxisomal matrix-protein import. PMID:24662292 RING peroxins are required for both modes of Pex5p ubiquitination, thus playing a pivotal role in Pex5p shuttling.
GO:0005778 peroxisomal membrane	IBA GO_REF:0000033	ACCEPT	Summary: PEX10 is an integral peroxisomal membrane protein with five transmembrane segments (PMID:35768507). Localization confirmed by immunofluorescence and fractionation (PMID:9922452, PMID:9700193). IBA annotation is well-supported. Reason: Core localization. PEX10 is an integral membrane protein of the peroxisome with multiple transmembrane domains. Confirmed experimentally and by structural analysis. Supporting Evidence: PMID:9922452 The CG7 cell line, PBD100, is homozygous for a splice donor site mutation in PEX10 and expresses a PEX10 mRNA with a large internal deletion that lacks PEX10 activity (Warren et al., 1998). PMID:35768507 contributes five transmembrane segments that co-assemble into an open channel.
GO:0005778 peroxisomal membrane	IEA GO_REF:0000120	ACCEPT	Summary: Automated annotation of peroxisomal membrane localization. Consistent with IBA and multiple IDA annotations for the same term. Reason: Redundant with IBA and IDA annotations but correct. PEX10 is indeed a peroxisomal membrane protein.
GO:0007031 peroxisome organization	IEA GO_REF:0000120	ACCEPT	Summary: PEX10 is involved in peroxisome biogenesis/organization. Loss of PEX10 function results in defective peroxisome biogenesis (Zellweger spectrum disorders). However, PEX10's primary role is specifically in matrix protein import via receptor recycling, not in peroxisome membrane formation or fission. Peroxisome ghosts (membrane structures) persist in PEX10-deficient cells (PMID:9683594). Reason: While PEX10 does not directly organize peroxisome membranes (peroxisome ghosts persist in PEX10-null cells), it is required for functional peroxisome biogenesis. The term is broad enough to encompass PEX10's role in enabling functional peroxisomes through matrix protein import. Supporting Evidence: PMID:9700193 HsPEX10 expression morphologically and biochemically restored peroxisome biogenesis in fibroblasts from Zellweger patients of complementation group B in Japan (complementation group VII in the USA).
GO:0008270 zinc ion binding	IEA GO_REF:0000120	ACCEPT	Summary: PEX10 contains a C3HC4 RING finger domain (aa 273-311) that coordinates two zinc ions. UniProt records eight zinc-binding residues. The cryo-EM structure of the homologous fungal complex confirms zinc coordination in the RING domains (PMID:35768507). Reason: The RING finger domain of PEX10 requires zinc ions for structural integrity and E3 ligase activity. Zinc binding is intrinsic to the RING domain fold. Supporting Evidence: PMID:35768507 Cys residues are shown in yellow and Zn2+ atoms in grey. PMID:9700193 This cDNA encodes a peroxisomal protein (a peroxin Pex10p) comprising 326 amino acids, with two putative transmembrane segments and a C3HC4zinc finger RING motif.
GO:0015031 protein transport	IEA GO_REF:0000043	ACCEPT	Summary: IEA from UniProt keyword mapping. PEX10 is involved in protein transport (specifically peroxisomal matrix protein import). The term is overly broad but not incorrect. Reason: While protein transport is very general, it is a valid parent term for PEX10's role in peroxisomal matrix protein import. More specific annotations (GO:0016558) are also present. IEA annotations at broader levels are acceptable alongside more specific ones.
GO:0016558 protein import into peroxisome matrix	IEA GO_REF:0000002	ACCEPT	Summary: IEA from InterPro mapping. Consistent with IBA and IDA annotations for the same term. PEX10 is well-established as required for peroxisomal matrix protein import. Reason: Correct automated annotation, redundant with IBA and experimental annotations.
GO:0016740 transferase activity	IEA GO_REF:0000043	ACCEPT	Summary: IEA from UniProt keyword mapping. PEX10 is classified as EC 2.3.2.27 (ubiquitin-protein transferase). Transferase activity is a very broad parent term but technically correct. Reason: Correct but very broad. PEX10 has ubiquitin-protein transferase activity (EC 2.3.2.27) which is a type of transferase. More specific MF annotations (GO:0061630 ubiquitin protein ligase activity) are present.
GO:0046872 metal ion binding	IEA GO_REF:0000043	ACCEPT	Summary: IEA from UniProt keyword mapping. PEX10 binds zinc ions through its RING finger domain. Metal ion binding is a broad parent of zinc ion binding (GO:0008270). Reason: Correct but broad. Redundant with the more specific zinc ion binding annotation (GO:0008270) also present.
GO:0061630 ubiquitin protein ligase activity	IEA GO_REF:0000003	ACCEPT	Summary: IEA from EC number mapping. PEX10 has E3 ubiquitin-protein ligase activity (EC 2.3.2.27) demonstrated in vitro with E2 UbcH5C (PMID:24662292). Consistent with IDA annotation for the same term. Reason: Core molecular function. PEX10 RING finger has demonstrated E3 ligase activity. Consistent with IDA evidence.
GO:0016558 protein import into peroxisome matrix	NAS PMID:24662292 Distinct modes of ubiquitination of peroxisome-targeting sig...	ACCEPT	Summary: NAS annotation based on PMID:24662292. This paper directly demonstrates PEX10 E3 ligase activity is required for PEX5 ubiquitination and recycling, which is essential for matrix protein import. The paper shows that RING finger mutants of PEX10 cannot restore peroxisomal protein import. Reason: Core function well-supported by this reference. PMID:24662292 provides direct evidence that PEX10 E3 activity is essential for peroxisomal matrix protein import. Supporting Evidence: PMID:24662292 Several lines of evidence with lysine-to-arginine mutants of Pex5p demonstrate that Pex10p RING E3-mediated ubiquitination of Pex5p is required for its efficient export from peroxisomes to the cytosol and peroxisomal matrix protein import.
GO:0016567 protein ubiquitination	IEA GO_REF:0000041	ACCEPT	Summary: IEA from UniPathway mapping. PEX10 is involved in protein ubiquitination, specifically ubiquitination of PEX5 receptor. Consistent with the demonstrated E3 ligase activity (PMID:24662292). Reason: Correct. PEX10 catalyzes ubiquitination of PEX5 as its primary enzymatic function. More specific annotations for polyubiquitination and monoubiquitination aspects are also present.
GO:0000209 protein polyubiquitination	IDA PMID:24662292 Distinct modes of ubiquitination of peroxisome-targeting sig...	ACCEPT	Summary: PMID:24662292 demonstrates that PEX10 catalyzes polyubiquitination of PEX5 in vitro. The cryo-EM structure (PMID:35768507) further clarifies that when recycling is compromised, PEX5 is polyubiquitinated by the concerted action of RF10 and RF12 and degraded via the RADAR pathway. Polyubiquitination is a secondary/quality-control function distinct from the primary monoubiquitination for recycling. Reason: Experimentally demonstrated function of PEX10. While monoubiquitination for receptor recycling is the primary function, polyubiquitination for degradation is also a genuine activity of PEX10, particularly as part of the RADAR quality control pathway. Supporting Evidence: PMID:24662292 The Pex10p·Pex12p complex catalyzes monoubiquitination of Pex5p at one of multiple lysine residues in vitro, following the dissociation of Pex5p from Pex14p and the PTS1 cargo. PMID:35768507 If recycling is compromised, receptors are polyubiquitylated by the concerted action of RF10 and RF12 and degraded.
GO:0005778 peroxisomal membrane	IDA PMID:12751901 The peroxisomal membrane targeting elements of human peroxin...	ACCEPT	Summary: PMID:12751901 is primarily about PEX2 membrane targeting, not PEX10. The paper studies PEX2 targeting elements and uses PEX10/PEX12 for comparison in some experiments. PEX10 localization to peroxisomal membrane is well-established from other references. Reason: While this specific reference focuses on PEX2, PEX10 peroxisomal membrane localization is well-established from multiple other sources. The annotation itself is correct. Supporting Evidence: PMID:12751901 Peroxin 2 (PEX2) is a 35-kDa integral peroxisomal membrane protein with two transmembrane regions and a zinc RING domain within its cytoplasmically exposed C-terminus.
GO:0005778 peroxisomal membrane	IDA PMID:9090384 Isolation of the human PEX12 gene, mutated in group 3 of the...	ACCEPT	Summary: PMID:9090384 is about PEX12 isolation and characterization, not directly about PEX10. The paper shows PEX12 localizes to peroxisome membrane and mentions PEX10 and PEX2 as related RING peroxins. Attribution of PEX10 localization to this reference may be indirect. Reason: While the reference is primarily about PEX12, it establishes the RING peroxin family context. PEX10 peroxisomal membrane localization is unambiguously confirmed by other references. The annotation is correct. Supporting Evidence: PMID:9090384 PEX12 shared the same subcellular distribution as yeast Pex12p and localized to the peroxisome membrane.
GO:0006515 protein quality control for misfolded or incompletely synthesized proteins	ISS PMID:35768507 A peroxisomal ubiquitin ligase complex forms a retrotransloc...	KEEP AS NON CORE	Summary: PMID:35768507 demonstrates that the PEX2-PEX10-PEX12 complex mediates polyubiquitination and proteasomal degradation of import receptors when recycling fails (RADAR pathway). The paper also shows this pathway maintains homeostasis of other peroxisomal import factors. This is analogous to ERAD quality control. However, GO:0006515 specifically refers to misfolded/incompletely synthesized proteins, whereas PEX10 targets functional import receptors that are stuck in the membrane, not misfolded proteins per se. Reason: The RADAR pathway is a quality control mechanism, but it targets import receptors that fail to recycle rather than classically misfolded proteins. The term is somewhat imprecise for this function but captures the quality control aspect. This is not a core function of PEX10. Supporting Evidence: PMID:35768507 When the normal recycling of Pex5 or the other receptors is blocked, for example, by inactivating the Pex1–Pex6 ATPase, the receptors are instead polyubiquitylated on Lys residues and subsequently degraded by the proteasome.
GO:0008320 protein transmembrane transporter activity	ISS PMID:35768507 A peroxisomal ubiquitin ligase complex forms a retrotransloc...	ACCEPT	Summary: PMID:35768507 demonstrates through cryo-EM that the PEX2-PEX10-PEX12 complex forms a retrotranslocation channel with a ~10 Angstrom pore. PEX10 contributes five transmembrane segments to this channel. The channel facilitates passage of PEX5 through the peroxisomal membrane. This is based on the fungal complex structure but is inferred by sequence similarity for the human complex. Reason: The structural evidence from PMID:35768507 strongly supports that PEX10 is part of a transmembrane protein transporter (retrotranslocation channel for PEX5). ISS from the fungal structure is well-justified given high conservation. Supporting Evidence: PMID:35768507 Each subunit of the complex contributes five transmembrane segments that co-assemble into an open channel.
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: PMID:26344566 shows that the PEX2/PEX10/PEX12 E3 ligase is involved in pexophagy in response to ROS. However, PEX10 is not directly sensing or responding to ROS; rather ATM kinase senses ROS and phosphorylates PEX5, which then gets ubiquitinated by the PEX2/10/12 complex. The E3 ligase activity of PEX10 exists independently of ROS signaling. PEX10's role here is as a downstream effector (E3 ligase) rather than a direct participant in ROS response signaling. Reason: PEX10 is not directly involved in sensing or responding to ROS. The paper demonstrates that ATM is the ROS sensor that phosphorylates PEX5, which then becomes a better substrate for ubiquitination by the PEX2/10/12 complex. PEX10 performs its constitutive E3 ligase activity on PEX5 regardless of ROS status. Annotating PEX10 to cellular response to ROS conflates the constitutive E3 ligase function with the ATM-mediated ROS signaling pathway. Supporting Evidence: PMID:26344566 The RING peroxins PEX2, PEX10 and PEX12 are part of a peroxisome-localized E3 ligase responsible for polyubiquitination of PEX534, and as expected, siRNA knockdown of these peroxins reduced polyubiquitination of PEX5 (Supplementary Fig. S5d).
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process	ISS PMID:35768507 A peroxisomal ubiquitin ligase complex forms a retrotransloc...	KEEP AS NON CORE	Summary: PMID:35768507 demonstrates that when receptor recycling is blocked, the PEX2-PEX10-PEX12 complex polyubiquitinates PEX5 and other import factors, targeting them for proteasomal degradation (RADAR pathway). ISS inference from the fungal system is well-justified. Reason: This is a secondary quality control function (RADAR pathway) rather than the primary function of PEX10, which is monoubiquitination for receptor recycling. The proteasomal degradation pathway activates when normal recycling fails. Supporting Evidence: PMID:35768507 If recycling is compromised, receptors are polyubiquitylated by the concerted action of RF10 and RF12 and degraded. This polyubiquitylation pathway also maintains the homeostasis of other peroxisomal import factors.
GO:0005778 peroxisomal membrane	IDA PMID:9922452 Peroxisome synthesis in the absence of preexisting peroxisom...	ACCEPT	Summary: PMID:9922452 (South and Gould 1999) used PEX10-deficient PBD100 cells as a control and characterized PEX16. The paper describes PBD100 as CG7 with a PEX10 splice mutation. PEX10 localization to peroxisomal membrane is established by the epitope tagging and immunofluorescence work referenced in this paper and prior publications. Reason: PEX10 peroxisomal membrane localization is well-established. UniProt records peroxisome membrane localization with evidence from PMID:9922452. Supporting Evidence: PMID:9922452 The CG7 cell line, PBD100, is homozygous for a splice donor site mutation in PEX10 and expresses a PEX10 mRNA with a large internal deletion that lacks PEX10 activity (Warren et al., 1998).
GO:0044721 protein import into peroxisome matrix, substrate release	ISS PMID:35768507 A peroxisomal ubiquitin ligase complex forms a retrotransloc...	KEEP AS NON CORE	Summary: PMID:35768507 shows the PEX2-PEX10-PEX12 complex forms a retrotranslocation channel. The paper discusses that cargo release occurs after PEX5 docking and before receptor recycling. PEX10 is part of the translocation complex involved in cargo delivery. However, the specific role of PEX10 in substrate release (as opposed to receptor recycling) is less directly demonstrated. Reason: While PEX10 is part of the translocation machinery, its primary demonstrated function is in receptor ubiquitination/recycling rather than substrate release specifically. The substrate release step involves the broader DTM complex. This annotation is not wrong but represents a secondary or indirect function. Supporting Evidence: PMID:35768507 We propose that the N terminus of a recycling receptor is inserted from the peroxisomal lumen into the pore and monoubiquitylated by RF2 to enable extraction into the cytosol.
GO:0016562 protein import into peroxisome matrix, receptor recycling	IDA PMID:24662292 Distinct modes of ubiquitination of peroxisome-targeting sig...	ACCEPT	Summary: PMID:24662292 directly demonstrates that PEX10 E3 ligase activity is essential for PEX5 receptor recycling. The paper shows PEX10 ubiquitinates PEX5, which is required for PEX5 export from peroxisomes back to the cytosol. RING finger mutations abolish both E3 activity and peroxisome-restoring function. Reason: Core function. PEX10-mediated ubiquitination of PEX5 is the key step enabling receptor recycling. This is the most specific and accurate annotation for PEX10's primary biological process function. Supporting Evidence: PMID:24662292 Here, we establish an in vitro ubiquitination assay system and demonstrate that RING finger Pex10p functions as an E3 with an E2, UbcH5C. The E3 activity of Pex10p is essential for its peroxisome-restoring activity, being enhanced by another RING peroxin, Pex12p. PMID:24662292 Several lines of evidence with lysine-to-arginine mutants of Pex5p demonstrate that Pex10p RING E3-mediated ubiquitination of Pex5p is required for its efficient export from peroxisomes to the cytosol and peroxisomal matrix protein import.
GO:0061630 ubiquitin protein ligase activity	IDA PMID:24662292 Distinct modes of ubiquitination of peroxisome-targeting sig...	ACCEPT	Summary: PMID:24662292 provides direct experimental evidence that PEX10 RING finger has E3 ubiquitin ligase activity with UbcH5C as E2, and that this activity is enhanced by PEX12. Mutations C273A and C310G abolish ligase activity, as does the disease mutation H290Q. Reason: Core molecular function directly demonstrated by in vitro ubiquitination assays. This is PEX10's primary enzymatic activity. Supporting Evidence: PMID:24662292 Here, we establish an in vitro ubiquitination assay system and demonstrate that RING finger Pex10p functions as an E3 with an E2, UbcH5C.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-8953917	ACCEPT	Summary: Reactome pathway step describing PEX2:PEX10:PEX12 binding PEX5 and ubiquitin-conjugating enzymes at the peroxisomal membrane. Consistent with established localization. Reason: Correct localization annotation from Reactome. Redundant with other peroxisomal membrane annotations but valid.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-8953946	ACCEPT	Summary: Reactome step for PEX2:PEX10:PEX12 monoubiquitinating PEX5 at Cys11. Peroxisomal membrane localization is correct. Reason: Correct. Redundant with other peroxisomal membrane annotations.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033235	ACCEPT	Summary: Reactome step for cargo translocation. PEX10 is at the peroxisomal membrane during this process as part of the DTM. Reason: Correct. Redundant with other peroxisomal membrane annotations.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033236	ACCEPT	Summary: Reactome step for PEX5 cargo binding to the docking and translocation module at the peroxisomal membrane. Reason: Correct. Redundant with other peroxisomal membrane annotations.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033485	ACCEPT	Summary: Reactome step for PEX5L monoubiquitination at Cys11 at the peroxisomal membrane. Reason: Correct. Redundant with other peroxisomal membrane annotations.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033499	ACCEPT	Summary: Reactome step for PEX1/PEX6-mediated receptor extraction from the peroxisomal membrane. Reason: Correct. Redundant with other peroxisomal membrane annotations.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033514	ACCEPT	Summary: Reactome step for PEX5L:PEX7 cargo translocation at the peroxisomal membrane. Reason: Correct. Redundant with other peroxisomal membrane annotations.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033516	ACCEPT	Summary: Reactome step for receptor export complex assembly at the peroxisomal membrane. Reason: Correct. Redundant with other peroxisomal membrane annotations.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033527	ACCEPT	Summary: Reactome step for PEX5L binding and ubiquitin-conjugating enzyme recruitment at the peroxisomal membrane. Reason: Correct. Redundant with other peroxisomal membrane annotations.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033533	ACCEPT	Summary: Reactome step for receptor export complex assembly at the peroxisomal membrane. Reason: Correct. Redundant with other peroxisomal membrane annotations.
GO:0008270 zinc ion binding	NAS O60683-2 PMID:10862081 Phenotype-genotype relationships in PEX10-deficient peroxiso...	ACCEPT	Summary: PMID:10862081 discusses PEX10 genotype-phenotype relationships and emphasizes the importance of the C-terminal zinc-binding domain (RING finger) for PEX10 function. The paper notes that the zinc-binding domain is critical for PEX10 function. Zinc binding is a property of the RING domain present in both isoforms (isoform 2 has an insertion at position 200, before the RING domain at 273-311). Reason: Correct. The RING finger domain coordinates zinc ions, and this is essential for PEX10 function. Both isoforms retain the RING domain. Supporting Evidence: PMID:10862081 These results demonstrate serious flaws in the PEX10 functional complementation assay, they do suggest that the C-terminal zinc-binding domain is critical for PEX10 function.
GO:0016558 protein import into peroxisome matrix	IMP O60683-2 PMID:10862081 Phenotype-genotype relationships in PEX10-deficient peroxiso...	ACCEPT	Summary: PMID:10862081 reports phenotype-genotype relationships in PEX10-deficient patients. Mutations in PEX10 cause defective peroxisomal protein import (IMP evidence from mutant phenotype analysis). The functional complementation assay showed that PEX10 expression restores matrix protein import in PEX10-deficient cells. Reason: Core function confirmed by mutant phenotype analysis. PEX10 mutations cause loss of peroxisomal matrix protein import, demonstrating PEX10 is required for this process. Supporting Evidence: PMID:10862081 All four PEX10-deficient Zellweger Syndrome (ZS) patients were found to have nonsense, frameshift, or splice site mutations that remove large portions of the PEX10 coding region.
GO:0005777 peroxisome	IDA PMID:9922452 Peroxisome synthesis in the absence of preexisting peroxisom...	ACCEPT	Summary: PMID:9922452 uses PEX10-deficient cells as a control line. PEX10 localizes to peroxisomes. The more specific term peroxisomal membrane (GO:0005778) is also annotated with multiple evidence lines. GO:0005777 (peroxisome) is the parent term. Reason: Correct localization. While GO:0005778 (peroxisomal membrane) is more specific and also annotated, GO:0005777 (peroxisome) is a valid broader annotation.
GO:0005515 protein binding	IPI PMID:10837480 Molecular anatomy of the peroxin Pex12p: ring finger domain ...	MARK AS OVER ANNOTATED	Summary: PMID:10837480 demonstrates that PEX10 interacts with PEX12, PEX2, and PEX5 using yeast two-hybrid and in vitro binding assays. PEX12 RING finger binds PEX10, and PEX10 also interacts with PEX2 and PEX5. PEX12 was co-immunoprecipitated with PEX10 from CHO-K1 cells. However, protein binding is an uninformative annotation. Reason: GO:0005515 (protein binding) is too vague to be informative. PEX10 has specific interactions with PEX12 (within the E3 ligase complex), PEX2 (within the retrotranslocation channel), and transiently with PEX5 (the ubiquitination substrate). These are functional interactions reflecting complex assembly within the peroxisomal import machinery, not generic protein binding. The complex membership this evidence actually supports is captured by the proposed NEW GO:0000151 (ubiquitin ligase complex) annotation below, and the catalytic function by the existing GO:0061630 IDA annotation. Same treatment as the corresponding PMID:10837480 protein binding annotation on PEX2. Supporting Evidence: PMID:10837480 The RING finger of Pex12p bound to Pex10p and the PTS1-receptor Pex5p
GO:0007031 peroxisome organization	IDA PMID:9700193 Mutations in PEX10 is the cause of Zellweger peroxisome defi...	ACCEPT	Summary: PMID:9700193 shows that PEX10 expression restores peroxisome biogenesis in complementation group B fibroblasts. The paper demonstrates that PEX10 is required for functional peroxisome assembly, though its specific role is in matrix protein import rather than membrane assembly. Reason: PEX10 is essential for peroxisome organization as demonstrated by restoration of peroxisome biogenesis upon PEX10 expression in patient cells. While the primary mechanism is through matrix protein import/receptor recycling, this directly impacts peroxisome organization. Supporting Evidence: PMID:9700193 HsPEX10 expression morphologically and biochemically restored peroxisome biogenesis in fibroblasts from Zellweger patients of complementation group B in Japan (complementation group VII in the USA).
GO:0016558 protein import into peroxisome matrix	IDA PMID:9683594 Identification of PEX10, the gene defective in complementati...	ACCEPT	Summary: PMID:9683594 is the original identification of PEX10 as the gene defective in complementation group 7. The paper shows PEX10 expression rescues peroxisomal matrix-protein import in CG7 patient fibroblasts, and PEX10-deficient cells fail to import matrix proteins while membrane protein import is normal. Reason: Core function with direct experimental evidence. This is the founding paper demonstrating PEX10 is required for peroxisomal matrix protein import. Supporting Evidence: PMID:9683594 We identified the human orthologue of yeast PEX10 and observed that its expression rescues peroxisomal matrix-protein import in PBD patients' fibroblasts from complementation group 7 (CG7). PMID:9683594 PEX10-deficient PBD100 cells contain many peroxisomes and import peroxisomal membrane proteins but do not import peroxisomal matrix proteins, indicating that loss of PEX10 has its most pronounced effect on peroxisomal matrix-protein import.
GO:0000151 ubiquitin ligase complex	IDA PMID:35768507 A peroxisomal ubiquitin ligase complex forms a retrotransloc...	NEW	Summary: PEX10 is a constitutive subunit of the PEX2-PEX10-PEX12 heterotrimeric RING E3 ubiquitin ligase complex embedded in the peroxisomal membrane. Complex formation with PEX12 dramatically augments PEX10's E3 activity (PMID:24662292), PEX10 co-immunoprecipitates with PEX12 from cells (PMID:10837480), and the cryo-EM structure shows the three RING peroxins assembling into a single complex that is both a ubiquitin ligase and a retrotranslocation channel (PMID:35768507). The deep research synthesis of recent reviews frames this heterotrimeric ligase complex as the central concept for PEX10 annotation. GOA currently lacks any complex-membership CC annotation for PEX10 despite this being central to its function. Reason: Proposed new annotation to capture PEX10's well-established membership in the peroxisomal PEX2-PEX10-PEX12 ubiquitin ligase complex, which is structurally demonstrated (PMID:35768507), biochemically supported (PMID:24662292, PMID:10837480), and mirrored in Reactome (R-HSA-8953917 etc.). This reflects the in_complex assignment in core_functions and replaces the uninformative protein binding annotation as the record of PEX10's complex assembly. Supporting Evidence: PMID:35768507 Recycling requires receptor modification by a membrane-embedded ubiquitin ligase complex comprising three RING finger domain-containing proteins (Pex2, Pex10 and Pex12) PMID:24662292 Here, we report that RING finger of human Pex10p possesses ubiquitin ligase activity with E2 UbcH5C and that the E3 activity is dramatically augmented by formation of a Pex10p complex with Pex12p file:human/PEX10/PEX10-deep-research-falcon.md the peroxisomal membrane contains a heterotrimeric RING E3 ligase complex composed of PEX2, PEX10, and PEX12, which mediates ubiquitination events essential for receptor recycling and quality control

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

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