PEX7

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005053 peroxisome matrix targeting signal-2 binding	IBA GO_REF:0000033	MODIFY	Summary: IBA annotation for PTS2 binding. This is the defining molecular function of PEX7 across eukaryotes -- it is the PTS2 receptor. Multiple experimental studies in human confirm direct binding of PEX7 to PTS2 signals via its WD40 groove (PMID:9090381, PMID:11931631, PMID:22057399, PMID:25538232). The IBA annotation is well-supported by phylogenetic inference and experimental data. Reason: PTS2 binding is the core, defining molecular function of PEX7. This is supported by extensive experimental evidence from multiple groups. GO:0005053 (peroxisome matrix targeting signal-2 binding) is obsolete as of GO release 2026-07-26 (replaced_by GO:0000268, now labelled 'peroxisome signal sequence receptor activity' and covering PTS1, PTS2 and mPTS receptors), so the annotation is carried forward on GO:0000268. Proposed replacements: peroxisome signal sequence receptor activity Supporting Evidence: PMID:9090381 PEX7, a candidate gene for RCDP identified in yeast, encodes the receptor for peroxisomal matrix proteins with the type-2 peroxisome targeting signal (PTS2). PMID:11931631 Specific binding of human Pex7p to PTS2 could be demonstrated only when Pex7p was formed in vitro by a coupled transcription/translation system or synthesized in vivo in Chinese hamster ovary K1 cells PMID:22057399 Three-dimensional structural modeling of the PTS2 receptor PEX7 reveals a groove with an evolutionarily conserved charge distribution complementary to PTS2 signals.
GO:0016558 protein import into peroxisome matrix	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for the biological process of peroxisomal matrix protein import. PEX7 is an essential component of the PTS2-dependent import pathway, acting as the cargo receptor. Loss of PEX7 leads to failure of PTS2 protein import (PMID:9090381, PMID:9090383, PMID:9090382). Reason: Protein import into peroxisome matrix is the core biological process in which PEX7 functions. This is the central role of PEX7 as the PTS2 receptor. Supporting Evidence: PMID:9090381 expression of either corrects the PTS2-import defect characteristic of RCDP cells PMID:9090383 expression of human PEX7 in RCDP cells rescues PTS2 targeting
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for cytosolic localization. PEX7 is a cycling receptor that shuttles between the cytosol and the peroxisomal matrix. Multiple studies confirm its cytosolic localization (PMID:11931631, PMID:25538232). Reason: Cytosol is a well-established localization for PEX7 as a soluble receptor that binds cargo in the cytosol before transport to peroxisomes. Supporting Evidence: PMID:11931631 Pex7p-GFP was located both in the lumen of peroxisomes and in the cytosol. PMID:25538232 PEX7 variants harboring a mutation in the cargo-binding groove are solely cytosolic.
GO:0005782 peroxisomal matrix	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for peroxisomal matrix localization. PEX7 translocates into the peroxisomal matrix as part of the import cycle, together with PTS2-cargo and PEX5L (PMID:11931631, PMID:25538232). Reason: Peroxisomal matrix localization is well established for PEX7 as a cycling receptor. It enters the matrix with cargo and is then recycled back to the cytosol. Supporting Evidence: PMID:11931631 Pex7p-GFP was located both in the lumen of peroxisomes and in the cytosol.
GO:0005053 peroxisome matrix targeting signal-2 binding	IEA GO_REF:0000002	MODIFY	Summary: IEA annotation from InterPro mapping. PEX7 contains WD40 domains (InterPro IPR044536, PEX7 family) that are correctly mapped to PTS2 binding. This is consistent with all experimental evidence. Reason: The InterPro-based mapping is correct. PEX7 is indeed the PTS2 receptor. This IEA annotation is concordant with the IBA and IDA annotations for the same term. GO:0005053 (peroxisome matrix targeting signal-2 binding) is obsolete as of GO release 2026-07-26 (replaced_by GO:0000268, now labelled 'peroxisome signal sequence receptor activity' and covering PTS1, PTS2 and mPTS receptors), so the annotation is carried forward on GO:0000268. Proposed replacements: peroxisome signal sequence receptor activity
GO:0005782 peroxisomal matrix	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation from UniProt subcellular location mapping. UniProt records PEX7 as localized to the peroxisome matrix, consistent with experimental data. Reason: Correct mapping from UniProt subcellular location. Concordant with IBA and IDA evidence.
GO:0005829 cytosol	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation from combined automated methods. Cytosol localization is well established experimentally for PEX7. Reason: Correct automated annotation. Concordant with IBA and IDA evidence for cytosolic localization.
GO:0015031 protein transport	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation from UniProt keyword mapping to the broad term "protein transport." PEX7 is involved in transport of proteins into peroxisomes. This is a broad parent term of the more specific "protein import into peroxisome matrix" (GO:0016558). Reason: While this is a broad term, it is not incorrect. The more specific term GO:0016558 is already annotated via IBA and IDA. It is acceptable for an IEA to be broader than what is captured by IBA or literature.
GO:0016558 protein import into peroxisome matrix	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation from combined automated methods for peroxisomal matrix protein import. This is the core biological process of PEX7. Reason: Correct automated annotation, concordant with IBA and IDA evidence.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: IPI protein binding annotation from a large-scale interactome study (BioPlex). This is a high-throughput study that detected interactions with PEX7 but the generic "protein binding" term is uninformative. Reason: "Protein binding" is an uninformative term per curation guidelines. High-throughput interactome studies detect many interactions, but for a well-characterized protein like PEX7, the specific binding functions (PTS2 binding, PEX5L interaction) are already captured by more informative terms.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: IPI protein binding from a neurodegenerative disease interactome mapping study. This is a high-throughput study and the generic protein binding term is uninformative for PEX7. Reason: "Protein binding" is uninformative. PEX7's specific binding activities are captured by GO:0000268 (peroxisome signal sequence receptor activity) and other more specific terms.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: IPI protein binding from the BioPlex 3.0 dual proteome-scale interactome study. High-throughput detection of protein interactions with PEX7. The generic term is uninformative. Reason: "Protein binding" is uninformative per curation guidelines. PEX7's specific binding functions are already well-annotated.
GO:0005515 protein binding	IPI PMID:40739340 PEX39 facilitates the peroxisomal import of PTS2-containing ...	REMOVE	Summary: IPI protein binding from a recent study identifying PEX39 as a facilitator of PTS2 import. This study identified PEX7 as interacting with PEX39 in the context of PTS2-dependent protein import. While the specific interaction is biologically meaningful, the generic "protein binding" term is uninformative. Reason: "Protein binding" is uninformative. The PEX7-PEX39 interaction is biologically interesting but should be annotated with a more specific term if warranted.
GO:0005053 peroxisome matrix targeting signal-2 binding	IDA PMID:22057399 Structural requirements for interaction of peroxisomal targe...	MODIFY	Summary: IDA annotation for PTS2 binding from Kunze et al. (2011). This study used mammalian two-hybrid assays to demonstrate the direct interaction between PEX7 and PTS2-carrying cargo proteins, and identified the structural basis: a conserved groove on PEX7 with charge complementarity to the PTS2 amphipathic helix. Charge-inverting mutations E113R and E200R in PEX7 abolished PTS2 binding. Reason: Strong direct experimental evidence for PTS2 binding by PEX7, with structural and mutational validation. GO:0005053 (peroxisome matrix targeting signal-2 binding) is obsolete as of GO release 2026-07-26 (replaced_by GO:0000268, now labelled 'peroxisome signal sequence receptor activity' and covering PTS1, PTS2 and mPTS receptors), so the annotation is carried forward on GO:0000268. Proposed replacements: peroxisome signal sequence receptor activity Supporting Evidence: PMID:22057399 Three-dimensional structural modeling of the PTS2 receptor PEX7 reveals a groove with an evolutionarily conserved charge distribution complementary to PTS2 signals. Mammalian two-hybrid assays and cross-complementation of a mutation in PTS2 by a compensatory mutation in PEX7 confirm the interaction site.
GO:0005053 peroxisome matrix targeting signal-2 binding	IDA PMID:25538232 Mechanistic insights into PTS2-mediated peroxisomal protein ...	MODIFY	Summary: IDA annotation for PTS2 binding from Kunze et al. (2015). This study demonstrated that PEX7-PTS2 interaction is drastically stabilized (about 20-fold) by the co-receptor PEX5L, forming a trimeric complex. Mutations in the PTS2-binding groove (E113R, E200R) abolished cargo binding, while E287R affected PEX5L interaction. Reason: Direct experimental evidence for PTS2 binding, with detailed mechanistic insights into the trimeric complex formation. GO:0005053 (peroxisome matrix targeting signal-2 binding) is obsolete as of GO release 2026-07-26 (replaced_by GO:0000268, now labelled 'peroxisome signal sequence receptor activity' and covering PTS1, PTS2 and mPTS receptors), so the annotation is carried forward on GO:0000268. Proposed replacements: peroxisome signal sequence receptor activity Supporting Evidence: PMID:25538232 the interaction strength between cargo and PEX7 is drastically increased in the presence of the co-receptor PEX5L PMID:25538232 cargo binding is a prerequisite for the interaction between PEX7 and PEX5L
GO:0005515 protein binding	IPI PMID:11546814 Domain mapping of human PEX5 reveals functional and structur...	REMOVE	Summary: IPI protein binding from Dodt et al. (2001). This study mapped the regions of PEX5L involved in PEX7 interaction (amino acids 191-222 of PEX5L are sufficient for PEX7 interaction). The PEX5L-PEX7 interaction is biologically critical for PTS2-dependent import. However, "protein binding" is an uninformative term. Reason: The underlying biology is the PEX7-PEX5L co-receptor interaction, which is essential for PTS2 import. However, "protein binding" is too general, and GO has no specific MF for this peroxin-peroxin interaction; GO:0000268 (peroxisome signal sequence receptor activity) would misstate it as signal-sequence recognition. The interaction is part of the PTS2 import process captured by the BP annotations. Removal reflects that the generic term is uninformative; it does not mean the PEX7-PEX5L interaction is false. Supporting Evidence: PMID:11546814 PEX5L physically interacts with PEX7, the import receptor for PTS2-containing proteins. In this report we map the regions of human PEX5L involved in PTS2 protein import, PEX7 interaction
GO:0005515 protein binding	IPI PMID:25538232 Mechanistic insights into PTS2-mediated peroxisomal protein ...	REMOVE	Summary: IPI protein binding from Kunze et al. (2015). This study demonstrated PEX7 interactions with PEX5L and cargo proteins, forming a trimeric complex. The generic "protein binding" is uninformative for this well-characterized functional interaction. Reason: "Protein binding" is uninformative. The specific interactions (PTS2 binding and PEX5L co-receptor interaction) are already captured by GO:0000268 (formerly GO:0005053) annotations.
GO:0005782 peroxisomal matrix	IDA PMID:11546814 Domain mapping of human PEX5 reveals functional and structur...	ACCEPT	Summary: IDA annotation for peroxisomal matrix localization from Dodt et al. (2001). The study showed PEX7 localization at peroxisomes via PEX5L-mediated docking and translocation. Reason: Experimental evidence supports PEX7 translocation into the peroxisomal matrix as part of the import cycle. Supporting Evidence: PMID:11546814 amino acids 1-214 are sufficient for targeting to peroxisomes
GO:0005782 peroxisomal matrix	IDA PMID:25538232 Mechanistic insights into PTS2-mediated peroxisomal protein ...	ACCEPT	Summary: IDA annotation for peroxisomal matrix localization from Kunze et al. (2015). This study showed that peroxisomal targeting of PEX7 depends on cargo binding and can be stimulated by overexpression of cargo protein. Reason: Direct experimental evidence showing cargo-dependent peroxisomal targeting of PEX7. Supporting Evidence: PMID:25538232 the peroxisomal transfer of PEX7 depends on cargo binding and that ectopic overexpression of cargo protein stimulates this process
GO:0005829 cytosol	IDA PMID:25538232 Mechanistic insights into PTS2-mediated peroxisomal protein ...	ACCEPT	Summary: IDA annotation for cytosol localization from Kunze et al. (2015). Cytosolic PEX7 was directly observed, especially for cargo-binding mutants that remain exclusively cytosolic. Reason: Direct experimental evidence. PEX7 mutants that cannot bind cargo (E113R, E200R) are exclusively cytosolic, confirming cytosol as a genuine localization for PEX7. Supporting Evidence: PMID:25538232 PEX7 variants harboring a mutation in the cargo-binding groove are solely cytosolic
GO:0016558 protein import into peroxisome matrix	IDA PMID:11546814 Domain mapping of human PEX5 reveals functional and structur...	ACCEPT	Summary: IDA annotation for peroxisomal matrix protein import from Dodt et al. (2001). This study demonstrated the essential role of PEX5L in PTS2 protein import and mapped the PEX7-interacting region of PEX5L. Reason: Direct experimental evidence that PEX7, in concert with PEX5L, mediates PTS2-dependent protein import into the peroxisomal matrix. Supporting Evidence: PMID:11546814 amino acids 1-230 of PEX5L are required for PTS2 protein import
GO:0016558 protein import into peroxisome matrix	IDA PMID:22057399 Structural requirements for interaction of peroxisomal targe...	ACCEPT	Summary: IDA annotation for peroxisomal protein import from Kunze et al. (2011). This study demonstrated that PEX7 mutations (E113R) destroy the ability to complement PEX7 deficiency in RCDP1 fibroblasts, confirming PEX7's role in PTS2-dependent import. Reason: Complementation of RCDP1 fibroblasts and mutational analysis directly demonstrate PEX7's role in peroxisomal import. Supporting Evidence: PMID:22057399 the mutation E113R in myc-hPEX7 destroyed its ability to complement PEX7 deficiency in RCDP1 fibroblasts
GO:0016558 protein import into peroxisome matrix	IDA PMID:25538232 Mechanistic insights into PTS2-mediated peroxisomal protein ...	ACCEPT	Summary: IDA annotation for peroxisomal protein import from Kunze et al. (2015). This study provided detailed mechanistic insight into the sequential assembly of the PEX7-cargo-PEX5L trimeric complex required for import. Reason: Detailed mechanistic evidence for PEX7's role in peroxisomal protein import through the trimeric complex. Supporting Evidence: PMID:25538232 the sequential formation of a highly stable trimeric complex involving cargo protein, PEX7 and PEX5L stabilizes cargo binding and is a prerequisite for PTS2-mediated peroxisomal import
GO:0005515 protein binding	IPI PMID:30204880 A newly isolated Pex7-binding, atypical PTS2 protein P7BP2 i...	REMOVE	Summary: IPI protein binding from Niwa et al. (2018). This study identified VWA8 (P7BP2) as a novel PEX7-binding protein with an atypical PTS2. The interaction is between PEX7 and VWA8's PTS2, making this essentially a PTS2-binding interaction. Reason: "Protein binding" is uninformative. The PEX7-VWA8 interaction is mediated via PTS2 recognition, which is already captured by GO:0000268 (formerly GO:0005053) annotations. The interaction demonstrates a new PTS2 cargo, not a new binding activity. Supporting Evidence: PMID:30204880 The binding to Pex7p and peroxisomal localization of P7BP2 depends on the cleavable PTS2 in the N-terminal region
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033485	ACCEPT	Summary: TAS annotation for peroxisomal membrane from Reactome. This reaction describes PEX2:PEX10:PEX12 monoubiquitination of PEX5L at the peroxisomal membrane. PEX7 is transiently associated with the peroxisomal membrane during the import cycle when it docks at the PEX13-PEX14 complex as part of the PEX5L-PEX7-cargo trimeric complex. Reason: PEX7 transiently associates with the peroxisomal membrane during the import cycle as part of the docking and translocation process. While not a permanent membrane resident, this transient association is biologically meaningful.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033499	ACCEPT	Summary: TAS annotation for peroxisomal membrane from Reactome. This reaction describes PEX1:PEX6:PEX26 dissociating PEX5L and PEX7 from the peroxisomal membrane for recycling. Reason: PEX7 is present at the peroxisomal membrane during the recycling step of the import cycle, which is well established.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033514	ACCEPT	Summary: TAS annotation for peroxisomal membrane from Reactome. This reaction describes translocation of PEX5L:PEX7 cargo from cytosol to peroxisomal matrix, during which PEX7 passes through the membrane. Reason: PEX7 transits through the peroxisomal membrane during cargo translocation. Transient membrane association is biologically accurate.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033516	ACCEPT	Summary: TAS annotation for peroxisomal membrane from Reactome. Describes PEX2:PEX10:PEX12:Ub:PEX5L:PEX7:PEX13:PEX14 binding to PEX1:PEX6:PEX26 complex at the membrane. Reason: PEX7 is part of the membrane-associated complex during the import and recycling cycle.
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9033527	ACCEPT	Summary: TAS annotation for peroxisomal membrane from Reactome. Describes PEX2:PEX10:PEX12 binding PEX5L within the membrane-associated complex containing PEX7. Reason: Part of the well-established membrane-associated import machinery complex involving PEX7.
GO:0005829 cytosol	TAS Reactome:R-HSA-9033232	ACCEPT	Summary: TAS annotation for cytosol from Reactome. This reaction describes PEX7 binding cargo proteins containing PTS2 in the cytosol. Reason: PEX7 binds PTS2-cargo in the cytosol before transport to peroxisomes. This is the initial step of the import cycle.
GO:0005829 cytosol	TAS Reactome:R-HSA-9033499	ACCEPT	Summary: TAS annotation for cytosol from Reactome. Describes PEX7 recycling from peroxisomal membrane back to cytosol. Reason: PEX7 is recycled to the cytosol after cargo delivery. Well established.
GO:0005829 cytosol	TAS Reactome:R-HSA-9033514	ACCEPT	Summary: TAS annotation for cytosol from Reactome. Cargo translocation from cytosol to matrix involves PEX7 starting in the cytosol. Reason: PEX7 starts in the cytosol as part of the translocation process. Concordant with other evidence.
GO:0005829 cytosol	TAS Reactome:R-NUL-9033857	ACCEPT	Summary: TAS annotation for cytosol from Reactome (non-human species reaction). Describes Pex14 binding PEX5L:PEX7:Acaa1a in the cytosol (mouse reaction used to infer human). Reason: Cytosolic localization of PEX7 is well established and conserved.
GO:0005829 cytosol	TAS Reactome:R-NUL-9033896	ACCEPT	Summary: TAS annotation for cytosol from Reactome (non-human species reaction). Describes PEX5L binding PEX7:Acaa1a in cytosol (mouse reaction). Reason: Cytosolic localization of PEX7 is well established and conserved.
GO:0005053 peroxisome matrix targeting signal-2 binding	IDA PMID:9090383 Rhizomelic chondrodysplasia punctata is caused by deficiency...	MODIFY	Summary: IDA annotation for PTS2 binding from Purdue et al. (1997). One of the original papers identifying human PEX7 as the PTS2 receptor. Showed that PEX7 expression in RCDP cells rescues PTS2 targeting and restores DHAP-AT activity. The authors concluded "these results imply that several peroxisomal proteins are targeted by PTS2 signals." Reason: Foundational paper demonstrating PEX7 is the human PTS2 receptor. GO:0005053 (peroxisome matrix targeting signal-2 binding) is obsolete as of GO release 2026-07-26 (replaced_by GO:0000268, now labelled 'peroxisome signal sequence receptor activity' and covering PTS1, PTS2 and mPTS receptors), so the annotation is carried forward on GO:0000268. Proposed replacements: peroxisome signal sequence receptor activity Supporting Evidence: PMID:9090383 expression of human PEX7 in RCDP cells rescues PTS2 targeting and restores some activity of dihydroxyacetone phosphate acyltransferase (DHAP-AT)
GO:0005053 peroxisome matrix targeting signal-2 binding	IDA PMID:11931631 Functional studies on human Pex7p: subcellular localization ...	MODIFY	Summary: IDA annotation for PTS2 binding from Ghys et al. (2002). This study demonstrated specific binding of human PEX7 to PTS2 using multiple approaches, and showed that only monomeric PEX7 binds PTS2. The interaction is reduced by cysteine alkylation and impaired by N-terminal truncation. Reason: Direct demonstration of PEX7-PTS2 binding with characterization of binding requirements. GO:0005053 (peroxisome matrix targeting signal-2 binding) is obsolete as of GO release 2026-07-26 (replaced_by GO:0000268, now labelled 'peroxisome signal sequence receptor activity' and covering PTS1, PTS2 and mPTS receptors), so the annotation is carried forward on GO:0000268. Proposed replacements: peroxisome signal sequence receptor activity Supporting Evidence: PMID:11931631 Specific binding of human Pex7p to PTS2 could be demonstrated only when Pex7p was formed in vitro by a coupled transcription/translation system or synthesized in vivo in Chinese hamster ovary K1 cells PMID:11931631 only monomeric Pex7p binds to PTS2. The interaction is reduced upon cysteine alkylation and is impaired upon truncation of the N-terminus of Pex7p.
GO:0005782 peroxisomal matrix	IDA PMID:11931631 Functional studies on human Pex7p: subcellular localization ...	ACCEPT	Summary: IDA annotation for peroxisomal matrix localization from Ghys et al. (2002). GFP-tagged PEX7 was directly observed in the peroxisomal lumen. Reason: Direct visualization of PEX7-GFP in the peroxisomal lumen. Supporting Evidence: PMID:11931631 Pex7p-GFP was located both in the lumen of peroxisomes and in the cytosol.
GO:0005829 cytosol	IDA PMID:11931631 Functional studies on human Pex7p: subcellular localization ...	ACCEPT	Summary: IDA annotation for cytosol localization from Ghys et al. (2002). GFP-tagged PEX7 was observed in both peroxisomes and cytosol. Reason: Direct visualization of PEX7-GFP in the cytosol. Supporting Evidence: PMID:11931631 Pex7p-GFP was located both in the lumen of peroxisomes and in the cytosol.
GO:0019899 enzyme binding	IPI PMID:11931631 Functional studies on human Pex7p: subcellular localization ...	MODIFY	Summary: IPI annotation for enzyme binding from Ghys et al. (2002). This reflects PEX7 binding to PTS2-carrying enzymes (thiolase, PHYH, AGPS). However, this binding is specifically mediated through the PTS2 signal on these enzymes, making GO:0000268 (peroxisome signal sequence receptor activity; formerly GO:0005053 PTS2 binding) the more appropriate and informative term. Reason: "Enzyme binding" is technically not wrong since PEX7 does bind enzymes (thiolase, PHYH, AGPS), but it mischaracterizes the nature of the interaction. PEX7 binds these proteins specifically through their PTS2 signals, not through enzyme-specific features. The more informative and accurate term is GO:0000268 (peroxisome signal sequence receptor activity), into which GO:0005053 (PTS2 binding) was merged. Proposed replacements: peroxisome signal sequence receptor activity Supporting Evidence: PMID:11931631 Pex7p is a WD40-containing protein involved in peroxisomal import of proteins containing an N-terminal peroxisome-targeting signal (PTS2)
GO:0042803 protein homodimerization activity	IDA PMID:11931631 Functional studies on human Pex7p: subcellular localization ...	MARK AS OVER ANNOTATED	Summary: IDA annotation for protein homodimerization from Ghys et al. (2002). This is problematic. The same paper explicitly states that "only monomeric Pex7p binds to PTS2," and that interaction of Pex7p with other peroxins "could not be demonstrated in bacterial or yeast two-hybrid screens, or in pull-down binding assays." While some homodimerization may have been detected, the paper emphasizes that the functionally active form is the monomer. This annotation likely represents an over-annotation of an observation that is not functionally relevant. Reason: While some PEX7 homodimerization may be detected, the same paper (PMID:11931631) states that only monomeric PEX7 binds PTS2, indicating that homodimerization is not functionally important for PEX7's known biological roles. This likely represents an over-annotation. Supporting Evidence: PMID:11931631 only monomeric Pex7p binds to PTS2
GO:0007031 peroxisome organization	IMP PMID:10022913 Identification and characterization of the human orthologue ...	MARK AS OVER ANNOTATED	Summary: IMP annotation for peroxisome organization from Will et al. (1999). This paper is primarily about HsPex14p, not PEX7. The annotation likely derives from the observation that PEX7 mutations (in RCDP patient cells) affect peroxisomal protein import and consequently peroxisome organization. However, PEX7 loss specifically disrupts PTS2-dependent protein import, not peroxisome organization broadly. Peroxisomes are still present and functional for PTS1-dependent import in RCDP cells. Reason: PEX7 mutations cause specific PTS2 import deficiency, not global peroxisome organization defects. RCDP cells still have peroxisomes with normal PTS1 import. "Peroxisome organization" is too broad and implies a more general role than what PEX7 performs. The core process is "protein import into peroxisome matrix" (GO:0016558). Supporting Evidence: PMID:9090382 RCDP cells from CG11 cannot import a PTS2 reporter protein PMID:9090383 the peroxisomal targeting and proteolytic removal of the amino-terminal type 2 peroxisomal targeting sequence (PTS2) of thiolase are defective, whereas the biogenesis of proteins targeted by carboxyterminal type 1 peroxisomal targeting sequences (PTS1) is unimpaired
GO:0005777 peroxisome	IDA PMID:9090382 Rhizomelic chondrodysplasia punctata is a peroxisomal protei...	ACCEPT	Summary: IDA annotation for peroxisome localization from Motley et al. (1997). This is one of the three simultaneous papers identifying human PEX7 as the PTS2 receptor. The broader term "peroxisome" (GO:0005777) is acceptable as a parent term, though more specific terms (peroxisomal matrix, peroxisomal membrane) are also annotated. Reason: Peroxisome localization is established. While more specific CC terms (peroxisomal matrix, peroxisomal membrane) exist, this broader term is acceptable as it was annotated from one of the foundational papers. Supporting Evidence: PMID:9090382 expression of PEX7 in RCDP fibroblasts from CG11 rescues the PTS2 protein import deficiency
GO:0008611 ether lipid biosynthetic process	IMP PMID:12522768 Identification of PEX7 as the second gene involved in Refsum...	KEEP AS NON CORE	Summary: IMP annotation for ether lipid biosynthesis from van den Brink et al. (2003). PEX7 mutations cause deficiency of plasmalogen synthesis due to failure to import AGPS (alkyldihydroxyacetonephosphate synthase), a PTS2-carrying enzyme involved in plasmalogen/ether lipid synthesis. The connection to ether lipid biosynthesis is indirect -- PEX7 imports the enzyme, not directly catalyzes the pathway. Reason: PEX7 is not directly involved in ether lipid biosynthesis. The effect on ether lipid synthesis is an indirect consequence of failing to import the PTS2-carrying enzyme AGPS into peroxisomes. This is a downstream phenotypic consequence, not a core function of PEX7. Supporting Evidence: PMID:12522768 Biochemical analyses of the patients with RD revealed defects not only in phytanic acid alpha-oxidation but also in plasmalogen synthesis and peroxisomal thiolase.
GO:0008611 ether lipid biosynthetic process	IMP PMID:9090383 Rhizomelic chondrodysplasia punctata is caused by deficiency...	KEEP AS NON CORE	Summary: IMP annotation for ether lipid biosynthesis from Purdue et al. (1997). PEX7 expression in RCDP cells restores DHAP-AT activity (involved in plasmalogen/ether lipid synthesis) by enabling import of AGPS. The ether lipid deficiency is a downstream consequence of PTS2 import failure. Reason: Ether lipid biosynthesis is a downstream consequence of PEX7's role in PTS2 import, not a direct function. PEX7 imports AGPS which is needed for ether lipid synthesis, but PEX7 does not directly participate in the biosynthetic pathway. Supporting Evidence: PMID:9090383 expression of human PEX7 in RCDP cells rescues PTS2 targeting and restores some activity of dihydroxyacetone phosphate acyltransferase (DHAP-AT), a peroxisomal enzyme of plasmalogen biosynthesis
GO:0005053 peroxisome matrix targeting signal-2 binding	IDA PMID:9090381 Human PEX7 encodes the peroxisomal PTS2 receptor and is resp...	MODIFY	Summary: IDA annotation for PTS2 binding from Braverman et al. (1997). One of the original papers identifying human PEX7 as the PTS2 receptor. Demonstrated that PEX7 expression corrects the PTS2-import defect in RCDP cells, and identified RCDP-causing mutations in PEX7. Reason: Foundational experimental evidence establishing PEX7 as the human PTS2 receptor. GO:0005053 (peroxisome matrix targeting signal-2 binding) is obsolete as of GO release 2026-07-26 (replaced_by GO:0000268, now labelled 'peroxisome signal sequence receptor activity' and covering PTS1, PTS2 and mPTS receptors), so the annotation is carried forward on GO:0000268. Proposed replacements: peroxisome signal sequence receptor activity Supporting Evidence: PMID:9090381 PEX7, a candidate gene for RCDP identified in yeast, encodes the receptor for peroxisomal matrix proteins with the type-2 peroxisome targeting signal (PTS2).
GO:0016558 protein import into peroxisome matrix	IMP PMID:12522768 Identification of PEX7 as the second gene involved in Refsum...	ACCEPT	Summary: IMP annotation for peroxisomal protein import from van den Brink et al. (2003). PEX7 mutations in Refsum disease patients cause defects in PTS2-dependent protein import (thiolase, PHYH, AGPS import failures). Reason: Mutations in PEX7 in human patients cause PTS2-dependent import deficiency, confirming PEX7's role in peroxisomal protein import. Supporting Evidence: PMID:12522768 mutations in the PEX7 gene may result in a broad clinical spectrum ranging from severe rhizomelic chondrodysplasia punctata to relatively mild RD
GO:0016558 protein import into peroxisome matrix	IDA PMID:9090381 Human PEX7 encodes the peroxisomal PTS2 receptor and is resp...	ACCEPT	Summary: IDA annotation for peroxisomal protein import from Braverman et al. (1997). Expression of PEX7 corrects the PTS2-import defect in RCDP cells, directly demonstrating PEX7's role in peroxisomal import. Reason: Direct experimental evidence: PEX7 expression corrects PTS2 import defect in RCDP cells. Supporting Evidence: PMID:9090381 expression of either corrects the PTS2-import defect characteristic of RCDP cells

Gene Description

Existing Annotations Review

References

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