PEX5 is the peroxisomal targeting signal 1 (PTS1) receptor, a soluble cycling receptor that recognizes C-terminal PTS1 tripeptide motifs (-SKL and variants) on peroxisomal matrix proteins in the cytosol. PEX5 contains an N-terminal intrinsically disordered region with eight PEX14-binding WxxxF/Y motifs and a C-terminal TPR domain that binds PTS1 cargo. After cargo binding, PEX5 docks at the peroxisomal membrane via PEX13/PEX14, delivers cargo into the matrix, and is recycled to the cytosol through mono-ubiquitination at Cys11 by the PEX2/PEX10/PEX12 RING complex and extraction by the PEX1/PEX6 AAA ATPase. The long isoform (PEX5L) additionally co-receptors PEX7 for PTS2 cargo import. PEX5 also participates in pexophagy signaling through ATM-mediated phosphorylation and ubiquitination. Mutations cause peroxisome biogenesis disorders (Zellweger spectrum).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005052 peroxisome matrix targeting signal-1 binding | IBA GO_REF:0000033 | MODIFY | Summary: PTS1 binding is the core molecular function of PEX5. The IBA annotation is phylogenetically well-supported and consistent with extensive experimental data showing PEX5 recognizes C-terminal PTS1 tripeptide motifs via its TPR domain (PMID:21976670, PMID:10514471, PMID:12456682). Reason: PTS1 binding is the primary molecular function of PEX5, deeply conserved from yeast to human, and supported by IBA phylogenetic inference as well as numerous IDA/IPI annotations. GO:0005052 (peroxisome matrix targeting signal-1 binding) is obsolete as of GO release 2026-07-26 (replaced_by GO:0000268, now labelled 'peroxisome signal sequence receptor activity' and covering PTS1, PTS2 and mPTS receptors),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:21976670 PEX5 protein binds monomeric catalase blocking its tetramerization and releases it upon binding the N-terminal domain of PEX14 PMID:10514471 HsPMP20 bound directly to the human peroxisomal targeting signal 1 receptor, HsPEX5 |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PEX5 is predominantly cytosolic, cycling between the cytosol and the peroxisomal membrane. The IBA annotation is consistent with experimental localization data (PMID:16314507, PMID:11336669). Reason: PEX5 is a predominantly cytosolic receptor that transiently associates with the peroxisomal membrane during the import cycle. Cytosol localization is well established by IBA and multiple experimental studies. Supporting Evidence: PMID:11336669 human Pex5p does not just bind cargo and deliver it to the peroxisome membrane, but participates in multiple rounds of entry into the peroxisome matrix and export to the cytosol PMID:16314507 Shuttling mechanism of peroxisome targeting signal type 1 receptor Pex5: ATP-independent import and ATP-dependent export |
| GO:0005778 peroxisomal membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PEX5 transiently localizes to the peroxisomal membrane during the import cycle, docking via PEX13/PEX14. The IBA annotation is consistent with the cycling receptor model supported by extensive experimental data (PMID:16314507, PMID:11336669). Reason: Peroxisomal membrane localization is integral to PEX5 function as a cycling receptor. IBA annotation is phylogenetically well-supported. Supporting Evidence: PMID:16314507 Pex5 was in two distinct, 500- and 800-kDa complexes comprising different sets of peroxins, such as Pex14 and Pex2 |
| GO:0016560 protein import into peroxisome matrix, docking | IBA GO_REF:0000033 | ACCEPT | Summary: Docking of PEX5 at the peroxisomal membrane via PEX13/PEX14 is a core step in the PTS1 import pathway. The IBA annotation is consistent with the well-characterized docking mechanism (PMID:21976670, PMID:19197237). Reason: Docking is a defined sub-step of the PEX5 import cycle, phylogenetically conserved and well-supported experimentally. Supporting Evidence: PMID:21976670 PEX5 protein binds monomeric catalase blocking its tetramerization and releases it upon binding the N-terminal domain of PEX14 |
| GO:0005782 peroxisomal matrix | IEA GO_REF:0000044 | ACCEPT | Summary: PEX5 transiently enters the peroxisomal matrix during the import cycle. This IEA annotation from UniProt subcellular location mapping is consistent with the established cycling mechanism (PMID:11336669). Reason: IEA annotation is consistent with the well-established cycling mechanism where PEX5 enters the peroxisomal matrix to deliver cargo before being recycled. Supporting Evidence: PMID:11336669 human Pex5p does not just bind cargo and deliver it to the peroxisome membrane, but participates in multiple rounds of entry into the peroxisome matrix and export to the cytosol |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: Cytosol localization of PEX5 is well established. This IEA annotation is broader than the IBA annotation for the same term but consistent. Reason: Redundant with IBA annotation for the same term, but not incorrect. IEA from UniProt subcellular location mapping is consistent with experimental data. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | ACCEPT | Summary: PEX5 mediates protein transport to peroxisomes. This IEA annotation from UniProt keyword mapping is very general. The more specific term GO:0016558 (protein import into peroxisome matrix) is already annotated with multiple experimental evidence codes. Reason: While very general, this IEA annotation is not incorrect. More specific terms are annotated separately with experimental evidence. The IEA-derived broader term does not conflict. |
| GO:0005515 protein binding | IPI PMID:10562279 PEX12 interacts with PEX5 and PEX10 and acts downstream of r... | MARK AS OVER ANNOTATED | Summary: PMID:10562279 demonstrates PEX5 interaction with PEX12 and PEX10 in the peroxisomal import pathway. Protein binding is uninformative; the actual function is involvement in the RING complex interaction during cargo translocation. Reason: Protein binding is too vague. PEX5 interacts with PEX12 as part of the ubiquitin ligase complex interaction during the import cycle. This peroxin-peroxin contact at the docking/RING complex is not signal-sequence recognition, so GO:0000268 (peroxisome signal sequence receptor activity) would misstate it, and GO has no specific MF for this interaction; the biology is captured by the protein import into peroxisome matrix BP annotations. Supporting Evidence: PMID:10562279 PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in peroxisomal matrix protein import |
| GO:0005515 protein binding | IPI PMID:12096124 Analysis of mammalian peroxin interactions using a non-trans... | MARK AS OVER ANNOTATED | Summary: PMID:12096124 used a non-transcription-based bacterial two-hybrid to analyze peroxin interactions including PEX5. Protein binding is uninformative for the actual function. Reason: Protein binding is too vague for a protein whose core function is defined by specific binding activities (PTS1 binding, PEX14 interaction). The peroxin-peroxin interactions are better captured by process and more specific MF terms. |
| GO:0005515 protein binding | IPI PMID:19197237 Structural basis for competitive interactions of Pex14 with ... | MARK AS OVER ANNOTATED | Summary: PMID:19197237 provides structural basis for competitive interactions of PEX14 with PEX5 and PEX19. This describes the key PEX5-PEX14 docking interaction. Reason: Protein binding is too vague. The PEX5-PEX14 interaction is better captured by GO:0016560 (protein import into peroxisome matrix, docking) which is already annotated. |
| GO:0005515 protein binding | IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi... | MARK AS OVER ANNOTATED | Summary: PMID:21044950 is a genome-wide YFP fluorescence complementation screen for telomere signaling regulators. The relevance to PEX5 core function is unclear. Reason: High-throughput screen result. Protein binding is uninformative and the telomere signaling context is unlikely to represent a core PEX5 function. |
| GO:0005515 protein binding | IPI PMID:21525035 PEX14 is required for microtubule-based peroxisome motility ... | MARK AS OVER ANNOTATED | Summary: PMID:21525035 shows PEX14 is required for microtubule-based peroxisome motility. PEX5 may interact with PEX14 in this context but the primary annotation is about PEX14. Reason: Protein binding is too vague. The PEX5-PEX14 interaction is better captured by docking and import terms already annotated. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: PMID:25416956 is a proteome-scale map of the human interactome network. High-throughput interaction data. Reason: Protein binding from a high-throughput interactome screen is uninformative for PEX5 whose specific binding functions are well characterized. |
| GO:0005515 protein binding | IPI P50542-1 PMID:22529745 Molecular requirements for peroxisomal targeting of alanine-... | MARK AS OVER ANNOTATED | Summary: PMID:22529745 examines molecular requirements for peroxisomal targeting of AGT as a determinant in primary hyperoxaluria type 1. PEX5L interaction with AGT is part of its PTS1 receptor function. Reason: Protein binding is too vague. The interaction with AGT represents PEX5 performing its core PTS1 receptor function (cargo recognition), already captured by GO:0000268 (peroxisome signal sequence receptor activity). |
| GO:0016558 protein import into peroxisome matrix | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation for protein import into peroxisome matrix via Ensembl Compara ortholog transfer. Consistent with the well-established core function of PEX5. Reason: Correct IEA annotation consistent with the core function of PEX5 as PTS1 receptor mediating peroxisomal matrix protein import. |
| GO:0005794 Golgi apparatus | IDA GO_REF:0000052 | REMOVE | Summary: Golgi apparatus localization from immunofluorescence data curation. PEX5 is not known to function at the Golgi. This may reflect antibody cross-reactivity or misidentification in high-throughput immunofluorescence studies. Reason: PEX5 is a cytosolic/peroxisomal cycling receptor with no known Golgi function. This localization is not supported by the extensive literature on PEX5 subcellular distribution and is likely an artifact. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosol localization from immunofluorescence data curation. Consistent with the well-established predominantly cytosolic localization of PEX5. Reason: Cytosol localization is well established for PEX5 as a cycling receptor. |
| GO:0140597 protein carrier chaperone | IDA PMID:28765278 The peroxisomal matrix protein translocon is a large cavity-... | ACCEPT | Summary: PMID:28765278 demonstrates that PEX5 enters a large cavity-forming protein assembly (the translocon) to release its cargo. This supports protein carrier activity as PEX5 physically carries folded cargo into the peroxisome. Reason: Protein carrier activity accurately describes PEX5 function as it physically escorts folded PTS1 cargo from cytosol into the peroxisomal matrix translocon. Supporting Evidence: PMID:28765278 the peroxisomal matrix protein translocon is a large cavity-forming protein assembly into which PEX5 protein enters to release its cargo |
| GO:0016562 protein import into peroxisome matrix, receptor recycling | IDA PMID:29884772 Peroxisomal monoubiquitinated PEX5 interacts with the AAA AT... | ACCEPT | Summary: PMID:29884772 shows monoubiquitinated PEX5 interacts with PEX1/PEX6 AAA ATPases and is unfolded during dislocation into the cytosol. This directly demonstrates receptor recycling. Reason: Receptor recycling is a core step in the PEX5 import cycle, directly demonstrated by this study. Supporting Evidence: PMID:29884772 Peroxisomal monoubiquitinated PEX5 interacts with the AAA ATPases PEX1 and PEX6 and is unfolded during its dislocation into the cytosol |
| GO:0000425 pexophagy | IDA PMID:26344566 ATM functions at the peroxisome to induce pexophagy in respo... | KEEP AS NON CORE | Summary: PMID:26344566 shows ATM functions at the peroxisome to induce pexophagy in response to ROS. PEX5 is phosphorylated by ATM and ubiquitinated to recruit autophagy adaptors. PEX5 participates in pexophagy but this is not its primary evolved function. Reason: PEX5 serves as a substrate for ATM-mediated pexophagy signaling, but pexophagy is a secondary quality control process rather than the core evolved function of PEX5 as a PTS1 import receptor. Supporting Evidence: PMID:26344566 ATM functions at the peroxisome to induce pexophagy in response to ROS |
| GO:0005052 peroxisome matrix targeting signal-1 binding | IDA PMID:26344566 ATM functions at the peroxisome to induce pexophagy in respo... | MODIFY | Summary: PMID:26344566 also demonstrates PTS1 binding by PEX5 in the context of pexophagy studies. PTS1 binding is the core molecular function of PEX5. Reason: PTS1 binding is the core molecular function of PEX5, demonstrated here in the pexophagy context. GO:0005052 (peroxisome matrix targeting signal-1 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 | IC P50542-1 PMID:24662292 Distinct modes of ubiquitination of peroxisome-targeting sig... | ACCEPT | Summary: Peroxisomal matrix localization by IC (inferred by curator) from PMID:24662292 which studies ubiquitination modes regulating PTS1 receptor Pex5p and PTS1 protein import. PEX5 transiently enters the matrix. Reason: PEX5 enters the peroxisomal matrix during the import cycle. IC from the ubiquitination study is consistent. |
| GO:0005829 cytosol | IDA P50542-1 PMID:25538232 Mechanistic insights into PTS2-mediated peroxisomal protein ... | ACCEPT | Summary: PMID:25538232 provides mechanistic insights into PTS2-mediated peroxisomal protein import and localizes PEX5L to the cytosol. Reason: Cytosol localization of PEX5L is well established and consistent with its role as a cycling receptor. |
| GO:0016558 protein import into peroxisome matrix | IDA PMID:26344566 ATM functions at the peroxisome to induce pexophagy in respo... | ACCEPT | Summary: PMID:26344566 demonstrates PEX5-mediated protein import into the peroxisome matrix in the context of pexophagy/ROS studies. Reason: Protein import into peroxisome matrix is the core biological process function of PEX5. |
| GO:0016558 protein import into peroxisome matrix | IDA P50542-1 PMID:25538232 Mechanistic insights into PTS2-mediated peroxisomal protein ... | ACCEPT | Summary: PMID:25538232 demonstrates PEX5L-mediated peroxisomal matrix protein import via PTS2 pathway with PEX7 as co-receptor. Reason: Core function of PEX5L isoform in PTS2-mediated import. |
| GO:0044721 protein import into peroxisome matrix, substrate release | IC P50542-1 PMID:25538232 Mechanistic insights into PTS2-mediated peroxisomal protein ... | ACCEPT | Summary: Substrate release is a defined sub-step of the PEX5 import cycle, inferred by curator from PTS2 import mechanistic data. Reason: Substrate release is a necessary step in the PEX5 cycling mechanism. |
| GO:0140597 protein carrier chaperone | IDA PMID:26344566 ATM functions at the peroxisome to induce pexophagy in respo... | ACCEPT | Summary: Protein carrier activity demonstrated in context of PMID:26344566 pexophagy studies. PEX5 carries PTS1 cargo. Reason: Protein carrier activity is a core molecular function of PEX5. |
| GO:0140597 protein carrier chaperone | IDA P50542-1 PMID:25538232 Mechanistic insights into PTS2-mediated peroxisomal protein ... | ACCEPT | Summary: Protein carrier activity of PEX5L isoform in PTS2-mediated import. Reason: Core molecular function of PEX5L as a carrier for PTS2 cargo via PEX7. |
| GO:0034614 cellular response to reactive oxygen species | IDA PMID:26344566 ATM functions at the peroxisome to induce pexophagy in respo... | KEEP AS NON CORE | Summary: PMID:26344566 shows PEX5 is involved in cellular response to ROS at peroxisomes, linking ROS to ATM-mediated pexophagy signaling. This is a secondary/downstream role. Reason: PEX5 serves as a substrate in the ROS-ATM-pexophagy signaling axis, but this is not its primary evolved function. It is a consequence of PEX5 being at the peroxisomal membrane where it can be phosphorylated by ATM in response to ROS. Supporting Evidence: PMID:26344566 ATM functions at the peroxisome to induce pexophagy in response to ROS |
| GO:0044721 protein import into peroxisome matrix, substrate release | IDA PMID:26344566 ATM functions at the peroxisome to induce pexophagy in respo... | ACCEPT | Summary: Substrate release demonstrated by PMID:26344566. PEX5 releases cargo into the peroxisomal matrix. Reason: Substrate release is a defined sub-step of the PEX5 import cycle. |
| GO:0016562 protein import into peroxisome matrix, receptor recycling | IDA PMID:22371489 Identification of ubiquitin-specific protease 9X (USP9X) as ... | ACCEPT | Summary: PMID:22371489 identifies USP9X as a deubiquitinase acting on ubiquitin-PEX5 thioester conjugate, supporting receptor recycling. Reason: Receptor recycling is a core step in the PEX5 import cycle. USP9X deubiquitination enables PEX5 recycling. Supporting Evidence: PMID:22371489 Identification of ubiquitin-specific protease 9X (USP9X) as a deubiquitinase acting on ubiquitin-peroxin 5 (PEX5) thioester conjugate |
| GO:0005515 protein binding | IPI PMID:25538232 Mechanistic insights into PTS2-mediated peroxisomal protein ... | MARK AS OVER ANNOTATED | Summary: PMID:25538232 demonstrates that PEX5L drastically increases the interaction strength between cargo protein and receptor PEX7 in PTS2-mediated import. Reason: Protein binding is too vague. The PEX5L-PEX7 co-receptor interaction is better captured by GO:0016558 (protein import into peroxisome matrix) annotations already present. |
| GO:0005515 protein binding | IPI P50542-1 PMID:11546814 Domain mapping of human PEX5 reveals functional and structur... | MARK AS OVER ANNOTATED | Summary: PMID:11546814 maps PEX5 domains showing functional and structural similarities to yeast Pex18p/Pex21p. Demonstrates PEX5L isoform interaction with PEX7. Reason: Protein binding is too vague. The PEX5-PEX7 interaction for PTS2 import is better captured by process terms already annotated. A more specific MF term would be preferred. |
| GO:0005782 peroxisomal matrix | IDA P50542-1 PMID:11546814 Domain mapping of human PEX5 reveals functional and structur... | ACCEPT | Summary: PMID:11546814 maps PEX5 domains and localizes PEX5L to peroxisomal matrix. Consistent with the cycling receptor model. Reason: Peroxisomal matrix localization of PEX5 is consistent with its cycling through the matrix during cargo delivery. Supporting Evidence: PMID:11546814 Domain mapping of human PEX5 reveals functional and structural similarities to Saccharomyces cerevisiae Pex18p and Pex21p |
| GO:0016558 protein import into peroxisome matrix | IDA P50542-1 PMID:11546814 Domain mapping of human PEX5 reveals functional and structur... | ACCEPT | Summary: PMID:11546814 demonstrates PEX5L-mediated peroxisomal matrix protein import. Core function. Reason: Core biological process function of PEX5. |
| GO:0140597 protein carrier chaperone | IDA P50542-1 PMID:11546814 Domain mapping of human PEX5 reveals functional and structur... | ACCEPT | Summary: PMID:11546814 demonstrates PEX5L protein carrier activity in peroxisomal import. Reason: Core molecular function of PEX5 as a protein carrier. |
| GO:0005052 peroxisome matrix targeting signal-1 binding | IDA PMID:21976670 PEX5 protein binds monomeric catalase blocking its tetrameri... | MODIFY | Summary: PMID:21976670 shows PEX5 binds monomeric catalase (a PTS1 cargo) and blocks its tetramerization, releasing it upon PEX14 binding. Directly demonstrates PTS1 binding. Reason: Core molecular function. PTS1 binding is the primary cargo recognition mechanism of PEX5. GO:0005052 (peroxisome matrix targeting signal-1 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:21976670 PEX5 protein binds monomeric catalase blocking its tetramerization and releases it upon binding the N-terminal domain of PEX14 |
| GO:0005515 protein binding | IPI PMID:24235149 A novel Pex14 protein-interacting site of human Pex5 is crit... | MARK AS OVER ANNOTATED | Summary: PMID:24235149 identifies a novel PEX14 protein-interacting site on PEX5 critical for matrix protein import. Reason: Protein binding is too vague. The PEX5-PEX14 interaction is the docking step, already captured by GO:0016560. |
| GO:0005782 peroxisomal matrix | IDA PMID:16314507 Shuttling mechanism of peroxisome targeting signal type 1 re... | ACCEPT | Summary: PMID:16314507 uses cell-free systems to demonstrate PEX5 import into and export from peroxisomes. Directly supports peroxisomal matrix localization. Reason: Directly demonstrated by cell-free translocation assays. Supporting Evidence: PMID:16314507 ATP was not required for (35)S-Pex5 import but was indispensable for export |
| GO:0005782 peroxisomal matrix | IMP PMID:33389129 A missense allele of PEX5 is responsible for the defective i... | ACCEPT | Summary: PMID:33389129 identifies a PEX5 missense allele responsible for defective PTS2 cargo import. IMP evidence supports PEX5 role in peroxisomal matrix localization via mutant phenotype. Reason: Mutant phenotype analysis demonstrates PEX5 role in peroxisomal matrix protein delivery. Supporting Evidence: PMID:33389129 A missense allele of PEX5 is responsible for the defective import of PTS2 cargo proteins into peroxisomes |
| GO:0005829 cytosol | IDA PMID:16314507 Shuttling mechanism of peroxisome targeting signal type 1 re... | ACCEPT | Summary: PMID:16314507 demonstrates PEX5 cytosolic localization via cell-free translocation assays showing ATP-dependent export to cytosol. Reason: Cytosol localization directly demonstrated by the shuttling mechanism study. |
| GO:0016558 protein import into peroxisome matrix | IDA PMID:16314507 Shuttling mechanism of peroxisome targeting signal type 1 re... | ACCEPT | Summary: PMID:16314507 directly demonstrates PEX5-mediated protein import into peroxisome matrix using cell-free systems. Reason: Core biological process function of PEX5, directly demonstrated. Supporting Evidence: PMID:16314507 ATP was not required for (35)S-Pex5 import but was indispensable for export |
| GO:0016558 protein import into peroxisome matrix | IDA PMID:21976670 PEX5 protein binds monomeric catalase blocking its tetrameri... | ACCEPT | Summary: PMID:21976670 demonstrates PEX5-mediated peroxisomal import in context of catalase tetramerization study. Reason: Core function of PEX5. |
| GO:0016558 protein import into peroxisome matrix | IDA PMID:24235149 A novel Pex14 protein-interacting site of human Pex5 is crit... | ACCEPT | Summary: PMID:24235149 identifies a novel PEX14-interacting site on PEX5 critical for matrix protein import. Reason: Core biological process function of PEX5. |
| GO:0016558 protein import into peroxisome matrix | IMP PMID:33389129 A missense allele of PEX5 is responsible for the defective i... | ACCEPT | Summary: PMID:33389129 demonstrates that a PEX5 missense allele causes defective PTS2 cargo protein import. Reason: Mutant phenotype directly links PEX5 to peroxisomal matrix protein import. Supporting Evidence: PMID:33389129 A missense allele of PEX5 is responsible for the defective import of PTS2 cargo proteins into peroxisomes |
| GO:0016562 protein import into peroxisome matrix, receptor recycling | IDA PMID:11336669 The human peroxisomal targeting signal receptor, Pex5p, is t... | ACCEPT | Summary: PMID:11336669 demonstrates PEX5 is translocated into the peroxisomal matrix and recycled to the cytosol, directly showing receptor recycling. Reason: Receptor recycling is a core step in the PEX5 cycling mechanism. This landmark paper directly demonstrates the shuttling/recycling mechanism. Supporting Evidence: PMID:11336669 human Pex5p does not just bind cargo and deliver it to the peroxisome membrane, but participates in multiple rounds of entry into the peroxisome matrix and export to the cytosol |
| GO:0044721 protein import into peroxisome matrix, substrate release | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation for substrate release from orthologs. Substrate release is a well-established step in the PEX5 import cycle. Reason: Substrate release is a conserved step in the cycling mechanism. |
| GO:0140597 protein carrier chaperone | IDA PMID:16314507 Shuttling mechanism of peroxisome targeting signal type 1 re... | ACCEPT | Summary: PMID:16314507 demonstrates PEX5 protein carrier activity in cell-free translocation systems. Reason: Core molecular function of PEX5 as a protein carrier. |
| GO:0140597 protein carrier chaperone | IDA PMID:21976670 PEX5 protein binds monomeric catalase blocking its tetrameri... | ACCEPT | Summary: PMID:21976670 demonstrates PEX5 carrier activity for catalase. Reason: Core molecular function of PEX5. |
| GO:0140597 protein carrier chaperone | IDA PMID:24235149 A novel Pex14 protein-interacting site of human Pex5 is crit... | ACCEPT | Summary: PMID:24235149 supports PEX5 protein carrier activity via PEX14 interaction site critical for import. Reason: Core molecular function of PEX5. |
| GO:0140597 protein carrier chaperone | IMP PMID:33389129 A missense allele of PEX5 is responsible for the defective i... | ACCEPT | Summary: PMID:33389129 mutant phenotype supports PEX5 protein carrier activity for PTS2 cargo proteins. Reason: Core molecular function of PEX5 demonstrated by mutant phenotype. |
| GO:0005052 peroxisome matrix targeting signal-1 binding | IDA PMID:17157249 Recognition of a functional peroxisome type 1 target by the ... | MODIFY | Summary: PMID:17157249 demonstrates recognition of a functional PTS1 target by the dynamic import receptor PEX5. Reason: Core molecular function. PTS1 binding demonstrated experimentally. GO:0005052 (peroxisome matrix targeting signal-1 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 | IDA PMID:24662292 Distinct modes of ubiquitination of peroxisome-targeting sig... | ACCEPT | Summary: PMID:24662292 studies distinct modes of PEX5 ubiquitination regulating PTS1 import, supporting peroxisomal matrix localization. Reason: Peroxisomal matrix localization consistent with PEX5 cycling mechanism. |
| GO:0016558 protein import into peroxisome matrix | IDA PMID:17157249 Recognition of a functional peroxisome type 1 target by the ... | ACCEPT | Summary: PMID:17157249 demonstrates PEX5-mediated peroxisomal matrix protein import. Reason: Core biological process function of PEX5. |
| GO:0016558 protein import into peroxisome matrix | IDA PMID:24662292 Distinct modes of ubiquitination of peroxisome-targeting sig... | ACCEPT | Summary: PMID:24662292 demonstrates PEX5-mediated peroxisomal import in context of ubiquitination studies. Reason: Core biological process function of PEX5. |
| GO:0140597 protein carrier chaperone | IDA PMID:17157249 Recognition of a functional peroxisome type 1 target by the ... | ACCEPT | Summary: PMID:17157249 supports PEX5 protein carrier activity. Reason: Core molecular function of PEX5. |
| GO:0140597 protein carrier chaperone | IDA PMID:24662292 Distinct modes of ubiquitination of peroxisome-targeting sig... | ACCEPT | Summary: PMID:24662292 supports PEX5 protein carrier activity in context of ubiquitination regulation. Reason: Core molecular function of PEX5. |
| GO:0005515 protein binding | IPI PMID:12488033 Mammalian Pex14p: membrane topology and characterisation of ... | MARK AS OVER ANNOTATED | Summary: PMID:12488033 characterizes PEX14 membrane topology and PEX14-PEX14 interaction, with PEX5 as an interacting partner. Reason: Protein binding is too vague. PEX5-PEX14 docking interaction is captured by more specific terms. |
| GO:0031333 negative regulation of protein-containing complex assembly | IDA PMID:21976670 PEX5 protein binds monomeric catalase blocking its tetrameri... | KEEP AS NON CORE | Summary: PMID:21976670 shows PEX5 binds monomeric catalase and blocks its tetramerization. This negative regulation of complex assembly is a mechanistic consequence of PEX5 binding monomeric PTS1 cargo to prevent premature oligomerization before import. Reason: This is a mechanistic consequence of PEX5 binding monomeric catalase for import, not an independent function. The anti-tetramerization effect ensures catalase is imported as a monomer. It is a secondary effect of the primary PTS1 cargo binding function. Supporting Evidence: PMID:21976670 PEX5 protein binds monomeric catalase blocking its tetramerization and releases it upon binding the N-terminal domain of PEX14 |
| GO:0033328 peroxisome membrane targeting sequence binding | IPI PMID:21976670 PEX5 protein binds monomeric catalase blocking its tetrameri... | UNDECIDED | Summary: PMID:21976670 shows PEX5 binds the peroxisome membrane targeting sequence in the context of PEX14 interaction. However, PEX5 is the PTS1 receptor, not a PMP targeting sequence receptor. The annotation may reflect PEX5 interaction with PEX14 N-terminal domain. Reason: PEX5 recognizes PTS1 signals, not peroxisome membrane targeting sequences (mPTS). PEX19 is the mPTS receptor. This annotation may be a mis-annotation or may refer to PEX5 binding a specific motif on PEX14 that overlaps with mPTS-like sequences. Needs clarification. GO:0033328 is obsolete as of GO release 2026-07-26 (replaced_by GO:0000268). The merge removes the mPTS-specific reading objected to above (post-merge the row asserts only that PEX5 is a peroxisome signal sequence receptor, which is true and already held by IDA). UNDECIDED is kept because the original curator's mPTS-specific claim from PMID:21976670 was never verified, and the replacement adds nothing beyond the existing IDA GO:0000268 row. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9664855 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9664862 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9664879 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9664880 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9664881 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9664883 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9664888 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9664892 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9674127 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9674131 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005515 protein binding | IPI PMID:10514471 Characterization of human and murine PMP20 peroxisomal prote... | MARK AS OVER ANNOTATED | Summary: PMID:10514471 characterizes PMP20 (PRDX5) as a PTS1 cargo that binds PEX5 via its C-terminal SQL tripeptide. This demonstrates PEX5 PTS1 receptor function rather than generic protein binding. Reason: Protein binding is too vague. This interaction reflects PEX5 recognizing PMP20 as a PTS1 cargo, which is the core PTS1 receptor function already captured by GO:0000268 (peroxisome signal sequence receptor activity). Supporting Evidence: PMID:10514471 HsPMP20 bound directly to the human peroxisomal targeting signal 1 receptor, HsPEX5. Mutagenesis analysis showed that the C-terminal tripeptide sequence, SQL, of HsPMP20 is necessary for its binding to HsPEX5 |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-8953917 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-8953946 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9033235 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9033485 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9033499 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9033514 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9033516 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9033527 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9033533 | ACCEPT | Summary: Reactome TAS annotation for peroxisomal membrane localization. PEX5 transiently associates with the peroxisomal membrane during the import cycle via docking with PEX13/PEX14. Multiple Reactome reactions represent different steps of the import and recycling cycle at the membrane. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. Reactome models different steps of the cycle (docking, ubiquitination, cargo release, recycling, pexophagy) that all involve PEX5 at the peroxisomal membrane. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9033491 | ACCEPT | Summary: Reactome TAS annotation for cytosol localization. PEX5 is predominantly cytosolic and returns to the cytosol after each import cycle. Reason: Cytosol localization is correct for PEX5 as a predominantly cytosolic cycling receptor. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9033499 | ACCEPT | Summary: Reactome TAS annotation for cytosol localization. PEX5 is predominantly cytosolic and returns to the cytosol after each import cycle. Reason: Cytosol localization is correct for PEX5 as a predominantly cytosolic cycling receptor. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9033509 | ACCEPT | Summary: Reactome TAS annotation for cytosol localization. PEX5 is predominantly cytosolic and returns to the cytosol after each import cycle. Reason: Cytosol localization is correct for PEX5 as a predominantly cytosolic cycling receptor. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9033235 | ACCEPT | Summary: Reactome TAS annotation for cytosol localization. PEX5 is predominantly cytosolic and returns to the cytosol after each import cycle. Reason: Cytosol localization is correct for PEX5 as a predominantly cytosolic cycling receptor. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9033236 | ACCEPT | Summary: Reactome TAS annotation for cytosol localization. PEX5 is predominantly cytosolic and returns to the cytosol after each import cycle. Reason: Cytosol localization is correct for PEX5 as a predominantly cytosolic cycling receptor. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9033514 | ACCEPT | Summary: Reactome TAS annotation for cytosol localization. PEX5 is predominantly cytosolic and returns to the cytosol after each import cycle. Reason: Cytosol localization is correct for PEX5 as a predominantly cytosolic cycling receptor. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9664850 | ACCEPT | Summary: Reactome TAS annotation for cytosol localization. PEX5 is predominantly cytosolic and returns to the cytosol after each import cycle. Reason: Cytosol localization is correct for PEX5 as a predominantly cytosolic cycling receptor. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9664883 | ACCEPT | Summary: Reactome TAS annotation for cytosol localization. PEX5 is predominantly cytosolic and returns to the cytosol after each import cycle. Reason: Cytosol localization is correct for PEX5 as a predominantly cytosolic cycling receptor. |
| GO:0005052 peroxisome matrix targeting signal-1 binding | IDA PMID:11463335 Identification of PEX5p-related novel peroxisome-targeting s... | MODIFY | Summary: PMID:11463335 identifies PEX5p-related novel PTS1-binding proteins and demonstrates PEX5 PTS1 binding in comparative assays. Reason: Core molecular function of PEX5 demonstrated in comparative binding assays. GO:0005052 (peroxisome matrix targeting signal-1 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:11463335 Identification of PEX5p-related novel peroxisome-targeting signal 1 (PTS1)-binding proteins in mammals |
| GO:0016558 protein import into peroxisome matrix | IMP PMID:11463335 Identification of PEX5p-related novel peroxisome-targeting s... | ACCEPT | Summary: PMID:11463335 demonstrates PEX5 role in peroxisomal matrix protein import via mutant phenotype. Reason: Core biological process function. |
| GO:0032991 protein-containing complex | IDA PMID:19584060 Solution structure of human Pex5.Pex14.PTS1 protein complexe... | ACCEPT | Summary: PMID:19584060 provides SAXS solution structure of PEX5-PEX14-PTS1 protein complexes. PEX5 forms defined complexes with PEX14 and PTS1 cargo. Reason: PEX5 forms specific protein complexes with PEX14 and cargo as part of the import mechanism. The annotation to protein-containing complex is accurate. |
| GO:0016560 protein import into peroxisome matrix, docking | IDA PMID:21976670 PEX5 protein binds monomeric catalase blocking its tetrameri... | ACCEPT | Summary: PMID:21976670 shows PEX5 docking at peroxisomal membrane via PEX14 interaction (releasing catalase upon PEX14 NTD binding). Reason: Docking is a core step in the PEX5 import cycle. Supporting Evidence: PMID:21976670 PEX5 protein binds monomeric catalase blocking its tetramerization and releases it upon binding the N-terminal domain of PEX14 |
| GO:0005052 peroxisome matrix targeting signal-1 binding | IPI PMID:21375735 The Peroxisomal Targeting Signal 1 in sterol carrier protein... | MODIFY | Summary: PMID:21375735 demonstrates that PTS1 in sterol carrier protein 2 is autonomous and essential for PEX5 receptor recognition. Reason: Core molecular function. PTS1 binding demonstrated via IPI with SCP2 cargo. GO:0005052 (peroxisome matrix targeting signal-1 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:0005515 protein binding | IPI PMID:19584060 Solution structure of human Pex5.Pex14.PTS1 protein complexe... | MARK AS OVER ANNOTATED | Summary: PMID:19584060 provides solution structure of PEX5-PEX14-PTS1 complexes by SAXS. Reason: Protein binding is too vague. Structural characterization of the PEX5-PEX14 complex supports docking (GO:0016560) already annotated. |
| GO:0005777 peroxisome | IDA PMID:21375735 The Peroxisomal Targeting Signal 1 in sterol carrier protein... | ACCEPT | Summary: PMID:21375735 localizes PEX5 to peroxisomes. This is broader than peroxisomal membrane (GO:0005778) or matrix (GO:0005782). Reason: PEX5 localizes to peroxisomes (both membrane and transiently matrix). The peroxisome annotation is accurate if less specific than the membrane/matrix annotations. |
| GO:0006625 protein targeting to peroxisome | IDA P50542-1 PMID:21375735 The Peroxisomal Targeting Signal 1 in sterol carrier protein... | ACCEPT | Summary: PMID:21375735 demonstrates PEX5L-mediated protein targeting to peroxisome with SCP2 as cargo. Reason: Core biological process function of PEX5. Protein targeting to peroxisome is the primary role. |
| GO:0045046 protein import into peroxisome membrane | IMP PMID:14709540 PEX19 is a predominantly cytosolic chaperone and import rece... | REMOVE | Summary: PMID:14709540 is about PEX19 as chaperone/import receptor for peroxisomal membrane proteins. PEX5 siRNA served as a control in this study demonstrating selective PMP import defects. The annotation of PEX5 to protein import into peroxisome membrane is likely incorrect - PEX5 imports matrix proteins, not membrane proteins. Reason: PEX5 is the PTS1 receptor for matrix protein import, not membrane protein import. PEX19 is the membrane protein import receptor. In PMID:14709540, PEX5 siRNA was used as a control showing selective matrix protein import deficiency, which is the opposite phenotype from PEX19 siRNA. Annotating PEX5 to membrane protein import is incorrect. Supporting Evidence: PMID:14709540 inhibition of PEX5 induced a selective deficit in peroxisomal matrix protein import... Inhibition of PEX19 induced the converse phenotype, a selective defect in PMP import |
| GO:0000268 peroxisome targeting sequence binding | IDA PMID:18346465 Comparison of the PTS1- and Rab8b-binding properties of Pex5... | ACCEPT | Summary: PMID:18346465 compares PTS1- and Rab8b-binding properties of PEX5 and PEX5Rp/TRIP8b. PEX5 binds peroxisome targeting sequences. Since GO release 2026-07-26, GO:0000268 (now labelled peroxisome signal sequence receptor activity) is the single merged PTS-receptor term, as the former PTS1, PTS2 and mPTS binding children (GO:0005052, GO:0005053, GO:0033328, GO:0036105) were obsoleted into it. Reason: PEX5 binds peroxisome targeting sequences (primarily PTS1) and PEX5 already holds this merged receptor term experimentally (IDA, this paper). It is the destination for the obsoleted GO:0005052 rows elsewhere in this review, so the PTS1 specificity now survives only in the description and review prose. Supporting Evidence: PMID:18346465 the TPR domains of Pex5p and Pex5Rp/TRIP8b have distinct but overlapping substrate specificities |
| GO:0016558 protein import into peroxisome matrix | IGI PMID:18346465 Comparison of the PTS1- and Rab8b-binding properties of Pex5... | ACCEPT | Summary: PMID:18346465 provides genetic interaction evidence for PEX5 role in peroxisomal matrix protein import via comparison with TRIP8b/PEX5Rp. Reason: Core biological process function of PEX5. |
| GO:0031267 small GTPase binding | IPI PMID:18346465 Comparison of the PTS1- and Rab8b-binding properties of Pex5... | MARK AS OVER ANNOTATED | Summary: PMID:18346465 shows PEX5 binds Rab8b small GTPase. However, this binding was compared to TRIP8b and the biological significance for PEX5 is unclear. PEX5 is not known to function as a Rab8b effector. Reason: Small GTPase binding by PEX5 may be a non-physiological interaction or a minor binding activity. PEX5 is not known to function as a Rab8b effector. TRIP8b is the primary Rab8b-binding TPR protein. Supporting Evidence: PMID:18346465 the TPR domains of Pex5p and Pex5Rp/TRIP8b have distinct but overlapping substrate specificities |
| GO:0019899 enzyme binding | IPI PMID:11060344 Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA ... | MODIFY | Summary: PMID:11060344 shows in vitro interaction between recombinant racemase (AMACR) and PEX5. AMACR is a PTS1 cargo (C-terminal -KASL), so this interaction reflects PTS1 receptor function. Reason: Enzyme binding is too generic. The interaction with AMACR reflects PEX5 PTS1 receptor function recognizing the KASL targeting signal. Better captured by GO:0000268 (peroxisome signal sequence receptor activity). Proposed replacements: peroxisome signal sequence receptor activity Supporting Evidence: PMID:11060344 the in vitro interaction between recombinant racemase and recombinant human PTS1 receptor (Pex5p)... we concluded that ASL is a new PTS1 variant |
| GO:0019899 enzyme binding | IPI PMID:11669066 Identification of a novel human peroxisomal 2,4-dienoyl-CoA ... | MODIFY | Summary: PMID:11669066 identifies a novel human peroxisomal 2,4-dienoyl-CoA reductase via PEX5 interaction using phage display. This likely reflects PTS1 cargo recognition. Reason: Enzyme binding is too generic. The interaction likely reflects PTS1 receptor cargo recognition function, better captured by GO:0000268 (peroxisome signal sequence receptor activity). Proposed replacements: peroxisome signal sequence receptor activity |
| GO:0005778 peroxisomal membrane | HDA PMID:21525035 PEX14 is required for microtubule-based peroxisome motility ... | ACCEPT | Summary: PMID:21525035 provides high-throughput direct assay evidence for PEX5 at the peroxisomal membrane. Consistent with PEX5 membrane association during import. Reason: Peroxisomal membrane localization is correct for PEX5 as a cycling receptor. |
| GO:0016558 protein import into peroxisome matrix | IGI P50542-1 PMID:11931631 Functional studies on human Pex7p: subcellular localization ... | ACCEPT | Summary: PMID:11931631 provides functional studies on human PEX7 including subcellular localization and interaction with PTS2-containing proteins and peroxins including PEX5L. IGI evidence for PEX5L role in peroxisomal matrix protein import. Reason: Core function of PEX5L in PTS2-mediated import via PEX7 co-receptor function. |
| GO:0016558 protein import into peroxisome matrix | NAS PMID:10514471 Characterization of human and murine PMP20 peroxisomal prote... | ACCEPT | Summary: PMID:10514471 reports PMP20/PRDX5 is imported into peroxisomal matrix via PEX5. NAS evidence supports PEX5 role in import. Reason: Core biological process function of PEX5. NAS evidence from a relevant cargo study. Supporting Evidence: PMID:10514471 these results indicate that HsPMP20 is imported into the peroxisomal matrix via PEX5p |
| GO:0005052 peroxisome matrix targeting signal-1 binding | IDA PMID:10514471 Characterization of human and murine PMP20 peroxisomal prote... | MODIFY | Summary: PMID:10514471 directly demonstrates PTS1 binding between PEX5 and PMP20 via C-terminal SQL tripeptide. Reason: Core molecular function. PTS1 binding directly demonstrated. GO:0005052 (peroxisome matrix targeting signal-1 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:10514471 HsPMP20 bound directly to the human peroxisomal targeting signal 1 receptor, HsPEX5. Mutagenesis analysis showed that the C-terminal tripeptide sequence, SQL, of HsPMP20 is necessary for its binding to HsPEX5 |
| GO:0005737 cytoplasm | IDA PMID:10514471 Characterization of human and murine PMP20 peroxisomal prote... | ACCEPT | Summary: PMID:10514471 localizes PEX5 to the cytoplasm. This is broader than cytosol (GO:0005829) which is already annotated. Reason: Cytoplasm localization is correct and broader than the more specific cytosol term. Both are valid. |
| GO:0016020 membrane | IDA PMID:10514471 Characterization of human and murine PMP20 peroxisomal prote... | MARK AS OVER ANNOTATED | Summary: PMID:10514471 reports PEX5 association with a particulate (membrane) fraction. The generic membrane term is very broad. Reason: The generic membrane term (GO:0016020) is too broad and uninformative when more specific localizations (peroxisomal membrane GO:0005778) are already annotated. |
| GO:0005515 protein binding | IPI PMID:9820813 C-terminal tripeptide Ser-Asn-Leu (SNL) of human D-aspartate... | MARK AS OVER ANNOTATED | Summary: PMID:9820813 shows that the C-terminal tripeptide SNL of D-aspartate oxidase is a functional PTS1 signal that binds PEX5. This is a PTS1 cargo recognition interaction. Reason: Protein binding is too vague. This interaction reflects PTS1 receptor function (GO:0000268, peroxisome signal sequence receptor activity) already annotated. Supporting Evidence: PMID:9820813 C-terminal tripeptide Ser-Asn-Leu (SNL) of human D-aspartate oxidase is a functional peroxisome-targeting signal |
| GO:0005777 peroxisome | IDA PMID:11829486 Pex13, the mouse ortholog of the human peroxisome biogenesis... | ACCEPT | Summary: PMID:11829486 characterizes mouse Pex13 and localizes it to peroxisomes, with PEX5 as an interacting partner localized to peroxisomes. Reason: Peroxisome localization is correct for PEX5. |
| GO:0005515 protein binding | IPI P50542-1 PMID:8858165 Pex13p is an SH3 protein of the peroxisome membrane and a do... | MARK AS OVER ANNOTATED | Summary: PMID:8858165 shows Pex13p is an SH3 protein of the peroxisome membrane and a docking factor for PEX5. This is the PEX5-PEX13 docking interaction. Reason: Protein binding is too vague. The PEX5-PEX13 interaction is part of the docking mechanism, captured by GO:0016560. Supporting Evidence: PMID:8858165 Pex13p is an SH3 protein of the peroxisome membrane and a docking factor for the predominantly cytoplasmic PTs1 receptor |
| GO:0005052 peroxisome matrix targeting signal-1 binding | IDA P50542-1 PMID:12456682 PEX5 binds the PTS1 independently of Hsp70 and the peroxin P... | MODIFY | Summary: PMID:12456682 shows PEX5 binds PTS1 independently of Hsp70 and PEX12. Directly demonstrates PTS1 binding. Reason: Core molecular function. GO:0005052 (peroxisome matrix targeting signal-1 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:12456682 PEX5 binds the PTS1 independently of Hsp70 and the peroxin PEX12 |
| GO:0051262 protein tetramerization | IDA P50542-1 PMID:12456682 PEX5 binds the PTS1 independently of Hsp70 and the peroxin P... | KEEP AS NON CORE | Summary: PMID:12456682 reports PEX5 tetramerization. This is a structural observation about PEX5 oligomerization state. Reason: Protein tetramerization is a structural property of PEX5 observed in vitro but not its primary functional role. The biological significance of PEX5 tetramerization for import function is not clearly established. |
| GO:0005052 peroxisome matrix targeting signal-1 binding | IMP P50542-1 PMID:9668159 An isoform of pex5p, the human PTS1 receptor, is required fo... | MODIFY | Summary: PMID:9668159 shows PEX5L isoform is required for PTS2 protein import, with PTS1 binding demonstrated by mutant complementation. IMP evidence supports PTS1 binding. Reason: Core molecular function demonstrated by mutant phenotype analysis. GO:0005052 (peroxisome matrix targeting signal-1 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:9668159 Transfection of PBD005 cells with PEX5S cDNA restores PTS1 but not PTS2 import; transfection with PXR5L cDNA restores both PTS1 and PTS2 protein import |
| GO:0006625 protein targeting to peroxisome | IMP P50542-1 PMID:9668159 An isoform of pex5p, the human PTS1 receptor, is required fo... | ACCEPT | Summary: PMID:9668159 demonstrates PEX5L is required for protein targeting to peroxisome (both PTS1 and PTS2 pathways). Reason: Core biological process function of PEX5. Supporting Evidence: PMID:9668159 the long isoform of the Pex5 protein is required for peroxisomal import of PTS2 proteins |
| GO:0005515 protein binding | IPI PMID:9653144 Identification of a human PTS1 receptor docking protein dire... | MARK AS OVER ANNOTATED | Summary: PMID:9653144 identifies PEX14 as a human PTS1 receptor docking protein directly required for peroxisomal protein import. This is the PEX5-PEX14 docking interaction. Reason: Protein binding is too vague. The PEX5-PEX14 docking interaction is captured by GO:0016560. Supporting Evidence: PMID:9653144 Identification of a human PTS1 receptor docking protein directly required for peroxisomal protein import |
| GO:0005515 protein binding | IPI PMID:15911627 Peroxisomal import of human alanine:glyoxylate aminotransfer... | MARK AS OVER ANNOTATED | Summary: PMID:15911627 shows peroxisomal import of AGT requires ancillary targeting information remote from its C terminus. Demonstrates PEX5 interaction with AGT cargo. Reason: Protein binding is too vague. PEX5-AGT interaction represents PTS1 receptor cargo recognition function, captured by GO:0000268 (peroxisome signal sequence receptor activity). |
| GO:0005515 protein binding | IPI PMID:10837480 Molecular anatomy of the peroxin Pex12p: ring finger domain ... | MARK AS OVER ANNOTATED | Summary: PMID:10837480 shows PEX12 ring finger domain interacts with PEX5 and PEX10. This is part of the ubiquitination machinery interaction during receptor recycling. Reason: Protein binding is too vague. PEX5-PEX12 interaction is part of the receptor recycling/ubiquitination mechanism, captured by GO:0016562. Supporting Evidence: PMID:10837480 ring finger domain is essential for Pex12p function and interacts with the peroxisome-targeting signal type 1-receptor Pex5p and a ring peroxin, Pex10p |
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