PEX19

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005778 peroxisomal membrane	IBA GO_REF:0000033	ACCEPT	Summary: PEX19 is a predominantly cytosolic protein that transiently associates with the peroxisomal membrane when delivering PMP cargo to PEX3. Multiple studies show PEX19 localizes to both cytoplasm and peroxisomal membrane (PMID:10704444, PMID:9339377). IBA annotation is phylogenetically well-supported and consistent with experimental data. Reason: PEX19 has been shown by immunofluorescence and subcellular fractionation to associate with the peroxisomal membrane in addition to its major cytosolic localization (PMID:10704444, PMID:9339377). This is a core localization for its function as a PMP import receptor. Supporting Evidence: PMID:10704444 At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of the protein in the cytoplasm. PMID:9339377 For the HsPXF protein, a carboxyterminal farnesylation at cysteine residues was demonstrated. Through the use of HsPXF-specific antibodies, the protein was shown to be attached to the outer surface of peroxisomes.
GO:0033328 peroxisome membrane targeting sequence binding	IBA GO_REF:0000033	MODIFY	Summary: PEX19 recognizes mPTS (membrane peroxisomal targeting signals) on PMPs. This is a core molecular function conserved across eukaryotes. The IBA annotation appropriately captures PEX19's general mPTS binding activity. Reason: PEX19's recognition of mPTS signals is its defining molecular function, well-established by multiple experimental studies (PMID:14709540, PMID:10704444, PMID:11402059). Before the merge, the IBA captured the right level of specificity for mPTS binding in general. GO:0033328 (peroxisome membrane targeting sequence binding) is obsolete as of GO release 2026-07-26 (replaced_by GO:0000268, now labelled 'peroxisome signal sequence receptor activity' and covering PTS1, PTS2 and mPTS receptors),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:14709540 PEX19 binds and stabilizes newly synthesized PMPs in the cytosol, binds to multiple PMP targeting signals (mPTSs), interacts with the hydrophobic domains of PMP targeting signals PMID:11402059 PEX19, a factor required for peroxisomal membrane biogenesis, interacts with the two minimal targeting regions of PMP34
GO:0045046 protein import into peroxisome membrane	IBA GO_REF:0000033	ACCEPT	Summary: PEX19 is essential for protein import into the peroxisome membrane. This IBA annotation represents one of the most well-characterized core biological processes for PEX19. Reason: PEX19 functions as a chaperone/receptor that delivers PMPs to the peroxisomal membrane via PEX3 docking. This is its primary biological process, supported by extensive experimental evidence (PMID:14709540, PMID:10704444, PMID:16280322). Supporting Evidence: PMID:14709540 PEX19 functions as both a chaperone and an import receptor for newly synthesized PMPs PMID:16280322 Pex19p translocates the membrane peroxins from the cytosol to peroxisomes in an ATP- and Pex3p-dependent manner and then shuttles back to the cytosol
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation from UniProt subcellular location mapping. PEX19 is predominantly cytoplasmic, well-supported by experimental data. Broader than cytosol (GO:0005829) but acceptable as a parallel annotation. Reason: PEX19 is predominantly cytoplasmic as shown by subcellular fractionation and immunofluorescence (PMID:10704444, PMID:14709540). The IEA correctly maps the UniProt annotation. Supporting Evidence: PMID:10704444 At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of the protein in the cytoplasm.
GO:0005777 peroxisome	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for peroxisome localization. PEX19 transiently associates with peroxisomes during PMP delivery. Broader than peroxisomal membrane but acceptable. Reason: PEX19 associates with peroxisomes as part of its PMP delivery cycle. This is well-established experimentally (PMID:10704444, PMID:9339377). Supporting Evidence: PMID:10704444 At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of the protein in the cytoplasm.
GO:0005778 peroxisomal membrane	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation for peroxisomal membrane. Consistent with the IBA annotation for the same term and with experimental evidence. Reason: Duplicate of IBA annotation for the same term. Both are correct; PEX19 associates with peroxisomal membrane during PMP delivery. Supporting Evidence: PMID:10704444 At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of the protein in the cytoplasm.
GO:0007031 peroxisome organization	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation from UniProt keyword mapping. PEX19 is essential for peroxisome biogenesis and organization. This is a broad but correct annotation. Reason: PEX19 is required for peroxisome membrane biogenesis; loss of PEX19 results in absence of detectable peroxisomal structures (PMID:10704444). Peroxisome organization is an appropriate parent term. Supporting Evidence: PMID:10704444 the loss of PEX19 results in degradation of PMPs and/or mislocalization of PMPs to the mitochondrion
GO:0016020 membrane	IEA GO_REF:0000117	ACCEPT	Summary: Very generic IEA annotation for membrane localization. While PEX19 does associate with peroxisomal membranes, this term is too broad to be informative and is redundant with more specific peroxisomal membrane annotations. Reason: While overly broad, this is technically correct since PEX19 does associate with membranes. More specific terms (peroxisomal membrane) are also annotated. IEA annotations at this level are acceptable as they subsume the more specific ones.
GO:0005515 protein binding	IPI PMID:10704444 PEX19 binds multiple peroxisomal membrane proteins, is predo...	REMOVE	Summary: Sacksteder et al. (2000) showed PEX19 binds a broad spectrum of PMPs using dihybrid assays and blot overlays. While the interactions are real, GO:0005515 is uninformative. The specific interactions are better captured by mPTS binding and protein carrier activity terms. Reason: Generic protein binding is uninformative for a protein whose core function is mPTS recognition and PMP chaperoning. The specific interactions with PMPs are better represented by GO:0000268 (peroxisome signal sequence receptor activity) and GO:0140597 (protein carrier activity).
GO:0005515 protein binding	IPI PMID:11402059 Multiple distinct targeting signals in integral peroxisomal ...	REMOVE	Summary: Jones et al. (2001) showed PEX19 binds multiple targeting regions of PMP34 and PEX13. This reflects PEX19's core mPTS binding function. Generic protein binding is uninformative. Reason: Specific PEX19-PMP interactions are better captured by mPTS binding terms. GO:0005515 is not informative here.
GO:0005515 protein binding	IPI PMID:12096124 Analysis of mammalian peroxin interactions using a non-trans...	REMOVE	Summary: Fransen et al. (2002) used bacterial two-hybrid to map peroxin interactions and showed farnesylation enhances PEX19 affinity for PEX13 and the CAAX motif enhances affinity for PEX11beta. These are peroxin-specific interactions better captured by mPTS binding. Reason: Generic protein binding is uninformative. PEX19-peroxin interactions are better captured by mPTS binding terms.
GO:0005515 protein binding	IPI PMID:14709540 PEX19 is a predominantly cytosolic chaperone and import rece...	REMOVE	Summary: Jones et al. (2004) demonstrated PEX19 is a PMP chaperone and import receptor. Interactions with PMPs are central to function but better captured by specific MF terms. Reason: Core PMP interactions are captured by GO:0000268 (peroxisome signal sequence receptor activity) and GO:0140597 (protein carrier activity). GO:0005515 is uninformative.
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	REMOVE	Summary: Rual et al. (2005) large-scale Y2H interactome mapping. High-throughput protein-protein interaction data. Generic protein binding from HTP study. Reason: Generic protein binding from high-throughput Y2H screen. Uninformative for PEX19 annotation.
GO:0005515 protein binding	IPI PMID:16280322 In vitro transport of membrane proteins to peroxisomes by sh...	REMOVE	Summary: Matsuzono & Fujiki (2006) demonstrated PEX19 shuttles PMPs to peroxisomes in vitro. Interactions with Pex16p, Pex26p, and Pex3p are core functions better captured by specific terms. Reason: PEX19-PMP interactions during shuttling are better captured by protein carrier activity and mPTS binding terms. GO:0005515 is uninformative.
GO:0005515 protein binding	IPI PMID:19197237 Structural basis for competitive interactions of Pex14 with ...	REMOVE	Summary: Neufeld et al. (2009) determined the structural basis for PEX19-PEX14 interaction via NMR. PEX19 residues 66-77 form an amphipathic helix binding PEX14 N-terminal domain competitively with PEX5. This is a specific structural interaction. Reason: While the PEX19-PEX14 structural interaction is well-characterized, GO:0005515 is still uninformative. The interaction with PEX14 is part of the peroxisomal import machinery and would be better captured by more specific terms.
GO:0005515 protein binding	IPI PMID:20531392 The peroxisomal receptor Pex19p forms a helical mPTS recogni...	REMOVE	Summary: Schueller et al. (2010) determined the crystal structure of PEX19 C-terminal mPTS recognition domain. This is a structural study of PEX19's mPTS binding function. Reason: The mPTS recognition function is better captured by GO:0000268 (peroxisome signal sequence receptor activity), into which GO:0033328 and its child GO:0036105 were merged. GO:0005515 is uninformative.
GO:0005515 protein binding	IPI PMID:21102411 Structural basis for docking of peroxisomal membrane protein...	REMOVE	Summary: Sato et al. (2010) solved the crystal structure of PEX3-PEX19 docking complex. PEX19 residues 1-44 form an alpha-helix when bound to PEX3. Core structural interaction. Reason: The PEX3-PEX19 docking interaction is a core function better captured by the protein carrier activity and PMP import process terms. GO:0005515 is uninformative.
GO:0005515 protein binding	IPI PMID:21525035 PEX14 is required for microtubule-based peroxisome motility ...	REMOVE	Summary: Bharti et al. (2011) identified PEX14 complexes by mass spec, including PEX19. The PEX19-PEX14 interaction is part of the peroxisomal import machinery. Reason: Generic protein binding from a proteomics study. The PEX19-PEX14 interaction is part of PEX19's import receptor function. GO:0005515 is uninformative.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: Rolland et al. (2014) proteome-scale human interactome map. High-throughput interaction data. Reason: Generic protein binding from high-throughput interactome screen. Uninformative.
GO:0005515 protein binding	IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam...	REMOVE	Summary: Massively parallel pipeline examining molecular phenotypes of disease mutations. High-throughput data. Reason: Generic protein binding from high-throughput study. Uninformative for PEX19.
GO:0005515 protein binding	IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi...	REMOVE	Summary: Barcode Fusion Genetics pooled-matrix protein interaction screens. High-throughput data. Reason: Generic protein binding from high-throughput screen. Uninformative.
GO:0005515 protein binding	IPI PMID:27107014 An inter-species protein-protein interaction network across ...	REMOVE	Summary: Inter-species protein-protein interaction network. High-throughput data. Reason: Generic protein binding from high-throughput inter-species interactome. Uninformative.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: Architecture of human interactome. High-throughput network study. Reason: Generic protein binding from high-throughput interactome study. Uninformative.
GO:0005515 protein binding	IPI PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid tec...	REMOVE	Summary: LuTHy bioluminescence-based two-hybrid technology for quantitative PPI mapping. High-throughput data. Reason: Generic protein binding from high-throughput two-hybrid screen. Uninformative.
GO:0005515 protein binding	IPI PMID:31467278 Maximizing binary interactome mapping with a minimal number ...	REMOVE	Summary: Maximizing binary interactome mapping study. High-throughput data. Reason: Generic protein binding from high-throughput interactome. Uninformative.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	REMOVE	Summary: Study of genetic variant disruption of protein interactions. High-throughput data. Reason: Generic protein binding from high-throughput variant effect study. Uninformative.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Reference map of human binary protein interactome. High-throughput data. Reason: Generic protein binding from high-throughput interactome. Uninformative.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Interactome mapping for neurodegenerative disease proteins. High-throughput data. Reason: Generic protein binding from high-throughput interactome focused on neurodegeneration. Uninformative.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Dual proteome-scale networks of cell-specific interactome remodeling. High-throughput data. Reason: Generic protein binding from high-throughput interactome. Uninformative.
GO:0005515 protein binding	IPI PMID:34819669 A multi-scale map of cell structure fusing protein images an...	REMOVE	Summary: Multi-scale map of cell structure fusing protein images and interactions. High-throughput data. Reason: Generic protein binding from high-throughput cell mapping study. Uninformative.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	REMOVE	Summary: OpenCell endogenous tagging for cartography of human cellular organization. High-throughput data. Reason: Generic protein binding from high-throughput cellular organization study. Uninformative.
GO:0005515 protein binding	IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc...	REMOVE	Summary: AI-guided pipeline for PPI drug discovery identifying SARS-CoV-2 inhibitor. High-throughput/computational data. Reason: Generic protein binding from computational/drug discovery study. Uninformative for PEX19.
GO:0005515 protein binding	IPI PMID:38225382 Systematic discovery of protein interaction interfaces using...	REMOVE	Summary: AlphaFold-based systematic discovery of protein interaction interfaces. Computational study. Reason: Generic protein binding from computational structural study. Uninformative.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	REMOVE	Summary: Multimodal cell maps as a foundation for structural and functional genomics. High-throughput data. Reason: Generic protein binding from high-throughput multimodal cell mapping. Uninformative.
GO:0005777 peroxisome	IDA GO_REF:0000052	ACCEPT	Summary: IDA from immunofluorescence curation (GO_REF:0000052). PEX19 localizes to peroxisomes as shown by multiple IF studies. Reason: PEX19 associates with peroxisomes, established by immunofluorescence and fractionation studies (PMID:10704444, PMID:9339377). Supporting Evidence: PMID:10704444 At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of the protein in the cytoplasm.
GO:0140597 protein carrier chaperone	IDA PMID:11402059 Multiple distinct targeting signals in integral peroxisomal ...	ACCEPT	Summary: Jones et al. (2001) demonstrated PEX19 binds PMP targeting regions and facilitates PMP solubility. This supports protein carrier/chaperone activity. Reason: PEX19 functions as a protein carrier that binds PMPs in the cytosol and delivers them to peroxisomes. This is a core molecular function (PMID:14709540, PMID:11402059). Supporting Evidence: PMID:11402059 PEX19 may play a central role in this process PMID:14709540 PEX19 functions as both a chaperone and an import receptor for newly synthesized PMPs
GO:0140597 protein carrier chaperone	IDA PMID:14709540 PEX19 is a predominantly cytosolic chaperone and import rece...	ACCEPT	Summary: Jones et al. (2004) directly demonstrated PEX19 as a cytosolic chaperone and import receptor for class 1 PMPs. Core molecular function annotation. Reason: This is the landmark paper establishing PEX19 as a chaperone/import receptor for PMPs. Protein carrier activity is an excellent term for PEX19's core function. Supporting Evidence: PMID:14709540 PEX19 binds and stabilizes newly synthesized PMPs in the cytosol, binds to multiple PMP targeting signals (mPTSs), interacts with the hydrophobic domains of PMP targeting signals, and is essential for PMP targeting and import.
GO:0005515 protein binding	IPI PMID:12488033 Mammalian Pex14p: membrane topology and characterisation of ...	REMOVE	Summary: Oliveira et al. (2002) characterized PEX14 membrane topology and PEX14-PEX14 interaction. PEX19 was identified as an interacting partner. Generic protein binding is uninformative. Reason: Generic protein binding uninformative for PEX19. The PEX19-PEX14 interaction is part of the peroxisomal import machinery captured by other terms.
GO:0005829 cytosol	TAS Reactome:R-HSA-382613	ACCEPT	Summary: Reactome annotation for PEX19 docking ABCD1/D2/D3 to peroxisomal membrane. PEX19 acts in the cytosol as a carrier for ABC transporters. Reason: PEX19 is predominantly cytosolic, well-established (PMID:10704444, PMID:14709540). Reactome pathway context is consistent. Supporting Evidence: PMID:10704444 At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of the protein in the cytoplasm.
GO:0005829 cytosol	TAS Reactome:R-HSA-9603775	ACCEPT	Summary: Reactome annotation for PEX3:PEX19:class I PMP dissociation. PEX19 acts in the cytosol. Reason: Duplicate cytosol annotation from different Reactome reaction. PEX19 is cytosolic, well-established.
GO:0005829 cytosol	TAS Reactome:R-HSA-9603784	ACCEPT	Summary: Reactome annotation for PEX19:class I PMP binding PEX3. PEX19 acts in the cytosol. Reason: Duplicate cytosol annotation from different Reactome reaction. PEX19 is cytosolic.
GO:0005829 cytosol	TAS Reactome:R-HSA-9603804	ACCEPT	Summary: Reactome annotation for PEX19 binding class I PMPs. PEX19 acts in the cytosol. Reason: Duplicate cytosol annotation from different Reactome reaction. PEX19 is cytosolic.
GO:0005829 cytosol	TAS Reactome:R-NUL-9604086	ACCEPT	Summary: Reactome annotation for PEX19:Pex3 binding PEX16. PEX19 acts in the cytosol. Reason: Duplicate cytosol annotation from different Reactome reaction. PEX19 is cytosolic.
GO:0005829 cytosol	TAS Reactome:R-NUL-9604093	ACCEPT	Summary: Reactome annotation for PEX19 binding Pex3. PEX19 acts in the cytosol. Reason: Duplicate cytosol annotation from different Reactome reaction. PEX19 is cytosolic.
GO:0005829 cytosol	TAS Reactome:R-NUL-9604116	ACCEPT	Summary: Reactome annotation for PEX16:PEX19:Pex3 dissociation. PEX19 acts in the cytosol. Reason: Duplicate cytosol annotation from different Reactome reaction. PEX19 is cytosolic.
GO:0006625 protein targeting to peroxisome	IMP PMID:19114594 The peroxisomal membrane protein import receptor Pex3p is di...	ACCEPT	Summary: Matsuzaki & Fujiki (2008) showed PEX19 is essential for targeting PEX3 to peroxisomes. Knockdown of PEX19 inhibits peroxisomal targeting of newly synthesized PEX3. Reason: PEX19 is required for protein targeting to peroxisomes, established by PEX19 knockdown experiments (PMID:19114594). This is a core biological process. Supporting Evidence: PMID:19114594 Knockdown of Pex19p inhibits peroxisomal targeting of newly synthesized full-length Pex3p and results in failure of the peroxisomal localization of Pex3p.
GO:0005515 protein binding	IPI PMID:19114594 The peroxisomal membrane protein import receptor Pex3p is di...	REMOVE	Summary: Matsuzaki & Fujiki (2008) showed PEX19 forms a soluble complex with newly synthesized PEX3 in the cytosol. This is a specific PEX19-PEX3 interaction, part of PMP import. Reason: Generic protein binding uninformative. PEX19-PEX3 interaction is part of the PMP import pathway captured by other terms.
GO:0005777 peroxisome	IDA PMID:19114594 The peroxisomal membrane protein import receptor Pex3p is di...	ACCEPT	Summary: Matsuzaki & Fujiki (2008) showed PEX19 localizes to peroxisomes by immunofluorescence. Reason: PEX19 associates with peroxisomes during PMP delivery. Well-established localization. Supporting Evidence: PMID:19114594 Pex19p forms a soluble complex with newly synthesized Pex3p in the cytosol and directly translocates it to peroxisomes.
GO:0005829 cytosol	IDA PMID:19114594 The peroxisomal membrane protein import receptor Pex3p is di...	ACCEPT	Summary: Matsuzaki & Fujiki (2008) showed PEX19 is cytosolic by subcellular fractionation. Reason: PEX19 is predominantly cytosolic, well-established by this and other studies. Supporting Evidence: PMID:19114594 Pex19p forms a soluble complex with newly synthesized Pex3p in the cytosol
GO:0005515 protein binding	IPI PMID:18782765 Targeting of hFis1 to peroxisomes is mediated by Pex19p.	REMOVE	Summary: Delille & Schrader (2008) showed PEX19 binds hFis1 via co-immunoprecipitation. hFis1 is a tail-anchored membrane protein shared between peroxisomes and mitochondria. Reason: Generic protein binding uninformative. The PEX19-hFis1 interaction reflects PEX19's PMP chaperone function for tail-anchored proteins.
GO:0016559 peroxisome fission	IMP PMID:18782765 Targeting of hFis1 to peroxisomes is mediated by Pex19p.	KEEP AS NON CORE	Summary: Delille & Schrader (2008) showed PEX19 mediates targeting of hFis1 to peroxisomes, and hFis1 regulates peroxisome fission. However, PEX19's role is in delivering hFis1, not directly in fission per se. Reason: PEX19 contributes to peroxisome fission indirectly by delivering the fission factor hFis1 to peroxisomes (PMID:18782765). This is a downstream consequence of PEX19's PMP chaperone function, not a direct role in fission machinery. Supporting Evidence: PMID:18782765 peroxisomal targeting of hFis1 depends on Pex19p, a peroxisomal membrane protein import factor
GO:0005515 protein binding	IPI PMID:18174172 Characterization of the interaction between recombinant huma...	REMOVE	Summary: Sato et al. (2008) characterized PEX3-PEX19 interaction biochemically. Kd of 3.4 nM. Specific structural interaction. Reason: Generic protein binding uninformative. The PEX3-PEX19 docking interaction is well-characterized but better captured by other functional terms.
GO:0032991 protein-containing complex	IDA PMID:18174172 Characterization of the interaction between recombinant huma...	ACCEPT	Summary: Sato et al. (2008) showed PEX3-PEX19 forms a 1:1 complex by gel filtration and tryptophan fluorescence. This is a specific PEX3-PEX19 docking complex. Reason: PEX19 forms a defined 1:1 complex with PEX3 (Kd = 3.4 nM). This is a core interaction for PMP import. The term is somewhat generic but accurately reflects the biochemical finding. Supporting Evidence: PMID:18174172 a one-to-one complex is formed between monomeric Pex3p and monomeric Pex19p
GO:0072663 establishment of protein localization to peroxisome	IMP PMID:18782765 Targeting of hFis1 to peroxisomes is mediated by Pex19p.	ACCEPT	Summary: Delille & Schrader (2008) showed silencing PEX19 reduces targeting of hFis1 to peroxisomes. PEX19 establishes protein localization to peroxisomes. Reason: PEX19 is essential for establishing PMP localization to peroxisomes. This is a core biological process directly supported by PEX19 knockdown experiments. Supporting Evidence: PMID:18782765 Silencing of Pex19p by small interference RNA reduced the targeting of hFis1 to peroxisomes, but not to mitochondria.
GO:0051117 ATPase binding	IPI PMID:11453642 Targeting elements in the amino-terminal part direct the hum...	REMOVE	Summary: Biermanns & Gaertner (2001) studied PMP70 targeting to peroxisomes and actually found that PEX19 does NOT specifically bind to PMP70 targeting elements. The abstract states "peroxin 19 (PEX19) interactions are not required for targeting human PMP70 to peroxisomes. PEX19 does not specifically bind to the targeting elements of human PMP70." Reason: This annotation appears to be an error. PMID:11453642 (Biermanns & Gaertner 2001) explicitly states PEX19 does NOT specifically bind PMP70 targeting elements. PMP70/ABCD3 is an ABC transporter (ATPase), but the cited paper contradicts this annotation. Other papers do show PEX19-ABCD3 interaction (PMID:10704444, PMID:10777694), but the term "ATPase binding" is misleading for PEX19's function. PEX19 binds PMPs via mPTS, not via ATPase domains. Supporting Evidence: PMID:11453642 peroxin 19 (PEX19) interactions are not required for targeting human PMP70 to peroxisomes. PEX19 does not specifically bind to the targeting elements of human PMP70.
GO:0007031 peroxisome organization	IMP PMID:14709540 PEX19 is a predominantly cytosolic chaperone and import rece...	ACCEPT	Summary: Jones et al. (2004) showed PEX19 is essential for peroxisome organization. Loss of PEX19 leads to loss of peroxisomes. Reason: PEX19 is required for peroxisome biogenesis and organization. This is a core biological process. Well-supported experimentally. Supporting Evidence: PMID:14709540 PEX19 binds and stabilizes newly synthesized PMPs in the cytosol, binds to multiple PMP targeting signals (mPTSs), interacts with the hydrophobic domains of PMP targeting signals, and is essential for PMP targeting and import.
GO:0005737 cytoplasm	IDA PMID:14709540 PEX19 is a predominantly cytosolic chaperone and import rece...	ACCEPT	Summary: Jones et al. (2004) showed PEX19 is predominantly cytoplasmic by immunofluorescence and subcellular fractionation. Reason: PEX19 is predominantly cytoplasmic, established by direct assay. Supporting Evidence: PMID:14709540 PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins
GO:0006457 protein folding	IDA PMID:14709540 PEX19 is a predominantly cytosolic chaperone and import rece...	MODIFY	Summary: Jones et al. (2004) showed PEX19 stabilizes newly synthesized PMPs, preventing aggregation. However, PEX19 does not catalyze protein folding in the classical sense; it functions as a chaperone that maintains PMP solubility by shielding hydrophobic transmembrane domains. Reason: PEX19 is a chaperone that prevents PMP aggregation, not a folding catalyst. The protein carrier chaperone activity (GO:0140597) more accurately describes this function. PEX19 shields hydrophobic segments rather than assisting productive folding. Proposed replacements: protein carrier chaperone Supporting Evidence: PMID:14709540 PEX19 binds and stabilizes newly synthesized PMPs in the cytosol PMID:16344115 When PMP70 was translated in the presence of purified Pex19p, a large part of PMP70 existed as soluble form...However, in the absence of Pex19p, PMP70 formed aggregates during translation.
GO:0036105 peroxisome membrane class-1 targeting sequence binding	IDA PMID:14709540 PEX19 is a predominantly cytosolic chaperone and import rece...	MODIFY	Summary: Jones et al. (2004) defined class 1 mPTS as those bound by PEX19 and imported in a PEX19-dependent manner. This is a highly specific and accurate annotation for PEX19's molecular function. Reason: PEX19 specifically recognizes class 1 mPTS, as demonstrated by Jones et al. Before the merge this was the most specific MF term available for PEX19's cargo recognition function. GO:0036105 (peroxisome membrane class-1 targeting sequence 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:14709540 We also demonstrate the existence of two PMP import mechanisms and two classes of mPTSs: class 1 mPTSs, which are bound by PEX19 and imported in a PEX19-dependent manner, and class 2 mPTSs, which are not bound by PEX19 and mediate protein import independently of PEX19
GO:0045046 protein import into peroxisome membrane	IDA PMID:14709540 PEX19 is a predominantly cytosolic chaperone and import rece...	ACCEPT	Summary: Jones et al. (2004) demonstrated PEX19 is essential for PMP import into the peroxisome membrane. Core biological process. Reason: PEX19-dependent PMP import is the protein's primary biological process. Supporting Evidence: PMID:14709540 PEX19 functions as both a chaperone and an import receptor for newly synthesized PMPs
GO:0050821 protein stabilization	IDA PMID:14709540 PEX19 is a predominantly cytosolic chaperone and import rece...	ACCEPT	Summary: Jones et al. (2004) showed PEX19 stabilizes newly synthesized PMPs in the cytosol, preventing their degradation or aggregation. Reason: PEX19 stabilizes PMPs by acting as a chaperone that prevents aggregation and degradation. This is a core function directly demonstrated by the study. Supporting Evidence: PMID:14709540 PEX19 binds and stabilizes newly synthesized PMPs in the cytosol
GO:0005778 peroxisomal membrane	HDA PMID:21525035 PEX14 is required for microtubule-based peroxisome motility ...	ACCEPT	Summary: Bharti et al. (2011) identified PEX19 associated with peroxisomal membrane protein complexes by mass spectrometry. HDA annotation. Reason: PEX19 associates with the peroxisomal membrane, confirmed by mass spec identification in peroxisomal membrane complexes. Supporting Evidence: PMID:21525035 almost all known human peroxins involved in protein import were identified as constituents of the PEX14 complexes
GO:0005515 protein binding	IPI PMID:10777694 Human adrenoleukodystrophy protein and related peroxisomal A...	REMOVE	Summary: Gloeckner et al. (2000) showed PEX19 interacts with ALDP, ALDRP, and PMP70 by Y2H and GST pull-down. These are specific PMP interactions reflecting PEX19's chaperone function for peroxisomal ABC transporters. Reason: Generic protein binding uninformative. The PEX19-ABC transporter interactions reflect PEX19's mPTS binding and chaperone functions captured by other terms.
GO:0005515 protein binding	IPI PMID:19715730 The cytosolic domain of PEX3, a protein involved in the biog...	REMOVE	Summary: Pinto et al. (2009) studied PEX3 cytosolic domain lipid binding. PEX19 was used as a binding partner control. The study is primarily about PEX3, not PEX19. Reason: Generic protein binding uninformative. PEX19-PEX3 interaction is captured by other terms.
GO:1900131 negative regulation of lipid binding	IDA PMID:19715730 The cytosolic domain of PEX3, a protein involved in the biog...	MARK AS OVER ANNOTATED	Summary: Pinto et al. (2009) showed PEX3 cytosolic domain binds membrane lipids, and PEX19 binding to PEX3 may modulate this lipid interaction. However, the paper is primarily about PEX3 lipid binding, and the GO annotation claims PEX19 negatively regulates lipid binding. The evidence for PEX19 specifically negatively regulating lipid binding is indirect. Reason: The annotation that PEX19 negatively regulates lipid binding appears to be based on the observation that PEX19 binding to PEX3 may compete with PEX3's lipid binding. This is an indirect inference from a study primarily about PEX3, not a direct demonstration of PEX19 as a negative regulator of lipid binding. Not a core function of PEX19. Supporting Evidence: PMID:19715730 this domain of PEX3 interacts with amphipathic molecules
GO:0005515 protein binding	IPI PMID:16344115 Role of Pex19p in the targeting of PMP70 to peroxisome.	REMOVE	Summary: Kashiwayama et al. (2005) showed PEX19 binds PMP70, keeping it soluble during translation. Specific chaperone interaction better captured by protein carrier activity. Reason: Generic protein binding uninformative. PEX19-PMP70 interaction is part of PEX19's chaperone function captured by GO:0140597.
GO:0006625 protein targeting to peroxisome	IDA PMID:16344115 Role of Pex19p in the targeting of PMP70 to peroxisome.	ACCEPT	Summary: Kashiwayama et al. (2005) showed PEX19 keeps PMP70 in proper conformation for peroxisomal localization. Deletion of PEX19 binding sites on PMP70 abolished peroxisomal targeting. Reason: PEX19 is essential for targeting PMPs including PMP70 to peroxisomes. Core function. Supporting Evidence: PMID:16344115 Pex19p binds to PMP70 co-translationally and keeps PMP70 as a proper conformation for the localization to peroxisome
GO:0005515 protein binding	IPI PMID:16763195 Targeting of the tail-anchored peroxisomal membrane proteins...	REMOVE	Summary: Halbach et al. (2006) showed PEX19 binds PEX26 at C-terminal sites including the TMD and luminal domain. Specific tail-anchored PMP interaction. Reason: Generic protein binding uninformative. The PEX19-PEX26 interaction reflects tail-anchored PMP recognition captured by mPTS binding terms.
GO:0006625 protein targeting to peroxisome	IDA PMID:16763195 Targeting of the tail-anchored peroxisomal membrane proteins...	ACCEPT	Summary: Halbach et al. (2006) showed PEX19 is essential for PEX26 import into the peroxisomal membrane. C-terminal PEX19-binding sites mark tail-anchored proteins for peroxisomal delivery. Reason: PEX19 is essential for targeting tail-anchored PMPs (PEX26) to peroxisomes. Core function. Supporting Evidence: PMID:16763195 C-terminal PEX19-binding sites mark tail-anchored proteins for delivery to peroxisomes
GO:0050821 protein stabilization	IDA PMID:16344115 Role of Pex19p in the targeting of PMP70 to peroxisome.	ACCEPT	Summary: Kashiwayama et al. (2005) showed PEX19 prevents PMP70 aggregation during translation, keeping it soluble. Direct chaperone-mediated stabilization. Reason: PEX19 stabilizes PMPs by preventing aggregation. Directly demonstrated for PMP70. Supporting Evidence: PMID:16344115 When PMP70 was translated in the presence of purified Pex19p, a large part of PMP70 existed as soluble form...However, in the absence of Pex19p, PMP70 formed aggregates during translation.
GO:0005515 protein binding	IPI PMID:11590176 Two different targeting signals direct human peroxisomal mem...	REMOVE	Summary: Brosius et al. (2002) showed both targeting regions of human PMP22 interact with PEX19. Specific PMP interaction reflecting PEX19's chaperone function. Reason: Generic protein binding uninformative. PEX19-PMP22 interaction is part of PEX19's PMP chaperone function captured by mPTS binding and protein carrier activity terms.
GO:0045046 protein import into peroxisome membrane	IDA PMID:11402059 Multiple distinct targeting signals in integral peroxisomal ...	ACCEPT	Summary: Jones et al. (2001) demonstrated PEX19 interacts with PMP targeting regions, supporting its role in PMP import into the peroxisome membrane. Reason: PEX19-mediated PMP import into peroxisome membrane is a core biological process. Supporting Evidence: PMID:11402059 PEX19, a factor required for peroxisomal membrane biogenesis, interacts with the two minimal targeting regions of PMP34
GO:0031526 brush border membrane	ISS GO_REF:0000024	REMOVE	Summary: ISS annotation from manual transfer of orthologue data. PEX19 localization to brush border membrane is not supported by any literature on PEX19. PEX19 is a cytosolic/peroxisomal protein with no known role in brush border. This appears to be an erroneous orthologue transfer. Reason: There is no evidence that PEX19 localizes to the brush border membrane. PEX19 is a predominantly cytosolic protein that transiently associates with peroxisomal membranes. Brush border localization is not consistent with known PEX19 biology and likely represents an erroneous orthologue-based transfer.
GO:0005778 peroxisomal membrane	IDA PMID:9339377 Genomic organization and molecular characterization of a gen...	ACCEPT	Summary: Kammerer et al. (1997) showed PEX19 (HsPXF) has peroxisomal localization and is farnesylated at C-terminal CaaX motif. Reason: PEX19 localizes to peroxisomal membrane. Early characterization study establishing this localization. Supporting Evidence: PMID:9339377 For the HsPXF protein, a carboxyterminal farnesylation at cysteine residues was demonstrated. Through the use of HsPXF-specific antibodies, the protein was shown to be attached to the outer surface of peroxisomes.
GO:0007031 peroxisome organization	NAS PMID:9339377 Genomic organization and molecular characterization of a gen...	ACCEPT	Summary: NAS (non-traceable author statement) annotation based on Kammerer et al. (1997). The paper describes PEX19 genomic organization but does not directly demonstrate a role in peroxisome organization. However, PEX19's role in peroxisome organization is well-established by other studies. Reason: While the specific reference is NAS, PEX19's role in peroxisome organization is well-established by multiple subsequent studies (PMID:10704444, PMID:14709540).
GO:0005737 cytoplasm	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation from orthologue transfer. PEX19 is predominantly cytoplasmic, well-established experimentally. Reason: PEX19 is predominantly cytoplasmic, consistent with direct experimental evidence.
GO:0005777 peroxisome	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation from orthologue transfer. PEX19 associates with peroxisomes. Reason: PEX19 associates with peroxisomes, consistent with direct experimental evidence.
GO:0006625 protein targeting to peroxisome	IMP PMID:10704444 PEX19 binds multiple peroxisomal membrane proteins, is predo...	ACCEPT	Summary: Sacksteder et al. (2000) showed mislocalization of PEX19 to the nucleus leads to nuclear accumulation of newly synthesized PMPs, and loss of PEX19 results in PMP degradation/mislocalization to mitochondria. Reason: PEX19 is essential for protein targeting to peroxisomes. Loss of PEX19 causes PMP mislocalization, demonstrating its requirement for targeting. Supporting Evidence: PMID:10704444 mislocalization of PEX19 to the nucleus leads to nuclear accumulation of newly synthesized PMPs PMID:10704444 the loss of PEX19 results in degradation of PMPs and/or mislocalization of PMPs to the mitochondrion
GO:0005654 nucleoplasm	IDA GO_REF:0000052	NEW	Summary: HPA-based IDA annotation for nucleoplasm localization. PEX19 is predominantly cytosolic and not known to have a nuclear function. However, some studies show that when PEX19 is mislocalized to the nucleus it can accumulate there with PMPs (PMID:10704444). Also, PEX19 has been reported to interact with CDKN2A/p19ARF and exclude it from the nucleus (PMID:11259404). Low-level nuclear detection by HPA is possible but not a core localization. Reason: HPA-based annotation for nucleoplasm localization. PEX19 is predominantly cytosolic and not known to have a nuclear function. Low-level nuclear detection by HPA is possible but not a core localization. This annotation from UniProt is not in GOA.
GO:0005634 nucleus	IMP GO_REF:0000052	NEW	Summary: Nuclear localization from immunofluorescence curation. PEX19 was shown to accumulate in the nucleus when an NLS is appended (PMID:10704444), and it has a reported role in excluding CDKN2A from the nucleus (PMID:11259404). However, nuclear localization is not a core property of PEX19. Reason: PEX19 is not normally a nuclear protein. Nuclear presence may relate to non-canonical CDKN2A interaction (PMID:11259404). This annotation from UniProt is not in GOA.
GO:0016557 peroxisome membrane biogenesis	IDA GO_REF:0000052	NEW	Summary: PEX19 is essential for peroxisome membrane biogenesis. Loss of PEX19 abolishes peroxisome membrane formation. This is a core biological process. Reason: PEX19 is required for peroxisome membrane biogenesis, one of only three peroxins (PEX3, PEX16, PEX19) whose loss abolishes peroxisomal membrane structures. This annotation from UniProt is not in GOA but is well-supported. Supporting Evidence: PMID:10704444 the loss of PEX19 results in degradation of PMPs and/or mislocalization of PMPs to the mitochondrion PMID:14709540 PEX19 functions as both a chaperone and an import receptor for newly synthesized PMPs

Gene Description

Existing Annotations Review

Core Functions

PEX19 recognizes class 1 membrane peroxisomal targeting signals (mPTS) on PMPs via its C-terminal alpha-helical domain, enabling specific cargo selection for PEX3-dependent import into the peroxisomal membrane.

References

Deep Research

Falcon

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