PEX3

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005778 peroxisomal membrane	IBA GO_REF:0000033	ACCEPT	Summary: PEX3 is a well-established integral peroxisomal membrane protein. IBA annotation is phylogenetically supported and consistent with extensive experimental evidence from multiple species. PEX3 has two transmembrane domains and localizes to the peroxisomal membrane in human cells (PMID:10430017, PMID:9657383). Reason: Core localization of PEX3. Peroxisomal membrane localization is confirmed by immunofluorescence in multiple studies and by UniProt topology annotation showing transmembrane helices at residues 16-36 and 117-140. Supporting Evidence: PMID:10430017 H sPEX3 is an integral peroxisomal membrane protein with the N-terminus inside the peroxisome and the C-terminus facing the cytoplasm PMID:9657383 human Pex3p is localized at the peroxisome
GO:0030674 protein-macromolecule adaptor activity	IBA GO_REF:0000033	ACCEPT	Summary: PEX3 functions as a membrane-anchored docking/adaptor for PEX19, bridging the cytosolic PEX19-PMP cargo complex to the peroxisomal membrane. This adaptor activity is well supported by structural (PMID:21102411) and functional (PMID:15007061) studies. The IBA annotation captures the molecular function at an appropriate level of specificity. Reason: PEX3 serves as a docking receptor/adaptor for PEX19 at the peroxisomal membrane, enabling PMP insertion. This is the core molecular function of PEX3. The term protein-macromolecule adaptor activity is appropriate as PEX3 bridges PEX19-cargo complexes to the membrane. Supporting Evidence: PMID:15007061 PEX3 is required for PEX19 to dock at peroxisomes, interacts specifically with the docking domain of PEX19, and is required for recruitment of the PEX19 docking domain to peroxisomes PMID:21102411 The interaction between Pex3p, which resides on the peroxisomal membrane, and Pex19p, which resides in the cytosol, is crucial for peroxisome formation and the post-translational targeting of peroxisomal membrane proteins
GO:0045046 protein import into peroxisome membrane	IBA GO_REF:0000033	ACCEPT	Summary: PEX3 is essential for the import of class I peroxisomal membrane proteins. Transient depletion of PEX3 specifically abrogates class I PMP import without affecting class II PMP import or matrix protein import (PMID:15007061). IBA annotation is phylogenetically well-supported and captures the core biological process. Reason: This is the central biological process function of PEX3. Fang et al. (2004) demonstrated that PEX3 depletion by RNAi specifically blocks class I PMP import, establishing PEX3 as essential for this process. Supporting Evidence: PMID:15007061 transient inhibition of PEX3 abrogates class I PMP import but has no effect on class II PMP import or peroxisomal matrix protein import
GO:0005778 peroxisomal membrane	IEA GO_REF:0000120	ACCEPT	Summary: Automated annotation of PEX3 to peroxisomal membrane. Consistent with the IBA and IDA annotations for the same term and well supported experimentally. Reason: Redundant with IBA and IDA annotations but correctly reflects the established localization. IEA annotations at this level are acceptable when confirmed by other evidence. Supporting Evidence: PMID:10430017 H sPEX3 is an integral peroxisomal membrane protein with the N-terminus inside the peroxisome and the C-terminus facing the cytoplasm
GO:0007031 peroxisome organization	IEA GO_REF:0000120	ACCEPT	Summary: Automated annotation of PEX3 to peroxisome organization. PEX3 is essential for peroxisome membrane biogenesis and thus for overall peroxisome organization. This is consistent with IMP annotations from multiple publications. Reason: Peroxisome organization is a parent term that encompasses peroxisome biogenesis. PEX3 is essential for peroxisome membrane assembly and cells lacking PEX3 have no detectable peroxisomes. The IEA is consistent with experimental evidence. Supporting Evidence: PMID:10958759 Expression of wild-type PEX3 in the mutant cell lines restored peroxisomal biogenesis, whereas transfection of mutated PEX3 cDNA did not
GO:0005515 protein binding	IPI PMID:10704444 PEX19 binds multiple peroxisomal membrane proteins, is predo...	MODIFY	Summary: Sacksteder et al. (2000) demonstrated that PEX19 binds multiple PMPs including PEX3, using two-hybrid and blot overlay assays. The interaction with PEX19 is the core molecular function of PEX3. However, 'protein binding' is too generic -- the IBA annotation for protein-macromolecule adaptor activity better captures this function. Reason: The PEX3-PEX19 interaction is real and well-documented, but 'protein binding' is uninformative. The more specific term 'protein-macromolecule adaptor activity' (GO:0030674) already captures this function. This annotation should be replaced with the more informative term. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:10704444 PEX19 binds a broad spectrum of PMPs, displays saturable PMP binding, and interacts with regions of PMPs required for their targeting to peroxisomes
GO:0005515 protein binding	IPI PMID:12096124 Analysis of mammalian peroxin interactions using a non-trans...	MODIFY	Summary: Fransen et al. (2002) used a bacterial two-hybrid system to analyze interactions among mammalian peroxins and confirmed PEX3-PEX19 interaction. This is a focused peroxin interaction study, not a generic high-throughput screen. The interaction is specific and well-characterized. Reason: The PEX3-PEX19 interaction documented here reflects PEX3's adaptor/docking function. 'Protein binding' is uninformative; this should be replaced with the more specific adaptor activity term. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:12096124 we report a detailed interaction map of these peroxins
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	MARK AS OVER ANNOTATED	Summary: Rual et al. (2005) is a large-scale proteome-wide yeast two-hybrid screen. While PEX3 interactions detected here may include PEX19, this is a high-throughput study and the generic 'protein binding' term provides no functional insight. Reason: High-throughput interactome screen. 'Protein binding' from a proteome-scale Y2H screen provides no specific functional information about PEX3. The meaningful interactions (PEX19, PEX16) are already captured by more specific annotations. Supporting Evidence: PMID:16189514 Towards a proteome-scale map of the human protein-protein interaction network
GO:0005515 protein binding	IPI PMID:16280322 In vitro transport of membrane proteins to peroxisomes by sh...	MODIFY	Summary: Matsuzono and Fujiki (2006) developed an in vitro cell-free PMP transport system and showed that PEX19 complexes with PMPs bind to PEX3 in vitro, and that PEX19 translocates PMPs to peroxisomes in a PEX3-dependent manner. This is a focused mechanistic study of the PEX3-PEX19 docking interaction. Reason: This study specifically demonstrates the PEX3-PEX19 docking interaction in the context of PMP transport. 'Protein binding' should be replaced with the more informative adaptor activity term. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: 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:0005515 protein binding	IPI PMID:21102411 Structural basis for docking of peroxisomal membrane protein...	MODIFY	Summary: Sato et al. (2010) solved the crystal structure of the PEX3-PEX19 complex (2.50 A), revealing the structural basis of the docking interaction. The PEX19 peptide forms an alpha-helix at the apex of the PEX3 spheroid. This is a definitive structural characterization of the core PEX3 function. Reason: This landmark structural study defines the PEX3-PEX19 docking interface at atomic resolution. 'Protein binding' does not capture the specificity of this interaction. The adaptor activity term is more appropriate. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:21102411 we present the three-dimensional structure of the complex between a cytosolic domain of Pex3p and the binding-region peptide of Pex19p
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Rolland et al. (2014) is a proteome-scale interactome mapping study. Generic high-throughput protein binding annotation for PEX3 is uninformative. Reason: High-throughput interactome screen. 'Protein binding' from this study does not add specific functional information about PEX3 beyond what is already captured by more informative terms. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network
GO:0005515 protein binding	IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam...	MARK AS OVER ANNOTATED	Summary: Wei et al. (2014) is a massively parallel pipeline for cloning DNA variants and examining molecular phenotypes. High-throughput study providing generic protein binding annotation. Reason: High-throughput methodology study. 'Protein binding' annotation from this pipeline is uninformative for PEX3 functional annotation. Supporting Evidence: PMID:25502805 A massively parallel pipeline to clone DNA variants and examine molecular phenotypes of human disease mutations
GO:0005515 protein binding	IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi...	MARK AS OVER ANNOTATED	Summary: Yachie et al. (2016) used Barcode Fusion Genetics for pooled-matrix protein interaction screens. High-throughput interaction data providing generic protein binding. Reason: High-throughput interactome screen. Generic 'protein binding' is uninformative for PEX3. Supporting Evidence: PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusion Genetics
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Huttlin et al. (2017) is a large-scale interactome mapping study defining protein communities and disease networks. High-throughput data. Reason: High-throughput interactome mapping. Generic 'protein binding' adds no specific insight into PEX3 function. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks
GO:0005515 protein binding	IPI PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid tec...	MARK AS OVER ANNOTATED	Summary: Wehr et al. (2019) developed LuTHy, a bioluminescence-based two-hybrid technology for mapping protein-protein interactions. Methodological study providing generic protein binding data. Reason: Method-development/high-throughput study. 'Protein binding' is uninformative for PEX3 function. Supporting Evidence: PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative mapping of protein-protein interactions in mammalian cells
GO:0005515 protein binding	IPI PMID:31467278 Maximizing binary interactome mapping with a minimal number ...	MARK AS OVER ANNOTATED	Summary: Choi et al. (2019) is a study on maximizing binary interactome mapping efficiency. High-throughput methodology study. Reason: High-throughput interactome methodology study. 'Protein binding' is uninformative. Supporting Evidence: PMID:31467278 Maximizing binary interactome mapping with a minimal number of assays
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: Sahni et al. (2019) studied disruption of protein interactions by genetic variants. High-throughput interactome study. Reason: High-throughput variant-interaction study. 'Protein binding' is uninformative for PEX3. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Luck et al. (2020) is a reference map of the human binary protein interactome. Large-scale high-throughput study. Reason: High-throughput interactome reference map. 'Protein binding' is uninformative for PEX3. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Haenig et al. (2020) studied interactome mapping of neurodegenerative disease proteins. High-throughput interaction study. Reason: High-throughput interactome mapping. 'Protein binding' is uninformative for PEX3. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Huttlin et al. (2021) mapped dual proteome-scale networks revealing cell-specific remodeling. High-throughput interactome study. Reason: High-throughput interactome mapping. 'Protein binding' is uninformative for PEX3. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	MARK AS OVER ANNOTATED	Summary: Cho et al. (2022) is the OpenCell project using endogenous tagging for cellular organization cartography. High-throughput proteomics/imaging study. Reason: High-throughput cellular organization mapping. 'Protein binding' is uninformative for PEX3. Supporting Evidence: PMID:35271311 OpenCell: Endogenous tagging for the cartography of human cellular organization
GO:0005515 protein binding	IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc...	MARK AS OVER ANNOTATED	Summary: Duran-Frigola et al. (2023) used AI-guided pipeline for PPI drug discovery, focusing on SARS-CoV-2. High-throughput/computational study. Reason: AI-guided drug discovery pipeline. 'Protein binding' is uninformative for PEX3 function. Supporting Evidence: PMID:37398436 AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor
GO:0005515 protein binding	IPI PMID:38225382 Systematic discovery of protein interaction interfaces using...	MARK AS OVER ANNOTATED	Summary: Humphreys et al. (2024) used AlphaFold for systematic discovery of protein interaction interfaces. Computational/high-throughput study. Reason: Computational high-throughput interaction interface study. 'Protein binding' is uninformative. Supporting Evidence: PMID:38225382 Systematic discovery of protein interaction interfaces using AlphaFold and experimental validation
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: Huttlin et al. (2025) is a multimodal cell maps study for structural and functional genomics. High-throughput study. Reason: High-throughput multimodal cellular mapping. 'Protein binding' is uninformative for PEX3. Supporting Evidence: PMID:40205054 Multimodal cell maps as a foundation for structural and functional genomics
GO:0005777 peroxisome	IDA GO_REF:0000052	ACCEPT	Summary: PEX3 localization to peroxisomes confirmed by immunofluorescence-based curation (GO_REF:0000052). This is consistent with extensive literature showing PEX3 at the peroxisomal membrane. However, the more specific term 'peroxisomal membrane' (GO:0005778) is also annotated and is more informative. Reason: Correct localization, albeit less specific than peroxisomal membrane. Peroxisome is a valid parent localization term and the IDA evidence from immunofluorescence curation is appropriate. Supporting Evidence: PMID:10430017 H sPEX3 is an integral peroxisomal membrane protein with the N-terminus inside the peroxisome and the C-terminus facing the cytoplasm
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	ACCEPT	Summary: Ghosh et al. (2010) defined the membrane proteome of NK cells by mass spectrometry and detected PEX3 in the membrane fraction. The term 'membrane' is extremely generic for an established integral peroxisomal membrane protein. Reason: While very generic, this HDA annotation from a proteomics study is not incorrect -- PEX3 is indeed an integral membrane protein. More specific peroxisomal membrane annotations exist. This is acceptable as a broad localization annotation from high-throughput data. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells
GO:0005515 protein binding	IPI PMID:18174172 Characterization of the interaction between recombinant huma...	MODIFY	Summary: Sato et al. (2008) characterized the PEX3-PEX19 interaction in detail using recombinant proteins, determining a KD of 3.4 nM and identifying Trp-104 as a critical binding residue. This is a focused mechanistic study of the core PEX3-PEX19 docking interaction. Reason: This study specifically characterizes the PEX3-PEX19 docking interaction at the biochemical level. 'Protein binding' should be replaced with the more informative adaptor activity term. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:18174172 the wild-type and the W104A and W104F mutants showed K(D) values of 3.4 nm, 1080 nm, and 66.2 nm, respectively
GO:0007031 peroxisome organization	IMP PMID:18174172 Characterization of the interaction between recombinant huma...	ACCEPT	Summary: Sato et al. (2008) showed that PEX3 Trp-104 mutations that disrupted PEX19 binding also impaired peroxisome restoring activity in pex3-deficient cells, demonstrating that the PEX3-PEX19 interaction is required for peroxisome organization. Reason: IMP evidence from mutational analysis showing that disrupting the PEX3-PEX19 interface impairs peroxisome biogenesis. This directly supports PEX3's role in peroxisome organization. Supporting Evidence: PMID:18174172 The affinity differences with mutation affected their peroxisome restoring activities in pex3 ZPG208 cells
GO:0005783 endoplasmic reticulum	IDA PMID:21768384 Sec16B is involved in the endoplasmic reticulum export of th...	KEEP AS NON CORE	Summary: Yonekawa et al. (2011) showed that when Sec16B is overexpressed, PEX3 and PEX16 are redistributed from peroxisomes to ER membranes, and that Sec16B knockdown suppresses PEX3 expression. This indicates PEX3 transits through the ER during peroxisome biogenesis. Reason: PEX3 transits through the ER during de novo peroxisome biogenesis, but the ER is not its primary steady-state location. The peroxisomal membrane is the core localization. ER localization represents a transient intermediate in the biogenesis pathway. Supporting Evidence: PMID:21768384 Concomitant with the overexpression of Sec16B, peroxisomal membrane biogenesis factors peroxin 3 (Pex3) and Pex16 were redistributed from peroxisomes to Sec16B-positive ER membranes
GO:0032991 protein-containing complex	IDA PMID:18174172 Characterization of the interaction between recombinant huma...	MARK AS OVER ANNOTATED	Summary: Sato et al. (2008) demonstrated that PEX3 and PEX19 form a 1:1 monomeric complex by gel filtration chromatography. PEX3 exists in a complex with PEX19. However, 'protein-containing complex' is extremely generic and uninformative. Reason: While PEX3 does form a complex with PEX19, the term 'protein-containing complex' is too generic to be informative. The complex formation is better captured by the adaptor activity and peroxisome organization annotations. Supporting Evidence: PMID:18174172 Gel filtration chromatography analyses and intrinsic tryptophan fluorescence titrations revealed that a one-to-one complex is formed between monomeric Pex3p and monomeric Pex19p
GO:0005778 peroxisomal membrane	HDA PMID:21525035 PEX14 is required for microtubule-based peroxisome motility ...	ACCEPT	Summary: Bharti et al. (2011) isolated native peroxisomal membrane protein complexes from human cells using PEX14 as bait and identified PEX3 as a constituent of peroxisomal membrane complexes by mass spectrometry. This confirms PEX3 peroxisomal membrane localization via proteomics. Reason: HDA evidence from native peroxisomal membrane complex isolation confirms PEX3 at the peroxisomal membrane, consistent with all other localization data. Supporting Evidence: PMID:21525035 almost all known human peroxins involved in protein import were identified as constituents of the PEX14 complexes
GO:0007031 peroxisome organization	IMP PMID:19479899 Pex3p-dependent peroxisomal biogenesis initiates in the endo...	ACCEPT	Summary: Toro et al. (2009) showed that Pex3p-GFP expressed in PEX3-deficient ZS cells (MR cell line) localizes first to the ER and then to newly formed peroxisomes, demonstrating PEX3 drives de novo peroxisome biogenesis from the ER. Reason: IMP evidence showing PEX3 expression restores peroxisome formation in PEX3-deficient Zellweger cells, directly demonstrating PEX3's essential role in peroxisome organization. Supporting Evidence: PMID:19479899 Pex3p-GFP expressed in a new ZS cell line (MR), which lacks peroxisomes due to a mutation in the PEX3 gene, localizes first in the ER and subsequently in newly formed peroxisomes
GO:0005783 endoplasmic reticulum	IDA PMID:19479899 Pex3p-dependent peroxisomal biogenesis initiates in the endo...	KEEP AS NON CORE	Summary: Toro et al. (2009) demonstrated by fluorescence microscopy that Pex3p-GFP localizes to the ER before redistributing to newly formed peroxisomes. An artificial N-glycosylation site confirmed ER targeting. This is the first demonstration of PEX3 ER transit in mammalian cells. Reason: PEX3 transits through the ER during de novo peroxisome biogenesis, as directly observed by Toro et al. However, the ER is a transient intermediate, not the primary steady-state localization. Supporting Evidence: PMID:19479899 Pex3p bearing an artificial N-glycosylation site shows an electrophoretic shift indicative of ER targeting while en route to preformed peroxisomes in normal fibroblast
GO:0032994 protein-lipid complex	IDA PMID:19715730 The cytosolic domain of PEX3, a protein involved in the biog...	UNDECIDED	Summary: Pinto et al. (2009) showed that recombinant PEX3 cytosolic domain interacts with liposomes causing their flocculation or partial solubilization. This suggests a protein-lipid complex formation. However, this is an in vitro observation with recombinant protein and its physiological relevance is uncertain. Reason: The lipid interaction was observed in vitro with recombinant protein. While potentially relevant to PEX3's membrane insertion function, the physiological significance of a PEX3-lipid complex is not established. The study itself notes that the implications need further investigation. Supporting Evidence: PMID:19715730 this recombinant protein actually precipitates when incubated with mild detergents, suggesting that this domain of PEX3 interacts with amphipathic molecules
GO:0005515 protein binding	IPI PMID:19715730 The cytosolic domain of PEX3, a protein involved in the biog...	MARK AS OVER ANNOTATED	Summary: Pinto et al. (2009) is primarily about PEX3 lipid binding, not protein-protein interactions. Any protein binding observation in this context is secondary and the generic term is uninformative. Reason: This paper focuses on PEX3 lipid binding. 'Protein binding' annotation from this study is tangential and uninformative. Supporting Evidence: PMID:19715730 The cytosolic domain of PEX3, a protein involved in the biogenesis of peroxisomes, binds membrane lipids
GO:0008289 lipid binding	IDA PMID:19715730 The cytosolic domain of PEX3, a protein involved in the biog...	KEEP AS NON CORE	Summary: Pinto et al. (2009) demonstrated that recombinant PEX3 cytosolic domain binds liposomes strongly, causing flocculation or partial solubilization. This is an in vitro finding. Lipid binding may relate to PEX3's role in membrane insertion of PMPs but the physiological relevance is not firmly established. Reason: The lipid binding activity was demonstrated in vitro and may reflect PEX3's membrane-associated function. However, lipid binding is not the primary characterized function of PEX3 (which is PEX19 docking/adaptor activity). This is a potential secondary activity. Supporting Evidence: PMID:19715730 we tested this recombinant protein in lipid-binding assays and found that it interacts strongly with liposomes inducing their flocculation or even partial solubilization
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-382613	ACCEPT	Summary: Reactome pathway annotation for PEX3 involvement in docking of ABCD1/D2/D3 (ABC transporters) to the peroxisomal membrane via PEX19. This is consistent with PEX3's role as the membrane docking factor for the PEX19-PMP import pathway. Reason: Reactome correctly places PEX3 at the peroxisomal membrane in the context of ABC transporter PMP import. This is well supported by the established PEX3-PEX19 docking model. Supporting Evidence: PMID:15007061 PEX3 is required for PEX19 to dock at peroxisomes
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9603775	ACCEPT	Summary: Reactome pathway annotation for PEX3:PEX19:class I PMP complex dissociation at the peroxisomal membrane. This correctly places PEX3 at the peroxisomal membrane during PMP release. Reason: Reactome correctly represents PEX3 at the peroxisomal membrane during the PMP insertion cycle. Supporting Evidence: PMID:15007061 PEX3 is also sufficient to dock PEX19 at heterologous organelles
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9603784	ACCEPT	Summary: Reactome pathway annotation for PEX19:class I PMP binding to PEX3 at the peroxisomal membrane. This correctly represents the docking step. Reason: Reactome correctly represents PEX3 at the peroxisomal membrane during PEX19:PMP docking. Supporting Evidence: PMID:15007061 PEX3 is required for PEX19 to dock at peroxisomes, interacts specifically with the docking domain of PEX19
GO:0005778 peroxisomal membrane	IDA PMID:10430017 Identification and characterization of the human peroxin PEX...	ACCEPT	Summary: Soukupova et al. (1999) identified and characterized human PEX3 as an integral peroxisomal membrane protein using N- and C-terminal tags and immunofluorescence microscopy. The N-terminus is inside the peroxisome and the C-terminus faces the cytoplasm. Reason: Primary experimental evidence for PEX3 peroxisomal membrane localization by immunofluorescence. This is one of the foundational characterization studies of human PEX3. Supporting Evidence: PMID:10430017 H sPEX3 is an integral peroxisomal membrane protein with the N-terminus inside the peroxisome and the C-terminus facing the cytoplasm
GO:0005778 peroxisomal membrane	IDA PMID:9657383 Cloning and characterization of the gene encoding the human ...	ACCEPT	Summary: Kammerer et al. (1998) cloned human PEX3 and showed by transfection of epitope-tagged constructs and immunofluorescence that PEX3 is localized at the peroxisome. The N-terminal 40 amino acids were sufficient for peroxisomal targeting. Reason: Original cloning and characterization of human PEX3 confirming peroxisomal localization. One of the first studies establishing PEX3 at the peroxisomal membrane. Supporting Evidence: PMID:9657383 human Pex3p is localized at the peroxisome. The N-terminal 40 amino acids were revealed to be sufficient to target a GFP reporter protein to the peroxisome
GO:0007031 peroxisome organization	IMP PMID:10958759 Defective peroxisome membrane synthesis due to mutations in ...	ACCEPT	Summary: Muntau et al. (2000) demonstrated that homozygous PEX3 mutations in two Zellweger syndrome patients (complementation group G) cause complete loss of peroxisomal membrane structures. Expression of wild-type PEX3 restored peroxisomal biogenesis, confirming PEX3 is required for peroxisome organization. Reason: Definitive human genetic and complementation evidence that PEX3 is essential for peroxisome organization. Loss of PEX3 causes absence of detectable peroxisomes; re-expression restores them. Supporting Evidence: PMID:10958759 Two patients assigned to complementation group G who had not been linked previously to a specific gene defect were confirmed as displaying a cellular phenotype characterized by a lack of even residual peroxisomal membrane structures PMID:10958759 Expression of wild-type PEX3 in the mutant cell lines restored peroxisomal biogenesis, whereas transfection of mutated PEX3 cDNA did not
GO:0045046 protein import into peroxisome membrane	IMP PMID:15007061 PEX3 functions as a PEX19 docking factor in the import of cl...	ACCEPT	Summary: Fang et al. (2004) demonstrated using PEX3 RNAi in human fibroblasts that PEX3 depletion specifically abrogates class I PMP import without affecting class II PMP import or matrix protein import. PEX3 is both necessary and sufficient for PEX19 docking at peroxisomes. Reason: This is the key study establishing PEX3 as the PEX19 docking factor essential for class I PMP import. The IMP evidence from RNAi knockdown is strong and specific. Supporting Evidence: PMID:15007061 transient inhibition of PEX3 abrogates class I PMP import but has no effect on class II PMP import or peroxisomal matrix protein import PMID:15007061 PEX3 is required for PEX19 to dock at peroxisomes, interacts specifically with the docking domain of PEX19, and is required for recruitment of the PEX19 docking domain to peroxisomes. PEX3 is also sufficient to dock PEX19 at heterologous organelles
GO:0005777 peroxisome	IMP PMID:12924628 The interaction between human PEX3 and PEX19 characterized b...	ACCEPT	Summary: Muntau et al. (2003) used FRET analysis to visualize the PEX3-PEX19 interaction in living cells and confirmed the peroxisome as the main intracellular site of this interaction. PEX3 expression in PEX3-deficient cells restored import-competent peroxisomes. Reason: FRET analysis directly demonstrates PEX3 localization to peroxisomes and shows the PEX3-PEX19 interaction occurs primarily at peroxisomes. Consistent with all other localization data. Supporting Evidence: PMID:12924628 the peroxisome was identified to be the main intracellular site of the PEX3-PEX19 interaction
GO:0007031 peroxisome organization	IMP PMID:12924628 The interaction between human PEX3 and PEX19 characterized b...	ACCEPT	Summary: Muntau et al. (2003) showed that transfection of tagged PEX3 into PEX3-deficient human fibroblasts from Zellweger patients led to reformation of import-competent peroxisomes, providing IMP evidence for PEX3's role in peroxisome organization. Reason: Complementation of PEX3-deficient cells restoring peroxisome biogenesis is direct IMP evidence for PEX3's role in peroxisome organization. Supporting Evidence: PMID:12924628 Functionality of the fusion proteins was shown by transfection of human PEX3- and PEX19-deficient fibroblasts from Zellweger patients with tagged versions of PEX3 and PEX19. This led to reformation of import-competent peroxisomes in both cell lines previously lacking detectable peroxisomal membrane structures
GO:0005515 protein binding	IPI PMID:11883941 Two splice variants of human PEX19 exhibit distinct function...	MODIFY	Summary: Mayerhofer et al. (2002) studied two PEX19 splice variants and showed both interact with full-length PEX3 by in vitro protein interaction studies. This is a focused peroxin interaction study, not a generic high-throughput screen. Reason: The PEX19-PEX3 interaction documented here reflects PEX3's adaptor/docking function. 'Protein binding' should be replaced with the more informative adaptor activity term. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:11883941 Both interact with peroxisomal ABC transporters (ALDP, ALDRP, PMP70) and with full-length PEX3 as shown by in vitro protein interaction studies
GO:0005777 peroxisome	IDA PMID:9922452 Peroxisome synthesis in the absence of preexisting peroxisom...	ACCEPT	Summary: South and Gould (1999) studied peroxisome synthesis in the absence of preexisting peroxisomes in PEX16-deficient cells. While this study primarily focuses on PEX16, PEX3 is contextualized as one of the few peroxins required for peroxisome membrane synthesis. The IDA for PEX3 peroxisome localization from this study may be indirect. Reason: PEX3 is mentioned as a peroxisomal protein in this study. The localization is well established from other sources, and this annotation is consistent with the overall body of evidence. Supporting Evidence: PMID:9922452 other human PMPs, including PEX3myc (Kammerer et al., 1998), PEX10myc (Warren et al., 1998)

Gene Description

Existing Annotations Review

References

Deep Research

Falcon

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