{"gene":"PEX19","run_date":"2026-06-10T05:19:53","timeline":{"discoveries":[{"year":2000,"finding":"PEX19 binds a broad spectrum of peroxisomal membrane proteins (PMPs), displays saturable PMP binding, interacts with regions of PMPs required for their targeting to peroxisomes, and is bimodally distributed between the cytoplasm (predominantly) and peroxisome membrane. Mislocalization of PEX19 to the nucleus causes nuclear accumulation of newly synthesized PMPs; loss of PEX19 results in degradation and/or mislocalization of PMPs to the mitochondrion.","method":"Co-immunoprecipitation, subcellular fractionation, immunofluorescence, nuclear mislocalization experiments, PEX19-deficient cell complementation","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP, fractionation, mislocalization assay, loss-of-function), foundational paper replicated by subsequent studies","pmids":["10704444"],"is_preprint":false},{"year":2004,"finding":"PEX19 functions as both a cytosolic chaperone and an import receptor for class 1 PMPs: it binds and stabilizes newly synthesized PMPs in the cytosol, binds multiple PMP targeting signals (mPTSs) via their hydrophobic domains, and is essential for their targeting and import. A second PMP import class (class 2) is PEX19-independent.","method":"In vitro binding assays, stabilization assays, mPTS mutagenesis, PEX19-deficient cell complementation","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro binding with mutagenesis, loss-of-function complementation, two orthogonal approaches, replicated across labs","pmids":["14709540"],"is_preprint":false},{"year":2004,"finding":"PEX3 is the docking factor for PEX19 at the peroxisome membrane: PEX3 is required for PEX19 to dock at peroxisomes, binds specifically to the docking domain of PEX19 via a conserved motif, is sufficient to dock PEX19 at heterologous organelles, and is selectively required for class I PMP import but not class II PMP import or matrix protein import.","method":"Co-immunoprecipitation, heterologous organelle docking assay, dominant-negative inhibition, cell-free import assay, PEX3-deficient cell complementation","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, heterologous docking, functional complementation, multiple orthogonal methods, replicated by subsequent structural studies","pmids":["15007061"],"is_preprint":false},{"year":1999,"finding":"Human PEX19 encodes a 299-aa hydrophilic protein with a C-terminal CAAX farnesylation motif; farnesylated PEX19 is partly anchored in the peroxisomal membrane with its N-terminal part exposed to the cytosol. PEX19 is required for peroxisome membrane assembly before matrix protein import; a frameshift mutation (A764 insertion) in PEX19 causes Zellweger syndrome complementation group J.","method":"Functional complementation of CHO mutant cells, Western blot, immunofluorescence, fibroblast complementation, mutation analysis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — functional complementation with biochemical and cell biological validation, first identification paper, findings replicated across multiple subsequent studies","pmids":["10051604"],"is_preprint":false},{"year":1994,"finding":"PEX19 (PxF) is farnesylated at its C-terminal CAAX motif and localizes to the outer surface of peroxisomes as determined by indirect immunofluorescence and electron microscopy.","method":"Protein purification, farnesyl group identification, cDNA cloning, indirect immunofluorescence, electron microscopy","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct biochemical identification of farnesylation, corroborated by EM localization, replicated by multiple subsequent studies","pmids":["8188701"],"is_preprint":false},{"year":2006,"finding":"The tail-anchored peroxisomal membrane protein PEX26 contains two PEX19-binding sites in its C-terminal targeting signal: one overlapping with its transmembrane domain and a second in the luminal domain that is essential for correct targeting and prevents mislocalization to mitochondria. PEX19 is essential for PEX26 import. The yeast tail-anchored Pex15p similarly harbors a luminal PEX19-binding site acting as a peroxisomal targeting motif.","method":"Peptide binding assays, targeting assays in cells, mutagenesis, heterologous TMD insertion experiments, PEX19-deficient cell complementation","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — mutagenesis combined with functional targeting assays, ortholog validation, multiple orthogonal methods","pmids":["16763195"],"is_preprint":false},{"year":2009,"finding":"The N-terminal domain of Pex14 (Pex14N) adopts a three-helical fold and binds both Pex5 and Pex19 competitively at the same surface but with opposite directionality. PEX19 uses a conserved F/YFxxxF sequence motif for binding. Mutations in this binding region disrupt Pex5 and/or Pex19 binding in vitro and impair peroxisomal membrane localization of Pex14 in vivo.","method":"NMR structure determination, X-ray crystallography, mutagenesis, in vitro binding assays, in vivo localization assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — NMR structure with mutagenesis and in vitro/in vivo functional validation, multiple orthogonal methods","pmids":["19197237"],"is_preprint":false},{"year":2010,"finding":"Crystal structure of the cytosolic domain of PEX3 in complex with a PEX19-derived peptide shows that PEX3 adopts a novel large helical bundle fold with a hydrophobic groove at its membrane-distal end that engages the PEX19 peptide with nanomolar affinity. Phenylalanine 29 in PEX19 is critical for this interaction, and key PEX3 residues involved are highly conserved across species.","method":"X-ray crystallography, isothermal titration calorimetry, mutagenesis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure combined with mutagenesis and binding affinity measurement","pmids":["20554521"],"is_preprint":false},{"year":2017,"finding":"NMR-derived structure of farnesylated human PEX19 C-terminal domain (CTD) reveals that the farnesyl moiety is buried in an internal hydrophobic cavity, inducing conformational changes that allosterically reshape the PEX19 surface to form two hydrophobic pockets for recognition of conserved aromatic/aliphatic side chains in PMPs. Mutations in residues mediating farnesyl contacts or PMP recognition abolish cargo binding and cannot complement ΔPEX19 Zellweger patient fibroblasts.","method":"NMR structure determination, mutagenesis, in vitro binding assays, functional complementation in patient fibroblasts","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — NMR structure with mutagenesis, in vitro binding validation, and in vivo functional complementation in a single rigorous study","pmids":["28281558"],"is_preprint":false},{"year":2013,"finding":"PEX19 forms a cytosolic complex with the tail-anchored peroxisomal protein PEX26 and delivers it to peroxisomes by interacting with PEX3. Unlike in yeast, the TRC40 ATPase (which delivers TA proteins to the ER) is dispensable for peroxisomal targeting of PEX26 in mammals. Basic amino acids in the luminal domain of PEX26 are essential for PEX19 binding and peroxisomal targeting.","method":"Co-immunoprecipitation, siRNA knockdown, dominant-negative assays, mutagenesis, subcellular fractionation","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, knockdown, mutagenesis, and mechanistic dissection of TRC40 independence, multiple orthogonal methods","pmids":["23460677"],"is_preprint":false},{"year":2005,"finding":"The PEX19-binding site predicted in the adrenoleukodystrophy protein (ALDP) is a true binding site for both human and yeast PEX19 and coincides with its peroxisomal targeting motif. The ALDP minimal PEX19-binding fragment targets correctly in both human fibroblasts and yeast in a PEX19-binding-site-dependent manner, and most predicted PEX19-binding sequences in human PMPs are bona fide binding sites, demonstrating evolutionary conservation of PMP targeting signals.","method":"In vitro binding assays (peptide arrays), in vivo targeting assays in human fibroblasts and yeast, cross-species complementation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vitro peptide binding combined with in vivo targeting assays in two species, multiple PMPs tested","pmids":["15781447"],"is_preprint":false},{"year":2003,"finding":"PEX3 and PEX19 interact predominantly at the peroxisome membrane (not in the cytoplasm) as demonstrated by FRET imaging. The PEX19-binding domain in the C-terminal half of PEX3 and the N-terminal peroxisomal targeting sequence of PEX3 are both required for proper PEX3 localization and interaction with PEX19.","method":"Fluorescence resonance energy transfer (FRET) imaging, donor fluorescence photobleaching, GFP/YFP/CFP fusion proteins, PEX3-deletion mutant analysis","journal":"European journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — FRET with quantification and photobleaching confirmation, deletion mutagenesis, single lab but two orthogonal approaches","pmids":["12924628"],"is_preprint":false},{"year":2002,"finding":"PEX19 has two functionally distinct splice variants: PEX19ΔE2 (lacking N-terminal domain D1) fails to restore peroxisomal biogenesis in PEX19-deficient fibroblasts despite binding PMPs, while PEX19ΔE8 (lacking C-terminal domain D3 including the CAAX/farnesylation motif) successfully restores biogenesis, demonstrating that farnesylation is not essential for peroxisomal biogenesis and that the N-terminal domain is required for function.","method":"In vitro protein interaction studies, functional complementation in PEX19-deficient fibroblasts, in vitro/in vivo farnesylation assay","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional complementation with interaction studies, single lab, two orthogonal approaches","pmids":["11883941"],"is_preprint":false},{"year":2012,"finding":"Three conserved surface regions on PEX3 are functionally distinct: the PEX19-binding region is required for PEX19 binding and PEX3 stability; a hydrophobic groove near the base of PEX3 is required for PMP insertion and maturation of preperoxisomes; and an acidic cluster has no apparent functional relevance. The PEX3-PEX19 interaction is crucial for de novo peroxisome formation.","method":"Site-directed mutagenesis, pulldown assays, functional complementation in peroxisome-deficient cells, crystallographic analysis","journal":"Traffic (Copenhagen, Denmark)","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — mutagenesis combined with biochemical and functional assays, single lab with multiple orthogonal approaches","pmids":["22624858"],"is_preprint":false},{"year":2017,"finding":"Functional mapping of Pex19 domains in Pichia pastoris shows: the N-terminal region (aa 1-150) contains the Pex3-binding site and its deletion disrupts Pex3 interaction while preserving Pex10 binding; the C-terminal region (aa 89-300) contains the mPTS-binding domain and its deletion disrupts Pex10 binding while leaving Pex3 interactions intact. Pex25 is critical for peroxisome formation with C-terminal deletion variants and enhances Pex3 interactions.","method":"Deletion mutagenesis, yeast two-hybrid, co-immunoprecipitation, functional growth assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — deletion mutagenesis with binding and functional assays, single lab, multiple orthogonal methods","pmids":["28526747"],"is_preprint":false},{"year":2018,"finding":"In budding yeast, Pex19 acts as an import mediator for a subset of mitochondrial outer membrane tail-anchored proteins (Fis1 and Gem1). Deletion of PEX19 reduces steady-state levels of Fis1 and Gem1, impairs their in organello import, causes growth defects under respiratory conditions and mitochondrial morphology alterations. Recombinant Pex19 binds directly to Fis1 and Gem1 tail-anchored proteins.","method":"In organello import assay, deletion mutant analysis, in vitro binding (pulldown), growth assays, mitochondrial morphology assessment","journal":"Traffic (Copenhagen, Denmark)","confidence":"High","confidence_rationale":"Tier 2 / Moderate — in vitro direct binding combined with in organello functional import assay and genetic loss-of-function, multiple orthogonal methods in single lab","pmids":["30033679"],"is_preprint":false},{"year":2022,"finding":"PEX19 mediates targeting of UBXD8 (a VCP/P97-recruitment factor) to lipid droplets via the ER, in a farnesylation-dependent manner, independently of peroxisome function. Non-farnesylated PEX19 fully restores peroxisomal metabolic activity, while farnesylated PEX19 controls neutral lipid metabolism through a peroxisome-independent mechanism involving sorting of a specific subset of proteins to lipid droplets. Loss of this PEX19-dependent lipid droplet proteome causes accumulation of excess triacylglycerols.","method":"Farnesylation-site mutagenesis, organelle proteomics, lipid metabolic assays, lipidomics, knockdown/knockout","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis combined with proteomics and metabolic assays, single lab, multiple orthogonal approaches","pmids":["35557938"],"is_preprint":false},{"year":2014,"finding":"PEX19 is an intrinsically disordered protein that becomes partially structured upon binding PEX3. Hydrogen-exchange mass spectrometry shows three regions become shielded in PEX19 upon PEX3 interaction: N-terminus, a short middle stretch (F64-L74), and C-terminus. PEX3's binding groove becomes more protected. The N-terminus of PEX19 likely initiates binding to PEX3, followed by subtle PEX3 conformational changes that stabilize PEX19 folding.","method":"Hydrogen exchange mass spectrometry (HX-MS), in vitro complex formation","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, single method (HX-MS), but detailed conformational analysis at peptide resolution","pmids":["25062251"],"is_preprint":false},{"year":2022,"finding":"Pex11 contains one Pex19-binding site (Pex19-BS) required for Pex19-dependent membrane insertion but non-essential for peroxisomal trafficking, and a second Pex19-independent mPTS for peroxisomal trafficking. Pex19 acts as a chaperone by binding the Pex19-BS in Pex11, protecting it from spontaneous oligomerization and aggregation. Both homo- and heterotypic interactions via Pex11 N-terminal helical domains mediate self-interaction.","method":"Mutagenesis, in vitro binding assays, aggregation protection assay, in vivo targeting assays, co-immunoprecipitation","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis with functional targeting assays and in vitro chaperone assay, single lab, multiple orthogonal methods","pmids":["35011719"],"is_preprint":false},{"year":2024,"finding":"A conserved PEX19 helix (αd) plays a dual role: it shields the PEX26 transmembrane domain from cytosolic chaperones, and it interacts with the cytosolic domain of PEX3 to trigger PEX26 release at the peroxisome membrane. The PEX3-G138E mutant abolishes the secondary PEX19-αd/PEX3 interaction, preventing PEX26 release from PEX19.","method":"Biochemical assays, mass spectrometry analysis, mutagenesis (PEX3-G138E), co-immunoprecipitation","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis combined with biochemical and MS analysis, single lab, multiple orthogonal methods","pmids":["38585659"],"is_preprint":false},{"year":2021,"finding":"Viperin (an interferon-stimulated gene) physically interacts with PEX19 and co-localizes with peroxisomal proteins in association with lipid droplets. Reduction of PEX19 expression abolishes the ability of viperin to augment RLR (RIG-I-like receptor) antiviral signaling through peroxisomal MAVS, suggesting viperin uses PEX19 to position peroxisomes at the mitochondrial/MAM MAVS signaling synapse.","method":"Proteomics-based screening, co-immunoprecipitation, co-localization, siRNA knockdown, IFN-β reporter assays","journal":"Life science alliance","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP interaction confirmed with functional knockdown, single lab, multiple orthogonal methods","pmids":["34108265"],"is_preprint":false},{"year":2022,"finding":"Dengue virus (DENV) and Zika virus (ZIKV) capsid proteins bind PEX19 through a conserved PEX19-binding motif similar to that found in cellular PMPs, but this interaction does not result in targeting of capsid proteins to peroxisomes. The presence of capsid protein causes peroxisome loss through impaired peroxisomal biogenesis via a PEX19-independent mechanism.","method":"Co-immunoprecipitation, virus infection in peroxisome-deficient cells, mutagenesis, immunofluorescence","journal":"Viruses","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP with functional cell assays, single lab, multiple orthogonal approaches","pmids":["35215846"],"is_preprint":false},{"year":2025,"finding":"Yeast Msp1 (dual-localized AAA-ATPase on mitochondria and peroxisomes) cooperates with the Pex19-Pex3 pathway for correct Pex15 localization: newly synthesized Pex15 targets to peroxisomes primarily via Pex19/Pex3; mistargeted Pex15 on mitochondrial OM is extracted by mitochondrial Msp1 and can be re-routed to peroxisomes via the Pex19-Pex3 pathway; and even correctly localized peroxisomal Pex15 is extracted by peroxisomal Msp1 but returned to peroxisomes via Pex19-Pex3.","method":"In vitro import assay, genetic epistasis (msp1Δ, pex19Δ mutants), co-immunoprecipitation, subcellular fractionation","journal":"The FEBS journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with import assays and fractionation, single lab, multiple orthogonal methods","pmids":["40344504"],"is_preprint":false},{"year":2017,"finding":"In Drosophila Pex19 mutants (peroxisome-deficient), Hnf4 signaling becomes hyperactivated, leading to up-regulation of lipase 3 and mitochondrial β-oxidation enzymes, resulting in enhanced lipolysis, elevated free fatty acids, maximal β-oxidation, and mitochondrial damage. Increased acid lipase expression and free fatty acid accumulation were also found in Pex19-deficient patient fibroblasts, suggesting conservation.","method":"Drosophila Pex19 loss-of-function mutants, transcriptomics, lipidomics, patient fibroblast analysis, genetic interaction with Hnf4","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Drosophila genetic model with biochemical validation, cross-species conservation tested in patient fibroblasts","pmids":["29282281"],"is_preprint":false},{"year":2024,"finding":"The C-terminus of PEX19 interacts with the cytoplasmic tail of IAV M2 protein. IAV infection or PEX19 knockdown reduces peroxisome numbers, leading to ROS accumulation and attenuation of peroxisome-MAVS-mediated antiviral response and downstream type III interferon production. M2-PEX19 interaction disrupts PEX19 binding to PEX14 and PMP24.","method":"Co-immunoprecipitation, siRNA knockdown, overexpression, virus growth assays, immunofluorescence","journal":"Viruses","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP combined with knockdown and functional antiviral assays, single lab, multiple orthogonal methods","pmids":["39205283"],"is_preprint":false},{"year":2017,"finding":"Rat PEX19i, a peroxisome-proliferator-inducible splice variant with a C-terminal hydrophobic segment instead of the CAAX box, can restore peroxisomes in pex19 mutant cells (with slightly lower efficiency). The C-terminal CAAX region of Pex19p is not essential for membrane association or interaction with Pex3p and Pex16p. Non-prenylated Pex19p interacts with Pex14p but more weakly than farnesylated Pex19p.","method":"Functional complementation assay, co-immunoprecipitation, in vitro binding assay","journal":"Journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional complementation with binding studies, single lab, two orthogonal approaches","pmids":["28391327"],"is_preprint":false}],"current_model":"PEX19 is a predominantly cytosolic, intrinsically disordered chaperone and import receptor that binds newly synthesized class I peroxisomal membrane proteins (PMPs) via hydrophobic PEX19-binding motifs in their membrane-peroxisomal targeting signals (mPTS); farnesylation of the C-terminal CAAX motif allosterically reshapes the PEX19 cargo-binding domain to enhance PMP recognition; the PEX19–PMP complex is delivered to peroxisomes by docking of PEX19's N-terminal domain onto PEX3, an integral peroxisomal membrane protein that serves as the receptor for PEX19, after which cargo is inserted into the membrane and PEX19 is recycled to the cytosol; PEX19 also functions as a chaperone for a subset of tail-anchored proteins destined for mitochondria and lipid droplets, and its farnesylated form independently coordinates neutral lipid storage and lipid droplet proteome composition, while additionally serving as a platform for peroxisome-based innate antiviral signaling through MAVS."},"narrative":{"mechanistic_narrative":"PEX19 is a predominantly cytosolic, intrinsically disordered chaperone and import receptor that drives the biogenesis of peroxisomal membranes by binding, stabilizing, and delivering newly synthesized class I peroxisomal membrane proteins (PMPs) [PMID:10704444, PMID:14709540, PMID:10051604]. It recognizes a broad spectrum of PMPs through hydrophobic PEX19-binding motifs embedded in their membrane targeting signals (mPTS), and these binding sites are evolutionarily conserved and functionally interchangeable between human and yeast cargo [PMID:14709540, PMID:15781447]. PEX19 is bimodally distributed, with loss of function causing PMP degradation or mislocalization to mitochondria and a failure of peroxisome membrane assembly that underlies Zellweger syndrome complementation group J [PMID:10704444, PMID:10051604]. Cargo recognition is allosterically tuned by farnesylation of the C-terminal CAAX motif, which buries the farnesyl group in an internal cavity of the PEX19 C-terminal domain and reshapes its surface into hydrophobic pockets that engage aromatic/aliphatic PMP side chains [PMID:8188701, PMID:28281558]. The PEX19–PMP complex is targeted to the peroxisome by docking of PEX19's N-terminal domain onto the integral membrane receptor PEX3: PEX3 binds a conserved phenylalanine-containing motif in disordered PEX19 with nanomolar affinity, inducing partial folding of PEX19, and a distinct PEX3 hydrophobic groove mediates subsequent PMP insertion [PMID:15007061, PMID:20554521, PMID:22624858, PMID:25062251]. PEX19 functions as a chaperone for tail-anchored PMPs such as PEX26 and PEX11, shielding their transmembrane domains from aggregation and triggering cargo release at the membrane through a secondary PEX19–PEX3 contact [PMID:16763195, PMID:35011719, PMID:38585659]. Beyond peroxisomes, PEX19 mediates import of a subset of mitochondrial outer-membrane tail-anchored proteins and, in its farnesylated form, sorts proteins to lipid droplets to control neutral lipid storage [PMID:30033679, PMID:35557938], and it serves as a platform for peroxisome-based RLR/MAVS antiviral signaling that is targeted by viral proteins [PMID:34108265, PMID:39205283].","teleology":[{"year":1994,"claim":"Establishing that PEX19 is post-translationally modified and peroxisome-associated set the biochemical groundwork for its membrane-targeting role.","evidence":"Protein purification, farnesyl identification, immunofluorescence and EM localization","pmids":["8188701"],"confidence":"High","gaps":["Function of farnesylation not yet defined","Cargo or partners unknown at this stage"]},{"year":1999,"claim":"Identifying PEX19 as a 299-aa CAAX protein required for peroxisome membrane assembly and as the gene mutated in Zellweger complementation group J answered whether PEX19 acts before matrix import and tied it to human disease.","evidence":"Functional complementation of CHO/fibroblast mutants, mutation analysis","pmids":["10051604"],"confidence":"High","gaps":["Molecular cargo-recognition mechanism not resolved","Docking receptor unidentified"]},{"year":2000,"claim":"Demonstrating saturable, broad-spectrum PMP binding and that mislocalizing PEX19 mislocalizes PMPs defined PEX19 as the cytosolic carrier of membrane proteins.","evidence":"Co-IP, fractionation, nuclear mislocalization, loss-of-function complementation","pmids":["10704444"],"confidence":"High","gaps":["Whether PEX19 is chaperone, receptor, or both unresolved","Targeting signal definition incomplete"]},{"year":2004,"claim":"Defining PEX19 as both cytosolic chaperone and import receptor for class I PMPs (with a PEX19-independent class II) and identifying PEX3 as its docking factor established the core import pathway.","evidence":"In vitro binding, mPTS mutagenesis, heterologous docking, cell-free import, complementation","pmids":["14709540","15007061"],"confidence":"High","gaps":["Structural basis of PEX19-PEX3 and PEX19-cargo binding unknown","Cargo release/recycling step undefined"]},{"year":2005,"claim":"Validating predicted PEX19-binding sites in human and yeast PMPs and showing they coincide with peroxisomal targeting motifs established evolutionary conservation of the mPTS code.","evidence":"Peptide-array binding, cross-species in vivo targeting assays","pmids":["15781447"],"confidence":"High","gaps":["Rules distinguishing class I from class II cargo incomplete"]},{"year":2006,"claim":"Mapping two PEX19-binding sites in the tail-anchored protein PEX26 showed PEX19 handles TA-PMPs and prevents their mitochondrial mistargeting.","evidence":"Peptide binding, targeting and mutagenesis assays, ortholog validation","pmids":["16763195"],"confidence":"High","gaps":["Delivery machinery for TA-PMPs not yet defined","Release mechanism unknown"]},{"year":2010,"claim":"The PEX3–PEX19 peptide co-crystal structure revealed a hydrophobic groove engaging PEX19 Phe29 with nanomolar affinity, giving the docking interaction atomic detail.","evidence":"X-ray crystallography, ITC, mutagenesis","pmids":["20554521"],"confidence":"High","gaps":["Conformational state of full-length PEX19 during docking unresolved","How cargo binding couples to docking unknown"]},{"year":2009,"claim":"Structural analysis of Pex14N showed PEX19 and Pex5 bind competitively at the same surface via a F/YFxxxF motif, linking PEX19 to the broader import apparatus.","evidence":"NMR/X-ray structures, mutagenesis, in vitro and in vivo binding","pmids":["19197237"],"confidence":"High","gaps":["Functional consequence of competition with Pex5 not fully defined"]},{"year":2013,"claim":"Showing PEX19 forms a cytosolic PEX26 complex delivered via PEX3 without requiring TRC40 distinguished the mammalian peroxisomal TA pathway from ER targeting.","evidence":"Reciprocal Co-IP, siRNA, dominant-negative, mutagenesis, fractionation","pmids":["23460677"],"confidence":"High","gaps":["Energetics of insertion not defined","Cargo release trigger unknown"]},{"year":2017,"claim":"The NMR structure of farnesylated PEX19 CTD showed farnesylation allosterically reshapes the cargo-binding surface, resolving why this lipid modification enhances PMP recognition.","evidence":"NMR structure, mutagenesis, in vitro binding, patient-fibroblast complementation","pmids":["28281558"],"confidence":"High","gaps":["Why some PEX19 functions are farnesylation-independent unresolved","Dynamics of cargo loading in cells not measured"]},{"year":2014,"claim":"Hydrogen-exchange MS established PEX19 as intrinsically disordered that partially folds upon PEX3 binding, with the N-terminus initiating the interaction.","evidence":"HX-MS, in vitro complex formation","pmids":["25062251"],"confidence":"Medium","gaps":["Single method, no high-resolution structure of the disordered regions","Order of cargo vs PEX3 engagement not directly observed"]},{"year":2002,"claim":"Splice-variant complementation showed the N-terminal domain is essential while the CAAX/farnesylation region is dispensable for peroxisome biogenesis, dissecting domain requirements.","evidence":"Functional complementation in PEX19-deficient fibroblasts, farnesylation assays","pmids":["11883941"],"confidence":"Medium","gaps":["Single lab","Apparent tension with farnesylation-dependent cargo recognition not reconciled"]},{"year":2012,"claim":"Functional dissection of three PEX3 surfaces separated PEX19-binding/stability from a distinct PMP-insertion groove, refining how docking and insertion are partitioned.","evidence":"Site-directed mutagenesis, pulldowns, complementation, crystallography","pmids":["22624858"],"confidence":"High","gaps":["Mechanism of PMP insertion through the groove undefined"]},{"year":2017,"claim":"Domain mapping in Pichia placed the Pex3-binding site in the N-terminus and the mPTS-binding site in the C-terminus, confirming a bipartite functional architecture across species.","evidence":"Deletion mutagenesis, yeast two-hybrid, Co-IP, growth assays","pmids":["28526747"],"confidence":"Medium","gaps":["Role of Pex25 in human cells untested","Single lab"]},{"year":2017,"claim":"A non-CAAX inducible rat splice variant that still complements showed the prenylation region is not essential for membrane association or PEX3/PEX16 binding, qualifying the role of farnesylation.","evidence":"Functional complementation, Co-IP, in vitro binding","pmids":["28391327"],"confidence":"Medium","gaps":["Generalizability to human PEX19 unclear","Reduced complementation efficiency mechanism undefined"]},{"year":2018,"claim":"Identifying Pex19 as an import mediator for mitochondrial outer-membrane TA proteins (Fis1, Gem1) extended its chaperone role beyond peroxisomes.","evidence":"In organello import, deletion analysis, in vitro binding, growth and morphology assays","pmids":["30033679"],"confidence":"High","gaps":["Mammalian relevance not established here","How specificity between mitochondrial and peroxisomal TA proteins is set unknown"]},{"year":2022,"claim":"Showing farnesylated PEX19 sorts UBXD8 to lipid droplets and controls neutral-lipid metabolism independently of peroxisome function revealed a distinct lipid-storage role.","evidence":"Farnesylation mutagenesis, organelle proteomics, lipidomics, knockdown/knockout","pmids":["35557938"],"confidence":"Medium","gaps":["Mechanism of LD-protein selection undefined","Single lab"]},{"year":2022,"claim":"Defining a Pex19-dependent insertion site and a Pex19-independent mPTS in Pex11, and an anti-aggregation chaperone activity, refined how PEX19 separates trafficking from insertion.","evidence":"Mutagenesis, in vitro binding, aggregation-protection, targeting assays, Co-IP","pmids":["35011719"],"confidence":"Medium","gaps":["Structural basis of aggregation protection unknown","Single lab"]},{"year":2024,"claim":"Identifying a PEX19 helix (αd) that shields the PEX26 TMD and engages PEX3 to trigger cargo release, abolished by PEX3-G138E, supplied a mechanism for the membrane release step.","evidence":"Biochemical assays, MS, mutagenesis (PEX3-G138E), Co-IP","pmids":["38585659"],"confidence":"Medium","gaps":["Whether the same release mechanism applies to other cargo unknown","In vivo kinetics of release not measured"]},{"year":2025,"claim":"Showing Msp1 cooperates with the Pex19-Pex3 pathway to extract and re-route mistargeted or extracted Pex15 added a quality-control dimension to PEX19-mediated TA targeting.","evidence":"In vitro import, genetic epistasis (msp1Δ, pex19Δ), Co-IP, fractionation","pmids":["40344504"],"confidence":"Medium","gaps":["Mammalian conservation untested","Signal triggering re-extraction undefined"]},{"year":2017,"claim":"Drosophila Pex19 loss showed peroxisome deficiency hyperactivates Hnf4-driven lipolysis and β-oxidation with mitochondrial damage, conserved in patient fibroblasts, linking PEX19 to systemic lipid homeostasis.","evidence":"Drosophila loss-of-function, transcriptomics, lipidomics, patient fibroblasts","pmids":["29282281"],"confidence":"Medium","gaps":["Direct vs secondary contribution of PEX19 unclear","Mammalian in vivo validation limited"]},{"year":2021,"claim":"Linking viperin and PEX19 to positioning of peroxisomes for RLR/MAVS antiviral signaling implicated PEX19 in innate immunity.","evidence":"Proteomic screen, Co-IP, co-localization, siRNA, IFN-β reporter","pmids":["34108265"],"confidence":"Medium","gaps":["Mechanism of peroxisome repositioning undefined","Direct vs indirect MAVS link unproven"]},{"year":2022,"claim":"DENV/ZIKV capsids binding PEX19 via a PMP-like motif without being targeted to peroxisomes, while causing PEX19-independent peroxisome loss, defined a viral subversion mode.","evidence":"Co-IP, infection in peroxisome-deficient cells, mutagenesis, immunofluorescence","pmids":["35215846"],"confidence":"Medium","gaps":["Functional consequence of capsid-PEX19 binding unclear","Mechanism of peroxisome loss undefined"]},{"year":2024,"claim":"IAV M2 binding the PEX19 C-terminus to disrupt PEX14/PMP24 interactions and attenuate peroxisome-MAVS antiviral signaling further established PEX19 as a viral target in innate immunity.","evidence":"Co-IP, siRNA, overexpression, virus growth assays, immunofluorescence","pmids":["39205283"],"confidence":"Medium","gaps":["Whether M2 competes with cargo at the same site untested","In vivo relevance not established"]},{"year":null,"claim":"How PEX19 mechanistically discriminates among peroxisomal, mitochondrial, and lipid-droplet destinations for overlapping tail-anchored/hydrophobic cargo, and how farnesylation-dependent versus -independent functions are balanced in cells, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model of organelle selectivity","Cellular regulation of farnesylation state unknown","Structure of full-length cargo-loaded PEX19 lacking"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0044183","term_label":"protein folding chaperone","supporting_discovery_ids":[1,0,18,15]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[1,5,9]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,2,0]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[8,4]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005777","term_label":"peroxisome","supporting_discovery_ids":[0,3,4,11]},{"term_id":"GO:0005811","term_label":"lipid droplet","supporting_discovery_ids":[16]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,1,2,3,13]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[1,5,9,18]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[1,18]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[16,23]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[20,24]}],"complexes":["PEX3-PEX19 docking complex","PEX19-PEX26 cytosolic complex"],"partners":["PEX3","PEX26","PEX14","PEX11","PEX16","UBXD8","RSAD2","FIS1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P40855","full_name":"Peroxisomal biogenesis factor 19","aliases":["33 kDa housekeeping protein","Peroxin-19","Peroxisomal farnesylated protein"],"length_aa":299,"mass_kda":32.8,"function":"Necessary for early peroxisomal biogenesis. Acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Binds and stabilizes newly synthesized PMPs in the cytoplasm by interacting with their hydrophobic membrane-spanning domains, and targets them to the peroxisome membrane by binding to the integral membrane protein PEX3. Excludes CDKN2A from the nucleus and prevents its interaction with MDM2, which results in active degradation of TP53","subcellular_location":"Cytoplasm; Peroxisome membrane","url":"https://www.uniprot.org/uniprotkb/P40855/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PEX19","classification":"Not Classified","n_dependent_lines":44,"n_total_lines":1208,"dependency_fraction":0.03642384105960265},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"PEX3","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/search/PEX19","total_profiled":1310},"omim":[{"mim_id":"617399","title":"PEROXISOMAL MEMBRANE PROTEIN 2; PXMP2","url":"https://www.omim.org/entry/617399"},{"mim_id":"614886","title":"PEROXISOME BIOGENESIS DISORDER 12A (ZELLWEGER); PBD12A","url":"https://www.omim.org/entry/614886"},{"mim_id":"600279","title":"PEROXISOME BIOGENESIS FACTOR 19; PEX19","url":"https://www.omim.org/entry/600279"},{"mim_id":"214100","title":"PEROXISOME BIOGENESIS DISORDER 1A (ZELLWEGER); PBD1A","url":"https://www.omim.org/entry/214100"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Peroxisomes","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PEX19"},"hgnc":{"alias_symbol":["HK33","D1S2223E","PMP1","PMPI","PXMP1"],"prev_symbol":["PXF"]},"alphafold":{"accession":"P40855","domains":[{"cath_id":"-","chopping":"78-140","consensus_level":"medium","plddt":74.3957,"start":78,"end":140},{"cath_id":"1.20.120.900","chopping":"184-269","consensus_level":"high","plddt":91.1667,"start":184,"end":269}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P40855","model_url":"https://alphafold.ebi.ac.uk/files/AF-P40855-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P40855-F1-predicted_aligned_error_v6.png","plddt_mean":70.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PEX19","jax_strain_url":"https://www.jax.org/strain/search?query=PEX19"},"sequence":{"accession":"P40855","fasta_url":"https://rest.uniprot.org/uniprotkb/P40855.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P40855/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P40855"}},"corpus_meta":[{"pmid":"10704444","id":"PMC_10704444","title":"PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis.","date":"2000","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/10704444","citation_count":259,"is_preprint":false},{"pmid":"14709540","id":"PMC_14709540","title":"PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins.","date":"2004","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/14709540","citation_count":207,"is_preprint":false},{"pmid":"15007061","id":"PMC_15007061","title":"PEX3 functions as a PEX19 docking factor in the import of class I peroxisomal membrane proteins.","date":"2004","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/15007061","citation_count":193,"is_preprint":false},{"pmid":"10051604","id":"PMC_10051604","title":"Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly.","date":"1999","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/10051604","citation_count":191,"is_preprint":false},{"pmid":"9427748","id":"PMC_9427748","title":"pmp1+, a suppressor of calcineurin deficiency, encodes a novel MAP kinase phosphatase in fission yeast.","date":"1998","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/9427748","citation_count":111,"is_preprint":false},{"pmid":"16763195","id":"PMC_16763195","title":"Targeting of the tail-anchored peroxisomal membrane proteins PEX26 and PEX15 occurs through C-terminal PEX19-binding sites.","date":"2006","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/16763195","citation_count":105,"is_preprint":false},{"pmid":"8188701","id":"PMC_8188701","title":"PxF, a prenylated protein of peroxisomes.","date":"1994","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/8188701","citation_count":84,"is_preprint":false},{"pmid":"23460677","id":"PMC_23460677","title":"Tail-anchored PEX26 targets peroxisomes via a PEX19-dependent and TRC40-independent class I pathway.","date":"2013","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/23460677","citation_count":81,"is_preprint":false},{"pmid":"19197237","id":"PMC_19197237","title":"Structural basis for competitive interactions of Pex14 with the import receptors Pex5 and Pex19.","date":"2009","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/19197237","citation_count":73,"is_preprint":false},{"pmid":"15781447","id":"PMC_15781447","title":"Function of the PEX19-binding site of human adrenoleukodystrophy protein as targeting motif in man and yeast. PMP targeting is evolutionarily conserved.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15781447","citation_count":63,"is_preprint":false},{"pmid":"30776093","id":"PMC_30776093","title":"The peroxisome biogenesis factors Pex3 and Pex19: multitasking proteins with disputed functions.","date":"2019","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/30776093","citation_count":55,"is_preprint":false},{"pmid":"20554521","id":"PMC_20554521","title":"Insights into peroxisome function from the structure of PEX3 in complex with a soluble fragment of PEX19.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20554521","citation_count":48,"is_preprint":false},{"pmid":"29282281","id":"PMC_29282281","title":"Unbalanced lipolysis results in lipotoxicity and mitochondrial damage in peroxisome-deficient Pex19 mutants.","date":"2017","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/29282281","citation_count":45,"is_preprint":false},{"pmid":"28281558","id":"PMC_28281558","title":"Allosteric modulation of peroxisomal membrane protein recognition by farnesylation of the peroxisomal import receptor PEX19.","date":"2017","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/28281558","citation_count":43,"is_preprint":false},{"pmid":"30033679","id":"PMC_30033679","title":"Pex19 is involved in importing dually targeted tail-anchored proteins to both mitochondria and peroxisomes.","date":"2018","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/30033679","citation_count":41,"is_preprint":false},{"pmid":"22624858","id":"PMC_22624858","title":"The role of conserved PEX3 regions in PEX19-binding and peroxisome biogenesis.","date":"2012","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/22624858","citation_count":39,"is_preprint":false},{"pmid":"12924628","id":"PMC_12924628","title":"The interaction between human PEX3 and PEX19 characterized by fluorescence resonance energy transfer (FRET) analysis.","date":"2003","source":"European journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/12924628","citation_count":39,"is_preprint":false},{"pmid":"15907560","id":"PMC_15907560","title":"Identification of trypanosomatid PEX19: functional characterization reveals impact on cell growth and glycosome size and number.","date":"2005","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15907560","citation_count":37,"is_preprint":false},{"pmid":"15525675","id":"PMC_15525675","title":"Requirement of the Caenorhabditis elegans RapGEF pxf-1 and rap-1 for epithelial integrity.","date":"2004","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/15525675","citation_count":29,"is_preprint":false},{"pmid":"17586720","id":"PMC_17586720","title":"Conservation of PEX19-binding motifs required for protein targeting to mammalian peroxisomal and trypanosome glycosomal membranes.","date":"2007","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/17586720","citation_count":26,"is_preprint":false},{"pmid":"8076834","id":"PMC_8076834","title":"Sequence of a putative human housekeeping gene (HK33) localized on chromosome 1.","date":"1994","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/8076834","citation_count":25,"is_preprint":false},{"pmid":"11883941","id":"PMC_11883941","title":"Two splice variants of human PEX19 exhibit distinct functions in peroxisomal assembly.","date":"2002","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/11883941","citation_count":22,"is_preprint":false},{"pmid":"11053135","id":"PMC_11053135","title":"PMP1 18-38, a yeast plasma membrane protein fragment, binds phosphatidylserine from bilayer mixtures with phosphatidylcholine: a (2)H-NMR study.","date":"2000","source":"Biophysical journal","url":"https://pubmed.ncbi.nlm.nih.gov/11053135","citation_count":21,"is_preprint":false},{"pmid":"28526747","id":"PMC_28526747","title":"Functional regions of the peroxin Pex19 necessary for peroxisome biogenesis.","date":"2017","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28526747","citation_count":18,"is_preprint":false},{"pmid":"28817674","id":"PMC_28817674","title":"New insights into the distribution, protein abundance and subcellular localisation of the endogenous peroxisomal biogenesis proteins PEX3 and PEX19 in different organs and cell types of the adult mouse.","date":"2017","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/28817674","citation_count":18,"is_preprint":false},{"pmid":"9782385","id":"PMC_9782385","title":"1H- and 2H-NMR studies of a fragment of PMP1, a regulatory subunit associated with the yeast plasma membrane H(+)-ATPase. Conformational properties and lipid-peptide interactions.","date":"1998","source":"Biochimie","url":"https://pubmed.ncbi.nlm.nih.gov/9782385","citation_count":16,"is_preprint":false},{"pmid":"29500918","id":"PMC_29500918","title":"Intracellular communication between lipid droplets and peroxisomes: the Janus face of PEX19.","date":"2018","source":"Biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/29500918","citation_count":13,"is_preprint":false},{"pmid":"20683989","id":"PMC_20683989","title":"A mutation in PEX19 causes a severe clinical phenotype in a patient with peroxisomal biogenesis disorder.","date":"2010","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/20683989","citation_count":12,"is_preprint":false},{"pmid":"34350186","id":"PMC_34350186","title":"A Small Molecule Inhibitor of Pex3-Pex19 Interaction Disrupts Glycosome Biogenesis and Causes Lethality in Trypanosoma brucei.","date":"2021","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/34350186","citation_count":10,"is_preprint":false},{"pmid":"35215846","id":"PMC_35215846","title":"Dengue and Zika Virus Capsid Proteins Contain a Common PEX19-Binding Motif.","date":"2022","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/35215846","citation_count":9,"is_preprint":false},{"pmid":"35557938","id":"PMC_35557938","title":"PEX19 Coordinates Neutral Lipid Storage in Cells in a Peroxisome-Independent Fashion.","date":"2022","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/35557938","citation_count":9,"is_preprint":false},{"pmid":"25062251","id":"PMC_25062251","title":"Association between the intrinsically disordered protein PEX19 and PEX3.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25062251","citation_count":8,"is_preprint":false},{"pmid":"34108265","id":"PMC_34108265","title":"Viperin interacts with PEX19 to mediate peroxisomal augmentation of the innate antiviral response.","date":"2021","source":"Life science alliance","url":"https://pubmed.ncbi.nlm.nih.gov/34108265","citation_count":8,"is_preprint":false},{"pmid":"15932519","id":"PMC_15932519","title":"Limkain b1, a novel human autoantigen localized to a subset of ABCD3 and PXF marked peroxisomes.","date":"2005","source":"Clinical and experimental immunology","url":"https://pubmed.ncbi.nlm.nih.gov/15932519","citation_count":8,"is_preprint":false},{"pmid":"35011719","id":"PMC_35011719","title":"Recognition and Chaperoning by Pex19, Followed by Trafficking and Membrane Insertion of the Peroxisome Proliferation Protein, Pex11.","date":"2022","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/35011719","citation_count":7,"is_preprint":false},{"pmid":"34988071","id":"PMC_34988071","title":"Novel Trypanocidal Inhibitors that Block Glycosome Biogenesis by Targeting PEX3-PEX19 Interaction.","date":"2021","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/34988071","citation_count":7,"is_preprint":false},{"pmid":"36403098","id":"PMC_36403098","title":"Crystal structure of the OrfX1-OrfX3 complex from the PMP1 neurotoxin gene cluster.","date":"2022","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/36403098","citation_count":6,"is_preprint":false},{"pmid":"20692117","id":"PMC_20692117","title":"In vitro assay of the interaction between Rnc1 protein and Pmp1 mRNA by affinity capillary electrophoresis with a carboxylated capillary.","date":"2010","source":"Journal of pharmaceutical and biomedical analysis","url":"https://pubmed.ncbi.nlm.nih.gov/20692117","citation_count":6,"is_preprint":false},{"pmid":"40344504","id":"PMC_40344504","title":"Msp1 and Pex19-Pex3 cooperate to achieve correct localization of Pex15 to peroxisomes.","date":"2025","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/40344504","citation_count":5,"is_preprint":false},{"pmid":"35207746","id":"PMC_35207746","title":"Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei.","date":"2022","source":"Journal of personalized medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35207746","citation_count":5,"is_preprint":false},{"pmid":"38585659","id":"PMC_38585659","title":"A dual role of the conserved PEX19 helix in safeguarding peroxisomal membrane proteins.","date":"2024","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/38585659","citation_count":5,"is_preprint":false},{"pmid":"19009320","id":"PMC_19009320","title":"Complete sequence of plasmid pMP1 from the marine environmental Vibrio vulnificus and location of its replication origin.","date":"2008","source":"Marine biotechnology (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/19009320","citation_count":5,"is_preprint":false},{"pmid":"39205283","id":"PMC_39205283","title":"The M2 Protein of the Influenza A Virus Interacts with PEX19 to Facilitate Virus Replication by Disrupting the Function of Peroxisome.","date":"2024","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/39205283","citation_count":4,"is_preprint":false},{"pmid":"36311020","id":"PMC_36311020","title":"PXF-1 promotes synapse development at the neuromuscular junction in Caenorhabditis elegans.","date":"2022","source":"Frontiers in molecular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/36311020","citation_count":4,"is_preprint":false},{"pmid":"21463579","id":"PMC_21463579","title":"Membrane interface composition drives the structure and the tilt of the single transmembrane helix protein PMP1: MD studies.","date":"2011","source":"Biophysical journal","url":"https://pubmed.ncbi.nlm.nih.gov/21463579","citation_count":4,"is_preprint":false},{"pmid":"39757991","id":"PMC_39757991","title":"Zellweger syndrome; identification of mutations in PEX19 and PEX26 gene in Saudi families.","date":"2025","source":"Annals of medicine","url":"https://pubmed.ncbi.nlm.nih.gov/39757991","citation_count":2,"is_preprint":false},{"pmid":"29510061","id":"PMC_29510061","title":"PmpI antibody reduces the inhibitory effect of Vp1 on Chlamydia trachomatis infectivity.","date":"2018","source":"Canadian journal of microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/29510061","citation_count":2,"is_preprint":false},{"pmid":"28391327","id":"PMC_28391327","title":"Peroxisome biogenesis: a novel inducible PEX19 splicing variant is involved in early stages of peroxisome proliferation.","date":"2017","source":"Journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28391327","citation_count":1,"is_preprint":false},{"pmid":"41874194","id":"PMC_41874194","title":"PEX19 restricts porcine deltacoronavirus replication through farnesylation-dependent and -independent mechanisms.","date":"2026","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/41874194","citation_count":0,"is_preprint":false},{"pmid":"38180723","id":"PMC_38180723","title":"Simultaneous PCR detection of Paenibacillus larvae targeting insertion sequence IS256 and Melissococcus plutonius targeting pMP1 plasmid from hive specimens.","date":"2024","source":"Folia microbiologica","url":"https://pubmed.ncbi.nlm.nih.gov/38180723","citation_count":0,"is_preprint":false},{"pmid":"41627762","id":"PMC_41627762","title":"Colab-PEX19BS: An Automated Google Colab Notebook-Based Tool for Detecting PEX19-Binding Sites.","date":"2026","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/41627762","citation_count":0,"is_preprint":false},{"pmid":"37763192","id":"PMC_37763192","title":"Correction: Noguchi et al. Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei. J. Pers. Med. 2022, 12, 258.","date":"2023","source":"Journal of personalized medicine","url":"https://pubmed.ncbi.nlm.nih.gov/37763192","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.11.03.686288","title":"Evolutionary Remodelling of a Remnant GET-Pathway Factor into PEX38, a Novel and Essential Peroxin in  <i>Euglenozoa</i>","date":"2025-11-04","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.03.686288","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.05.26.656179","title":"Insulin-like peptide secretion is mediated by peroxisome-Golgi interplay","date":"2025-05-27","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.26.656179","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.09.13.612636","title":"An inhibitor targeting glycosome membrane biogenesis kills  <i>Leishmania</i>  parasites","date":"2024-09-14","source":"bioRxiv","url":"https://doi.org/10.1101/2024.09.13.612636","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.12.10.627744","title":"Pex3 promotes formation of peroxisome-peroxisome and peroxisome-lipid droplet contact sites","date":"2024-12-12","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.10.627744","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":27427,"output_tokens":7006,"usd":0.093686,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":15961,"output_tokens":6385,"usd":0.119715,"stage2_stop_reason":"end_turn"},"total_usd":0.213401,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"PEX19 binds a broad spectrum of peroxisomal membrane proteins (PMPs), displays saturable PMP binding, interacts with regions of PMPs required for their targeting to peroxisomes, and is bimodally distributed between the cytoplasm (predominantly) and peroxisome membrane. Mislocalization of PEX19 to the nucleus causes nuclear accumulation of newly synthesized PMPs; loss of PEX19 results in degradation and/or mislocalization of PMPs to the mitochondrion.\",\n      \"method\": \"Co-immunoprecipitation, subcellular fractionation, immunofluorescence, nuclear mislocalization experiments, PEX19-deficient cell complementation\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP, fractionation, mislocalization assay, loss-of-function), foundational paper replicated by subsequent studies\",\n      \"pmids\": [\"10704444\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"PEX19 functions as both a cytosolic chaperone and an import receptor for class 1 PMPs: it binds and stabilizes newly synthesized PMPs in the cytosol, binds multiple PMP targeting signals (mPTSs) via their hydrophobic domains, and is essential for their targeting and import. A second PMP import class (class 2) is PEX19-independent.\",\n      \"method\": \"In vitro binding assays, stabilization assays, mPTS mutagenesis, PEX19-deficient cell complementation\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro binding with mutagenesis, loss-of-function complementation, two orthogonal approaches, replicated across labs\",\n      \"pmids\": [\"14709540\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"PEX3 is the docking factor for PEX19 at the peroxisome membrane: PEX3 is required for PEX19 to dock at peroxisomes, binds specifically to the docking domain of PEX19 via a conserved motif, is sufficient to dock PEX19 at heterologous organelles, and is selectively required for class I PMP import but not class II PMP import or matrix protein import.\",\n      \"method\": \"Co-immunoprecipitation, heterologous organelle docking assay, dominant-negative inhibition, cell-free import assay, PEX3-deficient cell complementation\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, heterologous docking, functional complementation, multiple orthogonal methods, replicated by subsequent structural studies\",\n      \"pmids\": [\"15007061\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Human PEX19 encodes a 299-aa hydrophilic protein with a C-terminal CAAX farnesylation motif; farnesylated PEX19 is partly anchored in the peroxisomal membrane with its N-terminal part exposed to the cytosol. PEX19 is required for peroxisome membrane assembly before matrix protein import; a frameshift mutation (A764 insertion) in PEX19 causes Zellweger syndrome complementation group J.\",\n      \"method\": \"Functional complementation of CHO mutant cells, Western blot, immunofluorescence, fibroblast complementation, mutation analysis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — functional complementation with biochemical and cell biological validation, first identification paper, findings replicated across multiple subsequent studies\",\n      \"pmids\": [\"10051604\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"PEX19 (PxF) is farnesylated at its C-terminal CAAX motif and localizes to the outer surface of peroxisomes as determined by indirect immunofluorescence and electron microscopy.\",\n      \"method\": \"Protein purification, farnesyl group identification, cDNA cloning, indirect immunofluorescence, electron microscopy\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct biochemical identification of farnesylation, corroborated by EM localization, replicated by multiple subsequent studies\",\n      \"pmids\": [\"8188701\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"The tail-anchored peroxisomal membrane protein PEX26 contains two PEX19-binding sites in its C-terminal targeting signal: one overlapping with its transmembrane domain and a second in the luminal domain that is essential for correct targeting and prevents mislocalization to mitochondria. PEX19 is essential for PEX26 import. The yeast tail-anchored Pex15p similarly harbors a luminal PEX19-binding site acting as a peroxisomal targeting motif.\",\n      \"method\": \"Peptide binding assays, targeting assays in cells, mutagenesis, heterologous TMD insertion experiments, PEX19-deficient cell complementation\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — mutagenesis combined with functional targeting assays, ortholog validation, multiple orthogonal methods\",\n      \"pmids\": [\"16763195\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The N-terminal domain of Pex14 (Pex14N) adopts a three-helical fold and binds both Pex5 and Pex19 competitively at the same surface but with opposite directionality. PEX19 uses a conserved F/YFxxxF sequence motif for binding. Mutations in this binding region disrupt Pex5 and/or Pex19 binding in vitro and impair peroxisomal membrane localization of Pex14 in vivo.\",\n      \"method\": \"NMR structure determination, X-ray crystallography, mutagenesis, in vitro binding assays, in vivo localization assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — NMR structure with mutagenesis and in vitro/in vivo functional validation, multiple orthogonal methods\",\n      \"pmids\": [\"19197237\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Crystal structure of the cytosolic domain of PEX3 in complex with a PEX19-derived peptide shows that PEX3 adopts a novel large helical bundle fold with a hydrophobic groove at its membrane-distal end that engages the PEX19 peptide with nanomolar affinity. Phenylalanine 29 in PEX19 is critical for this interaction, and key PEX3 residues involved are highly conserved across species.\",\n      \"method\": \"X-ray crystallography, isothermal titration calorimetry, mutagenesis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure combined with mutagenesis and binding affinity measurement\",\n      \"pmids\": [\"20554521\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"NMR-derived structure of farnesylated human PEX19 C-terminal domain (CTD) reveals that the farnesyl moiety is buried in an internal hydrophobic cavity, inducing conformational changes that allosterically reshape the PEX19 surface to form two hydrophobic pockets for recognition of conserved aromatic/aliphatic side chains in PMPs. Mutations in residues mediating farnesyl contacts or PMP recognition abolish cargo binding and cannot complement ΔPEX19 Zellweger patient fibroblasts.\",\n      \"method\": \"NMR structure determination, mutagenesis, in vitro binding assays, functional complementation in patient fibroblasts\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — NMR structure with mutagenesis, in vitro binding validation, and in vivo functional complementation in a single rigorous study\",\n      \"pmids\": [\"28281558\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PEX19 forms a cytosolic complex with the tail-anchored peroxisomal protein PEX26 and delivers it to peroxisomes by interacting with PEX3. Unlike in yeast, the TRC40 ATPase (which delivers TA proteins to the ER) is dispensable for peroxisomal targeting of PEX26 in mammals. Basic amino acids in the luminal domain of PEX26 are essential for PEX19 binding and peroxisomal targeting.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, dominant-negative assays, mutagenesis, subcellular fractionation\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, knockdown, mutagenesis, and mechanistic dissection of TRC40 independence, multiple orthogonal methods\",\n      \"pmids\": [\"23460677\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The PEX19-binding site predicted in the adrenoleukodystrophy protein (ALDP) is a true binding site for both human and yeast PEX19 and coincides with its peroxisomal targeting motif. The ALDP minimal PEX19-binding fragment targets correctly in both human fibroblasts and yeast in a PEX19-binding-site-dependent manner, and most predicted PEX19-binding sequences in human PMPs are bona fide binding sites, demonstrating evolutionary conservation of PMP targeting signals.\",\n      \"method\": \"In vitro binding assays (peptide arrays), in vivo targeting assays in human fibroblasts and yeast, cross-species complementation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vitro peptide binding combined with in vivo targeting assays in two species, multiple PMPs tested\",\n      \"pmids\": [\"15781447\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"PEX3 and PEX19 interact predominantly at the peroxisome membrane (not in the cytoplasm) as demonstrated by FRET imaging. The PEX19-binding domain in the C-terminal half of PEX3 and the N-terminal peroxisomal targeting sequence of PEX3 are both required for proper PEX3 localization and interaction with PEX19.\",\n      \"method\": \"Fluorescence resonance energy transfer (FRET) imaging, donor fluorescence photobleaching, GFP/YFP/CFP fusion proteins, PEX3-deletion mutant analysis\",\n      \"journal\": \"European journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — FRET with quantification and photobleaching confirmation, deletion mutagenesis, single lab but two orthogonal approaches\",\n      \"pmids\": [\"12924628\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"PEX19 has two functionally distinct splice variants: PEX19ΔE2 (lacking N-terminal domain D1) fails to restore peroxisomal biogenesis in PEX19-deficient fibroblasts despite binding PMPs, while PEX19ΔE8 (lacking C-terminal domain D3 including the CAAX/farnesylation motif) successfully restores biogenesis, demonstrating that farnesylation is not essential for peroxisomal biogenesis and that the N-terminal domain is required for function.\",\n      \"method\": \"In vitro protein interaction studies, functional complementation in PEX19-deficient fibroblasts, in vitro/in vivo farnesylation assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional complementation with interaction studies, single lab, two orthogonal approaches\",\n      \"pmids\": [\"11883941\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Three conserved surface regions on PEX3 are functionally distinct: the PEX19-binding region is required for PEX19 binding and PEX3 stability; a hydrophobic groove near the base of PEX3 is required for PMP insertion and maturation of preperoxisomes; and an acidic cluster has no apparent functional relevance. The PEX3-PEX19 interaction is crucial for de novo peroxisome formation.\",\n      \"method\": \"Site-directed mutagenesis, pulldown assays, functional complementation in peroxisome-deficient cells, crystallographic analysis\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — mutagenesis combined with biochemical and functional assays, single lab with multiple orthogonal approaches\",\n      \"pmids\": [\"22624858\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Functional mapping of Pex19 domains in Pichia pastoris shows: the N-terminal region (aa 1-150) contains the Pex3-binding site and its deletion disrupts Pex3 interaction while preserving Pex10 binding; the C-terminal region (aa 89-300) contains the mPTS-binding domain and its deletion disrupts Pex10 binding while leaving Pex3 interactions intact. Pex25 is critical for peroxisome formation with C-terminal deletion variants and enhances Pex3 interactions.\",\n      \"method\": \"Deletion mutagenesis, yeast two-hybrid, co-immunoprecipitation, functional growth assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — deletion mutagenesis with binding and functional assays, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"28526747\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"In budding yeast, Pex19 acts as an import mediator for a subset of mitochondrial outer membrane tail-anchored proteins (Fis1 and Gem1). Deletion of PEX19 reduces steady-state levels of Fis1 and Gem1, impairs their in organello import, causes growth defects under respiratory conditions and mitochondrial morphology alterations. Recombinant Pex19 binds directly to Fis1 and Gem1 tail-anchored proteins.\",\n      \"method\": \"In organello import assay, deletion mutant analysis, in vitro binding (pulldown), growth assays, mitochondrial morphology assessment\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro direct binding combined with in organello functional import assay and genetic loss-of-function, multiple orthogonal methods in single lab\",\n      \"pmids\": [\"30033679\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PEX19 mediates targeting of UBXD8 (a VCP/P97-recruitment factor) to lipid droplets via the ER, in a farnesylation-dependent manner, independently of peroxisome function. Non-farnesylated PEX19 fully restores peroxisomal metabolic activity, while farnesylated PEX19 controls neutral lipid metabolism through a peroxisome-independent mechanism involving sorting of a specific subset of proteins to lipid droplets. Loss of this PEX19-dependent lipid droplet proteome causes accumulation of excess triacylglycerols.\",\n      \"method\": \"Farnesylation-site mutagenesis, organelle proteomics, lipid metabolic assays, lipidomics, knockdown/knockout\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis combined with proteomics and metabolic assays, single lab, multiple orthogonal approaches\",\n      \"pmids\": [\"35557938\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PEX19 is an intrinsically disordered protein that becomes partially structured upon binding PEX3. Hydrogen-exchange mass spectrometry shows three regions become shielded in PEX19 upon PEX3 interaction: N-terminus, a short middle stretch (F64-L74), and C-terminus. PEX3's binding groove becomes more protected. The N-terminus of PEX19 likely initiates binding to PEX3, followed by subtle PEX3 conformational changes that stabilize PEX19 folding.\",\n      \"method\": \"Hydrogen exchange mass spectrometry (HX-MS), in vitro complex formation\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, single method (HX-MS), but detailed conformational analysis at peptide resolution\",\n      \"pmids\": [\"25062251\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Pex11 contains one Pex19-binding site (Pex19-BS) required for Pex19-dependent membrane insertion but non-essential for peroxisomal trafficking, and a second Pex19-independent mPTS for peroxisomal trafficking. Pex19 acts as a chaperone by binding the Pex19-BS in Pex11, protecting it from spontaneous oligomerization and aggregation. Both homo- and heterotypic interactions via Pex11 N-terminal helical domains mediate self-interaction.\",\n      \"method\": \"Mutagenesis, in vitro binding assays, aggregation protection assay, in vivo targeting assays, co-immunoprecipitation\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis with functional targeting assays and in vitro chaperone assay, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"35011719\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"A conserved PEX19 helix (αd) plays a dual role: it shields the PEX26 transmembrane domain from cytosolic chaperones, and it interacts with the cytosolic domain of PEX3 to trigger PEX26 release at the peroxisome membrane. The PEX3-G138E mutant abolishes the secondary PEX19-αd/PEX3 interaction, preventing PEX26 release from PEX19.\",\n      \"method\": \"Biochemical assays, mass spectrometry analysis, mutagenesis (PEX3-G138E), co-immunoprecipitation\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis combined with biochemical and MS analysis, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"38585659\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Viperin (an interferon-stimulated gene) physically interacts with PEX19 and co-localizes with peroxisomal proteins in association with lipid droplets. Reduction of PEX19 expression abolishes the ability of viperin to augment RLR (RIG-I-like receptor) antiviral signaling through peroxisomal MAVS, suggesting viperin uses PEX19 to position peroxisomes at the mitochondrial/MAM MAVS signaling synapse.\",\n      \"method\": \"Proteomics-based screening, co-immunoprecipitation, co-localization, siRNA knockdown, IFN-β reporter assays\",\n      \"journal\": \"Life science alliance\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP interaction confirmed with functional knockdown, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"34108265\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Dengue virus (DENV) and Zika virus (ZIKV) capsid proteins bind PEX19 through a conserved PEX19-binding motif similar to that found in cellular PMPs, but this interaction does not result in targeting of capsid proteins to peroxisomes. The presence of capsid protein causes peroxisome loss through impaired peroxisomal biogenesis via a PEX19-independent mechanism.\",\n      \"method\": \"Co-immunoprecipitation, virus infection in peroxisome-deficient cells, mutagenesis, immunofluorescence\",\n      \"journal\": \"Viruses\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP with functional cell assays, single lab, multiple orthogonal approaches\",\n      \"pmids\": [\"35215846\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Yeast Msp1 (dual-localized AAA-ATPase on mitochondria and peroxisomes) cooperates with the Pex19-Pex3 pathway for correct Pex15 localization: newly synthesized Pex15 targets to peroxisomes primarily via Pex19/Pex3; mistargeted Pex15 on mitochondrial OM is extracted by mitochondrial Msp1 and can be re-routed to peroxisomes via the Pex19-Pex3 pathway; and even correctly localized peroxisomal Pex15 is extracted by peroxisomal Msp1 but returned to peroxisomes via Pex19-Pex3.\",\n      \"method\": \"In vitro import assay, genetic epistasis (msp1Δ, pex19Δ mutants), co-immunoprecipitation, subcellular fractionation\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with import assays and fractionation, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"40344504\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"In Drosophila Pex19 mutants (peroxisome-deficient), Hnf4 signaling becomes hyperactivated, leading to up-regulation of lipase 3 and mitochondrial β-oxidation enzymes, resulting in enhanced lipolysis, elevated free fatty acids, maximal β-oxidation, and mitochondrial damage. Increased acid lipase expression and free fatty acid accumulation were also found in Pex19-deficient patient fibroblasts, suggesting conservation.\",\n      \"method\": \"Drosophila Pex19 loss-of-function mutants, transcriptomics, lipidomics, patient fibroblast analysis, genetic interaction with Hnf4\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Drosophila genetic model with biochemical validation, cross-species conservation tested in patient fibroblasts\",\n      \"pmids\": [\"29282281\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The C-terminus of PEX19 interacts with the cytoplasmic tail of IAV M2 protein. IAV infection or PEX19 knockdown reduces peroxisome numbers, leading to ROS accumulation and attenuation of peroxisome-MAVS-mediated antiviral response and downstream type III interferon production. M2-PEX19 interaction disrupts PEX19 binding to PEX14 and PMP24.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, overexpression, virus growth assays, immunofluorescence\",\n      \"journal\": \"Viruses\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP combined with knockdown and functional antiviral assays, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"39205283\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Rat PEX19i, a peroxisome-proliferator-inducible splice variant with a C-terminal hydrophobic segment instead of the CAAX box, can restore peroxisomes in pex19 mutant cells (with slightly lower efficiency). The C-terminal CAAX region of Pex19p is not essential for membrane association or interaction with Pex3p and Pex16p. Non-prenylated Pex19p interacts with Pex14p but more weakly than farnesylated Pex19p.\",\n      \"method\": \"Functional complementation assay, co-immunoprecipitation, in vitro binding assay\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional complementation with binding studies, single lab, two orthogonal approaches\",\n      \"pmids\": [\"28391327\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PEX19 is a predominantly cytosolic, intrinsically disordered chaperone and import receptor that binds newly synthesized class I peroxisomal membrane proteins (PMPs) via hydrophobic PEX19-binding motifs in their membrane-peroxisomal targeting signals (mPTS); farnesylation of the C-terminal CAAX motif allosterically reshapes the PEX19 cargo-binding domain to enhance PMP recognition; the PEX19–PMP complex is delivered to peroxisomes by docking of PEX19's N-terminal domain onto PEX3, an integral peroxisomal membrane protein that serves as the receptor for PEX19, after which cargo is inserted into the membrane and PEX19 is recycled to the cytosol; PEX19 also functions as a chaperone for a subset of tail-anchored proteins destined for mitochondria and lipid droplets, and its farnesylated form independently coordinates neutral lipid storage and lipid droplet proteome composition, while additionally serving as a platform for peroxisome-based innate antiviral signaling through MAVS.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PEX19 is a predominantly cytosolic, intrinsically disordered chaperone and import receptor that drives the biogenesis of peroxisomal membranes by binding, stabilizing, and delivering newly synthesized class I peroxisomal membrane proteins (PMPs) [#0, #1, #3]. It recognizes a broad spectrum of PMPs through hydrophobic PEX19-binding motifs embedded in their membrane targeting signals (mPTS), and these binding sites are evolutionarily conserved and functionally interchangeable between human and yeast cargo [#1, #10]. PEX19 is bimodally distributed, with loss of function causing PMP degradation or mislocalization to mitochondria and a failure of peroxisome membrane assembly that underlies Zellweger syndrome complementation group J [#0, #3]. Cargo recognition is allosterically tuned by farnesylation of the C-terminal CAAX motif, which buries the farnesyl group in an internal cavity of the PEX19 C-terminal domain and reshapes its surface into hydrophobic pockets that engage aromatic/aliphatic PMP side chains [#4, #8]. The PEX19–PMP complex is targeted to the peroxisome by docking of PEX19's N-terminal domain onto the integral membrane receptor PEX3: PEX3 binds a conserved phenylalanine-containing motif in disordered PEX19 with nanomolar affinity, inducing partial folding of PEX19, and a distinct PEX3 hydrophobic groove mediates subsequent PMP insertion [#2, #7, #13, #17]. PEX19 functions as a chaperone for tail-anchored PMPs such as PEX26 and PEX11, shielding their transmembrane domains from aggregation and triggering cargo release at the membrane through a secondary PEX19–PEX3 contact [#5, #18, #19]. Beyond peroxisomes, PEX19 mediates import of a subset of mitochondrial outer-membrane tail-anchored proteins and, in its farnesylated form, sorts proteins to lipid droplets to control neutral lipid storage [#15, #16], and it serves as a platform for peroxisome-based RLR/MAVS antiviral signaling that is targeted by viral proteins [#20, #24].\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Establishing that PEX19 is post-translationally modified and peroxisome-associated set the biochemical groundwork for its membrane-targeting role.\",\n      \"evidence\": \"Protein purification, farnesyl identification, immunofluorescence and EM localization\",\n      \"pmids\": [\"8188701\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Function of farnesylation not yet defined\", \"Cargo or partners unknown at this stage\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Identifying PEX19 as a 299-aa CAAX protein required for peroxisome membrane assembly and as the gene mutated in Zellweger complementation group J answered whether PEX19 acts before matrix import and tied it to human disease.\",\n      \"evidence\": \"Functional complementation of CHO/fibroblast mutants, mutation analysis\",\n      \"pmids\": [\"10051604\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular cargo-recognition mechanism not resolved\", \"Docking receptor unidentified\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Demonstrating saturable, broad-spectrum PMP binding and that mislocalizing PEX19 mislocalizes PMPs defined PEX19 as the cytosolic carrier of membrane proteins.\",\n      \"evidence\": \"Co-IP, fractionation, nuclear mislocalization, loss-of-function complementation\",\n      \"pmids\": [\"10704444\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether PEX19 is chaperone, receptor, or both unresolved\", \"Targeting signal definition incomplete\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Defining PEX19 as both cytosolic chaperone and import receptor for class I PMPs (with a PEX19-independent class II) and identifying PEX3 as its docking factor established the core import pathway.\",\n      \"evidence\": \"In vitro binding, mPTS mutagenesis, heterologous docking, cell-free import, complementation\",\n      \"pmids\": [\"14709540\", \"15007061\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of PEX19-PEX3 and PEX19-cargo binding unknown\", \"Cargo release/recycling step undefined\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Validating predicted PEX19-binding sites in human and yeast PMPs and showing they coincide with peroxisomal targeting motifs established evolutionary conservation of the mPTS code.\",\n      \"evidence\": \"Peptide-array binding, cross-species in vivo targeting assays\",\n      \"pmids\": [\"15781447\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Rules distinguishing class I from class II cargo incomplete\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Mapping two PEX19-binding sites in the tail-anchored protein PEX26 showed PEX19 handles TA-PMPs and prevents their mitochondrial mistargeting.\",\n      \"evidence\": \"Peptide binding, targeting and mutagenesis assays, ortholog validation\",\n      \"pmids\": [\"16763195\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Delivery machinery for TA-PMPs not yet defined\", \"Release mechanism unknown\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"The PEX3–PEX19 peptide co-crystal structure revealed a hydrophobic groove engaging PEX19 Phe29 with nanomolar affinity, giving the docking interaction atomic detail.\",\n      \"evidence\": \"X-ray crystallography, ITC, mutagenesis\",\n      \"pmids\": [\"20554521\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Conformational state of full-length PEX19 during docking unresolved\", \"How cargo binding couples to docking unknown\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Structural analysis of Pex14N showed PEX19 and Pex5 bind competitively at the same surface via a F/YFxxxF motif, linking PEX19 to the broader import apparatus.\",\n      \"evidence\": \"NMR/X-ray structures, mutagenesis, in vitro and in vivo binding\",\n      \"pmids\": [\"19197237\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of competition with Pex5 not fully defined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Showing PEX19 forms a cytosolic PEX26 complex delivered via PEX3 without requiring TRC40 distinguished the mammalian peroxisomal TA pathway from ER targeting.\",\n      \"evidence\": \"Reciprocal Co-IP, siRNA, dominant-negative, mutagenesis, fractionation\",\n      \"pmids\": [\"23460677\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Energetics of insertion not defined\", \"Cargo release trigger unknown\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The NMR structure of farnesylated PEX19 CTD showed farnesylation allosterically reshapes the cargo-binding surface, resolving why this lipid modification enhances PMP recognition.\",\n      \"evidence\": \"NMR structure, mutagenesis, in vitro binding, patient-fibroblast complementation\",\n      \"pmids\": [\"28281558\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Why some PEX19 functions are farnesylation-independent unresolved\", \"Dynamics of cargo loading in cells not measured\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Hydrogen-exchange MS established PEX19 as intrinsically disordered that partially folds upon PEX3 binding, with the N-terminus initiating the interaction.\",\n      \"evidence\": \"HX-MS, in vitro complex formation\",\n      \"pmids\": [\"25062251\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single method, no high-resolution structure of the disordered regions\", \"Order of cargo vs PEX3 engagement not directly observed\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Splice-variant complementation showed the N-terminal domain is essential while the CAAX/farnesylation region is dispensable for peroxisome biogenesis, dissecting domain requirements.\",\n      \"evidence\": \"Functional complementation in PEX19-deficient fibroblasts, farnesylation assays\",\n      \"pmids\": [\"11883941\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Apparent tension with farnesylation-dependent cargo recognition not reconciled\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Functional dissection of three PEX3 surfaces separated PEX19-binding/stability from a distinct PMP-insertion groove, refining how docking and insertion are partitioned.\",\n      \"evidence\": \"Site-directed mutagenesis, pulldowns, complementation, crystallography\",\n      \"pmids\": [\"22624858\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of PMP insertion through the groove undefined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Domain mapping in Pichia placed the Pex3-binding site in the N-terminus and the mPTS-binding site in the C-terminus, confirming a bipartite functional architecture across species.\",\n      \"evidence\": \"Deletion mutagenesis, yeast two-hybrid, Co-IP, growth assays\",\n      \"pmids\": [\"28526747\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Role of Pex25 in human cells untested\", \"Single lab\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"A non-CAAX inducible rat splice variant that still complements showed the prenylation region is not essential for membrane association or PEX3/PEX16 binding, qualifying the role of farnesylation.\",\n      \"evidence\": \"Functional complementation, Co-IP, in vitro binding\",\n      \"pmids\": [\"28391327\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Generalizability to human PEX19 unclear\", \"Reduced complementation efficiency mechanism undefined\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Identifying Pex19 as an import mediator for mitochondrial outer-membrane TA proteins (Fis1, Gem1) extended its chaperone role beyond peroxisomes.\",\n      \"evidence\": \"In organello import, deletion analysis, in vitro binding, growth and morphology assays\",\n      \"pmids\": [\"30033679\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mammalian relevance not established here\", \"How specificity between mitochondrial and peroxisomal TA proteins is set unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Showing farnesylated PEX19 sorts UBXD8 to lipid droplets and controls neutral-lipid metabolism independently of peroxisome function revealed a distinct lipid-storage role.\",\n      \"evidence\": \"Farnesylation mutagenesis, organelle proteomics, lipidomics, knockdown/knockout\",\n      \"pmids\": [\"35557938\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of LD-protein selection undefined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Defining a Pex19-dependent insertion site and a Pex19-independent mPTS in Pex11, and an anti-aggregation chaperone activity, refined how PEX19 separates trafficking from insertion.\",\n      \"evidence\": \"Mutagenesis, in vitro binding, aggregation-protection, targeting assays, Co-IP\",\n      \"pmids\": [\"35011719\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of aggregation protection unknown\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identifying a PEX19 helix (αd) that shields the PEX26 TMD and engages PEX3 to trigger cargo release, abolished by PEX3-G138E, supplied a mechanism for the membrane release step.\",\n      \"evidence\": \"Biochemical assays, MS, mutagenesis (PEX3-G138E), Co-IP\",\n      \"pmids\": [\"38585659\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the same release mechanism applies to other cargo unknown\", \"In vivo kinetics of release not measured\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showing Msp1 cooperates with the Pex19-Pex3 pathway to extract and re-route mistargeted or extracted Pex15 added a quality-control dimension to PEX19-mediated TA targeting.\",\n      \"evidence\": \"In vitro import, genetic epistasis (msp1Δ, pex19Δ), Co-IP, fractionation\",\n      \"pmids\": [\"40344504\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mammalian conservation untested\", \"Signal triggering re-extraction undefined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Drosophila Pex19 loss showed peroxisome deficiency hyperactivates Hnf4-driven lipolysis and β-oxidation with mitochondrial damage, conserved in patient fibroblasts, linking PEX19 to systemic lipid homeostasis.\",\n      \"evidence\": \"Drosophila loss-of-function, transcriptomics, lipidomics, patient fibroblasts\",\n      \"pmids\": [\"29282281\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs secondary contribution of PEX19 unclear\", \"Mammalian in vivo validation limited\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Linking viperin and PEX19 to positioning of peroxisomes for RLR/MAVS antiviral signaling implicated PEX19 in innate immunity.\",\n      \"evidence\": \"Proteomic screen, Co-IP, co-localization, siRNA, IFN-β reporter\",\n      \"pmids\": [\"34108265\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of peroxisome repositioning undefined\", \"Direct vs indirect MAVS link unproven\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"DENV/ZIKV capsids binding PEX19 via a PMP-like motif without being targeted to peroxisomes, while causing PEX19-independent peroxisome loss, defined a viral subversion mode.\",\n      \"evidence\": \"Co-IP, infection in peroxisome-deficient cells, mutagenesis, immunofluorescence\",\n      \"pmids\": [\"35215846\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of capsid-PEX19 binding unclear\", \"Mechanism of peroxisome loss undefined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"IAV M2 binding the PEX19 C-terminus to disrupt PEX14/PMP24 interactions and attenuate peroxisome-MAVS antiviral signaling further established PEX19 as a viral target in innate immunity.\",\n      \"evidence\": \"Co-IP, siRNA, overexpression, virus growth assays, immunofluorescence\",\n      \"pmids\": [\"39205283\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether M2 competes with cargo at the same site untested\", \"In vivo relevance not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PEX19 mechanistically discriminates among peroxisomal, mitochondrial, and lipid-droplet destinations for overlapping tail-anchored/hydrophobic cargo, and how farnesylation-dependent versus -independent functions are balanced in cells, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model of organelle selectivity\", \"Cellular regulation of farnesylation state unknown\", \"Structure of full-length cargo-loaded PEX19 lacking\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0044183\", \"supporting_discovery_ids\": [1, 0, 18, 15]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [1, 5, 9]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 2, 0]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [8, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005777\", \"supporting_discovery_ids\": [0, 3, 4, 11]},\n      {\"term_id\": \"GO:0005811\", \"supporting_discovery_ids\": [16]},\n      {\"term_id\": \"GO:0005741\", \"supporting_discovery_ids\": [15]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 1, 2, 3, 13]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [1, 5, 9, 18]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [1, 18]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [16, 23]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [20, 24]}\n    ],\n    \"complexes\": [\n      \"PEX3-PEX19 docking complex\",\n      \"PEX19-PEX26 cytosolic complex\"\n    ],\n    \"partners\": [\n      \"PEX3\",\n      \"PEX26\",\n      \"PEX14\",\n      \"PEX11\",\n      \"PEX16\",\n      \"UBXD8\",\n      \"RSAD2\",\n      \"FIS1\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}