Affinage

PEX3

Peroxisomal biogenesis factor 3 · UniProt P56589

Length
373 aa
Mass
42.1 kDa
Annotated
2026-06-10
58 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PEX3 is an integral peroxisomal membrane protein that serves as the central membrane platform for peroxisomal membrane protein (PMP) import, peroxisome biogenesis, and the regulated turnover, inheritance, and contact-site organization of peroxisomes (PMID:15007061, PMID:10430017). It adopts a single-spanning topology with an N-terminal luminal segment whose first ~33 residues are sufficient for peroxisomal targeting and a cytoplasmic C-terminal domain (PMID:10430017); this cytosolic domain folds into a novel large helical bundle that presents a membrane-distal hydrophobic groove engaging the cytosolic import receptor PEX19 with nanomolar affinity through a critical PEX19 phenylalanine (F29) (PMID:20554521). Acting as the membrane docking factor for PEX19, PEX3 is required and sufficient to dock PEX19 at organelles and to drive class I PMP import while leaving matrix and class II import intact (PMID:15007061, PMID:12924628), with reciprocal stabilization of the otherwise aggregation-prone PEX3 by PEX19 (PMID:25062251). PEX3 itself reaches peroxisomes through the ER: it inserts co-translationally via the SRP/Sec61 route and exits in ATP-dependent budding vesicles (PMID:26572236), using redundant N-terminal sorting signals and its transmembrane segment for intra-ER routing (PMID:23951409), a step dependent on PEX16 (PMID:25002403); reintroduction of PEX3 can both reassemble peroxisomes via the ER and mature pre-existing preperoxisomal vesicles (PMID:16487342, PMID:24590171). Beyond biogenesis, PEX3 nucleates selective autophagic degradation of peroxisomes by recruiting and activating pexophagy receptors (Atg36 in S. cerevisiae, Atg30 in P. pastoris) and directly promoting their phosphorylation by Hrr25 kinase to initiate pexophagy (PMID:22643220, PMID:25694426, PMID:32958557), a function balanced against PEX3 import partners that compete for overlapping surfaces on PEX3 and on the receptor (PMID:29260977, PMID:40847603). PEX3 additionally controls peroxisome inheritance as a class V myosin receptor (PMID:19822674), retention via Inp1 bridging to plasma-membrane PI(4,5)P2 (PMID:32970792), and contact-site formation with lipid droplets (PMID:40628847). Inactivating PEX3 mutations cause Zellweger syndrome by abolishing peroxisome membrane synthesis and mislocalizing PMPs (PMID:10871277), and in mammals PEX3 regulates plasmalogen metabolism that activates AKT/GSK3β/ITGB3 signaling in myocardial repair and is required for spermiogenesis (PMID:38951640, PMID:38062668).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Established the basic identity and topology of PEX3 as an integral peroxisomal membrane protein and its physical link to PEX19, defining the molecular entity to be studied.

    Evidence Topology mapping, GFP truncation analysis, mammalian two-hybrid, and Co-IP of in vitro translated proteins

    PMID:10430017

    Open questions at the time
    • Functional role of the PEX3-PEX19 interaction not yet defined
    • Mechanism of N-terminal targeting unresolved
  2. 2000 High

    Showed PEX3 is essential for peroxisome membrane synthesis and that its trafficking is independent of classical COPI/COPII secretory routes, while linking PEX3 loss to human disease.

    Evidence Brefeldin A, dominant-negative SAR1, and microscopy in Zellweger patient cells

    PMID:10871277

    Open questions at the time
    • Actual trafficking route of PEX3 left unspecified
    • Which PMPs are mislocalized and why was not fully resolved
  3. 2003 High

    Localized the PEX3-PEX19 interaction in living cells to the peroxisome and mapped targeting versus binding domains, distinguishing PEX3's two functional modules.

    Evidence Live-cell FRET imaging and domain-deletion rescue in patient fibroblasts

    PMID:12924628

    Open questions at the time
    • Structural basis of binding not yet known
    • Dynamics of the docking cycle unresolved
  4. 2004 High

    Defined PEX3 as the membrane docking factor that is necessary and sufficient to recruit PEX19 and to drive class I but not class II PMP import, establishing pathway selectivity.

    Evidence Co-IP, heterologous organelle docking, dominant-negative inhibition, class I/II import assays

    PMID:15007061

    Open questions at the time
    • Molecular interface not defined at residue level
    • How docking converts to membrane insertion unclear
  5. 2010 High

    Provided the atomic-resolution mechanism of PEX19 recognition, revealing a novel helical bundle fold and a hydrophobic groove engaging PEX19 F29 with nanomolar affinity.

    Evidence X-ray crystallography of the PEX3 cytosolic domain with PEX19 peptide plus binding and mutagenesis

    PMID:20554521

    Open questions at the time
    • Crystallized only a PEX19-derived peptide, not full-length PEX19
    • Membrane-embedded context not captured
  6. 2012 High

    Functionally validated the crystallographically identified groove as required for PMP insertion and preperoxisome maturation, and discovered PEX3's role in recruiting the pexophagy receptor.

    Evidence Mutagenesis of groove residues with biogenesis assays; pexophagy-specific pex3 alleles and Atg36 mislocalization in yeast

    PMID:22624858 PMID:22643220

    Open questions at the time
    • How a single groove serves both PEX19 docking and Atg36 recruitment unclear
    • Mechanism of Atg36 activation not yet defined
  7. 2013 Medium

    Resolved how PEX3 reaches peroxisomes via the ER, identifying redundant N-terminal sorting signals and a transmembrane-dependent exit step conserved across species.

    Evidence Pex3/Sec66 chimeras and domain swaps in yeast and Drosophila cells

    PMID:23951409

    Open questions at the time
    • Identity of the ER subdomain machinery unresolved
    • Vesicle budding factors not identified
  8. 2014 Medium

    Refined the biogenesis model by showing preperoxisomal vesicles can form without PEX3 and that PEX3 sorts to and matures them, while PEX16 mediates ER-to-peroxisome PEX3 transport; also defined a mammalian pexophagy pathway and a myosin V receptor role.

    Evidence Microscopy/fractionation with pex3 atg1 double deletions; ssPEX3 time-lapse imaging with PEX16 perturbation; PEX3 overexpression with NBR1/p62 knockdown; myosin globular-tail binding in Y. lipolytica

    PMID:19822674 PMID:24590171 PMID:25002403 PMID:25007327

    Open questions at the time
    • De novo versus preexisting-vesicle origin of peroxisomes still debated across systems
    • Ubiquitinated peroxisomal target in PEX3-driven pexophagy unidentified
    • Whether mammalian PEX3 acts as a myosin receptor untested
  9. 2015 High

    Defined the early secretory entry of PEX3 (SRP/Sec61 co-translational insertion, ATP-dependent ER exit) and showed PEX3 actively initiates pexophagy by promoting receptor phosphorylation rather than mere docking.

    Evidence Photocrosslinking and fluorescence spectroscopy of nascent chains plus ER exit assay; binding/phosphorylation/Atg11 recruitment assays in P. pastoris

    PMID:25694426 PMID:26572236

    Open questions at the time
    • Budding vesicle coat machinery unidentified
    • Kinase responsible for Atg30 phosphorylation not yet pinned in this study
  10. 2018 Medium

    Revealed competitive regulation of pexophagy through overlapping binding of Pex3 and Atg37 on Atg30, showing Pex3 negatively and Atg37 positively tune Hrr25 phosphorylation; also implicated Pex3 in peroxisome-vacuole contact sites.

    Evidence Binding competition and phosphorylation assays in P. pastoris; EM/fluorescence with Pex3 overexpression in H. polymorpha

    PMID:29260977 PMID:30595161

    Open questions at the time
    • Contact-site role rests on overexpression microscopy without mechanistic dissection
    • How competing inputs are integrated to set pexophagy threshold unclear
  11. 2019 Medium

    Extended PEX3's PEX19-docking function to a divergent eukaryote, establishing Pex3 as essential master regulator of glycosome biogenesis in trypanosomes.

    Evidence RNAi depletion, fractionation, microscopy, and Co-IP in trypanosomes (two independent studies)

    PMID:31341002 PMID:31369765

    Open questions at the time
    • Structural basis of the divergent trypanosomal interface not solved
    • Therapeutic exploitation untested
  12. 2020 High

    Reconstituted the catalytic role of Pex3 in pexophagy and resolved the molecular basis of peroxisome retention, showing Pex3 directly drives Hrr25 phosphorylation of Atg36 and bridges Inp1 to plasma-membrane PI(4,5)P2.

    Evidence In vitro phosphorylation with recombinant Pex3/Hrr25/Atg36 plus Co-IP and genetics; artificial PM-PER tether rescue with PI(4,5)P2 binding assays

    PMID:32958557 PMID:32970792

    Open questions at the time
    • How Pex3 allosterically enhances the Atg36-Hrr25 reaction unresolved
    • Whether mammalian PEX3 uses an analogous retention tether unknown
  13. 2021 Medium

    Mapped the human PEX3-dependent clientele by proteomics, confirming peroxisomal and ER-hairpin clients and unexpectedly linking PEX3 deficiency to collagen-related proteins.

    Evidence Label-free quantitative proteomics in PEX3-depleted HeLa cells and Zellweger fibroblasts

    PMID:34884833

    Open questions at the time
    • Mechanism connecting PEX3 to collagen-pathway clients unresolved
    • Direct versus indirect dependence not distinguished
  14. 2024 Medium

    Linked PEX3 to organ-level physiology, showing it shapes plasmalogen metabolism that activates AKT/GSK3β/ITGB3 signaling for myocardial regeneration and is required for spermiogenesis.

    Evidence Cardiomyocyte-specific and germ cell-specific Pex3 knockout mice with lipidomics, proteomics, and pathway analysis

    PMID:38062668 PMID:38951640

    Open questions at the time
    • How plasmalogen changes mechanistically license ITGB3 membrane localization unclear
    • Whether spermatid defects are plasmalogen-dependent untested
  15. 2025 Medium

    Integrated PEX3 into a competitive partner network and contact-site biology, showing Pex19/Atg30/Inp1 compete for overlapping Pex3 surfaces, that Pex3 drives peroxisome-lipid droplet contacts, and that it cooperates in Msp1-mediated re-targeting of tail-anchored Pex15.

    Evidence H. polymorpha Pex3-Pex19 crystal structure with AlphaFold2 and overexpression competition; cross-species clustering assays; msp1/pex19/pex3 epistasis for Pex15

    PMID:40344504 PMID:40628847 PMID:40847603

    Open questions at the time
    • How partner competition is regulated physiologically rather than by overexpression unclear
    • Contact-site clustering function characterized largely by overexpression

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single PEX3 hydrophobic groove temporally coordinates competing biogenesis, inheritance, retention, and pexophagy partners, and how mammalian PEX3 lipid/signaling roles connect to its conserved membrane-import function, remain unresolved.
  • No unified model for spatiotemporal switching between PEX3 partners
  • Mammalian retention/inheritance and pexophagy roles largely inferred from yeast
  • Mechanistic link between PEX3 import function and plasmalogen/AKT signaling unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 1
Localization
GO:0005777 peroxisome 3 GO:0005783 endoplasmic reticulum 3 GO:0005635 nuclear envelope 1 GO:0005811 lipid droplet 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-9609507 Protein localization 3 R-HSA-9612973 Autophagy 3 R-HSA-1643685 Disease 1
Partners
ATG30ATG36ATG37HRR25INP1PEX15PEX16PEX19

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 PEX3 functions as a docking factor for PEX19 at the peroxisomal membrane: PEX3 is required for PEX19 to dock at peroxisomes, interacts specifically with the docking domain of PEX19, and is sufficient to dock PEX19 at heterologous organelles. PEX3 binds PEX19 via a conserved motif essential for docking activity. Transient inhibition of PEX3 abrogates class I PMP import but has no effect on class II PMP import or peroxisomal matrix protein import. Co-immunoprecipitation, heterologous organelle docking assay, transient inhibition with dominant-negative constructs, class I vs. class II PMP import assays The Journal of cell biology High 15007061
1999 Human PEX3 is an integral peroxisomal membrane protein with the N-terminus inside the peroxisome and C-terminus facing the cytoplasm. The N-terminal 33 amino acids are necessary and sufficient to direct PEX3 to peroxisomes. PEX19 interacts with PEX3 as shown by mammalian two-hybrid assay and co-immunoprecipitation of in vitro translated proteins. Immunofluorescence microscopy with N- and C-terminal tagged constructs, GFP fusion truncation analysis, mammalian two-hybrid assay, co-immunoprecipitation of in vitro translated proteins European journal of cell biology High 10430017
2000 Inactivating mutations in human PEX3 cause Zellweger syndrome, abrogate peroxisome membrane synthesis, and result in reduced abundance or mislocalization of PMPs to mitochondria. Inhibition of COPI function by brefeldin A and inhibition of COPII-dependent traffic by dominant-negative SAR1 mutant both fail to block PEX3 transport to peroxisomes or PEX3-mediated peroxisome biogenesis, indicating PEX3 targeting and peroxisome membrane synthesis occur independently of COPI and COPII. Brefeldin A treatment, dominant-negative SAR1 expression, fluorescence microscopy, immunoblotting The Journal of cell biology High 10871277
2010 Crystal structure of the cytosolic domain of human PEX3 in complex with a PEX19-derived peptide reveals that PEX3 adopts a novel large helical bundle fold. A hydrophobic groove at the membrane-distal end of PEX3 engages the PEX19 peptide with nanomolar affinity. Mutagenesis identifies phenylalanine 29 in PEX19 as critical for this interaction. Key PEX3 residues are highly conserved across species. X-ray crystallography, surface plasmon resonance/binding affinity measurement, site-directed mutagenesis The Journal of biological chemistry High 20554521
2012 In S. cerevisiae, Pex3 recruits the pexophagy receptor Atg36 to the peroxisomal membrane. pex3 alleles blocked specifically in pexophagy cannot recruit Atg36. When Pex3 is redirected to mitochondria, Atg36 also localizes there and restores mitophagy in cells lacking Atg32. Atg36 binds Atg8 and the autophagy adaptor Atg11. Genetic isolation of pex3 alleles, fluorescence microscopy, epistasis analysis, subcellular re-targeting experiments The EMBO journal High 22643220
2012 Mutations in the PEX19-binding region of PEX3 reduce affinity for PEX19 and destabilize PEX3. A hydrophobic groove near the base of PEX3 is required for peroxisomal membrane protein insertion and maturation of preperoxisomes. An acidic cluster on PEX3 surface does not appear to be functionally relevant. Site-directed mutagenesis, biochemical binding assays, functional peroxisome biogenesis assays in peroxisome-deficient cells Traffic (Copenhagen, Denmark) High 22624858
2003 FRET imaging shows that the main intracellular site of PEX3-PEX19 interaction is the peroxisome. PEX3 deletion proteins lacking the N-terminal peroxisomal targeting sequence mislocalize to the cytoplasm, and those lacking the PEX19-binding domain (C-terminal half) mislocalize to mitochondria; neither interacts with PEX19. FRET imaging (EYFP/ECFP fusion proteins), donor fluorescence photobleaching, transfection of PEX3- and PEX19-deficient Zellweger patient fibroblasts European journal of cell biology High 12924628
2014 PEX3 overexpression in mammalian cells induces peroxisome ubiquitination, clustering, and lysosomal degradation via ubiquitin- and NBR1-mediated pexophagy. Peroxisome targeting of PEX3 is essential for this degradation pathway. SQSTM1/p62 is required only for clustering, not degradation. A PEX3 mutant with all lysine and cysteine residues substituted still induces peroxisome ubiquitination, indicating ubiquitination of PEX3 itself is dispensable and an unidentified peroxisomal protein is ubiquitinated. PEX3 overexpression, siRNA knockdown of NBR1 and p62, autophagy inhibitor treatment, fluorescence microscopy, lysine/cysteine mutagenesis Autophagy Medium 25007327
2015 In P. pastoris, Pex3 activates the pexophagy receptor Atg30 by promoting its phosphorylation (a prerequisite for Atg30-Atg11 interaction) and by facilitating recruitment of Atg11 to the receptor-protein complex. Pex3 thus has a role beyond simple Atg30 docking, directly regulating pexophagy initiation. Binding site mapping by mutagenesis, phosphorylation assays, Atg11 recruitment assays The Journal of biological chemistry Medium 25694426
2013 Pex3 is a type III peroxisomal membrane protein that is inserted into the ER membrane and sorted via an ER subdomain (peroxisomal ER, pER) to peroxisomes. The N-terminal 17-amino acid segment of Pex3 contains two redundant signals sufficient for sorting to the pER. Subsequent transport to peroxisomes requires the Pex3 transmembrane segment. This intra-ER sorting mechanism is conserved in human and Drosophila Pex3. Chimeric protein construction (Pex3/Sec66 fusions), fluorescence microscopy in yeast and Drosophila S2R+ cells, domain swap analysis Biology open Medium 23951409
2015 Human PEX3 inserts co-translationally into the mammalian ER via the Sec61 translocon. The N-terminal transmembrane segment of ribosome-bound PEX3 is recognized by the signal recognition particle (SRP). PEX3 then exits the ER via budding vesicles in an ATP-dependent process. Photocrosslinking, fluorescence spectroscopy of ribosome-nascent chain complexes, biochemical ER exit assay (ATP-dependence) Traffic (Copenhagen, Denmark) High 26572236
2006 Upon reintroduction of Pex3p in H. polymorpha pex3 cells, Pex3-GFP initially localizes to the endoplasmic reticulum and nuclear envelope, then to a single developing peroxisome that multiplies by division. Fractionation confirms a small amount of ER/nuclear envelope marker in peroxisomes at the early stage, supporting a role for the ER/nuclear envelope in peroxisome reassembly from Pex3. Inducible GFP-Pex3 expression, live fluorescence microscopy, subcellular fractionation FEMS yeast research Medium 16487342
2014 Pex3 is not required for formation of peroxisomal membrane structures in yeast pex3 mutants; preperoxisomal vesicles containing Pex13, Pex14, Pex8, and alcohol oxidase exist in pex3 cells. When Pex3 is reintroduced, it sorts to these preperoxisomal structures (not to the ER de novo), and they mature into normal peroxisomes. Fluorescence microscopy, fractionation, double deletion (pex3 atg1) analysis to prevent autophagic degradation of vesicles The Journal of cell biology Medium 24590171
2014 PEX16 mediates the peroxisomal trafficking of PEX3 (and PMP34) via the ER, suggesting that PEX16 is required for ER-to-peroxisome transport of PEX3 and that the ER constitutively provides membrane proteins to pre-existing peroxisomes. ER-targeted PEX3 (ssPEX3) construct, quantitative time-lapse fluorescence microscopy, PEX16 depletion/overexpression Journal of cell science Medium 25002403
2009 In Yarrowia lipolytica, Pex3p and Pex3Bp function as peroxisomal receptors for class V myosin (Myo2p equivalent) through direct interaction with the myosin globular tail, mediating peroxisome inheritance. Cells lacking Pex3Bp retain peroxisomes in the mother cell; overexpression of Pex3Bp or Pex3p causes peroxisomes to transfer en masse to the bud. Direct interaction assay (globular tail binding), overexpression and deletion genetics, fluorescence microscopy of peroxisome inheritance The Journal of cell biology Medium 19822674
2009 The cytosolic domain of human PEX3 binds membrane lipids: a recombinant cytosolic domain of PEX3 interacts with liposomes, inducing their flocculation or partial solubilization, and precipitates in the presence of mild detergents. Recombinant protein purification, lipid-binding assays with liposomes, detergent precipitation Biochimica et biophysica acta Low 19715730
2018 In P. pastoris, Pex3 and Atg37 compete for overlapping binding sites in the middle domain of Atg30. Atg37 depends on Pex3 for its peroxisomal membrane localization. Pex3 binding to Atg30 negatively regulates Atg30 phosphorylation by Hrr25 kinase, while Atg37 binding positively regulates it. The binding of Pex3 and Atg37 to Atg30 is mutually exclusive within the middle domain. Binding competition assays, phosphorylation assays, fluorescence microscopy for localization dependence Autophagy Medium 29260977
2018 Pex3 accumulates in patches at peroxisome-vacuole contact sites in H. polymorpha under peroxisome proliferation conditions (methanol medium). Overproduction of Pex3 at non-proliferating conditions also induces peroxisome-vacuole associations, suggesting a direct role for Pex3 in forming a novel peroxisome-vacuole contact site involved in membrane growth. Electron microscopy, fluorescence microscopy, Pex3 overexpression Biochimica et biophysica acta. Molecular cell research Low 30595161
2020 In S. cerevisiae, Pex3 directly promotes Atg36 phosphorylation by the Hrr25 kinase: Atg36 phosphorylation is abolished in cells lacking Pex3 or expressing a Pex3 mutant defective in Atg36 interaction; recombinant Pex3 directly promotes Atg36 phosphorylation by Hrr25 in vitro; and Pex3 enhances the Atg36-Hrr25 interaction (shown by Co-IP). Pex3 binding also protects Atg36 from proteasomal degradation. In vitro phosphorylation assay with recombinant proteins, co-immunoprecipitation, pex3 deletion and point mutant analysis The Journal of biological chemistry High 32958557
2020 Inp1 acts as the plasma membrane-peroxisome (PM-PER) tether via an N-terminal domain that binds PI(4,5)P2 and a C-terminal Pex3-binding domain, forming a bridge between the peroxisomal membrane (via Pex3) and the plasma membrane. Expression of artificial PM-PER tethers restores peroxisome retention in inp1Δ cells. Artificial tether rescue assay, domain deletion and localization studies, PI(4,5)P2-binding assay The Journal of cell biology Medium 32970792
2014 PEX19 remains highly flexible during interaction with PEX3 (as determined by hydrogen exchange mass spectrometry). The N-terminus of PEX19 initiates binding to PEX3. A short stretch in PEX19 (F64-L74) and regions at the N- and C-terminus become shielded from hydrogen exchange upon complex formation. PEX3 becomes more protected in its PEX19-binding groove with only small changes elsewhere. PEX3 is stabilized by PEX19 binding, preventing PEX3 aggregation. Hydrogen exchange mass spectrometry (HX-MS) in vitro PloS one Medium 25062251
2019 Trypanosomal Pex3 localizes to glycosomes and directly interacts with Pex19. Depletion of Pex3 by RNAi leads to mislocalization of glycosomal proteins to the cytosol, reduced glycosome numbers, and parasite death, establishing Pex3 as an essential master regulator of glycosome biogenesis in trypanosomes. Fluorescence microscopy, biochemical fractionation, RNAi depletion, co-immunoprecipitation Life science alliance Medium 31341002
2019 Trypanosomal PEX3 directly interacts with PEX19 (confirmed by co-immunoprecipitation). RNAi knockdown of TbPEX3 causes mislocalization of glycosomal membrane and matrix proteins to the cytosol and severe growth defect. The PEX3-PEX19 interface shows structural differences from human PEX3-PEX19 interface. Co-immunoprecipitation, RNAi knockdown, fluorescence microscopy, secondary structure homology modeling Biochimica et biophysica acta. Molecular cell research Medium 31369765
2024 PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Cardiomyocyte-specific PEX3 knockout disrupts redox homeostasis and endogenous proliferation/development. Mechanistically, PEX3-regulated plasmalogen activates the AKT/GSK3β signaling pathway via plasma membrane localization of ITGB3. Cardiomyocyte-specific Pex3 knockout mice, lipid metabolomics, myocardium-targeted intervention, AKT/GSK3β pathway analysis Communications biology Medium 38951640
2023 Germ cell-specific deletion of Pex3 in mice causes male sterility: destruction of intercellular bridges between spermatids and formation of multinucleated giant cells. Sertoli cell-specific deletion does not affect spermatogenesis. Proteomic analysis reveals defective expression of peroxisomal and spermiogenesis-related proteins in Pex3-deleted spermatids. Conditional knockout (germ cell- and Sertoli cell-specific), fertility analysis, proteomics, fluorescence microscopy Journal of biomedical research Medium 38062668
2025 High levels of Pex3 in S. cerevisiae induce formation of peroxisome clusters surrounded by lipid droplets, mediated by peroxisome-peroxisome and peroxisome-lipid droplet contact sites. The cytosolic domain of Pex3 binds peroxisomes directly, suggesting a role in homotypic contact site formation. This clustering is independent of Pex3 partners Pex19, Inp1, and Atg36. Lipid droplet-peroxisome contact sites require the lipid droplet-localized triacylglycerol lipase Tgl4. Overexpression of Pex3 in Drosophila similarly alters peroxisome and lipid droplet morphology. Pex3 overexpression in yeast and Drosophila, fluorescence microscopy, cytosolic domain binding assay, epistasis with pex19, inp1, atg36 deletions Scientific reports Medium 40628847
2025 In yeast, Pex3 binding partners Pex19, Atg30, and Inp1 compete for overlapping interaction regions on Pex3 (confirmed by crystal structure of H. polymorpha Pex3-Pex19 complex and AlphaFold2 predictions). Overexpression of any binding partner affects peroxisomal processes, with the level of overexpression being the primary determinant of competition. Crystal structure of H. polymorpha Pex3-Pex19 complex, AlphaFold2 modeling, overexpression competition assays, functional peroxisome assays The FEBS journal Medium 40847603
2025 Newly synthesized Pex15 (a tail-anchored peroxisomal membrane protein) is targeted to peroxisomes primarily via the Pex19- and Pex3-dependent pathway. Mistargeted Pex15 on the mitochondrial outer membrane is extracted by Msp1 and returned to peroxisomes via the Pex19-Pex3 pathway. Peroxisome-resident Pex15 is also continuously extracted by peroxisomal Msp1 and re-targeted via Pex19-Pex3. Genetic epistasis (msp1, pex19, pex3 deletions), fluorescence microscopy of Pex15 localization, functional import assays The FEBS journal Medium 40344504
2021 Depletion of PEX3 from human HeLa cells (quantitative proteomics) negatively affects 12 peroxisomal proteins and two hairpin proteins of the ER, confirming PEX19/PEX3 as the pathway for these two client classes. PEX3 deficiency also negatively affects 14 collagen-related proteins with signal peptides or N-terminal transmembrane helices. Label-free quantitative mass spectrometry of total proteome in PEX3-depleted HeLa cells and PEX3-deficient Zellweger fibroblasts, differential protein abundance analysis International journal of molecular sciences Medium 34884833

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Pex3-anchored Atg36 tags peroxisomes for degradation in Saccharomyces cerevisiae. The EMBO journal 230 22643220
2004 PEX3 functions as a PEX19 docking factor in the import of class I peroxisomal membrane proteins. The Journal of cell biology 193 15007061
2000 Inhibitors of COPI and COPII do not block PEX3-mediated peroxisome synthesis. The Journal of cell biology 122 10871277
2014 The membrane peroxin PEX3 induces peroxisome-ubiquitination-linked pexophagy. Autophagy 104 25007327
1999 Identification and characterization of the human peroxin PEX3. European journal of cell biology 94 10430017
2000 Defective peroxisome membrane synthesis due to mutations in human PEX3 causes Zellweger syndrome, complementation group G. American journal of human genetics 80 10958759
2014 Preperoxisomal vesicles can form in the absence of Pex3. The Journal of cell biology 64 24590171
2000 PEX3 is the causal gene responsible for peroxisome membrane assembly-defective Zellweger syndrome of complementation group G. American journal of human genetics 63 10968777
2000 Identification of PEX3 as the gene mutated in a Zellweger syndrome patient lacking peroxisomal remnant structures. Human molecular genetics 59 10942428
2019 The peroxisome biogenesis factors Pex3 and Pex19: multitasking proteins with disputed functions. FEBS letters 55 30776093
2014 PEX16 contributes to peroxisome maintenance by constantly trafficking PEX3 via the ER. Journal of cell science 55 25002403
2010 Insights into peroxisome function from the structure of PEX3 in complex with a soluble fragment of PEX19. The Journal of biological chemistry 48 20554521
2018 WIPI1, BAG1, and PEX3 Autophagy-Related Genes Are Relevant Melanoma Markers. Oxidative medicine and cellular longevity 46 30622661
2006 Reassembly of peroxisomes in Hansenula polymorpha pex3 cells on reintroduction of Pex3p involves the nuclear envelope. FEMS yeast research 46 16487342
2015 Peroxisomal Pex3 activates selective autophagy of peroxisomes via interaction with the pexophagy receptor Atg30. The Journal of biological chemistry 42 25694426
2012 The role of conserved PEX3 regions in PEX19-binding and peroxisome biogenesis. Traffic (Copenhagen, Denmark) 39 22624858
2011 Drosophila carrying pex3 or pex16 mutations are models of Zellweger syndrome that reflect its symptoms associated with the absence of peroxisomes. PloS one 39 21826223
2003 The interaction between human PEX3 and PEX19 characterized by fluorescence resonance energy transfer (FRET) analysis. European journal of cell biology 39 12924628
2009 Pex3 peroxisome biogenesis proteins function in peroxisome inheritance as class V myosin receptors. The Journal of cell biology 34 19822674
2013 Intra-ER sorting of the peroxisomal membrane protein Pex3 relies on its luminal domain. Biology open 33 23951409
2018 Pex3 and Atg37 compete to regulate the interaction between the pexophagy receptor, Atg30, and the Hrr25 kinase. Autophagy 30 29260977
2018 Peroxisome development in yeast is associated with the formation of Pex3-dependent peroxisome-vacuole contact sites. Biochimica et biophysica acta. Molecular cell research 30 30595161
2017 Saccharomyces cerevisiae cells lacking Pex3 contain membrane vesicles that harbor a subset of peroxisomal membrane proteins. Biochimica et biophysica acta. Molecular cell research 26 28552664
2015 Human Peroxin PEX3 Is Co-translationally Integrated into the ER and Exits the ER in Budding Vesicles. Traffic (Copenhagen, Denmark) 23 26572236
2009 The cytosolic domain of PEX3, a protein involved in the biogenesis of peroxisomes, binds membrane lipids. Biochimica et biophysica acta 23 19715730
2012 Newly identified milder phenotype of peroxisome biogenesis disorder caused by mutated PEX3 gene. Brain & development 21 23245813
2020 The Pex3-Inp1 complex tethers yeast peroxisomes to the plasma membrane. The Journal of cell biology 18 32970792
2017 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. PloS one 18 28817674
2019 The early-acting glycosome biogenic protein Pex3 is essential for trypanosome viability. Life science alliance 16 31341002
2019 Evolutionary divergent PEX3 is essential for glycosome biogenesis and survival of trypanosomatid parasites. Biochimica et biophysica acta. Molecular cell research 16 31369765
2007 Overproduction of translation elongation factor 1-alpha (eEF1A) suppresses the peroxisome biogenesis defect in a Hansenula polymorpha pex3 mutant via translational read-through. FEMS yeast research 13 17425673
2024 PEX3 promotes regenerative repair after myocardial injury in mice through facilitating plasma membrane localization of ITGB3. Communications biology 12 38951640
2022 The Pex3-mediated peroxisome biogenesis plays a critical role in metabolic biosynthesis, stress response, and pathogenicity in Alternaria alternata. Microbiological research 12 36334316
2020 Pex3 confines pexophagy receptor activity of Atg36 to peroxisomes by regulating Hrr25-mediated phosphorylation and proteasomal degradation. The Journal of biological chemistry 12 32958557
2017 Biochemical and genetic characterization of an unusual mild PEX3-related Zellweger spectrum disorder. Molecular genetics and metabolism 11 28673549
2021 A Small Molecule Inhibitor of Pex3-Pex19 Interaction Disrupts Glycosome Biogenesis and Causes Lethality in Trypanosoma brucei. Frontiers in cell and developmental biology 10 34350186
2021 Quantitative Proteomics and Differential Protein Abundance Analysis after the Depletion of PEX3 from Human Cells Identifies Additional Aspects of Protein Targeting to the ER. International journal of molecular sciences 10 34884833
2022 rs9390123 and rs9399451 influence the DNA repair capacity of lung cancer by regulating PEX3 and PHACTR2‑AS1 expression instead of PHACTR2. Oncology reports 9 35059740
2016 Novel PEX3 Gene Mutations Resulting in a Moderate Zellweger Spectrum Disorder. JIMD reports 9 27557811
2022 The Effect of a Pex3 Mutation on Hearing and Lipid Content of the Inner Ear. Cells 8 36291074
2014 Association between the intrinsically disordered protein PEX19 and PEX3. PloS one 8 25062251
2021 Novel Trypanocidal Inhibitors that Block Glycosome Biogenesis by Targeting PEX3-PEX19 Interaction. Frontiers in cell and developmental biology 7 34988071
2025 Pex3 promotes formation of peroxisome-peroxisome and peroxisome-lipid droplet contact sites. Scientific reports 6 40628847
2000 The human PEX3 gene encoding a peroxisomal assembly protein: genomic organization, positional mapping, and mutation analysis in candidate phenotypes. Biochemical and biophysical research communications 6 10679269
2025 Msp1 and Pex19-Pex3 cooperate to achieve correct localization of Pex15 to peroxisomes. The FEBS journal 5 40344504
2020 Pex3 is involved in the genetic regulation of Nr3c2 expression in the amygdala of mice. Psychiatry research 5 32045820
2020 Genome sequencing identifies a rare case of moderate Zellweger spectrum disorder caused by a PEX3 defect: Case report and literature review. Molecular genetics and metabolism reports 5 33101983
1988 Purification of fusion proteins expressed by pEX3 and a truncated pEX3 derivative. FEBS letters 5 3136038
2025 Integrative Omics reveals changes in the cellular landscape of peroxisome-deficient pex3 yeast cells. Microbial cell (Graz, Austria) 4 40012703
2024 STED super-resolution microscopy unveils the dynamics of Atg30 on yeast Pex3-labeled peroxisomes. iScience 4 39156652
2025 USF2 regulates the JAK2/STAT3 pathway through PEX3-mediated SLC25A17 upregulation to affect lipid metabolism and promote the progression of lung adenocarcinoma. Toxicology and applied pharmacology 3 40885408
2022 Hypomorphic mutation of PEX3 with peroxisomal mosaicism reveals the oscillating nature of peroxisome biogenesis coupled with differential metabolic activities. Molecular genetics and metabolism 3 35932552
2025 Molecular interactions of Toxoplasma gondii dense granule 23 (GRA23) with host proteins PEX3 and TRAP1. Frontiers in veterinary science 1 40417354
2023 Germ cell-specific deletion of Pex3 reveals essential roles of PEX3-dependent peroxisomes in spermiogenesis. Journal of biomedical research 1 38062668
2026 Identification of a new frameshift homozygous variant of PEX3 gene in a preterm infant with profound global developmental delay and bilateral ptosis: a case report and updated literature review. BMC pediatrics 0 41495707
2025 PEX3 gene knockout influences recombinant xylanase expression by Komagataella phaffii. Synthetic and systems biotechnology 0 40248486
2025 Competition between binding partners of yeast Pex3 affects peroxisome biology. The FEBS journal 0 40847603
2000 Genomic organization, expression analysis, and chromosomal localization of the mouse PEX3 gene encoding a peroxisomal assembly protein. Biological chemistry 0 10839463

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