Affinage

PEX1

Peroxisomal ATPase PEX1 · UniProt O43933

Length
1283 aa
Mass
142.9 kDa
Annotated
2026-06-10
78 papers in source corpus 25 papers cited in narrative 24 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

PEX1 is an AAA-family ATPase essential for peroxisomal matrix protein import; its loss produces import-incompetent peroxisomal membrane remnants ("ghosts") that retain membrane proteins but lack matrix content and can be rescued by PEX1 re-expression (PMID:9398847, PMID:9398848, PMID:26644511, PMID:36534601). PEX1 functions as an obligate partner of PEX6, with which it forms a heterohexameric double-ring complex in which the two subunits alternate; the N-terminal D1 ring is catalytically inactive and the C-terminal D2 ring carries out the ATP hydrolysis that powers the motor (PMID:26170309, PMID:26066397). This complex acts as a protein translocase that processively threads and unfolds substrates through its central pore via a pore-loop staircase, driven by D2 ATP hydrolysis and inter-subunit communication (PMID:29321502, PMID:37741838). Its critical substrate is monoubiquitinated PEX5, the recycled PTS1 import receptor, which engages the complex through its ubiquitin moiety and is globally unfolded during ATP-dependent extraction from the peroxisomal membrane (PMID:29884772); the complex similarly unfolds and is anchored to the membrane via the tether Pex15/PEX26, bound by the Pex6 N1 domain (PMID:29321502, PMID:38036174). PEX1 and PEX6 are mutually stabilizing, and disrupted assembly triggers proteasomal degradation of PEX1, a mechanism that underlies the common disease allele G843D, which destabilizes the D2 domain and impairs assembly while retaining residual motor activity (PMID:11439091, PMID:40158855). Mutations spanning loss of PEX1 protein to attenuated PEX1–PEX6 interaction cause the peroxisome biogenesis disorder spectrum from severe Zellweger syndrome to milder NALD/IRD, with residual protein levels and PEX6-binding capacity determining phenotypic severity (PMID:9671729, PMID:11439091, PMID:11389485). Loss of PEX1 secondarily activates ROS-driven pexophagy, which is a consequence rather than the cause of the import defect (PMID:32013259, PMID:41267209).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    Established PEX1 as an AAA-ATPase whose loss specifically abolishes matrix protein import while leaving peroxisomal membranes intact, distinguishing import failure from organelle absence.

    Evidence Functional complementation in CG1 patient fibroblasts with PEX5 Western blot

    PMID:9398847 PMID:9398848

    Open questions at the time
    • Mechanism by which PEX1 acts on PEX5 not yet defined
    • No partner protein identified at this stage
  2. 1998 High

    Identified PEX6 as the direct physical partner of PEX1 and showed the interaction is required for biogenesis, framing PEX1 function as dependent on heterocomplex formation.

    Evidence Yeast two-hybrid, in vitro pulldown, and allele-specific genetic suppression by PEX6 overexpression

    PMID:9671729

    Open questions at the time
    • Stoichiometry and architecture of the complex unknown
    • How the interaction enables import not addressed
  3. 1998 High

    Demonstrated that the common G843D allele is temperature-sensitive, defining it as a misfolded but partially functional protein rather than a null.

    Evidence Immunofluorescence and biochemical peroxisome assays at 30°C vs 37°C in patient fibroblasts and CHO mutants

    PMID:9817926

    Open questions at the time
    • Molecular basis of thermolability unresolved
    • Fate of misfolded protein not determined
  4. 2001 High

    Linked PEX1–PEX6 binding capacity and residual protein level to clinical severity, establishing the genotype-phenotype logic of the disease spectrum.

    Evidence Co-IP of PEX1 mutants with PEX6 and protein stability quantification across multiple alleles in patient fibroblasts

    PMID:11389485 PMID:11439091

    Open questions at the time
    • Degradation pathway for unstable PEX1 not identified
    • No structural explanation for binding loss
  5. 2004 High

    Solved the PEX1 N-terminal domain structure, revealing a double-psi-barrel fold shared with p97/VCP and NSF and implying an adaptor-binding role analogous to other membrane AAA-ATPases.

    Evidence X-ray crystallography at 2.05 Å with structural homology analysis (mouse N-domain)

    PMID:15328346

    Open questions at the time
    • Functional adaptor of the N-domain not identified
    • Full-length architecture unknown
  6. 2006 Medium

    Characterized two N-terminal/Walker-motif activities: phosphoinositide binding by the N-domain and a Walker A1 requirement for both PEX6 binding and peroxisomal targeting.

    Evidence Protein-lipid overlay with arginine mutagenesis; co-IP and localization of PEX1-G606E at permissive/non-permissive temperatures

    PMID:16723118 PMID:17018057

    Open questions at the time
    • Physiological role of lipid binding uncharacterized
    • Walker A1 data from a single unreplicated study
  7. 2015 High

    Resolved the complex as an alternating PEX1/PEX6 heterohexameric double ring with an inactive D1 and active D2 ATPase ring, defining it mechanistically as a p97-like protein-extraction machine and localizing catalytic activity to Pex6 D2.

    Evidence Cryo-EM in multiple nucleotide states plus ATPase assays and Walker B mutagenesis (yeast Pex1/Pex6)

    PMID:26066397 PMID:26170309

    Open questions at the time
    • Physiological substrate not yet captured
    • Translocation directionality and processivity unproven
  8. 2015 High

    Separated the complex's role from membrane biogenesis: Pex1 depletion blocks matrix import but spares membrane protein delivery, and pex1Δ ghosts can be matured to functional peroxisomes upon Pex1 restoration.

    Evidence Conditional Pex1 depletion with matrix vs membrane import assays; EM/tomography of ghosts with re-expression rescue (yeast)

    PMID:26644511 PMID:26644516

    Open questions at the time
    • Whether ghosts are import precursors or stalled intermediates not fully resolved
  9. 2018 High

    Identified direct substrates and showed processive unfolding: the complex threads and unfolds the membrane anchor Pex15 through its pore, and monoubiquitinated PEX5 engages PEX1/PEX6 via its ubiquitin and is globally unfolded during ATP-dependent extraction.

    Evidence In vitro unfolding and pore-loop mutagenesis with cryo-EM (Pex15); cell-free system with photoaffinity cross-linking and PEGylation (Ub-PEX5)

    PMID:29321502 PMID:29884772

    Open questions at the time
    • How ubiquitin recognition couples to pore engagement not fully defined
    • Fate of PEX5 after extraction not traced here
  10. 2023 High

    Defined the translocation mechanism at the residue level: a pore-1 loop staircase in D2 with a 'twin-seam' heterodimer that disengages to drive substrate movement, while the inactive D1 ring undergoes D2-fueled conformational cycling.

    Evidence Cryo-EM of S. cerevisiae Pex1/Pex6 with endogenous substrate trapped in the D2 pore

    PMID:37741838

    Open questions at the time
    • Identity of the trapped endogenous substrate not established
    • Full ATPase cycle kinetics incomplete
  11. 2023 High

    Assigned membrane tethering to the Pex6 N1 domain, which binds Pex15 and contacts a Pex1 D2 loop to stabilize the heterohexamer, with ATPase-active but biologically inactive complex when N1 is deleted.

    Evidence X-ray crystallography of Pex6 N1, cryo-EM, AlphaFold2 modeling, binding assays, in vivo complementation

    PMID:38036174

    Open questions at the time
    • Equivalent role of Pex1 N1 not fully resolved
    • Coupling of tethering to substrate extraction unclear
  12. 2025 High

    Explained the molecular pathology of G843D: it destabilizes the D2 domain and impairs PEX6 assembly while retaining residual motor activity, and impaired assembly itself triggers proteasomal degradation of PEX1, providing a rationale for stabilization-based rescue.

    Evidence In vitro ATPase assays, co-IP, proteasome inhibition, deubiquitinase-fusion stabilization, and import rescue in human cells

    PMID:40158855

    Open questions at the time
    • E3 ligase mediating PEX1 degradation not identified
    • Therapeutic generalizability across alleles untested
  13. 2022 Medium

    Distinguished primary import function from secondary effects: PEX1 absence increases ghost abundance, and an N-terminally truncated isoform fails to rescue import but alters pre-peroxisomal vesicle number, hinting at a moonlighting N-terminal role.

    Evidence CRISPR PEX1-KO HEK293 with full-length and truncated isoform re-expression and import assays

    PMID:36534601

    Open questions at the time
    • Mechanism of N-terminal vesicle-regulatory role undefined
    • Single lab
  14. 2025 Medium

    Resolved that pexophagy is downstream of import failure and mapped its molecular triggers: PEX1 loss drives ROS, activating a TBK1-MARCHF7-PXMP4-NBR1 axis, while blocking pexophagy does not restore import or β-oxidation.

    Evidence Yeast epistasis with β-oxidation/import assays; HeLa knockdown with co-IP, ubiquitination, phosphorylation and flux assays

    PMID:32013259 PMID:41267209

    Open questions at the time
    • Conservation of the TBK1-MARCHF7-PXMP4-NBR1 axis across cell types untested
    • How ROS arises from import failure not detailed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PEX1 dysfunction produces tissue-specific phenotypes such as inner hair cell synaptic defects, and the in vivo significance of N-domain lipid binding, remain unresolved.
  • Mechanism linking peroxisome loss to ribbon synapse/exocytosis defects unknown
  • Physiological role of phosphoinositide binding by the N-domain uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 3 GO:0140657 ATP-dependent activity 3 GO:0008289 lipid binding 1
Localization
GO:0005777 peroxisome 2 GO:0005829 cytosol 1
Pathway
R-HSA-9609507 Protein localization 3 R-HSA-9612973 Autophagy 3 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
HNRNPA1PEX15PEX26PEX5PEX6
Complex memberships
PEX1–PEX6 AAA-ATPase heterohexamer

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Human PEX1 encodes a 147-kDa AAA-family ATPase required for peroxisomal matrix protein import; PEX1-deficient cells show severe defects in matrix protein import and destabilization of PEX5 (the PTS1 receptor), even though peroxisomes are present and capable of importing membrane proteins. Functional complementation in CG1 patient fibroblasts; Western blot analysis of PEX5 levels Nature genetics High 9398847 9398848
1998 PEX1 and PEX6 physically interact with each other; this interaction is required for peroxisome biogenesis. The common G843D mutation in PEX1 attenuates the PEX1–PEX6 interaction in both yeast two-hybrid and in vitro binding assays, and overexpression of PEX6 can suppress PEX1 G843D phenotypes in an allele-specific manner. Yeast two-hybrid assay; in vitro binding (pulldown); genetic suppression by overexpression Proceedings of the National Academy of Sciences of the United States of America High 9671729
1998 The PEX1 G843D missense mutation causes temperature-sensitive peroxisome assembly: peroxisomes form at 30°C but not 37°C in patient fibroblasts and CHO cell mutants transfected with PEX1-G843D, demonstrating the mutation produces a misfolded but partially functional protein. Immunofluorescence microscopy and biochemical peroxisome assays in patient fibroblasts and transfected CHO mutants at 30°C vs. 37°C Human molecular genetics High 9817926
2001 PEX1-G843D protein is largely degraded in vivo at 37°C but present at normal levels at 30°C; ZS-associated PEX1 mutants (L664P, deletion 634–690) are stably expressed at both temperatures but fail to bind PEX6, whereas G843D retains ~50% of wild-type PEX6 binding. PEX1–PEX6 interaction is thus the key determinant of phenotypic severity. Western blot of patient fibroblasts at permissive/non-permissive temperatures; co-immunoprecipitation of PEX1 mutants with PEX6 The Biochemical journal High 11439091
2001 Residual PEX1 protein levels correlate with clinical phenotype severity: complete absence of PEX1 protein is associated with severe Zellweger syndrome, whereas NALD/IRD patients retain residual protein (especially those carrying the G843D allele). Growing G843D fibroblasts at 30°C increases PEX1 protein 2–3-fold with recovery of peroxisomal function, indicating G843D generates a misfolded, thermolabile protein. Western blot quantification of PEX1 protein in patient fibroblasts at 37°C and 30°C; biochemical peroxisome function assays American journal of human genetics High 11389485
2004 The crystal structure of the mouse PEX1 N-terminal domain was determined at 2.05-Å resolution, revealing a double-psi-barrel fold structurally similar to the N-terminal domains of p97/VCP and NSF (RMSD ~2.1–2.7 Å), suggesting a common adaptor-binding function in membrane-associated AAA-ATPases. X-ray crystallography at 2.05-Å resolution The Journal of biological chemistry High 15328346
2006 The N-terminal domain of PEX1 binds phosphoinositides, preferentially phosphatidylinositol 3-monophosphate and phosphatidylinositol 4-monophosphate; a conserved arginine residue (surrounded by hydrophobic residues) is essential for this lipid-binding activity, as shown by mutational analysis. Lipid-binding assays (protein–lipid overlay); site-directed mutagenesis of the conserved arginine The FEBS journal Medium 17018057
2006 A mutation in the Walker A1 motif of PEX1 (G606E) abolishes PEX1–PEX6 interaction at 37°C but not 30°C, and causes cytosolic mislocalization of PEX1 at the non-permissive temperature, demonstrating that the Walker A1 motif is essential for both PEX1–PEX6 interaction and peroxisomal targeting of PEX1. Co-immunoprecipitation; immunofluorescence localization of PEX1 in CHO cell mutants transfected with PEX1-G606E at 30°C vs. 37°C Biochemical and biophysical research communications Medium 16723118
2015 Cryo-EM structures of the Pex1/Pex6 complex reveal an unprecedented heterohexameric double ring in which Pex1 and Pex6 alternate. Each subunit has two N-terminal domains (N1, N2); N1 of Pex1 is mobile. The N-terminal D1 ATPase ring is inactive and symmetric; the C-terminal D2 ring is active and asymmetric with subunits likely in different nucleotide states. This organization is analogous to p97, suggesting a role in protein extraction from the peroxisomal membrane. Cryo-electron microscopy with computational model building (Monte Carlo placement + energy minimization); nucleotide state variation Proceedings of the National Academy of Sciences of the United States of America High 26170309
2015 Biochemical analysis of yeast Pex1/Pex6 heterohexamer shows that the C-terminal D2 domains of Pex6 constitute the main ATPase activity; ATP hydrolysis drives a pumping motion of the complex consistent with substrate translocation through the central channel. Walker B mutation in one D2 domain promotes ATP hydrolysis in the neighboring domain, revealing inter-domain communication. ATPase activity assays; cryo-EM structural analysis; Walker B mutagenesis Nature communications High 26066397
2015 Induced depletion of Pex1 in yeast blocks import of matrix proteins but does not affect peroxisomal membrane protein delivery, confirming that the primary role of the Pex1/Pex6 complex is in matrix protein import rather than peroxisomal membrane biogenesis or vesicle fusion. Conditional Pex1 depletion; immunofluorescence and biochemical assays for matrix vs. membrane protein import The Journal of cell biology Medium 26644516
2015 Yeast pex1Δ cells contain peroxisomal membrane remnants (ghosts) lacking matrix proteins but retaining major membrane proteins (Pex2, Pex10, Pex11, Pex13, Pex14). Upon re-introduction of Pex1, these ghosts rapidly incorporated peroxisomal matrix proteins and developed into functional peroxisomes. Electron microscopy (ultrathin sections, electron tomography); immunocytochemistry; Pex1 re-expression rescue The Journal of cell biology High 26644511
2014 Deficiency of Pex1 (along with Pex6 and Pex15) leads to enhanced pexophagy in S. cerevisiae, with almost all peroxisomal membranes associating with phagophore assembly sites in pex1Δ atg1Δ cells. This pexophagy depends on Atg11 and the pexophagy receptor Atg36. Preventing accumulation of ubiquitinated receptors at the peroxisomal membrane does not abolish pexophagy in yeast. Genetic analysis (double mutants); fluorescence microscopy; epistasis with atg mutants Autophagy Medium 24657987
2018 Pex1/Pex6 is a protein translocase that unfolds Pex15 (its membrane anchor) in a pore-loop-dependent and ATP-hydrolysis-dependent manner. Pex15 binds the N-terminal domains of Pex6, then its C-terminal disordered region engages with the pore loops of the motor, which processively threads Pex15 through the central pore. Pex15 also directly binds the cargo receptor Pex5, linking Pex1/Pex6 to the import machinery. In vitro unfolding assays; cryo-EM structural analysis of Pex15 alone and in complex with Pex1/Pex6; pore-loop mutagenesis; pulldown assays Nature communications High 29321502
2018 Peroxisomal monoubiquitinated PEX5 (Ub-PEX5) directly interacts with both PEX1 and PEX6 through its ubiquitin moiety, and the PEX5 polypeptide chain is globally unfolded during ATP-dependent extraction from the peroxisomal membrane, identifying DTM-embedded Ub-PEX5 as a direct substrate of the PEX1–PEX6 complex. Cell-free in vitro system; photoaffinity cross-linking; protein PEGylation assays (to detect unfolding) The Journal of biological chemistry High 29884772
2023 CryoEM structures of S. cerevisiae Pex1/Pex6 with an endogenous substrate trapped in the D2 pore reveal that Pex1/Pex6(D2) subdomains engage substrate via a staircase of pore-1 loops with distinct properties. The D1 ring is catalytically inactive but undergoes conformational changes (alternating pore widening/narrowing) fueled by D2 ATP hydrolysis. A 'twin-seam' Pex1/Pex6(D2) heterodimer disengages from the staircase to drive substrate translocation through a unique inter-subunit communication mechanism. Cryo-EM with endogenous substrate trapped in the pore Nature communications High 37741838
2023 The N1 domain of Pex6 (not Pex1) directly mediates binding to the peroxisomal membrane tether Pex15 and also contacts an extended loop from the D2 ATPase domain of Pex1, influencing Pex1/Pex6 heterohexamer stability. Pex1/ΔN1-Pex6 retains ATPase activity in vitro but fails to support peroxisome function in vivo. X-ray crystallography of Pex6 N1 domain; cryo-EM of Pex1/Pex6; AlphaFold2 modeling; biochemical binding assays; in vivo complementation The Journal of biological chemistry High 38036174
2017 In Arabidopsis, PEX1 stabilizes PEX6 protein levels and vice versa. A pex1 missense allele (pex1-2) reduces both PEX1 and PEX6 protein levels and causes peroxisome dysfunction that is temperature-sensitive and partially rescued by PEX6 overexpression. A second allele (pex1-3) is semidominant, consistent with PEX1 forming a heterooligomer with PEX6 that is poisoned by mutant subunits. Blocking autophagy partially rescues pex1-3 defects and restores normal peroxisome size. Genetic analysis of Arabidopsis pex1 alleles; Western blot of PEX1 and PEX6 levels; PEX6 overexpression rescue; autophagy mutant epistasis Plant physiology Medium 28600347
2020 Blocking pexophagy specifically in pex1Δ yeast (via deletion of pexophagy genes) does not restore peroxisomal matrix protein import or β-oxidation function, demonstrating that PEX1 is directly and essentially involved in peroxisomal matrix protein import and that pex1-induced pexophagy is a consequence rather than the cause of the import defect. Genetic analysis in S. cerevisiae (pex1Δ combined with pexophagy-null mutants); β-oxidation functional assays; matrix protein import assays International journal of molecular sciences Medium 32013259
2021 HNRNPA1 controls PEX1 expression at the post-transcriptional level; depletion of HNRNPA1 reduces PEX1 protein levels, increases peroxisomal ROS, and induces pexophagy (blocked in ATG5-KO cells). Inhibiting ROS with NAC suppresses pexophagy in HNRNPA1-deficient cells. siRNA knockdown of HNRNPA1; Western blot of PEX1; ROS measurement; pexophagy assays; ATG5-KO epistasis Biochemical and biophysical research communications Medium 33545634
2022 In PEX1-KO HEK293 cells, complete absence of PEX1 significantly increases the number of peroxisomal ghosts (import-incompetent membrane vesicles). Re-expression of full-length PEX1 restores peroxisome import competence and abundance. An alternatively spliced PEX1 isoform lacking 321 N-terminal amino acids fails to rescue peroxisomal import defects but reduces the number of peroxisomal vesicles, suggesting a 'moonlighting' role for the N-terminal region of PEX1 in regulating pre-peroxisomal vesicles. CRISPR/Cas9 PEX1-KO in HEK293 cells; re-expression of full-length and truncated PEX1 isoforms; immunofluorescence quantification of peroxisomal ghosts; matrix protein import assays Biological chemistry Medium 36534601
2025 PEX1-G843D (and its yeast homolog ScPex1-G700D) destabilizes Pex1's active D2 ATPase domain and impairs assembly with Pex6, but retains residual AAA-ATPase motor activity in vitro. In human cells, PEX1-G843D is rapidly degraded by the proteasome; impaired Pex1/Pex6 assembly is itself sufficient to trigger proteasomal degradation of PEX1-WT. Fusing a deubiquitinase to PEX1-G843D substantially stabilizes the protein. Induced overexpression of PEX1-G843D restores peroxisome import. In vitro ATPase assays; co-IP for PEX1–PEX6 assembly; proteasome inhibitor treatment; deubiquitinase fusion stabilization; peroxisome import assays in human cell lines The Journal of biological chemistry High 40158855
2025 PEX1 depletion in HeLa cells activates a TBK1-MARCHF7-PXMP4-NBR1 pexophagy axis: PEX1 deficiency induces ROS accumulation that activates TBK1 (phospho-S172), which phosphorylates MARCHF7 (an E3 ligase); MARCHF7 ubiquitinates PXMP4 at K20, and ubiquitinated PXMP4 recruits NBR1 as a pexophagy receptor. siRNA knockdown; functional screening; co-IP; ubiquitination assays; phosphorylation analysis; pexophagy flux assays; PXMP4 K20R mutant rescue Autophagy Medium 41267209
2022 Conditional deletion of Pex1 specifically in inner hair cells (IHCs) of the mouse inner ear causes progressive hearing loss, decreased ABR wave I amplitude (indicative of synaptic defects), decreased ribbon synapse volume, altered IHC exocytosis, and reduced peroxisome number in IHCs, establishing a direct role for PEX1 in IHC synapse development and auditory function. Conditional knockout mice (Gfi1-Cre or VGlut3-Cre × floxed Pex1); ABR electrophysiology; IHC synapse immunofluorescence; exocytosis assays; peroxisome counting Cells Medium 36552747

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders. Nature genetics 193 9398847
1997 Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders. Nature genetics 128 9398848
1998 Disruption of a PEX1-PEX6 interaction is the most common cause of the neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease. Proceedings of the National Academy of Sciences of the United States of America 105 9671729
1998 Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I. Proceedings of the National Academy of Sciences of the United States of America 98 9539740
2001 Disorders of peroxisome biogenesis due to mutations in PEX1: phenotypes and PEX1 protein levels. American journal of human genetics 77 11389485
1995 Pex1, a pollen-specific gene with an extensin-like domain. Proceedings of the National Academy of Sciences of the United States of America 77 7724520
2015 Unique double-ring structure of the peroxisomal Pex1/Pex6 ATPase complex revealed by cryo-electron microscopy. Proceedings of the National Academy of Sciences of the United States of America 71 26170309
2015 Molecular snapshots of the Pex1/6 AAA+ complex in action. Nature communications 68 26066397
2004 Structure of the N-terminal domain of PEX1 AAA-ATPase. Characterization of a putative adaptor-binding domain. The Journal of biological chemistry 66 15328346
1998 Temperature-sensitive mutation in PEX1 moderates the phenotypes of peroxisome deficiency disorders. Human molecular genetics 63 9817926
2018 The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading. Nature communications 57 29321502
2014 Deficiency of the exportomer components Pex1, Pex6, and Pex15 causes enhanced pexophagy in Saccharomyces cerevisiae. Autophagy 57 24657987
2010 Recovery of PEX1-Gly843Asp peroxisome dysfunction by small-molecule compounds. Proceedings of the National Academy of Sciences of the United States of America 52 20212125
2002 PEX1 mutations in complementation group 1 of Zellweger spectrum patients correlate with severity of disease. Pediatric research 51 12032265
1999 Identification of a common PEX1 mutation in Zellweger syndrome. Human mutation 50 10447258
2014 The Pex1-G844D mouse: a model for mild human Zellweger spectrum disorder. Molecular genetics and metabolism 49 24503136
2005 Genetic and clinical aspects of Zellweger spectrum patients with PEX1 mutations. Journal of medical genetics 42 16141001
2018 Peroxisomal monoubiquitinated PEX5 interacts with the AAA ATPases PEX1 and PEX6 and is unfolded during its dislocation into the cytosol. The Journal of biological chemistry 40 29884772
2015 Reevaluation of the role of Pex1 and dynamin-related proteins in peroxisome membrane biogenesis. The Journal of cell biology 37 26644516
2001 Phenotype-genotype relationships in peroxisome biogenesis disorders of PEX1-defective complementation group 1 are defined by Pex1p-Pex6p interaction. The Biochemical journal 36 11439091
2002 Novel PEX1 mutations and genotype-phenotype correlations in Australasian peroxisome biogenesis disorder patients. Human mutation 32 12402331
1999 A common PEX1 frameshift mutation in patients with disorders of peroxisome biogenesis correlates with the severe Zellweger syndrome phenotype. Human genetics 32 10480353
2019 A longitudinal study of retinopathy in the PEX1-Gly844Asp mouse model for mild Zellweger Spectrum Disorder. Experimental eye research 30 31254513
2006 The common phospholipid-binding activity of the N-terminal domains of PEX1 and VCP/p97. The FEBS journal 27 17018057
2005 PEX1 mutations in the Zellweger spectrum of the peroxisome biogenesis disorders. Human mutation 27 16086329
2016 Severe early onset retinitis pigmentosa in a Moroccan patient with Heimler syndrome due to novel homozygous mutation of PEX1 gene. European journal of medical genetics 25 27633571
2015 Yeast pex1 cells contain peroxisomal ghosts that import matrix proteins upon reintroduction of Pex1. The Journal of cell biology 25 26644511
2017 Structure and Function of p97 and Pex1/6 Type II AAA+ Complexes. Frontiers in molecular biosciences 24 28611990
2019 Structural Mapping of Missense Mutations in the Pex1/Pex6 Complex. International journal of molecular sciences 20 31374812
2018 Zellweger spectrum disorder patient-derived fibroblasts with the PEX1-Gly843Asp allele recover peroxisome functions in response to flavonoids. Journal of cellular biochemistry 19 30362618
2000 Temperature-sensitive mutation of PEX6 in peroxisome biogenesis disorders in complementation group C (CG-C): comparative study of PEX6 and PEX1. Pediatric research 19 11004248
2021 AAV-mediated PEX1 gene augmentation improves visual function in the PEX1-Gly844Asp mouse model for mild Zellweger spectrum disorder. Molecular therapy. Methods & clinical development 18 34703844
2017 The PEX1 ATPase Stabilizes PEX6 and Plays Essential Roles in Peroxisome Biology. Plant physiology 18 28600347
2023 Structure of the peroxisomal Pex1/Pex6 ATPase complex bound to a substrate. Nature communications 17 37741838
2020 Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female. Molecular genetics and metabolism reports 15 32596134
2020 Longitudinal study of Pex1-G844D NMRI mouse model: A robust pre-clinical model for mild Zellweger spectrum disorder. Biochimica et biophysica acta. Molecular basis of disease 14 32693164
2005 Novel PEX1 coding mutations and 5' UTR regulatory polymorphisms. Human mutation 14 16088892
2016 Transcription factor PEX1 modulates extracellular matrix turnover through regulation of MMP-9 expression. Cell and tissue research 13 27826738
2004 PEX1 deficiency presenting as Leber congenital amaurosis. Pediatric neurology 13 15301838
2019 Mild Zellweger syndrome due to functionally confirmed novel PEX1 variants. Journal of applied genetics 12 31628608
2019 A Mechanistic Perspective on PEX1 and PEX6, Two AAA+ Proteins of the Peroxisomal Protein Import Machinery. International journal of molecular sciences 12 31652724
2012 Analysis of a Chinese pedigree with Zellweger syndrome reveals a novel PEX1 mutation by next-generation sequencing. Clinica chimica acta; international journal of clinical chemistry 12 23247051
2022 Comparison of human PEX knockout cell lines suggests a dual role of PEX1 in peroxisome biogenesis. Biological chemistry 9 36534601
2021 Depletion of HNRNPA1 induces peroxisomal autophagy by regulating PEX1 expression. Biochemical and biophysical research communications 9 33545634
2023 The lignin-degrading abilities of Gelatoporia subvermispora gat1 and pex1 mutants generated via CRISPR/Cas9. Environmental microbiology 7 36959722
2022 Loss of Pex1 in Inner Ear Hair Cells Contributes to Cochlear Synaptopathy and Hearing Loss. Cells 7 36552747
2017 A novel PEX1 mutation in a Moroccan family with Zellweger spectrum disorders. Human genome variation 7 28446956
2025 Spatial characterization of RPE structure and lipids in the PEX1-p.Gly844Asp mouse model for Zellweger spectrum disorder. Journal of lipid research 6 40058592
2021 Two siblings with Heimler syndrome caused by PEX1 variants: follow-up of ophthalmologic findings. Ophthalmic genetics 6 33955814
2020 The Peroxisomal PTS1-Import Defect of PEX1- Deficient Cells Is Independent of Pexophagy in Saccharomyces cerevisiae. International journal of molecular sciences 6 32013259
2016 Dysmorphic Facial Features and Other Clinical Characteristics in Two Patients with PEX1 Gene Mutations. Case reports in pediatrics 6 27882258
2023 The N1 domain of the peroxisomal AAA-ATPase Pex6 is required for Pex15 binding and proper assembly with Pex1. The Journal of biological chemistry 5 38036174
2022 Diagnostic Odyssey in an Adult Patient with Ophthalmologic Abnormalities and Hearing Loss: Contribution of RNA-Seq to the Diagnosis of a PEX1 Deficiency. International journal of molecular sciences 5 36293220
2012 Zellweger syndrome and associated brain malformations: report of a novel Peroxin1 (PEX1) mutation in a Native American infant. Journal of child neurology 5 22378672
2024 PEX1 is essential for glycosome biogenesis and trypanosomatid parasite survival. Frontiers in cellular and infection microbiology 4 38510966
2021 A Chinese newborn with Zellweger syndrome and compound heterozygous mutations novel in the PEX1 gene: a case report and literature review. Translational pediatrics 4 33708531
2021 Compound heterozygous p. Arg949Trp and p. Gly970Ala mutations deteriorated the function of PEX1p: A study on PEX1 in a patient with Zellweger syndrome. Journal of cellular biochemistry 4 33955040
2011 Two novel PEX1 mutations in a patient with Zellweger syndrome: the first Korean case confirmed by biochemical, and molecular evidence. Annals of clinical and laboratory science 4 21844578
2024 Zebrafish PEX1 Is Required for the Generation of GABAergic Neuron in p3 Domain. Development & reproduction 3 39845513
2011 Characterization of two common 5' polymorphisms in PEX1 and correlation to survival in PEX1 peroxisome biogenesis disorder patients. BMC medical genetics 3 21846392
2006 A temperature-sensitive CHO pex1 mutant with a novel mutation in the AAA Walker A1 motif. Biochemical and biophysical research communications 3 16723118
2025 Heimler Syndrome With Tooth Agenesis, Abnormal Enamel and Dentin Mineralization, Root Maldevelopment, and PEX1 Mutation. International dental journal 2 40466212
2023 Ophthalmic Manifestations of Heimler Syndrome in Two Siblings With PEX1 Variants. Journal of pediatric ophthalmology and strabismus 2 37092661
2023 Analysis of Altered Flowering Related Genes in a Multi-Silique Rapeseed (Brassica napus L.) Line zws-ms Based on Combination of Genome, Transcriptome and Proteome Data. Plants (Basel, Switzerland) 2 37446989
2021 Allogeneic Hematopoietic Stem Cell Transplantation for PEX1-Related Zellweger Spectrum Disorder: A Case Report and Literature Review. Frontiers in pediatrics 2 34513757
2017 Novel compound heterozygous mutations in the PEX1 gene in two Chinese newborns with Zellweger syndrome based on whole exome sequencing. Clinica chimica acta; international journal of clinical chemistry 2 28432012
2025 PEX1G843D remains functional in peroxisome biogenesis but is rapidly degraded by the proteasome. The Journal of biological chemistry 1 40158855
2025 Estimation of PEX1-mediated Zellweger spectrum disorder births and population prevalence by population genetics modeling. Genetics in medicine open 1 40519747
2025 Regulation of pexophagy by a novel TBK1-MARCHF7-PXMP4-NBR1 axis in PEX1-depleted HeLa cells. Autophagy 1 41267209
2023 A novel compound heterozygous PEX1 variant in Heimler syndrome. Experimental eye research 1 37871882
2022 PEX1 is a mediator of α1-adrenergic signaling attenuating doxorubicin-induced cardiotoxicity. Journal of biochemical and molecular toxicology 1 35979984
2004 Crystallographic characterization of the N-terminal domain of PEX1. Acta crystallographica. Section D, Biological crystallography 1 15502339
2026 Clinically relevant AAV8- PEX1 gene therapy preserves retinal integrity and function long-term in a murine model of Zellweger spectrum disorder. bioRxiv : the preprint server for biology 0 42182139
2025 Pex1 loss-of-function in zebrafish is viable and recapitulates hallmarks of Zellweger spectrum disorders. Frontiers in molecular neuroscience 0 41268363
2024 PEX1G843D remains functional in peroxisome biogenesis but is rapidly degraded by the proteasome. bioRxiv : the preprint server for biology 0 39713301
2023 Purification of a Recombinant Human PEX1/PEX6 AAA+ ATPase Complex from HEK293TT Cells. Methods in molecular biology (Clifton, N.J.) 0 36952198
2023 Novel PEX1 mutations in fibroblasts from children with Zellweger spectrum disorders exhibit temperature sensitive characteristics. Epilepsy & behavior : E&B 0 37385119
2023 The Pex6 N1 domain is required for Pex15 binding and proper assembly with Pex1. bioRxiv : the preprint server for biology 0 37745580

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