Affinage

PEX10

Peroxisome biogenesis factor 10 · UniProt O60683

Length
326 aa
Mass
37.1 kDa
Annotated
2026-04-29
22 papers in source corpus 7 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PEX10 is an integral peroxisomal membrane protein with two transmembrane segments and a cytosol-facing C3HC4 zinc RING domain that functions as a core component of the Pex2/Pex10/Pex12 E3-ubiquitin ligase complex required for peroxisomal matrix protein import (PMID:9700193, PMID:9683594). PEX10 acts downstream of PTS1 receptor (PEX5) docking at the peroxisomal membrane; loss of PEX10 does not impair PEX5 membrane association but blocks matrix protein translocation, while peroxisome membrane biogenesis remains intact (PMID:10562279). The RING domain is the essential functional element: missense mutations within it attenuate complementation activity, and the domain mediates physical interaction with PEX12 to coordinate PEX5 ubiquitination and recycling after cargo delivery (PMID:10862081, PMID:10562279). Biallelic loss-of-function mutations in PEX10 cause peroxisome biogenesis disorders of the Zellweger spectrum (PMID:9700193).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 1998 High

    Identification of PEX10 as the gene mutated in a peroxisome biogenesis disorder complementation group established that it encodes an integral peroxisomal membrane protein whose loss selectively abolishes matrix protein import without affecting membrane biogenesis.

    Evidence Expression of epitope-tagged PEX10 in patient fibroblasts with complementation assays and topology mapping in two independent labs

    PMID:9683594 PMID:9700193

    Open questions at the time
    • Position of PEX10 within the import pathway relative to receptor docking was unknown
    • Functional role of the RING domain had not been tested by mutagenesis
    • Direct binding partners on the peroxisome membrane were uncharacterized
  2. 1999 High

    Demonstration that PEX12 physically interacts with both PEX5 and PEX10 through its RING domain, and that PEX10/PEX12 loss does not reduce PEX5 docking, placed PEX10 at a post-docking step in the import cycle.

    Evidence Two-hybrid, blot overlay, co-immunoprecipitation, and genetic suppression assays in mammalian and yeast systems

    PMID:10562279

    Open questions at the time
    • Whether PEX10 directly ubiquitinates PEX5 or acts indirectly was not resolved
    • Stoichiometry and architecture of the PEX2/PEX10/PEX12 complex were unknown
  3. 2000 Medium

    Mutagenesis of the RING zinc-binding domain proved it is the key functional element of PEX10, with a point mutation (H290Q) causing partial loss of activity that correlates with a milder clinical phenotype.

    Evidence Site-directed mutagenesis and functional complementation in patient fibroblasts

    PMID:10862081

    Open questions at the time
    • Biochemical activity of the RING domain (E3 ligase activity) was not directly assayed
    • Single-lab study without independent replication of genotype–phenotype correlation
  4. 2006 Medium

    Physical interaction between plant PEX19 and the C-terminus of PEX10 identified PEX19 as the likely chaperone/receptor for PEX10 targeting to the peroxisomal membrane.

    Evidence Co-immunoprecipitation and GST pull-down with recombinant Arabidopsis proteins

    PMID:16923726

    Open questions at the time
    • Demonstrated in plant orthologs; direct binding in mammalian system not shown in this study
    • Whether PEX19 binding is required for PEX10 membrane insertion was not tested
  5. 2024 Medium

    Discovery that androgen receptor and FOXA1 cooperatively drive PEX10 transcription in prostate cancer cells, and that PEX10 reduces intracellular ROS, linked peroxisomal biogenesis to cancer-cell redox homeostasis.

    Evidence ROS assays, AR ChIP/enhancer analysis, enzalutamide treatment with PEX10 knockdown/overexpression in prostate cancer cell lines

    PMID:39097593

    Open questions at the time
    • Single-lab study; whether AR-driven PEX10 expression is relevant beyond prostate cancer is untested
    • Whether ROS reduction is a direct consequence of restored peroxisomal import or an indirect effect is unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The precise catalytic contribution of PEX10 within the Pex2/Pex10/Pex12 RING complex—whether PEX10 directly transfers ubiquitin to PEX5 or serves a structural/scaffolding role—remains unresolved, as does a high-resolution structure of the mammalian complex.
  • No in vitro ubiquitin transfer assay with purified mammalian PEX10 has been reported
  • High-resolution structure of the human Pex2/Pex10/Pex12 complex is lacking
  • Regulation of complex assembly and turnover during the import cycle is not understood

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0043226 organelle 3
Pathway
R-HSA-9609507 Protein localization 3 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
PEX12PEX19PEX2PEX5
Complex memberships
Pex2/Pex10/Pex12 E3 ligase complex

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 PEX10 encodes an integral peroxisomal membrane protein with two transmembrane segments and a C3HC4 zinc finger RING motif; both N- and C-terminal regions are exposed to the cytosol. Loss of PEX10 function blocks peroxisomal matrix protein import while peroxisome membrane protein import and peroxisome formation remain intact. Expression of epitope-tagged PEX10 in patient fibroblasts, functional complementation assay, mutation analysis Human molecular genetics High 9683594 9700193
1999 PEX12 physically interacts with both PEX5 (PTS1 receptor) and PEX10 through its zinc-binding RING domain; loss of PEX10 or PEX12 does not reduce PEX5 docking to the peroxisome membrane, placing PEX10 and PEX12 downstream of the receptor-docking step in the peroxisomal matrix protein import pathway. Two-hybrid assays, blot overlay assays, coimmunoprecipitation, genetic suppression by overexpression, missense patient mutation analysis The Journal of cell biology High 10562279
2000 The C-terminal zinc-binding RING domain of PEX10 is critical for its function; missense mutation H290Q in this domain reduces activity and correlates with milder clinical phenotype, while nonsense/frameshift mutations removing only the C-terminal third also attenuate activity, demonstrating the zinc-binding domain is the key functional element. Functional complementation assay in patient fibroblasts, site-directed mutagenesis of PEX10 cDNA constructs Human mutation Medium 10862081
2025 PEX10 forms part of a peroxisomal Pex2/Pex10/Pex12 E3-ubiquitin ligase complex that, upon Pex5-Pex8 complex formation, initiates recycling (ubiquitination) of the PTS1 receptor Pex5 after cargo translocation into peroxisomes. Structural (cryo-EM/X-ray of Pex8-Pex5 complex), biochemical interaction assays, functional translocation assays in yeast bioRxivpreprint Medium bio_10.1101_2025.08.30.673231
2024 In prostate cancer cells, PEX10 expression is transcriptionally induced by reactive oxygen species (ROS) activators; the androgen receptor (AR) promotes PEX10 expression in cooperation with FOXA1 as an enhancer. PEX10 reduces intracellular ROS levels, and enzalutamide inhibits PEX10 expression by blocking AR function, thereby sensitizing cells to ROS activators. ROS assays, AR ChIP/enhancer analysis with FOXA1, enzalutamide treatment with PEX10 knockdown/overexpression in prostate cancer cell lines Cell death & disease Medium 39097593
2006 Arabidopsis PEX19 (a cytosolic peroxisomal membrane protein chaperone) physically binds PEX10 through the C-terminus of PEX10, as demonstrated by co-immunoprecipitation and GST pull-down assays, indicating PEX10 is a cargo/client of PEX19 for targeting to the peroxisome membrane. In vitro translation and co-immunoprecipitation, GST pull-down with recombinant proteins Molecular membrane biology Medium 16923726

Source papers

Stage 0 corpus · 22 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in peroxisomal matrix protein import. The Journal of cell biology 115 10562279
1998 Identification of PEX10, the gene defective in complementation group 7 of the peroxisome-biogenesis disorders. American journal of human genetics 103 9683594
2003 An Arabidopsis pex10 null mutant is embryo lethal, implicating peroxisomes in an essential role during plant embryogenesis. Plant physiology 88 14576288
1998 Mutations in PEX10 is the cause of Zellweger peroxisome deficiency syndrome of complementation group B. Human molecular genetics 88 9700193
2007 Requirement of the C3HC4 zinc RING finger of the Arabidopsis PEX10 for photorespiration and leaf peroxisome contact with chloroplasts. Proceedings of the National Academy of Sciences of the United States of America 76 17215364
2010 Different functions of the C3HC4 zinc RING finger peroxins PEX10, PEX2, and PEX12 in peroxisome formation and matrix protein import. Proceedings of the National Academy of Sciences of the United States of America 47 20679226
2006 Identification of novel mutations in PEX2, PEX6, PEX10, PEX12, and PEX13 in Zellweger spectrum patients. Human mutation 39 17041890
2005 Identification and characterization of three peroxins--PEX6, PEX10 and PEX12--involved in glycosome biogenesis in Trypanosoma brucei. Biochimica et biophysica acta 37 16388862
2021 Increased Accumulation of Squalene in Engineered Yarrowia lipolytica through Deletion of PEX10 and URE2. Applied and environmental microbiology 31 34132586
2008 A PEX10 defect in a patient with no detectable defect in peroxisome assembly or metabolism in cultured fibroblasts. Journal of inherited metabolic disease 31 19127411
2003 Genetic heterogeneity of peroxisome biogenesis disorders among Japanese patients: evidence for a founder haplotype for the most common PEX10 gene mutation. American journal of medical genetics. Part A 25 12794690
2000 Phenotype-genotype relationships in PEX10-deficient peroxisome biogenesis disorder patients. Human mutation 22 10862081
2006 Arabidopsis PEX19 is a dimeric protein that binds the peroxin PEX10. Molecular membrane biology 21 16923726
2014 Association study between polymorphisms of PRMT6, PEX10, SOX5, and nonobstructive azoospermia in the Han Chinese population. Biology of reproduction 19 24648396
2019 PEX10, SIRPA-SIRPG, and SOX5 gene polymorphisms are strongly associated with nonobstructive azoospermia susceptibility. Journal of assisted reproduction and genetics 17 30863997
2017 Ataxic form of autosomal recessive PEX10-related peroxisome biogenesis disorders with a novel compound heterozygous gene mutation and characteristic clinical phenotype. Journal of the neurological sciences 9 28320181
2017 Identification of a novel mutation in PEX10 in a patient with attenuated Zellweger spectrum disorder: a case report. Journal of medical case reports 8 28784167
2024 Enzalutamide inhibits PEX10 function and sensitizes prostate cancer cells to ROS activators. Cell death & disease 6 39097593
2019 Ataxia with novel compound heterozygous PEX10 mutations and a literature review of PEX10-related peroxisome biogenesis disorders. Clinical neurology and neurosurgery 6 30640048
2022 How to Detect Isolated PEX10-Related Cerebellar Ataxia? Neuropediatrics 3 35038753
2025 Identification of novel compound heterozygous variants in the PEX10 gene in a Han-Chinese family with PEX10-related peroxisome biogenesis disorders. PloS one 1 40267090
2015 [Abnormal expression of PEX10 gene may be related to epilepsy associated with 1p36 copy number variations]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 25636090