Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on Enzyme Commission mapping
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniPathway vocabulary mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Combined Automated Annotation using Multiple IEA Methods
Falcon deep research report for human PEX10
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Deep research synthesis of 2024 reviews identifies the heterotrimeric PEX2/PEX10/PEX12 RING E3 ligase complex as the central concept for PEX10 annotation, functioning both as a membrane-embedded ubiquitin ligase and as a retrotranslocation channel for receptor export.
"the peroxisomal membrane contains a heterotrimeric RING E3 ligase complex composed of **PEX2, PEX10, and PEX12**, which mediates ubiquitination events essential for receptor recycling and quality control"
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The synthesis distinguishes PEX10 (with PEX12) as implicated in RADAR-pathway polyubiquitination, versus PEX2's monoubiquitination role.
"PEX10 (often with PEX12) is implicated in polyubiquitination (RADAR pathway), distinct from PEX2's monoubiquitination role."
Molecular anatomy of the peroxin Pex12p: ring finger domain is essential for Pex12p function and interacts with the peroxisome-targeting signal type 1-receptor Pex5p and a ring peroxin, Pex10p.
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PEX10 interacts with PEX12 RING finger, PEX2, and PEX5 in yeast two-hybrid and in vitro binding assays
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PEX12 co-immunoprecipitates with PEX10 from CHO-K1 cells
Phenotype-genotype relationships in PEX10-deficient peroxisome biogenesis disorder patients.
The peroxisomal membrane targeting elements of human peroxin 2 (PEX2).
Distinct modes of ubiquitination of peroxisome-targeting signal type 1 (PTS1) receptor Pex5p regulate PTS1 protein import.
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PEX10 RING finger has E3 ubiquitin ligase activity with E2 UbcH5C
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E3 activity enhanced by PEX12
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PEX10-PEX12 complex monoubiquitinates PEX5 at multiple lysine residues
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PEX10 E3 activity required for PEX5 export and peroxisomal protein import
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RING finger mutations C273A and C310G abolish E3 activity
ATM functions at the peroxisome to induce pexophagy in response to ROS.
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PEX2/10/12 E3 ligase participates in PEX5 ubiquitination during pexophagy
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Knockdown of RING peroxins reduces both mono- and polyubiquitination of PEX5
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ATM phosphorylates PEX5 at S141 to promote ubiquitination
A peroxisomal ubiquitin ligase complex forms a retrotranslocation channel.
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Cryo-EM structure of PEX2-PEX10-PEX12 complex at 3.1 Angstrom resolution
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Each subunit contributes 5 TM segments forming an open channel with 10 Angstrom pore
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RF10 and RF12 have extensive interface mediating RING-RING interaction
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RF2 positioned above pore for monoubiquitination; RF10 and RF12 cooperate for polyubiquitination
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Channel facilitates retrotranslocation of PEX5 through peroxisomal membrane
Isolation of the human PEX12 gene, mutated in group 3 of the peroxisome biogenesis disorders.
Identification of PEX10, the gene defective in complementation group 7 of the peroxisome-biogenesis disorders.
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PEX10 identified as gene defective in CG7 of PBDs
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PEX10 expression rescues matrix protein import in CG7 cells
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PEX10-deficient cells import membrane but not matrix proteins
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H290Q missense mutation in zinc-binding domain identified in NALD patient
Mutations in PEX10 is the cause of Zellweger peroxisome deficiency syndrome of complementation group B.
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PEX10 encodes 326 aa protein with two TM segments and C3HC4 RING motif
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Both N- and C-terminal regions exposed to cytosol
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PEX10 expression restores peroxisome biogenesis in CG-B patients
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RING finger required for biological function
Peroxisome synthesis in the absence of preexisting peroxisomes.
PEX2:PEX10:PEX12 binds PEX5S,L (in PEX5S:PEX13:PEX14) and Ub:UBE2D1,2,3
PEX2:PEX10:PEX12 monoubiquitinates PEX5S,L at cysteine-11
Cargo of PEX5S,L translocates from the cytosol to the peroxisomal matrix
PEX5S,L:Cargo binds PEX13:PEX14:PEX2:PEX10:PEX12 (Docking and Translocation Module)
PEX2:PEX10:PEX12 monoubiquitinates PEX5L at cysteine-11
PEX1:PEX6:PEX26:ZFAND6 dissociates Ub:PEX5L and PEX7 from PEX14:PEX13:PEX2:PEX10:PEX12 and translocates PEX5L and PEX7 from the peroxisomal membrane to the cytosol
Cargo of PEX5L:PEX7 translocates from the cytosol to the peroxisomal matrix
PEX2:PEX10:PEX12:Ub:PEX5L:PEX7:PEX13:PEX14 binds PEX1:PEX6:PEX26 and ZFAND6
PEX2:PEX10:PEX12 binds PEX5L (in PEX5L:PEX7:PEX13:PEX14:PEX2:PEX10:PEX12) and Ub:UBE2D1,2,3
PEX2:PEX10:PEX12:Ub:PEX5S,L:PEX13:PEX14 binds PEX1:PEX6:PEX26 and ZFAND6