id: P28328
gene_symbol: PEX2
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  PEX2 (Peroxisome biogenesis factor 2 / Peroxin-2) is an integral peroxisomal membrane
  protein containing a RING-type zinc finger domain. It functions as an E3 ubiquitin ligase
  subunit of the PEX2-PEX10-PEX12 retrotranslocation channel complex. This complex catalyzes
  monoubiquitination of the PTS1 receptor PEX5 at Cys-11, a modification required for
  ATP-dependent receptor recycling to the cytosol. Each subunit contributes five transmembrane
  segments that co-assemble into an open channel through which PEX5 is exported. PEX2 also
  independently mediates ubiquitination of peroxisomal membrane proteins (PEX5, PMP70/ABCD3)
  during amino acid starvation to induce pexophagy, and ubiquitinates ATGL/PNPLA2 for
  proteasomal degradation in response to ROS, thereby regulating lipolysis. Mutations in
  PEX2 cause Zellweger spectrum disorders (complementation group 10).
existing_annotations:
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PEX2 is well-established as an integral peroxisomal membrane protein with five
      transmembrane segments (PMID:35768507, PMID:12751901). UniProt confirms peroxisome
      membrane localization (PMID:12751901). IBA annotation is phylogenetically consistent.
    action: ACCEPT
    reason: >-
      Core localization for PEX2. Confirmed by multiple experimental studies including
      subcellular fractionation and fluorescence microscopy (PMID:12751901), and cryo-EM
      structural analysis showing five TM segments (PMID:35768507).
    supported_by:
      - reference_id: PMID:12751901
        supporting_text: >-
          Peroxin 2 (PEX2) is a 35-kDa integral peroxisomal membrane protein with two
          transmembrane regions and a zinc RING domain within its cytoplasmically exposed C-terminus
      - reference_id: PMID:35768507
        supporting_text: >-
          Each subunit of the complex contributes five transmembrane segments that
          co-assemble into an open channel.
- term:
    id: GO:0007031
    label: peroxisome organization
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PEX2 is essential for peroxisome biogenesis and organization. Loss of PEX2 function
      leads to absence of functional peroxisomes in Zellweger syndrome patients (PMID:1546315).
      IBA annotation is phylogenetically well-supported.
    action: ACCEPT
    reason: >-
      Core function. PEX2 was originally identified as a gene responsible for Zellweger
      syndrome affecting peroxisome assembly (PMID:1546315). PEX2 mutations lead to
      defective peroxisome assembly and organization (PMID:9765053).
    supported_by:
      - reference_id: PMID:1546315
        supporting_text: >-
          A human complementary DNA has been cloned that complements the disease's symptoms
          (including defective peroxisome assembly) in fibroblasts from a patient with
          Zellweger syndrome.
      - reference_id: PMID:9765053
        supporting_text: >-
          The mutant Chinese hamster ovary (CHO) cell line Z78/C has defective peroxisome
          assembly due to a missense mutation in PEX2, the gene which encodes the 35 kDa
          peroxisomal integral membrane protein
- term:
    id: GO:0000038
    label: very long-chain fatty acid metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PEX2 deficiency leads to impaired VLCFA metabolism as a downstream consequence of
      defective peroxisomal matrix protein import. PEX2-deficient cells show impaired
      beta-oxidation of VLCFA (PMID:9765053). IBA annotation is phylogenetically consistent.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a downstream consequence of PEX2's role in peroxisomal protein import, not
      a direct molecular function. PEX2 does not directly metabolize VLCFA; rather, loss
      of PEX2 impairs import of VLCFA metabolizing enzymes into peroxisomes.
    supported_by:
      - reference_id: PMID:9765053
        supporting_text: >-
          expression of human PEX2 restores peroxisomal biogenesis in all of these
          clones... the beta-oxidation of very long chain fatty acids (VLCFA).
- term:
    id: GO:0006635
    label: fatty acid beta-oxidation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PEX2 deficiency leads to impaired fatty acid beta-oxidation as a downstream
      consequence of defective peroxisome biogenesis (PMID:9765053). IBA is phylogenetically
      consistent.
    action: KEEP_AS_NON_CORE
    reason: >-
      PEX2 does not directly catalyze beta-oxidation. Rather, loss of PEX2 disrupts
      peroxisomal protein import, preventing beta-oxidation enzymes from reaching the
      peroxisomal matrix. This is an indirect effect.
    supported_by:
      - reference_id: PMID:9765053
        supporting_text: >-
          the beta-oxidation of very long chain fatty acids (VLCFA).
- term:
    id: GO:0016593
    label: Cdc73/Paf1 complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      This annotation is INCORRECT for PEX2. It results from confusion between PEX2's
      old synonym PAF1 (Peroxisome Assembly Factor 1) and the PAF1 gene encoding the
      transcription elongation factor that is a component of the Cdc73/Paf1 complex.
      PEX2 is a peroxisomal membrane E3 ubiquitin ligase and has no known association
      with the nuclear Cdc73/Paf1 transcriptional regulatory complex.
    action: REMOVE
    reason: >-
      Gene name confusion. PEX2 has the old synonym PAF1 (Peroxisome Assembly Factor 1),
      which is distinct from the PAF1 gene (RNA polymerase II-associated factor 1 homolog)
      that encodes the actual component of the Cdc73/Paf1 complex. There is no evidence
      that PEX2 is part of the Cdc73/Paf1 complex.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Automated annotation consistent with extensive experimental evidence for PEX2
      localization to the peroxisomal membrane (PMID:12751901, PMID:35768507).
    action: ACCEPT
    reason: >-
      Correct IEA annotation. PEX2 is an integral peroxisomal membrane protein confirmed
      by multiple experimental approaches.
    supported_by:
      - reference_id: PMID:12751901
        supporting_text: >-
          Peroxin 2 (PEX2) is a 35-kDa integral peroxisomal membrane protein with two
          transmembrane regions and a zinc RING domain within its cytoplasmically exposed
          C-terminus
- term:
    id: GO:0007031
    label: peroxisome organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Automated annotation consistent with PEX2's established role in peroxisome
      biogenesis and organization (PMID:1546315).
    action: ACCEPT
    reason: >-
      Correct. PEX2 is essential for peroxisome organization. Duplicate of the IBA
      annotation above with different evidence code, both acceptable.
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      PEX2 contains a RING-type zinc finger domain (residues 244-284) that coordinates
      two zinc ions. The zinc binding is integral to the RING domain structure required
      for E3 ubiquitin ligase activity. UniProt lists 8 zinc-binding residues.
    action: ACCEPT
    reason: >-
      Correct. The RING-HC zinc finger domain of PEX2 requires zinc ion coordination
      for its structural integrity and E3 ligase function. Well-supported by domain
      analysis and structural data.
- term:
    id: GO:0015031
    label: protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      PEX2 is involved in protein transport indirectly through its role in the peroxisomal
      matrix protein import pathway. The more specific term GO:0016558 (protein import
      into peroxisome matrix) is preferred.
    action: ACCEPT
    reason: >-
      While quite broad, this IEA annotation is technically correct as PEX2 is involved
      in protein transport to peroxisomes. More specific annotations exist (GO:0016558).
- term:
    id: GO:0016558
    label: protein import into peroxisome matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      PEX2 is a component of the retrotranslocation channel essential for peroxisomal
      matrix protein import via PEX5 receptor recycling (PMID:24662292, PMID:35768507).
    action: ACCEPT
    reason: >-
      Core function. PEX2 is required for peroxisomal matrix protein import through
      its role in PEX5 receptor recycling. IEA annotation consistent with experimental
      evidence.
    supported_by:
      - reference_id: PMID:24662292
        supporting_text: >-
          we establish an in vitro ubiquitination assay system and demonstrate that
          RING finger Pex10p functions as an E3 with an E2, UbcH5C
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      PEX2 has E3 ubiquitin ligase activity (EC 2.3.2.27 and EC 2.3.2.36), which is
      a type of transferase activity. This is technically correct but very broad.
    action: ACCEPT
    reason: >-
      Correct but broad IEA. PEX2's ubiquitin-protein ligase activity is a form of
      transferase activity. More specific annotations (GO:0061630) are also present.
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      PEX2 binds zinc ions through its RING-type zinc finger domain. This is correct
      but less specific than GO:0008270 (zinc ion binding).
    action: ACCEPT
    reason: >-
      Correct IEA. PEX2 binds metal ions (zinc) via its RING domain. More specific
      zinc ion binding annotation also exists.
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  review:
    summary: >-
      PEX2 has E3 ubiquitin protein ligase activity, catalyzing ubiquitination of PEX5,
      PMP70, and ATGL (PMID:27597759, PMID:34903883). EC 2.3.2.27 assigned by UniProt.
    action: ACCEPT
    reason: >-
      Core molecular function. PEX2 is an established E3 ubiquitin ligase confirmed
      by multiple experimental studies.
    supported_by:
      - reference_id: PMID:27597759
        supporting_text: >-
          the peroxisomal E3 ubiquitin ligase peroxin 2 (PEX2) is the causative agent
          for mammalian pexophagy.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20531392
  review:
    summary: >-
      PMID:20531392 is about PEX19 forming a helical mPTS recognition domain. PEX19
      is known to bind PEX2 as a chaperone/receptor for peroxisomal membrane protein
      import. UniProt confirms PEX2 interacts with PEX19 (IntAct). However, protein
      binding is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction between PEX2 and PEX19 is real and biologically meaningful (PEX19
      is the receptor/chaperone for PEX2 membrane targeting), but GO:0005515 (protein
      binding) is too generic to be informative. A more specific term would be preferable.
    supported_by:
      - reference_id: PMID:20531392
        supporting_text: >-
          The protein Pex19p functions as a receptor and chaperone of peroxisomal membrane
          proteins (PMPs).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: >-
      PMID:33961781 is a large-scale interactome study. Protein binding annotations from
      high-throughput interaction screens are typically uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      GO:0005515 (protein binding) is uninformative. This is from a large-scale
      proteomics interactome study and does not provide specific functional insight
      about PEX2's molecular function.
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      PEX2 localizes to the peroxisome (specifically the peroxisomal membrane). This
      broader term is acceptable alongside the more specific peroxisomal membrane
      annotation.
    action: ACCEPT
    reason: >-
      Correct. PEX2 is a peroxisomal protein. The more specific GO:0005778 (peroxisomal
      membrane) is also annotated.
- term:
    id: GO:0016558
    label: protein import into peroxisome matrix
  evidence_type: NAS
  original_reference_id: PMID:24662292
  review:
    summary: >-
      PMID:24662292 demonstrates that RING finger peroxins (PEX10, PEX12, and by
      implication PEX2) are required for PEX5 ubiquitination, which is essential for
      PTS1 protein import. The study directly shows the PEX2-PEX10-PEX12 complex is
      involved in PEX5 receptor recycling, a critical step in matrix protein import.
    action: ACCEPT
    reason: >-
      Core function. PEX2 is a component of the retrotranslocation channel essential
      for peroxisomal matrix protein import via PEX5 receptor recycling.
    supported_by:
      - reference_id: PMID:24662292
        supporting_text: >-
          we establish an in vitro ubiquitination assay system and demonstrate that
          RING finger Pex10p functions as an E3 with an E2, UbcH5C
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  review:
    summary: >-
      PEX2 catalyzes protein ubiquitination as part of its E3 ligase activity.
      Substrates include PEX5 (monoubiquitination at Cys-11), PMP70, and ATGL
      (PMID:27597759, PMID:34903883).
    action: ACCEPT
    reason: >-
      Core function. PEX2 is an established E3 ubiquitin ligase with well-characterized
      substrates.
    supported_by:
      - reference_id: PMID:27597759
        supporting_text: >-
          We identify PEX5 and PMP70 as substrates of PEX2 that are ubiquitinated during
          amino acid starvation.
- term:
    id: GO:0000425
    label: pexophagy
  evidence_type: IDA
  original_reference_id: PMID:26344566
  review:
    summary: >-
      PMID:26344566 is primarily about ATM-mediated pexophagy in response to ROS. The
      paper shows that ATM phosphorylates PEX5 at Ser141, promoting PEX5 monoubiquitination
      and pexophagy. However, the paper does not specifically identify PEX2 as the E3
      ligase responsible. The PEX2-specific pexophagy role is better supported by
      PMID:27597759.
    action: UNDECIDED
    reason: >-
      PMID:26344566 does not appear to directly test PEX2 in the pexophagy assays
      described. The paper focuses on ATM and PEX5 phosphorylation/ubiquitination. While
      PEX2 is likely involved (as shown by PMID:27597759), the direct experimental
      attribution to PEX2 from this specific paper is unclear.
    supported_by:
      - reference_id: PMID:26344566
        supporting_text: >-
          Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM
          phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation
          at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor
          protein p62, directing the autophagosome to peroxisomes to induce pexophagy
- term:
    id: GO:0006513
    label: protein monoubiquitination
  evidence_type: IDA
  original_reference_id: PMID:27597759
  review:
    summary: >-
      PMID:27597759 directly demonstrates that PEX2 ubiquitinates PEX5 and PMP70 during
      amino acid starvation. The paper shows PEX2 overexpression leads to gross
      ubiquitination of peroxisomal proteins, and PEX2 knockdown abolishes PEX5 and
      PMP70 ubiquitination during starvation.
    action: ACCEPT
    reason: >-
      Core function. Direct experimental evidence showing PEX2 mediates ubiquitination
      of PEX5 and PMP70. Note that in the context of pexophagy this may include both
      mono- and polyubiquitination. The monoubiquitination of PEX5 at Cys-11 for receptor
      recycling is a distinct function also attributed to the PEX2/10/12 complex.
    supported_by:
      - reference_id: PMID:27597759
        supporting_text: >-
          We identify PEX5 and PMP70 as substrates of PEX2 that are ubiquitinated during
          amino acid starvation.
      - reference_id: PMID:27597759
        supporting_text: >-
          Here, we found that only the loss of PEX2 expression resulted in the loss of
          PEX5 and PMP70 ubiquitination, whereas both peroxisomal membrane proteins were
          found to be ubiquitinated in cells depleted of either PEX10 or PEX12
- term:
    id: GO:0008320
    label: protein transmembrane transporter activity
  evidence_type: ISS
  original_reference_id: PMID:35768507
  review:
    summary: >-
      PMID:35768507 demonstrates that the PEX2/PEX10/PEX12 complex forms a
      retrotranslocation channel through which PEX5 is transported across the
      peroxisomal membrane. The cryo-EM structure reveals an open channel pore
      formed by the transmembrane segments of all three subunits.
    action: ACCEPT
    reason: >-
      Supported by structural evidence. The PEX2/10/12 complex functions as a
      retrotranslocation channel for PEX5 export from the peroxisomal membrane
      to the cytosol. This transmembrane protein transporter activity is a core
      function of the complex.
    supported_by:
      - reference_id: PMID:35768507
        supporting_text: >-
          Each subunit of the complex contributes five transmembrane segments that
          co-assemble into an open channel.
- term:
    id: GO:0034614
    label: cellular response to reactive oxygen species
  evidence_type: IDA
  original_reference_id: PMID:26344566
  review:
    summary: >-
      PMID:26344566 shows that peroxisomal ROS activates ATM signaling to induce
      pexophagy. However, the paper focuses on ATM and PEX5 phosphorylation, not
      directly on PEX2's response to ROS. PEX2 as a ROS sensor is more directly
      supported by PMID:34903883, which shows ROS regulates PEX2 protein levels via
      disulfide bond-mediated stabilization.
    action: KEEP_AS_NON_CORE
    reason: >-
      PEX2 does respond to ROS through disulfide bond stabilization (PMID:34903883),
      and participates in ROS-induced pexophagy pathways. However, PMID:26344566
      primarily describes ATM-mediated signaling rather than PEX2 directly. The ROS
      response is secondary to PEX2's core E3 ligase function.
    supported_by:
      - reference_id: PMID:34903883
        supporting_text: >-
          PEX2 acts as a ROS sensor in peroxisomes
      - reference_id: PMID:34903883
        supporting_text: >-
          Peroxisomal beta-oxidation-derived ROS regulate PEX2 protein levels
- term:
    id: GO:0006513
    label: protein monoubiquitination
  evidence_type: ISS
  original_reference_id: PMID:35768507
  review:
    summary: >-
      PMID:35768507 provides structural evidence that the PEX2/PEX10/PEX12 complex
      catalyzes monoubiquitination of PEX5 at Cys-11 during its passage through the
      retrotranslocation channel.
    action: ACCEPT
    reason: >-
      Core function. Structural evidence supports monoubiquitination as a key activity
      of the PEX2-containing complex during receptor recycling.
    supported_by:
      - reference_id: PMID:35768507
        supporting_text: >-
          We propose that the N terminus of a recycling receptor is inserted from the
          peroxisomal lumen into the pore and monoubiquitylated by RF2 to enable
          extraction into the cytosol
- term:
    id: GO:0044721
    label: protein import into peroxisome matrix, substrate release
  evidence_type: ISS
  original_reference_id: PMID:35768507
  review:
    summary: >-
      PMID:35768507 shows the PEX2/PEX10/PEX12 complex functions as a retrotranslocation
      channel. Substrate release (cargo delivery to the matrix followed by receptor
      export) is linked to the channel function.
    action: ACCEPT
    reason: >-
      Supported by structural evidence. The retrotranslocation channel formed by
      PEX2/10/12 is directly involved in the substrate release phase of peroxisomal
      matrix protein import.
    supported_by:
      - reference_id: PMID:35768507
        supporting_text: >-
          biochemical and in vivo experiments reveals its function as a retrotranslocation
          channel for peroxisomal import receptors.
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: ISS
  original_reference_id: PMID:35768507
  review:
    summary: >-
      PMID:35768507 provides structural evidence for the RING domain-mediated E3 ubiquitin
      ligase activity of the PEX2/PEX10/PEX12 complex, with RING fingers positioned
      above the channel pore for receptor ubiquitination.
    action: ACCEPT
    reason: >-
      Core molecular function. Structural evidence confirms the E3 ubiquitin ligase
      activity of PEX2 within the retrotranslocation channel complex.
    supported_by:
      - reference_id: PMID:35768507
        supporting_text: >-
          Recycling requires receptor modification by a membrane-embedded ubiquitin
          ligase complex comprising three RING finger domain-containing proteins
          (Pex2, Pex10 and Pex12)
- term:
    id: GO:0000425
    label: pexophagy
  evidence_type: IDA
  original_reference_id: PMID:27597759
  review:
    summary: >-
      PMID:27597759 directly demonstrates that PEX2 is the E3 ubiquitin ligase required
      for pexophagy during amino acid starvation. PEX2 overexpression induces peroxisome
      degradation via autophagy, and PEX2 knockdown blocks starvation-induced pexophagy.
      PEX2-mediated pexophagy requires NBR1 as the autophagy receptor.
    action: ACCEPT
    reason: >-
      Core function supported by direct experimental evidence. PEX2 specifically (not
      PEX10 or PEX12) mediates pexophagy through ubiquitination of peroxisomal membrane
      proteins during starvation.
    supported_by:
      - reference_id: PMID:27597759
        supporting_text: >-
          the peroxisomal E3 ubiquitin ligase peroxin 2 (PEX2) is the causative agent
          for mammalian pexophagy. Expression of PEX2 leads to gross ubiquitination of
          peroxisomes and degradation of peroxisomes in an NBR1-dependent autophagic process.
      - reference_id: PMID:27597759
        supporting_text: >-
          PEX2, but not PEX10 or PEX12, acts as the E3 ubiquitin ligase to selectively
          ubiquitinate peroxisomal membrane proteins to designate peroxisomes for
          autophagy-mediated degradation during amino acid starvation conditions.
- term:
    id: GO:0016562
    label: protein import into peroxisome matrix, receptor recycling
  evidence_type: IDA
  original_reference_id: PMID:24662292
  review:
    summary: >-
      PMID:24662292 demonstrates that RING peroxins PEX10 and PEX12 function as E3
      ubiquitin ligases for PEX5 monoubiquitination, and that PEX2 plays a role in
      PEX5 shuttling. The study shows the PEX2-PEX10-PEX12 complex catalyzes
      monoubiquitination of PEX5, enabling receptor recycling.
    action: ACCEPT
    reason: >-
      Core function. PEX2 is part of the retrotranslocation channel complex that
      ubiquitinates PEX5 for receptor recycling, a critical step in the peroxisomal
      matrix protein import cycle.
    supported_by:
      - reference_id: PMID:24662292
        supporting_text: >-
          The Pex10p·Pex12p complex catalyzes monoubiquitination of Pex5p at one of
          multiple lysine residues in vitro
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IDA
  original_reference_id: PMID:27597759
  review:
    summary: >-
      PMID:27597759 directly demonstrates PEX2's E3 ubiquitin ligase activity. PEX2
      ubiquitinates PEX5 and PMP70, and RING domain deletion mutants lose this activity.
      PEX2 knockdown specifically abolishes ubiquitination of these substrates during
      starvation.
    action: ACCEPT
    reason: >-
      Core molecular function with direct experimental evidence. RING domain is required
      for PEX2-mediated peroxisome loss (deletion mutants Δ243-306, Δ243-283, Δ270-283
      all lose activity).
    supported_by:
      - reference_id: PMID:27597759
        supporting_text: >-
          When expressed in cells, we found that none of the PEX2-GFP deletion mutants
          caused a significant loss of peroxisomes, suggesting that the E3 ligase
          activity is required for PEX2-mediated peroxisome loss
      - reference_id: PMID:27597759
        supporting_text: >-
          Here, we found that only the loss of PEX2 expression resulted in the loss of
          PEX5 and PMP70 ubiquitination, whereas both peroxisomal membrane proteins were
          found to be ubiquitinated in cells depleted of either PEX10 or PEX12
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IDA
  original_reference_id: PMID:34903883
  review:
    summary: >-
      PMID:34903883 demonstrates that PEX2 specifically polyubiquitinates ATGL/PNPLA2
      at K92 via K48-linkage for proteasomal degradation, regulating lipolysis.
      PEX2 acts as a ROS sensor whose protein levels are regulated by disulfide
      bond-mediated stabilization.
    action: ACCEPT
    reason: >-
      Direct experimental evidence for PEX2 E3 ubiquitin ligase activity on a novel
      substrate (ATGL), extending its known substrates beyond PEX5 and PMP70.
    supported_by:
      - reference_id: PMID:34903883
        supporting_text: >-
          PEX2 specifically poly-ubiquitinates lipolytic protein ATGL at the K92 site
          when ATGL distributes on the LD surface for proteasome-targeted degradation
          in different cell types.
      - reference_id: PMID:34903883
        supporting_text: >-
          PEX2 modulates ATGL protein levels via K48-linkage poly-ubiquitination.
- term:
    id: GO:1990928
    label: response to amino acid starvation
  evidence_type: IDA
  original_reference_id: PMID:27597759
  review:
    summary: >-
      PMID:27597759 demonstrates that PEX2 protein levels are up-regulated during
      amino acid starvation, and PEX2 mediates pexophagy in response to starvation.
      PEX2 expression is regulated by the mTORC1 pathway.
    action: ACCEPT
    reason: >-
      Directly supported by experimental evidence. PEX2 protein levels increase during
      amino acid starvation, and PEX2 mediates the pexophagy response to starvation.
      Validated in vivo in protein-restricted mice.
    supported_by:
      - reference_id: PMID:27597759
        supporting_text: >-
          PEX2 expression is up-regulated during both amino acid starvation and rapamycin
          treatment, suggesting that the mTORC1 pathway regulates pexophagy by regulating
          PEX2 expression levels.
      - reference_id: PMID:27597759
        supporting_text: >-
          PEX2 protein levels are significantly increased in just 1 h after starvation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9603775
  review:
    summary: >-
      Reactome R-HSA-9603775 models PEX3:PEX19:class I PMP dissociation. PEX2 is a
      class I peroxisomal membrane protein that transits through the cytosol bound to
      PEX19 before membrane insertion. This represents a transient cytosolic intermediate.
    action: KEEP_AS_NON_CORE
    reason: >-
      PEX2 passes through the cytosol as a PEX19 cargo during its biogenesis/membrane
      insertion. This is not its primary functional localization (peroxisomal membrane)
      but is a transient state during membrane protein targeting.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9603784
  review:
    summary: >-
      Reactome R-HSA-9603784 models PEX19:class I PMP binding to PEX3. Same cytosolic
      transit as above.
    action: KEEP_AS_NON_CORE
    reason: >-
      Duplicate cytosol annotation from another Reactome reaction in the same pathway.
      PEX2 transiently passes through the cytosol during membrane protein targeting.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9603804
  review:
    summary: >-
      Reactome R-HSA-9603804 models PEX19 binding to class I PMPs. Same cytosolic
      transit as above.
    action: KEEP_AS_NON_CORE
    reason: >-
      Duplicate cytosol annotation from another Reactome reaction in the same pathway.
      PEX2 transiently passes through the cytosol during membrane protein targeting.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8953917
  review:
    summary: >-
      Reactome R-HSA-8953917 models PEX2:PEX10:PEX12 binding PEX5 and Ub:UBE2D for
      ubiquitination. PEX2 functions at the peroxisomal membrane.
    action: ACCEPT
    reason: >-
      Correct localization. PEX2 functions at the peroxisomal membrane as part of the
      E3 ligase complex. Duplicate of other peroxisomal membrane annotations.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8953946
  review:
    summary: >-
      Reactome R-HSA-8953946 models PEX2:PEX10:PEX12 monoubiquitinating PEX5 at
      cysteine-11. PEX2 at peroxisomal membrane.
    action: ACCEPT
    reason: >-
      Correct. Duplicate peroxisomal membrane annotation from Reactome reaction modeling
      PEX5 monoubiquitination.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033235
  review:
    summary: >-
      Reactome R-HSA-9033235 models cargo translocation from cytosol to peroxisomal
      matrix. PEX2 at peroxisomal membrane.
    action: ACCEPT
    reason: >-
      Correct. Duplicate peroxisomal membrane annotation from Reactome.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033236
  review:
    summary: >-
      Reactome R-HSA-9033236 models PEX5:cargo binding to the docking/translocation
      module. PEX2 at peroxisomal membrane.
    action: ACCEPT
    reason: >-
      Correct. Duplicate peroxisomal membrane annotation from Reactome.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033485
  review:
    summary: >-
      Reactome R-HSA-9033485 models PEX2:PEX10:PEX12 monoubiquitinating PEX5L at
      cysteine-11. PEX2 at peroxisomal membrane.
    action: ACCEPT
    reason: >-
      Correct. Duplicate peroxisomal membrane annotation from Reactome.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033499
  review:
    summary: >-
      Reactome R-HSA-9033499 models PEX1:PEX6 dissociating Ub:PEX5 from PEX14:PEX13:
      PEX2:PEX10:PEX12. PEX2 at peroxisomal membrane.
    action: ACCEPT
    reason: >-
      Correct. Duplicate peroxisomal membrane annotation from Reactome.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033514
  review:
    summary: >-
      Reactome R-HSA-9033514 models cargo translocation for PEX5L:PEX7 pathway.
      PEX2 at peroxisomal membrane.
    action: ACCEPT
    reason: >-
      Correct. Duplicate peroxisomal membrane annotation from Reactome.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033516
  review:
    summary: >-
      Reactome R-HSA-9033516 models PEX2:PEX10:PEX12:Ub:PEX5L:PEX7:PEX13:PEX14
      binding PEX1:PEX6:PEX26 and ZFAND6. PEX2 at peroxisomal membrane.
    action: ACCEPT
    reason: >-
      Correct. Duplicate peroxisomal membrane annotation from Reactome.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033527
  review:
    summary: >-
      Reactome R-HSA-9033527 models PEX2:PEX10:PEX12 binding PEX5L and Ub:UBE2D.
      PEX2 at peroxisomal membrane.
    action: ACCEPT
    reason: >-
      Correct. Duplicate peroxisomal membrane annotation from Reactome.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033533
  review:
    summary: >-
      Reactome R-HSA-9033533 models Ub:PEX5:PEX13:PEX14:PEX2:PEX10:PEX12 binding
      PEX1:PEX6:PEX26 and ZFAND6. PEX2 at peroxisomal membrane.
    action: ACCEPT
    reason: >-
      Correct. Duplicate peroxisomal membrane annotation from Reactome.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9603775
  review:
    summary: >-
      Reactome R-HSA-9603775 models PEX3:PEX19:class I PMP dissociation. PEX2 at
      peroxisomal membrane after insertion.
    action: ACCEPT
    reason: >-
      Correct. PEX2 localizes to the peroxisomal membrane after PEX19-mediated targeting.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  review:
    summary: >-
      PMID:19946888 is a large-scale proteomics study of NK cell membranes. PEX2 was
      identified in the membrane fraction. This is consistent with PEX2 being an integral
      membrane protein, but the term is very broad.
    action: ACCEPT
    reason: >-
      Correct but very broad. PEX2 is an integral membrane protein. The more specific
      peroxisomal membrane annotation is more informative.
- term:
    id: GO:0000038
    label: very long-chain fatty acid metabolic process
  evidence_type: IMP
  original_reference_id: PMID:9765053
  review:
    summary: >-
      PMID:9765053 shows that PEX2 mutations disrupt peroxisome assembly, leading to
      impaired VLCFA beta-oxidation. Restoration of PEX2 restores VLCFA metabolism.
      However, PEX2 does not directly catalyze VLCFA metabolism.
    action: KEEP_AS_NON_CORE
    reason: >-
      Indirect effect. PEX2 mutations impair peroxisome assembly, which secondarily
      affects VLCFA metabolism because VLCFA beta-oxidation enzymes cannot be imported.
    supported_by:
      - reference_id: PMID:9765053
        supporting_text: >-
          expression of human PEX2 restores peroxisomal biogenesis in all of these
          clones... the beta-oxidation of very long chain fatty acids (VLCFA).
- term:
    id: GO:0006635
    label: fatty acid beta-oxidation
  evidence_type: IMP
  original_reference_id: PMID:9765053
  review:
    summary: >-
      PMID:9765053 shows that PEX2 mutations lead to impaired fatty acid beta-oxidation,
      which is restored by PEX2 expression. Indirect effect via peroxisome assembly.
    action: KEEP_AS_NON_CORE
    reason: >-
      Indirect effect. PEX2 does not catalyze beta-oxidation but is required for
      peroxisome assembly, which is prerequisite for beta-oxidation enzyme import.
    supported_by:
      - reference_id: PMID:9765053
        supporting_text: >-
          the beta-oxidation of very long chain fatty acids (VLCFA).
- term:
    id: GO:0007031
    label: peroxisome organization
  evidence_type: IMP
  original_reference_id: PMID:9765053
  review:
    summary: >-
      PMID:9765053 shows PEX2 mutations cause defective peroxisome assembly and that
      restoration of PEX2 restores peroxisome biogenesis.
    action: ACCEPT
    reason: >-
      Core function. Direct experimental evidence for PEX2's role in peroxisome
      organization/biogenesis.
    supported_by:
      - reference_id: PMID:9765053
        supporting_text: >-
          The mutant Chinese hamster ovary (CHO) cell line Z78/C has defective peroxisome
          assembly due to a missense mutation in PEX2, the gene which encodes the 35 kDa
          peroxisomal integral membrane protein
      - reference_id: PMID:9765053
        supporting_text: >-
          expression of human PEX2 restores peroxisomal biogenesis in all of these clones.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: HDA
  original_reference_id: PMID:21525035
  review:
    summary: >-
      PMID:21525035 is about PEX14 and peroxisome motility. PEX2 was presumably
      identified in isolated peroxisomal membrane fractions by mass spectrometry.
    action: ACCEPT
    reason: >-
      Correct localization. PEX2 is an integral peroxisomal membrane protein detected
      in purified peroxisomal membrane preparations.
- term:
    id: GO:0006635
    label: fatty acid beta-oxidation
  evidence_type: IMP
  original_reference_id: PMID:10528859
  review:
    summary: >-
      PMID:10528859 characterizes a PEX2 E55K mutation in a patient with infantile
      Refsum disease. The mutation leads to mosaic activities of peroxisomal protein
      import and residual beta-oxidation function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Indirect effect. PEX2 mutation impairs peroxisome biogenesis, secondarily
      affecting beta-oxidation. PEX2 does not directly catalyze fatty acid beta-oxidation.
    supported_by:
      - reference_id: PMID:10528859
        supporting_text: >-
          we noted the E55K mutation had mosaic activities of peroxisomal protein import
          machinery and residual activities of peroxisomal functions, including
          dihydroxyacetone phosphate acyltransferase and beta oxidation of very long
          chain fatty acids
- term:
    id: GO:0016558
    label: protein import into peroxisome matrix
  evidence_type: IMP
  original_reference_id: PMID:10528859
  review:
    summary: >-
      PMID:10528859 shows that PEX2 mutations affect peroxisomal protein import
      machinery, with the E55K mutation showing mosaic import activities.
    action: ACCEPT
    reason: >-
      Core function. Direct evidence that PEX2 is required for peroxisomal matrix
      protein import.
    supported_by:
      - reference_id: PMID:10528859
        supporting_text: >-
          we noted the E55K mutation had mosaic activities of peroxisomal protein import
          machinery and residual activities of peroxisomal functions, including
          dihydroxyacetone phosphate acyltransferase and beta oxidation of very long
          chain fatty acids
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11590176
  review:
    summary: >-
      PMID:11590176 is about PMP22 (peroxisomal membrane protein 22) targeting signals
      and their interaction with PEX19. PEX2 is not the focus of this study. The
      annotation may be based on co-detection or indirect interaction data.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      GO:0005515 (protein binding) is uninformative. PMID:11590176 focuses on PMP22
      targeting signals interacting with PEX19, not PEX2 directly. The annotation
      may reflect indirect or tangential evidence.
- term:
    id: GO:0016593
    label: Cdc73/Paf1 complex
  evidence_type: IDA
  original_reference_id: PMID:18987311
  review:
    summary: >-
      PMID:18987311 is about the parafibromin tumor suppressor protein and the PAF1
      transcriptional regulatory complex. This paper studies the PAF1 gene (RNA
      polymerase II-associated factor 1), NOT PEX2. PEX2's old synonym PAF1 (Peroxisome
      Assembly Factor 1) was confused with the unrelated PAF1 transcription factor.
      PEX2 has no known role in the Cdc73/Paf1 complex.
    action: REMOVE
    reason: >-
      INCORRECT annotation due to gene name confusion. PMID:18987311 studies the PAF1
      transcription factor (RNA polymerase II-associated factor 1 homolog), not PEX2
      (Peroxisome Assembly Factor 1). PEX2 is a peroxisomal membrane E3 ubiquitin
      ligase with no connection to the Cdc73/Paf1 transcriptional complex.
    supported_by:
      - reference_id: PMID:18987311
        supporting_text: >-
          Human parafibromin binds to RNA polymerase II as part of a PAF1 transcriptional
          regulatory complex.
- term:
    id: GO:0031648
    label: protein destabilization
  evidence_type: IMP
  original_reference_id: PMID:18987311
  review:
    summary: >-
      PMID:18987311 discusses c-myc protein stabilization in the context of parafibromin
      and the PAF1 transcriptional complex. This annotation is based on the WRONG gene
      (PAF1 transcription factor, not PEX2).
    action: REMOVE
    reason: >-
      INCORRECT annotation due to gene name confusion. PMID:18987311 studies the PAF1
      transcription factor and parafibromin effects on c-myc protein stability. PEX2
      (Peroxisome Assembly Factor 1) is an unrelated gene. While PEX2 does mediate
      protein destabilization through ATGL ubiquitination (PMID:34903883), that is not
      what this annotation references.
    supported_by:
      - reference_id: PMID:18987311
        supporting_text: >-
          This effect results from both c-myc protein stabilization and activation of
          the c-myc promoter, without alleviation of the c-myc transcriptional pause
- term:
    id: GO:0048147
    label: negative regulation of fibroblast proliferation
  evidence_type: IMP
  original_reference_id: PMID:18987311
  review:
    summary: >-
      PMID:18987311 discusses parafibromin and PAF1 complex effects on cell proliferation
      via c-myc repression. This has nothing to do with PEX2 (a peroxisomal E3 ligase).
    action: REMOVE
    reason: >-
      INCORRECT annotation due to gene name confusion. PMID:18987311 studies the PAF1
      transcription factor and parafibromin, not PEX2. There is no evidence that PEX2
      regulates fibroblast proliferation.
    supported_by:
      - reference_id: PMID:18987311
        supporting_text: >-
          We show here that RNA interference with the expression of parafibromin or Paf1
          stimulates cell proliferation and increases levels of the c-myc proto-oncogene
          product, a DNA-binding protein and established regulator of cell growth
- term:
    id: GO:0050680
    label: negative regulation of epithelial cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:18987311
  review:
    summary: >-
      Same gene name confusion as above. PMID:18987311 is about PAF1 transcription
      factor and parafibromin, not PEX2.
    action: REMOVE
    reason: >-
      INCORRECT annotation due to gene name confusion. PMID:18987311 studies the PAF1
      transcription factor and parafibromin effects on cell proliferation. PEX2 is
      an unrelated peroxisomal E3 ubiquitin ligase with no known role in epithelial
      cell proliferation regulation.
- term:
    id: GO:0007031
    label: peroxisome organization
  evidence_type: IMP
  original_reference_id: PMID:1546315
  review:
    summary: >-
      PMID:1546315 is the original cloning paper for PEX2 (then PAF-1), demonstrating
      that the gene complements Zellweger syndrome fibroblasts with defective peroxisome
      assembly.
    action: ACCEPT
    reason: >-
      Foundational evidence for PEX2's role in peroxisome organization. This is the
      original discovery paper showing PEX2 is required for peroxisome assembly.
    supported_by:
      - reference_id: PMID:1546315
        supporting_text: >-
          A human complementary DNA has been cloned that complements the disease's symptoms
          (including defective peroxisome assembly) in fibroblasts from a patient with
          Zellweger syndrome.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: IMP
  original_reference_id: PMID:12751901
  review:
    summary: >-
      PMID:12751901 directly characterizes the peroxisomal membrane targeting elements
      of PEX2 using GFP fusion constructs in COS-7 cells, demonstrating that PEX2 is
      targeted to the peroxisomal membrane via specific internal targeting signals.
    action: ACCEPT
    reason: >-
      Direct experimental evidence for PEX2's peroxisomal membrane localization.
    supported_by:
      - reference_id: PMID:12751901
        supporting_text: >-
          We found that the minimum peroxisomal targeting signal of human PEX2 consists
          of an internal protein region of 30 amino acids (AA130 to AA159) and the
          first transmembrane domain, and that adding the second transmembrane domain
          increases targeting efficiency
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10837480
  review:
    summary: >-
      PMID:10837480 studies PEX12 but shows that PEX12 RING finger interacts with PEX2
      and PEX5 in vitro. Pex10p interacted with Pex2p. These are functionally meaningful
      interactions within the PEX2/10/12 complex.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      GO:0005515 (protein binding) is uninformative. The interactions of PEX2 with PEX10,
      PEX12, and PEX5 are real and functionally significant (they form the E3 ligase
      retrotranslocation complex), but a more specific term should be used.
    supported_by:
      - reference_id: PMID:10837480
        supporting_text: >-
          Peroxins interacting with RING finger of Pex2p, Pex10p, and Pex12p... Pex10p
          and Pex12p are in the oligomeric complex in peroxisome membranes.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10528859
  title: Defective PEX gene products correlate with the protein import, biochemical
    abnormalities, and phenotypic heterogeneity in peroxisome biogenesis disorders.
  findings:
    - statement: PEX2 E55K mutation causes mosaic peroxisomal protein import and residual beta-oxidation activity
- id: PMID:10837480
  title: '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.'
  findings:
    - statement: PEX12 RING finger interacts with PEX2 and PEX5; PEX10 and PEX12 form oligomeric complex in peroxisome membranes
- id: PMID:11590176
  title: Two different targeting signals direct human peroxisomal membrane protein
    22 to peroxisomes.
  findings:
    - statement: PMP22 peroxisomal membrane targeting signals interact with PEX19
- id: PMID:12751901
  title: The peroxisomal membrane targeting elements of human peroxin 2 (PEX2).
  findings:
    - statement: PEX2 is targeted to the peroxisomal membrane via an internal targeting signal comprising TM1
- id: PMID:1546315
  title: A human gene responsible for Zellweger syndrome that affects peroxisome assembly.
  findings:
    - statement: PEX2 (PAF-1) cDNA complements Zellweger syndrome fibroblasts, restoring peroxisome assembly
- id: PMID:18987311
  title: The parafibromin tumor suppressor protein inhibits cell proliferation by
    repression of the c-myc proto-oncogene.
  findings:
    - statement: This paper is about PAF1 (RNA polymerase II-associated factor 1), NOT PEX2. Gene name confusion with PEX2 alias PAF1.
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings:
    - statement: Large-scale proteomics study identifying membrane proteins in NK cells
- id: PMID:20531392
  title: The peroxisomal receptor Pex19p forms a helical mPTS recognition domain.
  findings:
    - statement: PEX19 functions as receptor/chaperone for peroxisomal membrane proteins including PEX2
- id: PMID:21525035
  title: PEX14 is required for microtubule-based peroxisome motility in human cells.
  findings:
    - statement: Peroxisomal membrane proteomics identified PEX2 among peroxisomal membrane proteins
- id: PMID:24662292
  title: Distinct modes of ubiquitination of peroxisome-targeting signal type 1 (PTS1)
    receptor Pex5p regulate PTS1 protein import.
  findings:
    - statement: PEX10/PEX12 catalyze PEX5 monoubiquitination; PEX2 identified in the retrotranslocation channel complex
- id: PMID:26344566
  title: ATM functions at the peroxisome to induce pexophagy in response to ROS.
  findings:
    - statement: ATM phosphorylates PEX5 at Ser141 to promote ubiquitination and pexophagy; PEX2 not directly tested
- id: PMID:27597759
  title: PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation.
  findings:
    - statement: PEX2 specifically (not PEX10 or PEX12) ubiquitinates PEX5 and PMP70 during amino acid starvation
    - statement: PEX2 overexpression induces pexophagy via NBR1-dependent autophagy
    - statement: PEX2 protein levels regulated by mTORC1 pathway
    - statement: Validated in vivo in protein-restricted mice
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings:
    - statement: Large-scale interactome study
- id: PMID:34903883
  title: "Peroxisomal \u03B2-oxidation acts as a sensor for intracellular fatty acids and\
    \ regulates lipolysis."
  findings:
    - statement: PEX2 polyubiquitinates ATGL at K92 via K48-linkage for proteasomal degradation
    - statement: PEX2 acts as ROS sensor with disulfide bond-mediated protein stabilization
    - statement: Peroxisomal beta-oxidation derived ROS regulate PEX2 protein levels
- id: PMID:35768507
  title: A peroxisomal ubiquitin ligase complex forms a retrotranslocation channel.
  findings:
    - statement: Cryo-EM structure of PEX2/PEX10/PEX12 complex reveals retrotranslocation channel
    - statement: Each subunit contributes 5 TM segments forming open channel pore
    - statement: RING finger domains form cytosolic tower above channel for receptor ubiquitination
- id: PMID:9765053
  title: Restoration of PEX2 peroxisome assembly defects by overexpression of PMP70.
  findings:
    - statement: PEX2 mutations cause defective peroxisome assembly in CHO cells
    - statement: Human PEX2 expression restores peroxisome biogenesis and VLCFA beta-oxidation
- id: Reactome:R-HSA-8953917
  title: PEX2:PEX10:PEX12 binds PEX5S,L (in PEX5S:PEX13:PEX14) and Ub:UBE2D1,2,3
  findings: []
- id: Reactome:R-HSA-8953946
  title: PEX2:PEX10:PEX12 monoubiquitinates PEX5S,L at cysteine-11
  findings: []
- id: Reactome:R-HSA-9033235
  title: Cargo of PEX5S,L translocates from the cytosol to the peroxisomal matrix
  findings: []
- id: Reactome:R-HSA-9033236
  title: PEX5S,L:Cargo binds PEX13:PEX14:PEX2:PEX10:PEX12 (Docking and Translocation
    Module)
  findings: []
- id: Reactome:R-HSA-9033485
  title: PEX2:PEX10:PEX12 monoubiquitinates PEX5L at cysteine-11
  findings: []
- id: Reactome:R-HSA-9033499
  title: 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
  findings: []
- id: Reactome:R-HSA-9033514
  title: Cargo of PEX5L:PEX7 translocates from the cytosol to the peroxisomal matrix
  findings: []
- id: Reactome:R-HSA-9033516
  title: PEX2:PEX10:PEX12:Ub:PEX5L:PEX7:PEX13:PEX14 binds PEX1:PEX6:PEX26 and ZFAND6
  findings: []
- id: Reactome:R-HSA-9033527
  title: PEX2:PEX10:PEX12 binds PEX5L (in PEX5L:PEX7:PEX13:PEX14:PEX2:PEX10:PEX12)
    and Ub:UBE2D1,2,3
  findings: []
- id: Reactome:R-HSA-9033533
  title: PEX2:PEX10:PEX12:Ub:PEX5S,L:PEX13:PEX14 binds PEX1:PEX6:PEX26 and ZFAND6
  findings: []
- id: Reactome:R-HSA-9603775
  title: PEX3:PEX19:class I PMP dissociates
  findings: []
- id: Reactome:R-HSA-9603784
  title: PEX19:class I PMP binds PEX3
  findings: []
- id: Reactome:R-HSA-9603804
  title: PEX19 binds class I peroxisomal membrane proteins
  findings: []