id: P40855
gene_symbol: PEX19
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: PEX19 (peroxin-19) is a predominantly cytosolic chaperone and import receptor for peroxisomal membrane proteins
  (PMPs). It binds newly synthesized PMPs in the cytosol via their membrane peroxisomal targeting signals (mPTS), prevents
  their aggregation, and delivers them to the peroxisomal membrane by docking onto PEX3. PEX19 is farnesylated at its C-terminal
  CaaX motif (Cys296), which enhances PMP binding affinity. PEX19 interacts with a broad spectrum of PMPs including PEX3,
  PEX10, PEX11A/B, PEX12, PEX13, PEX14, PEX16, PEX26, PXMP2, PXMP4, SLC25A17, and the ABC transporters ABCD1/2/3. Loss of
  PEX19 abolishes peroxisome membrane biogenesis, causing Zellweger spectrum disorders (complementation group 14). Beyond
  peroxisomes, farnesylated PEX19 also functions in sorting proteins to ER/lipid droplets, coordinating neutral lipid storage.
alternative_products:
- name: 1 (PXF-all)
  id: P40855-1
- name: 2 (PXF-delta-2, PXF lacking exon 2)
  id: P40855-2
  sequence_note: Not described
- name: 3 (PXF-delta-4, PXF lacking exon 4)
  id: P40855-3
  sequence_note: Not described
- name: 4 (PXF-delta-8, PXF lacking part of exon 8)
  id: P40855-4
  sequence_note: Not described
- name: '6'
  id: P40855-6
  sequence_note: VSP_061572, VSP_061573
existing_annotations:
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: PEX19 is a predominantly cytosolic protein that transiently associates with the peroxisomal membrane when delivering
      PMP cargo to PEX3. Multiple studies show PEX19 localizes to both cytoplasm and peroxisomal membrane (PMID:10704444,
      PMID:9339377). IBA annotation is phylogenetically well-supported and consistent with experimental data.
    action: ACCEPT
    reason: PEX19 has been shown by immunofluorescence and subcellular fractionation to associate with the peroxisomal membrane
      in addition to its major cytosolic localization (PMID:10704444, PMID:9339377). This is a core localization for its function
      as a PMP import receptor.
    supported_by:
    - reference_id: PMID:10704444
      supporting_text: At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of
        the protein in the cytoplasm.
    - reference_id: PMID:9339377
      supporting_text: For the HsPXF protein, a carboxyterminal farnesylation at cysteine residues was demonstrated. Through
        the use of HsPXF-specific antibodies, the protein was shown to be attached to the outer surface of peroxisomes.
- term:
    id: GO:0033328
    label: peroxisome membrane targeting sequence binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: PEX19 recognizes mPTS (membrane peroxisomal targeting signals) on PMPs. This is a core molecular function conserved
      across eukaryotes. The IBA annotation appropriately captures PEX19's general mPTS binding activity.
    action: ACCEPT
    reason: PEX19's recognition of mPTS signals is its defining molecular function, well-established by multiple experimental
      studies (PMID:14709540, PMID:10704444, PMID:11402059). The IBA captures the right level of specificity for mPTS binding
      in general.
    supported_by:
    - reference_id: PMID:14709540
      supporting_text: PEX19 binds and stabilizes newly synthesized PMPs in the cytosol, binds to multiple PMP targeting signals
        (mPTSs), interacts with the hydrophobic domains of PMP targeting signals
    - reference_id: PMID:11402059
      supporting_text: PEX19, a factor required for peroxisomal membrane biogenesis, interacts with the two minimal targeting
        regions of PMP34
- term:
    id: GO:0045046
    label: protein import into peroxisome membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: PEX19 is essential for protein import into the peroxisome membrane. This IBA annotation represents one of the
      most well-characterized core biological processes for PEX19.
    action: ACCEPT
    reason: PEX19 functions as a chaperone/receptor that delivers PMPs to the peroxisomal membrane via PEX3 docking. This
      is its primary biological process, supported by extensive experimental evidence (PMID:14709540, PMID:10704444, PMID:16280322).
    supported_by:
    - reference_id: PMID:14709540
      supporting_text: PEX19 functions as both a chaperone and an import receptor for newly synthesized PMPs
    - reference_id: PMID:16280322
      supporting_text: Pex19p translocates the membrane peroxins from the cytosol to peroxisomes in an ATP- and Pex3p-dependent
        manner and then shuttles back to the cytosol
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: IEA annotation from UniProt subcellular location mapping. PEX19 is predominantly cytoplasmic, well-supported
      by experimental data. Broader than cytosol (GO:0005829) but acceptable as a parallel annotation.
    action: ACCEPT
    reason: PEX19 is predominantly cytoplasmic as shown by subcellular fractionation and immunofluorescence (PMID:10704444,
      PMID:14709540). The IEA correctly maps the UniProt annotation.
    supported_by:
    - reference_id: PMID:10704444
      supporting_text: At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of
        the protein in the cytoplasm.
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: IEA annotation for peroxisome localization. PEX19 transiently associates with peroxisomes during PMP delivery.
      Broader than peroxisomal membrane but acceptable.
    action: ACCEPT
    reason: PEX19 associates with peroxisomes as part of its PMP delivery cycle. This is well-established experimentally (PMID:10704444,
      PMID:9339377).
    supported_by:
    - reference_id: PMID:10704444
      supporting_text: At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of
        the protein in the cytoplasm.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: IEA annotation for peroxisomal membrane. Consistent with the IBA annotation for the same term and with experimental
      evidence.
    action: ACCEPT
    reason: Duplicate of IBA annotation for the same term. Both are correct; PEX19 associates with peroxisomal membrane during
      PMP delivery.
    supported_by:
    - reference_id: PMID:10704444
      supporting_text: At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of
        the protein in the cytoplasm.
- term:
    id: GO:0007031
    label: peroxisome organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: IEA annotation from UniProt keyword mapping. PEX19 is essential for peroxisome biogenesis and organization. This
      is a broad but correct annotation.
    action: ACCEPT
    reason: PEX19 is required for peroxisome membrane biogenesis; loss of PEX19 results in absence of detectable peroxisomal
      structures (PMID:10704444). Peroxisome organization is an appropriate parent term.
    supported_by:
    - reference_id: PMID:10704444
      supporting_text: the loss of PEX19 results in degradation of PMPs and/or mislocalization of PMPs to the mitochondrion
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Very generic IEA annotation for membrane localization. While PEX19 does associate with peroxisomal membranes,
      this term is too broad to be informative and is redundant with more specific peroxisomal membrane annotations.
    action: ACCEPT
    reason: While overly broad, this is technically correct since PEX19 does associate with membranes. More specific terms
      (peroxisomal membrane) are also annotated. IEA annotations at this level are acceptable as they subsume the more specific
      ones.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10704444
  review:
    summary: Sacksteder et al. (2000) showed PEX19 binds a broad spectrum of PMPs using dihybrid assays and blot overlays.
      While the interactions are real, GO:0005515 is uninformative. The specific interactions are better captured by mPTS
      binding and protein carrier activity terms.
    action: REMOVE
    reason: Generic protein binding is uninformative for a protein whose core function is mPTS recognition and PMP chaperoning.
      The specific interactions with PMPs are better represented by GO:0033328 (peroxisome membrane targeting sequence binding)
      and GO:0140597 (protein carrier activity).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11402059
  review:
    summary: Jones et al. (2001) showed PEX19 binds multiple targeting regions of PMP34 and PEX13. This reflects PEX19's core
      mPTS binding function. Generic protein binding is uninformative.
    action: REMOVE
    reason: Specific PEX19-PMP interactions are better captured by mPTS binding terms. GO:0005515 is not informative here.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12096124
  review:
    summary: Fransen et al. (2002) used bacterial two-hybrid to map peroxin interactions and showed farnesylation enhances
      PEX19 affinity for PEX13 and the CAAX motif enhances affinity for PEX11beta. These are peroxin-specific interactions
      better captured by mPTS binding.
    action: REMOVE
    reason: Generic protein binding is uninformative. PEX19-peroxin interactions are better captured by mPTS binding terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14709540
  review:
    summary: Jones et al. (2004) demonstrated PEX19 is a PMP chaperone and import receptor. Interactions with PMPs are central
      to function but better captured by specific MF terms.
    action: REMOVE
    reason: Core PMP interactions are captured by GO:0033328 (mPTS binding) and GO:0140597 (protein carrier activity). GO:0005515
      is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  review:
    summary: Rual et al. (2005) large-scale Y2H interactome mapping. High-throughput protein-protein interaction data. Generic
      protein binding from HTP study.
    action: REMOVE
    reason: Generic protein binding from high-throughput Y2H screen. Uninformative for PEX19 annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16280322
  review:
    summary: Matsuzono & Fujiki (2006) demonstrated PEX19 shuttles PMPs to peroxisomes in vitro. Interactions with Pex16p,
      Pex26p, and Pex3p are core functions better captured by specific terms.
    action: REMOVE
    reason: PEX19-PMP interactions during shuttling are better captured by protein carrier activity and mPTS binding terms.
      GO:0005515 is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19197237
  review:
    summary: Neufeld et al. (2009) determined the structural basis for PEX19-PEX14 interaction via NMR. PEX19 residues 66-77
      form an amphipathic helix binding PEX14 N-terminal domain competitively with PEX5. This is a specific structural interaction.
    action: REMOVE
    reason: While the PEX19-PEX14 structural interaction is well-characterized, GO:0005515 is still uninformative. The interaction
      with PEX14 is part of the peroxisomal import machinery and would be better captured by more specific terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20531392
  review:
    summary: Schueller et al. (2010) determined the crystal structure of PEX19 C-terminal mPTS recognition domain. This is
      a structural study of PEX19's mPTS binding function.
    action: REMOVE
    reason: The mPTS recognition function is better captured by GO:0033328 and GO:0036105. GO:0005515 is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21102411
  review:
    summary: Sato et al. (2010) solved the crystal structure of PEX3-PEX19 docking complex. PEX19 residues 1-44 form an alpha-helix
      when bound to PEX3. Core structural interaction.
    action: REMOVE
    reason: The PEX3-PEX19 docking interaction is a core function better captured by the protein carrier activity and PMP
      import process terms. GO:0005515 is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21525035
  review:
    summary: Bharti et al. (2011) identified PEX14 complexes by mass spec, including PEX19. The PEX19-PEX14 interaction is
      part of the peroxisomal import machinery.
    action: REMOVE
    reason: Generic protein binding from a proteomics study. The PEX19-PEX14 interaction is part of PEX19's import receptor
      function. GO:0005515 is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  review:
    summary: Rolland et al. (2014) proteome-scale human interactome map. High-throughput interaction data.
    action: REMOVE
    reason: Generic protein binding from high-throughput interactome screen. Uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25502805
  review:
    summary: Massively parallel pipeline examining molecular phenotypes of disease mutations. High-throughput data.
    action: REMOVE
    reason: Generic protein binding from high-throughput study. Uninformative for PEX19.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27107012
  review:
    summary: Barcode Fusion Genetics pooled-matrix protein interaction screens. High-throughput data.
    action: REMOVE
    reason: Generic protein binding from high-throughput screen. Uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27107014
  review:
    summary: Inter-species protein-protein interaction network. High-throughput data.
    action: REMOVE
    reason: Generic protein binding from high-throughput inter-species interactome. Uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  review:
    summary: Architecture of human interactome. High-throughput network study.
    action: REMOVE
    reason: Generic protein binding from high-throughput interactome study. Uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29997244
  review:
    summary: LuTHy bioluminescence-based two-hybrid technology for quantitative PPI mapping. High-throughput data.
    action: REMOVE
    reason: Generic protein binding from high-throughput two-hybrid screen. Uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31467278
  review:
    summary: Maximizing binary interactome mapping study. High-throughput data.
    action: REMOVE
    reason: Generic protein binding from high-throughput interactome. Uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  review:
    summary: Study of genetic variant disruption of protein interactions. High-throughput data.
    action: REMOVE
    reason: Generic protein binding from high-throughput variant effect study. Uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: Reference map of human binary protein interactome. High-throughput data.
    action: REMOVE
    reason: Generic protein binding from high-throughput interactome. Uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: Interactome mapping for neurodegenerative disease proteins. High-throughput data.
    action: REMOVE
    reason: Generic protein binding from high-throughput interactome focused on neurodegeneration. Uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: Dual proteome-scale networks of cell-specific interactome remodeling. High-throughput data.
    action: REMOVE
    reason: Generic protein binding from high-throughput interactome. Uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34819669
  review:
    summary: Multi-scale map of cell structure fusing protein images and interactions. High-throughput data.
    action: REMOVE
    reason: Generic protein binding from high-throughput cell mapping study. Uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: OpenCell endogenous tagging for cartography of human cellular organization. High-throughput data.
    action: REMOVE
    reason: Generic protein binding from high-throughput cellular organization study. Uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37398436
  review:
    summary: AI-guided pipeline for PPI drug discovery identifying SARS-CoV-2 inhibitor. High-throughput/computational data.
    action: REMOVE
    reason: Generic protein binding from computational/drug discovery study. Uninformative for PEX19.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:38225382
  review:
    summary: AlphaFold-based systematic discovery of protein interaction interfaces. Computational study.
    action: REMOVE
    reason: Generic protein binding from computational structural study. Uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  review:
    summary: Multimodal cell maps as a foundation for structural and functional genomics. High-throughput data.
    action: REMOVE
    reason: Generic protein binding from high-throughput multimodal cell mapping. Uninformative.
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: IDA from immunofluorescence curation (GO_REF:0000052). PEX19 localizes to peroxisomes as shown by multiple IF
      studies.
    action: ACCEPT
    reason: PEX19 associates with peroxisomes, established by immunofluorescence and fractionation studies (PMID:10704444,
      PMID:9339377).
    supported_by:
    - reference_id: PMID:10704444
      supporting_text: At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of
        the protein in the cytoplasm.
- term:
    id: GO:0140597
    label: protein carrier chaperone
  evidence_type: IDA
  original_reference_id: PMID:11402059
  review:
    summary: Jones et al. (2001) demonstrated PEX19 binds PMP targeting regions and facilitates PMP solubility. This supports
      protein carrier/chaperone activity.
    action: ACCEPT
    reason: PEX19 functions as a protein carrier that binds PMPs in the cytosol and delivers them to peroxisomes. This is
      a core molecular function (PMID:14709540, PMID:11402059).
    supported_by:
    - reference_id: PMID:11402059
      supporting_text: PEX19 may play a central role in this process
    - reference_id: PMID:14709540
      supporting_text: PEX19 functions as both a chaperone and an import receptor for newly synthesized PMPs
- term:
    id: GO:0140597
    label: protein carrier chaperone
  evidence_type: IDA
  original_reference_id: PMID:14709540
  review:
    summary: Jones et al. (2004) directly demonstrated PEX19 as a cytosolic chaperone and import receptor for class 1 PMPs.
      Core molecular function annotation.
    action: ACCEPT
    reason: This is the landmark paper establishing PEX19 as a chaperone/import receptor for PMPs. Protein carrier activity
      is an excellent term for PEX19's core function.
    supported_by:
    - reference_id: PMID:14709540
      supporting_text: PEX19 binds and stabilizes newly synthesized PMPs in the cytosol, binds to multiple PMP targeting signals
        (mPTSs), interacts with the hydrophobic domains of PMP targeting signals, and is essential for PMP targeting and import.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12488033
  review:
    summary: Oliveira et al. (2002) characterized PEX14 membrane topology and PEX14-PEX14 interaction. PEX19 was identified
      as an interacting partner. Generic protein binding is uninformative.
    action: REMOVE
    reason: Generic protein binding uninformative for PEX19. The PEX19-PEX14 interaction is part of the peroxisomal import
      machinery captured by other terms.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-382613
  review:
    summary: Reactome annotation for PEX19 docking ABCD1/D2/D3 to peroxisomal membrane. PEX19 acts in the cytosol as a carrier
      for ABC transporters.
    action: ACCEPT
    reason: PEX19 is predominantly cytosolic, well-established (PMID:10704444, PMID:14709540). Reactome pathway context is
      consistent.
    supported_by:
    - reference_id: PMID:10704444
      supporting_text: At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of
        the protein in the cytoplasm.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9603775
  review:
    summary: Reactome annotation for PEX3:PEX19:class I PMP dissociation. PEX19 acts in the cytosol.
    action: ACCEPT
    reason: Duplicate cytosol annotation from different Reactome reaction. PEX19 is cytosolic, well-established.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9603784
  review:
    summary: Reactome annotation for PEX19:class I PMP binding PEX3. PEX19 acts in the cytosol.
    action: ACCEPT
    reason: Duplicate cytosol annotation from different Reactome reaction. PEX19 is cytosolic.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9603804
  review:
    summary: Reactome annotation for PEX19 binding class I PMPs. PEX19 acts in the cytosol.
    action: ACCEPT
    reason: Duplicate cytosol annotation from different Reactome reaction. PEX19 is cytosolic.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9604086
  review:
    summary: Reactome annotation for PEX19:Pex3 binding PEX16. PEX19 acts in the cytosol.
    action: ACCEPT
    reason: Duplicate cytosol annotation from different Reactome reaction. PEX19 is cytosolic.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9604093
  review:
    summary: Reactome annotation for PEX19 binding Pex3. PEX19 acts in the cytosol.
    action: ACCEPT
    reason: Duplicate cytosol annotation from different Reactome reaction. PEX19 is cytosolic.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9604116
  review:
    summary: Reactome annotation for PEX16:PEX19:Pex3 dissociation. PEX19 acts in the cytosol.
    action: ACCEPT
    reason: Duplicate cytosol annotation from different Reactome reaction. PEX19 is cytosolic.
- term:
    id: GO:0006625
    label: protein targeting to peroxisome
  evidence_type: IMP
  original_reference_id: PMID:19114594
  review:
    summary: Matsuzaki & Fujiki (2008) showed PEX19 is essential for targeting PEX3 to peroxisomes. Knockdown of PEX19 inhibits
      peroxisomal targeting of newly synthesized PEX3.
    action: ACCEPT
    reason: PEX19 is required for protein targeting to peroxisomes, established by PEX19 knockdown experiments (PMID:19114594).
      This is a core biological process.
    supported_by:
    - reference_id: PMID:19114594
      supporting_text: Knockdown of Pex19p inhibits peroxisomal targeting of newly synthesized full-length Pex3p and results
        in failure of the peroxisomal localization of Pex3p.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19114594
  review:
    summary: Matsuzaki & Fujiki (2008) showed PEX19 forms a soluble complex with newly synthesized PEX3 in the cytosol. This
      is a specific PEX19-PEX3 interaction, part of PMP import.
    action: REMOVE
    reason: Generic protein binding uninformative. PEX19-PEX3 interaction is part of the PMP import pathway captured by other
      terms.
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:19114594
  review:
    summary: Matsuzaki & Fujiki (2008) showed PEX19 localizes to peroxisomes by immunofluorescence.
    action: ACCEPT
    reason: PEX19 associates with peroxisomes during PMP delivery. Well-established localization.
    supported_by:
    - reference_id: PMID:19114594
      supporting_text: Pex19p forms a soluble complex with newly synthesized Pex3p in the cytosol and directly translocates
        it to peroxisomes.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:19114594
  review:
    summary: Matsuzaki & Fujiki (2008) showed PEX19 is cytosolic by subcellular fractionation.
    action: ACCEPT
    reason: PEX19 is predominantly cytosolic, well-established by this and other studies.
    supported_by:
    - reference_id: PMID:19114594
      supporting_text: Pex19p forms a soluble complex with newly synthesized Pex3p in the cytosol
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18782765
  review:
    summary: Delille & Schrader (2008) showed PEX19 binds hFis1 via co-immunoprecipitation. hFis1 is a tail-anchored membrane
      protein shared between peroxisomes and mitochondria.
    action: REMOVE
    reason: Generic protein binding uninformative. The PEX19-hFis1 interaction reflects PEX19's PMP chaperone function for
      tail-anchored proteins.
- term:
    id: GO:0016559
    label: peroxisome fission
  evidence_type: IMP
  original_reference_id: PMID:18782765
  review:
    summary: Delille & Schrader (2008) showed PEX19 mediates targeting of hFis1 to peroxisomes, and hFis1 regulates peroxisome
      fission. However, PEX19's role is in delivering hFis1, not directly in fission per se.
    action: KEEP_AS_NON_CORE
    reason: PEX19 contributes to peroxisome fission indirectly by delivering the fission factor hFis1 to peroxisomes (PMID:18782765).
      This is a downstream consequence of PEX19's PMP chaperone function, not a direct role in fission machinery.
    supported_by:
    - reference_id: PMID:18782765
      supporting_text: peroxisomal targeting of hFis1 depends on Pex19p, a peroxisomal membrane protein import factor
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18174172
  review:
    summary: Sato et al. (2008) characterized PEX3-PEX19 interaction biochemically. Kd of 3.4 nM. Specific structural interaction.
    action: REMOVE
    reason: Generic protein binding uninformative. The PEX3-PEX19 docking interaction is well-characterized but better captured
      by other functional terms.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:18174172
  review:
    summary: Sato et al. (2008) showed PEX3-PEX19 forms a 1:1 complex by gel filtration and tryptophan fluorescence. This
      is a specific PEX3-PEX19 docking complex.
    action: ACCEPT
    reason: PEX19 forms a defined 1:1 complex with PEX3 (Kd = 3.4 nM). This is a core interaction for PMP import. The term
      is somewhat generic but accurately reflects the biochemical finding.
    supported_by:
    - reference_id: PMID:18174172
      supporting_text: a one-to-one complex is formed between monomeric Pex3p and monomeric Pex19p
- term:
    id: GO:0072663
    label: establishment of protein localization to peroxisome
  evidence_type: IMP
  original_reference_id: PMID:18782765
  review:
    summary: Delille & Schrader (2008) showed silencing PEX19 reduces targeting of hFis1 to peroxisomes. PEX19 establishes
      protein localization to peroxisomes.
    action: ACCEPT
    reason: PEX19 is essential for establishing PMP localization to peroxisomes. This is a core biological process directly
      supported by PEX19 knockdown experiments.
    supported_by:
    - reference_id: PMID:18782765
      supporting_text: Silencing of Pex19p by small interference RNA reduced the targeting of hFis1 to peroxisomes, but not
        to mitochondria.
- term:
    id: GO:0051117
    label: ATPase binding
  evidence_type: IPI
  original_reference_id: PMID:11453642
  review:
    summary: Biermanns & Gaertner (2001) studied PMP70 targeting to peroxisomes and actually found that PEX19 does NOT specifically
      bind to PMP70 targeting elements. The abstract states "peroxin 19 (PEX19) interactions are not required for targeting
      human PMP70 to peroxisomes. PEX19 does not specifically bind to the targeting elements of human PMP70."
    action: REMOVE
    reason: This annotation appears to be an error. PMID:11453642 (Biermanns & Gaertner 2001) explicitly states PEX19 does
      NOT specifically bind PMP70 targeting elements. PMP70/ABCD3 is an ABC transporter (ATPase), but the cited paper contradicts
      this annotation. Other papers do show PEX19-ABCD3 interaction (PMID:10704444, PMID:10777694), but the term "ATPase binding"
      is misleading for PEX19's function. PEX19 binds PMPs via mPTS, not via ATPase domains.
    supported_by:
    - reference_id: PMID:11453642
      supporting_text: peroxin 19 (PEX19) interactions are not required for targeting human PMP70 to peroxisomes. PEX19 does
        not specifically bind to the targeting elements of human PMP70.
- term:
    id: GO:0007031
    label: peroxisome organization
  evidence_type: IMP
  original_reference_id: PMID:14709540
  review:
    summary: Jones et al. (2004) showed PEX19 is essential for peroxisome organization. Loss of PEX19 leads to loss of peroxisomes.
    action: ACCEPT
    reason: PEX19 is required for peroxisome biogenesis and organization. This is a core biological process. Well-supported
      experimentally.
    supported_by:
    - reference_id: PMID:14709540
      supporting_text: PEX19 binds and stabilizes newly synthesized PMPs in the cytosol, binds to multiple PMP targeting signals
        (mPTSs), interacts with the hydrophobic domains of PMP targeting signals, and is essential for PMP targeting and import.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:14709540
  review:
    summary: Jones et al. (2004) showed PEX19 is predominantly cytoplasmic by immunofluorescence and subcellular fractionation.
    action: ACCEPT
    reason: PEX19 is predominantly cytoplasmic, established by direct assay.
    supported_by:
    - reference_id: PMID:14709540
      supporting_text: PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IDA
  original_reference_id: PMID:14709540
  review:
    summary: Jones et al. (2004) showed PEX19 stabilizes newly synthesized PMPs, preventing aggregation. However, PEX19 does
      not catalyze protein folding in the classical sense; it functions as a chaperone that maintains PMP solubility by shielding
      hydrophobic transmembrane domains.
    action: MODIFY
    reason: PEX19 is a chaperone that prevents PMP aggregation, not a folding catalyst. The protein carrier chaperone activity
      (GO:0140597) more accurately describes this function. PEX19 shields hydrophobic segments rather than assisting productive
      folding.
    proposed_replacement_terms:
    - id: GO:0140597
      label: protein carrier chaperone
    supported_by:
    - reference_id: PMID:14709540
      supporting_text: PEX19 binds and stabilizes newly synthesized PMPs in the cytosol
    - reference_id: PMID:16344115
      supporting_text: When PMP70 was translated in the presence of purified Pex19p, a large part of PMP70 existed as soluble
        form...However, in the absence of Pex19p, PMP70 formed aggregates during translation.
- term:
    id: GO:0036105
    label: peroxisome membrane class-1 targeting sequence binding
  evidence_type: IDA
  original_reference_id: PMID:14709540
  review:
    summary: Jones et al. (2004) defined class 1 mPTS as those bound by PEX19 and imported in a PEX19-dependent manner. This
      is a highly specific and accurate annotation for PEX19's molecular function.
    action: ACCEPT
    reason: PEX19 specifically recognizes class 1 mPTS, as demonstrated by Jones et al. This is the most specific and accurate
      MF term for PEX19's cargo recognition function.
    supported_by:
    - reference_id: PMID:14709540
      supporting_text: 'We also demonstrate the existence of two PMP import mechanisms and two classes of mPTSs: class 1 mPTSs,
        which are bound by PEX19 and imported in a PEX19-dependent manner, and class 2 mPTSs, which are not bound by PEX19
        and mediate protein import independently of PEX19'
- term:
    id: GO:0045046
    label: protein import into peroxisome membrane
  evidence_type: IDA
  original_reference_id: PMID:14709540
  review:
    summary: Jones et al. (2004) demonstrated PEX19 is essential for PMP import into the peroxisome membrane. Core biological
      process.
    action: ACCEPT
    reason: PEX19-dependent PMP import is the protein's primary biological process.
    supported_by:
    - reference_id: PMID:14709540
      supporting_text: PEX19 functions as both a chaperone and an import receptor for newly synthesized PMPs
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IDA
  original_reference_id: PMID:14709540
  review:
    summary: Jones et al. (2004) showed PEX19 stabilizes newly synthesized PMPs in the cytosol, preventing their degradation
      or aggregation.
    action: ACCEPT
    reason: PEX19 stabilizes PMPs by acting as a chaperone that prevents aggregation and degradation. This is a core function
      directly demonstrated by the study.
    supported_by:
    - reference_id: PMID:14709540
      supporting_text: PEX19 binds and stabilizes newly synthesized PMPs in the cytosol
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: HDA
  original_reference_id: PMID:21525035
  review:
    summary: Bharti et al. (2011) identified PEX19 associated with peroxisomal membrane protein complexes by mass spectrometry.
      HDA annotation.
    action: ACCEPT
    reason: PEX19 associates with the peroxisomal membrane, confirmed by mass spec identification in peroxisomal membrane
      complexes.
    supported_by:
    - reference_id: PMID:21525035
      supporting_text: almost all known human peroxins involved in protein import were identified as constituents of the PEX14
        complexes
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10777694
  review:
    summary: Gloeckner et al. (2000) showed PEX19 interacts with ALDP, ALDRP, and PMP70 by Y2H and GST pull-down. These are
      specific PMP interactions reflecting PEX19's chaperone function for peroxisomal ABC transporters.
    action: REMOVE
    reason: Generic protein binding uninformative. The PEX19-ABC transporter interactions reflect PEX19's mPTS binding and
      chaperone functions captured by other terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19715730
  review:
    summary: Pinto et al. (2009) studied PEX3 cytosolic domain lipid binding. PEX19 was used as a binding partner control.
      The study is primarily about PEX3, not PEX19.
    action: REMOVE
    reason: Generic protein binding uninformative. PEX19-PEX3 interaction is captured by other terms.
- term:
    id: GO:1900131
    label: negative regulation of lipid binding
  evidence_type: IDA
  original_reference_id: PMID:19715730
  review:
    summary: Pinto et al. (2009) showed PEX3 cytosolic domain binds membrane lipids, and PEX19 binding to PEX3 may modulate
      this lipid interaction. However, the paper is primarily about PEX3 lipid binding, and the GO annotation claims PEX19
      negatively regulates lipid binding. The evidence for PEX19 specifically negatively regulating lipid binding is indirect.
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation that PEX19 negatively regulates lipid binding appears to be based on the observation that PEX19
      binding to PEX3 may compete with PEX3's lipid binding. This is an indirect inference from a study primarily about PEX3,
      not a direct demonstration of PEX19 as a negative regulator of lipid binding. Not a core function of PEX19.
    supported_by:
    - reference_id: PMID:19715730
      supporting_text: this domain of PEX3 interacts with amphipathic molecules
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16344115
  review:
    summary: Kashiwayama et al. (2005) showed PEX19 binds PMP70, keeping it soluble during translation. Specific chaperone
      interaction better captured by protein carrier activity.
    action: REMOVE
    reason: Generic protein binding uninformative. PEX19-PMP70 interaction is part of PEX19's chaperone function captured
      by GO:0140597.
- term:
    id: GO:0006625
    label: protein targeting to peroxisome
  evidence_type: IDA
  original_reference_id: PMID:16344115
  review:
    summary: Kashiwayama et al. (2005) showed PEX19 keeps PMP70 in proper conformation for peroxisomal localization. Deletion
      of PEX19 binding sites on PMP70 abolished peroxisomal targeting.
    action: ACCEPT
    reason: PEX19 is essential for targeting PMPs including PMP70 to peroxisomes. Core function.
    supported_by:
    - reference_id: PMID:16344115
      supporting_text: Pex19p binds to PMP70 co-translationally and keeps PMP70 as a proper conformation for the localization
        to peroxisome
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16763195
  review:
    summary: Halbach et al. (2006) showed PEX19 binds PEX26 at C-terminal sites including the TMD and luminal domain. Specific
      tail-anchored PMP interaction.
    action: REMOVE
    reason: Generic protein binding uninformative. The PEX19-PEX26 interaction reflects tail-anchored PMP recognition captured
      by mPTS binding terms.
- term:
    id: GO:0006625
    label: protein targeting to peroxisome
  evidence_type: IDA
  original_reference_id: PMID:16763195
  review:
    summary: Halbach et al. (2006) showed PEX19 is essential for PEX26 import into the peroxisomal membrane. C-terminal PEX19-binding
      sites mark tail-anchored proteins for peroxisomal delivery.
    action: ACCEPT
    reason: PEX19 is essential for targeting tail-anchored PMPs (PEX26) to peroxisomes. Core function.
    supported_by:
    - reference_id: PMID:16763195
      supporting_text: C-terminal PEX19-binding sites mark tail-anchored proteins for delivery to peroxisomes
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IDA
  original_reference_id: PMID:16344115
  review:
    summary: Kashiwayama et al. (2005) showed PEX19 prevents PMP70 aggregation during translation, keeping it soluble. Direct
      chaperone-mediated stabilization.
    action: ACCEPT
    reason: PEX19 stabilizes PMPs by preventing aggregation. Directly demonstrated for PMP70.
    supported_by:
    - reference_id: PMID:16344115
      supporting_text: When PMP70 was translated in the presence of purified Pex19p, a large part of PMP70 existed as soluble
        form...However, in the absence of Pex19p, PMP70 formed aggregates during translation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11590176
  review:
    summary: Brosius et al. (2002) showed both targeting regions of human PMP22 interact with PEX19. Specific PMP interaction
      reflecting PEX19's chaperone function.
    action: REMOVE
    reason: Generic protein binding uninformative. PEX19-PMP22 interaction is part of PEX19's PMP chaperone function captured
      by mPTS binding and protein carrier activity terms.
- term:
    id: GO:0045046
    label: protein import into peroxisome membrane
  evidence_type: IDA
  original_reference_id: PMID:11402059
  review:
    summary: Jones et al. (2001) demonstrated PEX19 interacts with PMP targeting regions, supporting its role in PMP import
      into the peroxisome membrane.
    action: ACCEPT
    reason: PEX19-mediated PMP import into peroxisome membrane is a core biological process.
    supported_by:
    - reference_id: PMID:11402059
      supporting_text: PEX19, a factor required for peroxisomal membrane biogenesis, interacts with the two minimal targeting
        regions of PMP34
- term:
    id: GO:0031526
    label: brush border membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ISS annotation from manual transfer of orthologue data. PEX19 localization to brush border membrane is not supported
      by any literature on PEX19. PEX19 is a cytosolic/peroxisomal protein with no known role in brush border. This appears
      to be an erroneous orthologue transfer.
    action: REMOVE
    reason: There is no evidence that PEX19 localizes to the brush border membrane. PEX19 is a predominantly cytosolic protein
      that transiently associates with peroxisomal membranes. Brush border localization is not consistent with known PEX19
      biology and likely represents an erroneous orthologue-based transfer.
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: IDA
  original_reference_id: PMID:9339377
  review:
    summary: Kammerer et al. (1997) showed PEX19 (HsPXF) has peroxisomal localization and is farnesylated at C-terminal CaaX
      motif.
    action: ACCEPT
    reason: PEX19 localizes to peroxisomal membrane. Early characterization study establishing this localization.
    supported_by:
    - reference_id: PMID:9339377
      supporting_text: For the HsPXF protein, a carboxyterminal farnesylation at cysteine residues was demonstrated. Through
        the use of HsPXF-specific antibodies, the protein was shown to be attached to the outer surface of peroxisomes.
- term:
    id: GO:0007031
    label: peroxisome organization
  evidence_type: NAS
  original_reference_id: PMID:9339377
  review:
    summary: NAS (non-traceable author statement) annotation based on Kammerer et al. (1997). The paper describes PEX19 genomic
      organization but does not directly demonstrate a role in peroxisome organization. However, PEX19's role in peroxisome
      organization is well-established by other studies.
    action: ACCEPT
    reason: While the specific reference is NAS, PEX19's role in peroxisome organization is well-established by multiple subsequent
      studies (PMID:10704444, PMID:14709540).
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ISS annotation from orthologue transfer. PEX19 is predominantly cytoplasmic, well-established experimentally.
    action: ACCEPT
    reason: PEX19 is predominantly cytoplasmic, consistent with direct experimental evidence.
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ISS annotation from orthologue transfer. PEX19 associates with peroxisomes.
    action: ACCEPT
    reason: PEX19 associates with peroxisomes, consistent with direct experimental evidence.
- term:
    id: GO:0006625
    label: protein targeting to peroxisome
  evidence_type: IMP
  original_reference_id: PMID:10704444
  review:
    summary: Sacksteder et al. (2000) showed mislocalization of PEX19 to the nucleus leads to nuclear accumulation of newly
      synthesized PMPs, and loss of PEX19 results in PMP degradation/mislocalization to mitochondria.
    action: ACCEPT
    reason: PEX19 is essential for protein targeting to peroxisomes. Loss of PEX19 causes PMP mislocalization, demonstrating
      its requirement for targeting.
    supported_by:
    - reference_id: PMID:10704444
      supporting_text: mislocalization of PEX19 to the nucleus leads to nuclear accumulation of newly synthesized PMPs
    - reference_id: PMID:10704444
      supporting_text: the loss of PEX19 results in degradation of PMPs and/or mislocalization of PMPs to the mitochondrion
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: HPA-based IDA annotation for nucleoplasm localization. PEX19 is predominantly cytosolic and not known to have
      a nuclear function. However, some studies show that when PEX19 is mislocalized to the nucleus it can accumulate there
      with PMPs (PMID:10704444). Also, PEX19 has been reported to interact with CDKN2A/p19ARF and exclude it from the nucleus
      (PMID:11259404). Low-level nuclear detection by HPA is possible but not a core localization.
    action: NEW
    reason: HPA-based annotation for nucleoplasm localization. PEX19 is predominantly cytosolic and not known to have a nuclear
      function. Low-level nuclear detection by HPA is possible but not a core localization. This annotation from UniProt is
      not in GOA.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IMP
  original_reference_id: GO_REF:0000052
  review:
    summary: Nuclear localization from immunofluorescence curation. PEX19 was shown to accumulate in the nucleus when an NLS
      is appended (PMID:10704444), and it has a reported role in excluding CDKN2A from the nucleus (PMID:11259404). However,
      nuclear localization is not a core property of PEX19.
    action: NEW
    reason: PEX19 is not normally a nuclear protein. Nuclear presence may relate to non-canonical CDKN2A interaction (PMID:11259404).
      This annotation from UniProt is not in GOA.
- term:
    id: GO:0016557
    label: peroxisome membrane biogenesis
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: PEX19 is essential for peroxisome membrane biogenesis. Loss of PEX19 abolishes peroxisome membrane formation.
      This is a core biological process.
    action: NEW
    reason: PEX19 is required for peroxisome membrane biogenesis, one of only three peroxins (PEX3, PEX16, PEX19) whose loss
      abolishes peroxisomal membrane structures. This annotation from UniProt is not in GOA but is well-supported.
    supported_by:
    - reference_id: PMID:10704444
      supporting_text: the loss of PEX19 results in degradation of PMPs and/or mislocalization of PMPs to the mitochondrion
    - reference_id: PMID:14709540
      supporting_text: PEX19 functions as both a chaperone and an import receptor for newly synthesized PMPs
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence
    similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative
    changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10704444
  title: PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome
    membrane synthesis.
  findings:
  - statement: PEX19 binds a broad spectrum of PMPs
    supporting_text: PEX19 binds a broad spectrum of PMPs, displays saturable PMP binding, and interacts with regions of PMPs
      required for their targeting to peroxisomes.
  - statement: PEX19 is bimodally distributed between cytoplasm and peroxisome
    supporting_text: At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of the
      protein in the cytoplasm.
  - statement: Loss of PEX19 results in degradation and mislocalization of PMPs
    supporting_text: the loss of PEX19 results in degradation of PMPs and/or mislocalization of PMPs to the mitochondrion.
- id: PMID:10777694
  title: Human adrenoleukodystrophy protein and related peroxisomal ABC transporters interact with the peroxisomal assembly
    protein PEX19p.
  findings:
  - statement: PEX19 interacts with ALDP, ALDRP, and PMP70
    supporting_text: we identified the peroxin PEX19p as a novel interactor of ALDP, ALDRP, and PMP70.
  - statement: PEX19 is a cytosolic acceptor for peroxisomal ABC transporters
    supporting_text: Our data provide evidence that PEX19p is a cytosolic acceptor protein for the peroxisomal ABC transporters
      ALDP, PMP70, and ALDRP and might be involved in the intracellular sorting and trafficking of these proteins to the peroxisomal
      membrane.
- id: PMID:11402059
  title: Multiple distinct targeting signals in integral peroxisomal membrane proteins.
  findings:
  - statement: PMP34 contains at least two nonoverlapping mPTS
    supporting_text: the metabolite transporter PMP34, an integral PMP, contains at least two nonoverlapping sets of targeting
      information, either of which is sufficient for insertion into the peroxisome membrane.
  - statement: PEX19 binds both minimal targeting regions of PMP34
    supporting_text: we demonstrate that PEX19, a factor required for peroxisomal membrane biogenesis, interacts with the
      two minimal targeting regions of PMP34.
- id: PMID:11453642
  title: Targeting elements in the amino-terminal part direct the human 70-kDa peroxisomal integral membrane protein (PMP70)
    to peroxisomes.
  findings:
  - statement: PEX19 interactions are NOT required for targeting human PMP70 to peroxisomes
    supporting_text: peroxin 19 (PEX19) interactions are not required for targeting human PMP70 to peroxisomes.
  - statement: PEX19 does not specifically bind to the targeting elements of human PMP70
    supporting_text: PEX19 does not specifically bind to the targeting elements of human PMP70.
- id: PMID:11590176
  title: Two different targeting signals direct human peroxisomal membrane protein 22 to peroxisomes.
  findings:
  - statement: Both PMP22 targeting regions interact with PEX19
    supporting_text: Both of these peroxisomal targeting regions interact with PEX19, a factor required for peroxisome membrane
      synthesis.
- id: PMID:12096124
  title: Analysis of mammalian peroxin interactions using a non-transcription-based bacterial two-hybrid assay.
  findings:
  - statement: Farnesylation enhances PEX19 affinity for PEX13
    supporting_text: farnesylation, and not the CAAX motif, of Pex19p strongly enhances its affinity for Pex13p
  - statement: CAAX motif enhances PEX19 affinity for PEX11beta
    supporting_text: the CAAXmotif, and not farnesylation, of Pex19p strongly enhances its affinity for Pex11pbeta
- id: PMID:12488033
  title: 'Mammalian Pex14p: membrane topology and characterisation of the Pex14p-Pex14p interaction.'
  findings:
  - statement: PEX14 forms homopolymers via residues 147-278
    supporting_text: homopolymerisation of Pex14p involves a domain comprising amino acid residues 147-278 of this peroxin.
- id: PMID:14709540
  title: PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins.
  findings:
  - statement: PEX19 is a chaperone and import receptor for class 1 PMPs
    supporting_text: We show here that PEX19 has all of the properties one would expect for a bifunctional PMP chaperone/import
      receptor.
  - statement: PEX19 binds mPTS and stabilizes newly synthesized PMPs
    supporting_text: PEX19 binds and stabilizes newly synthesized PMPs in the cytosol, binds to multiple PMP targeting signals
      (mPTSs), interacts with the hydrophobic domains of PMP targeting signals, and is essential for PMP targeting and import.
  - statement: Two classes of mPTS defined - class 1 (PEX19-dependent) and class 2 (PEX19-independent)
    supporting_text: 'We also demonstrate the existence of two PMP import mechanisms and two classes of mPTSs: class 1 mPTSs,
      which are bound by PEX19 and imported in a PEX19-dependent manner, and class 2 mPTSs, which are not bound by PEX19 and
      mediate protein import independently of PEX19.'
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
- id: PMID:16280322
  title: In vitro transport of membrane proteins to peroxisomes by shuttling receptor Pex19p.
  findings:
  - statement: PEX19 shuttles PMPs from cytosol to peroxisomes
    supporting_text: Pex19p translocates the membrane peroxins from the cytosol to peroxisomes in an ATP- and Pex3p-dependent
      manner and then shuttles back to the cytosol.
  - statement: Transport is ATP- and PEX3-dependent
    supporting_text: Cell-free synthesized, 35S-labeled Pex19p was targeted to subcellular fractions containing peroxisomes
      from Chinese hamster ovary-K1 cells as well as peroxisomes isolated from rat liver in an ATP-dependent manner.
  - statement: PEX19 recycles back to cytosol
    supporting_text: Peroxisome-associated and partly Na2CO3-resistant 35S-Pex19p was released to the cytosolic fraction upon
      incubation in the absence of ATP, whereas 35S-Pex16p and 35S-Pex26p remained in the membranes.
- id: PMID:16344115
  title: Role of Pex19p in the targeting of PMP70 to peroxisome.
  findings:
  - statement: PEX19 keeps PMP70 soluble during translation
    supporting_text: When PMP70 was translated in the presence of purified Pex19p, a large part of PMP70 existed as soluble
      form and was co-immunoprecipitated with Pex19p.
  - statement: PMP70 aggregates in absence of PEX19
    supporting_text: in the absence of Pex19p, PMP70 formed aggregates during translation.
  - statement: PEX19 binds PMP70 co-translationally
    supporting_text: These results suggest that Pex19p binds to PMP70 co-translationally and keeps PMP70 as a proper conformation
      for the localization to peroxisome.
- id: PMID:16763195
  title: Targeting of the tail-anchored peroxisomal membrane proteins PEX26 and PEX15 occurs through C-terminal PEX19-binding
    sites.
  findings:
  - statement: PEX26 contains two PEX19-binding sites
    supporting_text: Its C-terminal-targeting signal contains two binding sites for PEX19, the import receptor for several
      peroxisomal membrane proteins.
  - statement: PEX19 is essential for PEX26 import
    supporting_text: we show that PEX19 is essential for PEX26 import.
  - statement: C-terminal PEX19-binding sites mark tail-anchored proteins for peroxisomal delivery
    supporting_text: We conclude that C-terminal PEX19-binding sites mark tail-anchored proteins for delivery to peroxisomes.
- id: PMID:18174172
  title: 'Characterization of the interaction between recombinant human peroxin Pex3p and Pex19p: identification of TRP-104
    IN Pex3p as a critical residue for the interaction.'
  findings:
  - statement: PEX3-PEX19 form a 1:1 complex
    supporting_text: Gel filtration chromatography analyses and intrinsic tryptophan fluorescence titrations revealed that
      a one-to-one complex is formed between monomeric Pex3p and monomeric Pex19p.
  - statement: Kd = 3.4 nM for wild-type interaction
    supporting_text: the wild-type and the W104A and W104F mutants showed K(D) values of 3.4 nm, 1080 nm, and 66.2 nm, respectively.
  - statement: Trp-104 of PEX3 is critical for PEX19 binding
    supporting_text: the indole ring of Trp-104 directly interacts with Pex19p to facilitate the specific peroxisomal translocation
      of the Pex19p-PMP complexes.
- id: PMID:18782765
  title: Targeting of hFis1 to peroxisomes is mediated by Pex19p.
  findings:
  - statement: PEX19 mediates hFis1 targeting to peroxisomes
    supporting_text: Here we demonstrate for the first time that peroxisomal targeting of hFis1 depends on Pex19p, a peroxisomal
      membrane protein import factor.
  - statement: PEX19 knockdown reduces hFis1 peroxisomal targeting
    supporting_text: Silencing of Pex19p by small interference RNA reduced the targeting of hFis1 to peroxisomes, but not
      to mitochondria.
  - statement: Peroxisomal and mitochondrial targeting of hFis1 are independent events
    supporting_text: Our findings indicate that targeting of hFis1 to peroxisomes and mitochondria are independent events
      and support a direct, Pex19p-dependent targeting of peroxisomal tail-anchored proteins.
- id: PMID:19114594
  title: The peroxisomal membrane protein import receptor Pex3p is directly transported to peroxisomes by a novel Pex19p-
    and Pex16p-dependent pathway.
  findings:
  - statement: PEX19 is a chaperone for full-length PEX3 in the cytosol
    supporting_text: We show here that Pex19p plays an essential role as the chaperone for full-length Pex3p in the cytosol.
  - statement: PEX19 knockdown inhibits PEX3 peroxisomal targeting
    supporting_text: Knockdown of Pex19p inhibits peroxisomal targeting of newly synthesized full-length Pex3p
  - statement: PEX16 is the docking receptor for PEX3-PEX19 complexes
    supporting_text: Pex16p is the membrane receptor for Pex3p
- id: PMID:19197237
  title: Structural basis for competitive interactions of Pex14 with the import receptors Pex5 and Pex19.
  findings:
  - statement: PEX19 and PEX5 bind competitively to PEX14 N-terminal domain
    supporting_text: Pex5 and Pex19 ligand helices bind competitively to the same surface in Pex14(N) albeit with opposite
      directionality.
  - statement: PEX19 uses FxxxF motif (residues 66-77) to bind PEX14
    supporting_text: The molecular recognition involves conserved aromatic side chains in the Pex5 WxxxF/Y motif and a newly
      identified F/YFxxxF sequence in Pex19.
- id: PMID:19715730
  title: The cytosolic domain of PEX3, a protein involved in the biogenesis of peroxisomes, binds membrane lipids.
  findings:
  - statement: PEX3 cytosolic domain binds membrane lipids
    supporting_text: a recombinant protein comprising the cytosolic domain of PEX3 can be purified in a soluble and monomeric
      form in the absence of detergents or other solubilizing agents.
  - statement: PEX19 interaction may modulate PEX3 lipid binding
    supporting_text: we tested this recombinant protein in lipid-binding assays and found that it interacts strongly with
      liposomes inducing their flocculation or even partial solubilization.
- id: PMID:20531392
  title: The peroxisomal receptor Pex19p forms a helical mPTS recognition domain.
  findings:
  - statement: Crystal structure of PEX19 C-terminal mPTS recognition domain
    supporting_text: The crystal structure of the folded C-terminal part of the receptor reveals a globular domain that displays
      a bundle of three long helices in an antiparallel arrangement.
  - statement: Alpha-helical bundle binds mPTS with ~10 uM affinity
    supporting_text: the structured alpha-helical domain binds PMP-targeting signal (mPTS) sequences with about 10 muM affinity.
- id: PMID:21102411
  title: Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto its receptor Pex3p.
  findings:
  - statement: Crystal structure of PEX3-PEX19 complex
    supporting_text: we present the three-dimensional structure of the complex between a cytosolic domain of Pex3p and the
      binding-region peptide of Pex19p.
  - statement: PEX19 residues 1-44 form an alpha-helix upon PEX3 binding
    supporting_text: A 16-residue region of the Pex19p peptide forms an alpha-helix and makes a contact with Pex3p; this helix
      is disordered in the unbound state.
  - statement: Leucine triad and Phe29 are critical for binding
    supporting_text: The Pex19p peptide contains a characteristic motif, consisting of the leucine triad (Leu18, Leu21, Leu22),
      and Phe29, which are critical for the Pex3p binding and peroxisome biogenesis.
- id: PMID:21525035
  title: PEX14 is required for microtubule-based peroxisome motility in human cells.
  findings:
  - statement: PEX19 identified in PEX14 complexes by mass spectrometry
    supporting_text: Using mass spectrometric analysis, almost all known human peroxins involved in protein import were identified
      as constituents of the PEX14 complexes.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:25502805
  title: A massively parallel pipeline to clone DNA variants and examine molecular phenotypes of human disease mutations.
  findings: []
- id: PMID:27107012
  title: Pooled-matrix protein interaction screens using Barcode Fusion Genetics.
  findings: []
- id: PMID:27107014
  title: An inter-species protein-protein interaction network across vast evolutionary distance.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:29997244
  title: 'LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative mapping of protein-protein
    interactions in mammalian cells.'
  findings: []
- id: PMID:31467278
  title: Maximizing binary interactome mapping with a minimal number of assays.
  findings: []
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation
    in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:34819669
  title: A multi-scale map of cell structure fusing protein images and interactions.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:37398436
  title: AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor.
  findings: []
- id: PMID:38225382
  title: Systematic discovery of protein interaction interfaces using AlphaFold and experimental validation.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:9339377
  title: Genomic organization and molecular characterization of a gene encoding HsPXF, a human peroxisomal farnesylated protein.
  findings:
  - statement: PEX19 is farnesylated at C-terminal CaaX motif
    supporting_text: For the HsPXF protein, a carboxyterminal farnesylation at cysteine residues was demonstrated.
  - statement: Peroxisomal localization demonstrated
    supporting_text: Through the use of HsPXF-specific antibodies, the protein was shown to be attached to the outer surface
      of peroxisomes.
  - statement: Four splice variants identified
    supporting_text: we detected four splice variants originating either from exon skipping or from alternative splicing events.
- id: Reactome:R-HSA-382613
  title: PEX-19 docks ABCD1/D2/D3 to peroximal membrane
  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: []
- id: Reactome:R-NUL-9604086
  title: PEX19:Pex3 binds PEX16
  findings: []
- id: Reactome:R-NUL-9604093
  title: PEX19 binds Pex3
  findings: []
- id: Reactome:R-NUL-9604116
  title: PEX16:PEX19:Pex3 dissociates
  findings: []
- id: PMID:11259404
  title: Pex19p dampens the p19ARF-p53-p21WAF1 tumor suppressor pathway.
  findings:
  - statement: PEX19 interacts with CDKN2A/p19ARF
    supporting_text: We isolated a 33-kDa protein, Pex19p/HK33/HsPXF, as a p19ARF-binding protein in a yeast two-hybrid screen.
  - statement: PEX19 excludes CDKN2A from nucleus
    supporting_text: Pex19p interacts with p19ARF in the cell cytoplasm and excludes p19ARF from the nucleus, leading to a
      concurrent inactivation of p53 function.
  - statement: Results in active degradation of TP53
    supporting_text: Down-regulation of Pex19p by its antisense expression resulted in increased levels of p19ARF, increased
      p53 function, and a p53/p21WAF1-mediated senescence-like cell cycle arrest.
core_functions:
- molecular_function:
    id: GO:0140597
    label: protein carrier chaperone
  directly_involved_in:
  - id: GO:0045046
    label: protein import into peroxisome membrane
  - id: GO:0016557
    label: peroxisome membrane biogenesis
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005778
    label: peroxisomal membrane
  description: PEX19 functions as a cytosolic chaperone and import receptor for peroxisomal membrane proteins (PMPs). It binds
    newly synthesized PMPs via their mPTS in the cytosol, prevents their aggregation (protein stabilization), and delivers
    them to PEX3 at the peroxisomal membrane for insertion. PEX19 is one of three essential peroxins (with PEX3 and PEX16)
    required for peroxisome membrane biogenesis.
- molecular_function:
    id: GO:0036105
    label: peroxisome membrane class-1 targeting sequence binding
  directly_involved_in:
  - id: GO:0006625
    label: protein targeting to peroxisome
  locations:
  - id: GO:0005829
    label: cytosol
  description: PEX19 recognizes class 1 membrane peroxisomal targeting signals (mPTS) on PMPs via its C-terminal alpha-helical
    domain, enabling specific cargo selection for PEX3-dependent import into the peroxisomal membrane.