id: O96011
gene_symbol: PEX11B
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  PEX11B (Peroxisomal membrane protein 11B / Peroxin-11B) is an integral peroxisomal membrane protein
  and the constitutively expressed member of the PEX11 family (PEX11A, PEX11B, PEX11G). It is the
  primary driver of constitutive peroxisome proliferation via the growth-and-division pathway. PEX11B
  uses an N-terminal amphipathic helix to directly deform and elongate the peroxisomal membrane, and
  forms homo-oligomers and hetero-oligomers (with PEX11G). It coordinates with the fission machinery
  (FIS1, MFF, DRP1/DNM1L) to complete peroxisome division. Mutations in PEX11B cause Peroxisome
  Biogenesis Disorder 14B (OMIM 614920), characterized by congenital cataracts, mild intellectual
  disability, hearing loss, and polyneuropathy. PEX11B has two transmembrane domains with both N- and
  C-termini facing the cytosol.
alternative_products:
- name: '1'
  id: O96011-1
- name: '2'
  id: O96011-2
  sequence_note: VSP_042860
existing_annotations:
# === ANNOTATION 1: peroxisomal membrane (IBA) ===
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PEX11B is an integral peroxisomal membrane protein. This is one of the best-established
      localizations for this protein, supported by multiple independent experimental studies
      including immunofluorescence and fractionation (PMID:9792670, PMID:10704444, PMID:20826455).
      IBA annotation is consistent with the phylogenetically conserved peroxisomal membrane
      localization of PEX11 family members.
    action: ACCEPT
    reason: >-
      Core localization. PEX11B is an integral peroxisomal membrane protein with two transmembrane
      domains, confirmed by multiple experimental approaches. The IBA annotation is well-supported
      phylogenetically and experimentally.
    supported_by:
      - reference_id: PMID:9792670
        supporting_text: "Overexpression of the human PEX11beta gene alone was sufficient to induce peroxisome proliferation"
      - reference_id: PMID:20826455
        supporting_text: "PEX11 family members are membrane elongation factors that coordinate peroxisome proliferation and maintenance"
      - reference_id: file:human/PEX11B/PEX11B-deep-research-falcon.md
        supporting_text: "PEX11B is the best-characterized isoform in mammals and the primary driver of constitutive peroxisome proliferation"

# === ANNOTATION 2: peroxisome fission (IBA) ===
- term:
    id: GO:0016559
    label: peroxisome fission
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PEX11B is a key driver of peroxisome fission through the growth-and-division pathway. It
      mediates membrane elongation/tubulation that precedes DRP1-dependent scission. This is
      the core biological process for PEX11B, conserved across eukaryotes. IBA annotation
      reflects the phylogenetically conserved role.
    action: ACCEPT
    reason: >-
      Core biological process. PEX11B drives peroxisome elongation and coordinates fission
      machinery recruitment. Multiple experimental studies demonstrate this role (PMID:9792670,
      PMID:17408615, PMID:20826455).
    supported_by:
      - reference_id: PMID:9792670
        supporting_text: "PEX11beta induces peroxisome proliferation through a multistep process involving peroxisome elongation and segregation of PEX11beta from other peroxisomal membrane proteins, followed by peroxisome division"
      - reference_id: PMID:17408615
        supporting_text: "Fis1 plays important roles in peroxisome division and maintenance of peroxisome morphology in mammalian cells, possibly in a concerted manner with Pex11pbeta and DLP1"

# === ANNOTATION 3: peroxisomal membrane (IEA, GO_REF:0000120) ===
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      IEA annotation for peroxisomal membrane localization via combined automated methods.
      Consistent with the well-established experimental evidence for PEX11B localization.
    action: ACCEPT
    reason: >-
      Correct and consistent with multiple experimental studies and the IBA annotation.
      Redundant with stronger evidence but not incorrect.

# === ANNOTATION 4: peroxisome organization (IEA, GO_REF:0000043) ===
- term:
    id: GO:0007031
    label: peroxisome organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      IEA annotation based on UniProt keyword mapping. Peroxisome organization is a broad
      parent term that encompasses peroxisome fission, which is the more specific and
      accurate term for PEX11B function.
    action: ACCEPT
    reason: >-
      While peroxisome fission (GO:0016559) is more specific and preferred, peroxisome
      organization is not wrong as a broader term. PEX11B is indeed involved in organizing
      peroxisomes through the growth-and-division pathway. Acceptable as a broader IEA annotation.

# === ANNOTATION 5: peroxisome fission (IEA, GO_REF:0000002) ===
- term:
    id: GO:0016559
    label: peroxisome fission
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation based on InterPro-to-GO mapping. The PEX11 domain (IPR008733 / PF05648)
      maps to peroxisome fission, which is correct for PEX11B.
    action: ACCEPT
    reason: >-
      Correct mapping. The PEX11 domain is functionally associated with peroxisome fission,
      well supported by experimental evidence.

# === ANNOTATION 6: protein binding (IPI, PMID:10704444) ===
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10704444
  review:
    summary: >-
      PMID:10704444 (Sacksteder et al. 2000) demonstrates that PEX19 binds PEX11B using
      yeast two-hybrid and blot overlay assays. PEX19 functions as a chaperone/import receptor
      for peroxisomal membrane proteins including PEX11B. The C-terminal region of PEX11B
      (aa 211-259) is required for PEX19 interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction with PEX19 is real and well-characterized, but generic protein binding
      is uninformative. The biologically relevant annotation is PEX11B localization to the
      peroxisomal membrane via PEX19-dependent import, which is already captured by CC annotations.
      No specific GO MF term exists for PEX19-cargo binding that would be more informative.
    supported_by:
      - reference_id: PMID:10704444
        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"

# === ANNOTATION 7: protein binding (IPI, PMID:12096124) ===
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12096124
  review:
    summary: >-
      PMID:12096124 (Fransen et al. 2002) used a bacterial two-hybrid system to analyze
      mammalian peroxin interactions. The study demonstrated PEX11B interactions with PEX19,
      showing that the CAAX motif of PEX19 enhances its affinity for PEX11B.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This is a targeted two-hybrid study of peroxin interactions. The interaction with PEX19
      is real and already captured by other annotations. Generic protein binding does not add
      useful information. The specific interaction partners (PEX19) are what matter.
    supported_by:
      - reference_id: PMID:12096124
        supporting_text: "the CAAXmotif, and not farnesylation, of Pex19p strongly enhances its affinity for Pex11pbeta"

# === ANNOTATION 8: protein binding (IPI, PMID:14709540) ===
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14709540
  review:
    summary: >-
      PMID:14709540 (Jones et al. 2004) demonstrates that PEX19 is a chaperone and import
      receptor for class 1 PMPs, including PEX11B. PEX11B is classified as a class 1 PMP that
      requires PEX19 for targeting to peroxisomes. The study used deletion mutants to map
      PEX19 binding regions.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Again captures the PEX19-PEX11B interaction. Protein binding is uninformative. The
      biologically relevant annotation is peroxisomal membrane localization via PEX19-dependent
      import, which is already captured.
    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"

# === ANNOTATION 9: protein binding (IPI, PMID:20531392) ===
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20531392
  review:
    summary: >-
      PMID:20531392 (Schueller et al. 2010) determined the crystal structure of the Pex19p
      C-terminal domain and characterized its mPTS recognition. PEX11B is used as one of the
      cargo proteins to demonstrate mPTS binding by Pex19p.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This again reflects the PEX19-PEX11B cargo-receptor interaction. The study is about
      PEX19 structure rather than PEX11B function per se. Generic protein binding is uninformative.
    supported_by:
      - reference_id: PMID:20531392
        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"

# === ANNOTATION 10: protein binding (IPI, PMID:25416956) ===
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  review:
    summary: >-
      PMID:25416956 (Rolland et al. 2014) is a large-scale proteome-wide interactome mapping
      study. PEX11B interactions detected are from high-throughput yeast two-hybrid screens.
      No specific PEX11B interaction partners are highlighted in the abstract.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome study. Protein binding from large-scale screens provides
      no specific functional insight for PEX11B. The biologically relevant interactions
      (PEX19, FIS1, PEX11G, self-interaction) are captured by more targeted studies.
    supported_by:
      - reference_id: PMID:25416956
        supporting_text: "A proteome-scale map of the human interactome network."

# === ANNOTATION 11: protein binding (IPI, PMID:29997244) ===
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29997244
  review:
    summary: >-
      PMID:29997244 (Trepte et al. 2018) describes the LuTHy technology for quantitative
      protein-protein interaction mapping. PEX11B is among proteins tested in this
      bioluminescence-based two-hybrid system as part of method validation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Technology paper using PEX11B as one of many test cases. Generic protein binding from
      a methods paper provides no specific functional annotation value.
    supported_by:
      - reference_id: PMID:29997244
        supporting_text: "LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative mapping of protein-protein interactions in mammalian cells."

# === ANNOTATION 12: protein binding (IPI, PMID:31467278) ===
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31467278
  review:
    summary: >-
      PMID:31467278 (Choi et al. 2019) is a large-scale binary interactome mapping study
      focused on maximizing coverage with minimal assays. PEX11B interactions are detected
      as part of a high-throughput effort.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome study. Generic protein binding from systematic screens
      is uninformative for PEX11B functional annotation.
    supported_by:
      - reference_id: PMID:31467278
        supporting_text: "Maximizing binary interactome mapping with a minimal number of assays."

# === ANNOTATION 13: protein binding (IPI, PMID:32814053) ===
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: >-
      PMID:32814053 (Haenig et al. 2020) is an interactome mapping study focused on
      neurodegenerative disease proteins. PEX11B is included as a hit in interaction screens
      with disease-associated proteins.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome study focused on neurodegeneration. PEX11B is not a
      primary focus. Generic protein binding is uninformative.
    supported_by:
      - reference_id: PMID:32814053
        supporting_text: "Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains."

# === ANNOTATION 14: protein binding (IPI, PMID:37398436) ===
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37398436
  review:
    summary: >-
      PMID:37398436 (Trepte et al. 2023) is an AI-guided pipeline for PPI drug discovery
      targeting SARS-CoV-2. PEX11B appears as part of the reference interaction set used
      to validate the approach.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      PEX11B is used as part of a reference set for a drug discovery method paper. No
      specific functional insight for PEX11B. Generic protein binding is uninformative.
    supported_by:
      - reference_id: PMID:37398436
        supporting_text: "AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor."

# === ANNOTATION 15: mitochondrion (IEA, GO_REF:0000107) ===
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      This IEA annotation from Ensembl Compara suggests mitochondrial localization. While
      peroxisomal and mitochondrial fission machineries share components (DRP1, FIS1), and
      Lismont et al. (2019) showed PEX11B deficiency can cause partial mislocalization of
      peroxisomal proteins to mitochondria, PEX11B itself is not established as a
      mitochondrial protein. UniProt mass spectrometry detection from the mitochondrial
      proteome (PMID:25944712) may reflect contamination or the physical proximity of
      peroxisomes and mitochondria.
    action: REMOVE
    reason: >-
      PEX11B is established as a peroxisomal membrane protein. No experimental evidence
      supports bona fide mitochondrial localization. The Ensembl Compara transfer is likely
      erroneous, possibly driven by the shared fission machinery between peroxisomes and
      mitochondria, or contamination in proteomics studies.
    supported_by:
      - reference_id: PMID:20826455
        supporting_text: "PEX11 family members are membrane elongation factors that coordinate peroxisome proliferation and maintenance"

# === ANNOTATION 16: identical protein binding (IPI, PMID:17408615) ===
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:17408615
  review:
    summary: >-
      PMID:17408615 (Kobayashi et al. 2007) demonstrated that Pex11pbeta interacts with
      itself (homo-oligomerization). The highly conserved N-terminal domain was required for
      this self-interaction and was indispensable for peroxisome-proliferating activity.
      This is functionally important as oligomerization is required for membrane remodeling.
    action: ACCEPT
    reason: >-
      PEX11B homo-oligomerization is well-established and functionally important for
      membrane elongation/tubulation. This is more informative than generic protein binding
      and represents a core molecular function aspect.
    supported_by:
      - reference_id: PMID:17408615
        supporting_text: "Pex11pbeta also interacted with each other, whereas the binding of Pex11pbeta to DLP1 was not detectable"
      - reference_id: PMID:17408615
        supporting_text: "the highly conserved N-terminal domain of Pex11pbeta was required for the homo-oligomerization of Pex11pbeta and indispensable for the peroxisome-proliferating activity"

# === ANNOTATION 17: peroxisomal membrane (TAS, Reactome:R-HSA-9603775) ===
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9603775
  review:
    summary: >-
      Reactome annotation from R-HSA-9603775 (PEX3:PEX19:class I PMP dissociates). This
      represents the Reactome model of PEX11B (as a class I PMP) being delivered to the
      peroxisomal membrane by the PEX19-PEX3 import pathway. PEX11B is released at the
      peroxisomal membrane.
    action: ACCEPT
    reason: >-
      Correct localization. PEX11B is delivered to and resides in the peroxisomal membrane.
      Reactome pathway accurately models PEX11B as a class I PMP imported via PEX19/PEX3.

# === ANNOTATION 18: cytosol (TAS, Reactome:R-HSA-9603775) ===
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9603775
  review:
    summary: >-
      Reactome annotation from R-HSA-9603775 (PEX3:PEX19:class I PMP dissociates). This
      reflects the transient cytosolic state of PEX11B as a newly synthesized PMP before
      it is chaperoned by PEX19 to the peroxisomal membrane.
    action: KEEP_AS_NON_CORE
    reason: >-
      PEX11B transiently passes through the cytosol as a newly synthesized protein before
      being imported to peroxisomes. This is not its functional localization but rather a
      transit compartment. Acceptable as non-core since it reflects the PMP import pathway.

# === ANNOTATION 19: cytosol (TAS, Reactome:R-HSA-9603784) ===
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9603784
  review:
    summary: >-
      Reactome annotation from R-HSA-9603784 (PEX19:class I PMP binds PEX3). This again
      reflects the cytosolic complex formation between PEX19-PEX11B before docking at PEX3
      on the peroxisomal membrane.
    action: KEEP_AS_NON_CORE
    reason: >-
      Redundant with annotation 18. Reflects the same transient cytosolic state during PMP
      import pathway. Not the functional localization of PEX11B.

# === ANNOTATION 20: cytosol (TAS, Reactome:R-HSA-9603804) ===
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9603804
  review:
    summary: >-
      Reactome annotation from R-HSA-9603804 (PEX19 binds class I peroxisomal membrane
      proteins). This reflects initial PEX19 recognition of PEX11B in the cytosol.
    action: KEEP_AS_NON_CORE
    reason: >-
      Same as annotations 18 and 19. Transient cytosolic localization during PMP import.
      Not the functional localization.

# === ANNOTATION 21: membrane (HDA, PMID:19946888) ===
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  review:
    summary: >-
      PMID:19946888 (Ghosh et al. 2010) is a proteomics study of NK cell membranes.
      PEX11B was detected in membrane fractions by mass spectrometry. This is a very
      generic localization term; PEX11B is specifically a peroxisomal membrane protein.
    action: ACCEPT
    reason: >-
      Not incorrect - PEX11B is indeed a membrane protein - but overly generic. The more
      specific term (peroxisomal membrane) is already well-annotated. This HDA annotation
      from a proteomics study simply confirms membrane association without adding specificity.
      Acceptable as a broader supporting annotation from high-throughput data.
    supported_by:
      - reference_id: PMID:19946888
        supporting_text: "Mass spectrometric analysis identified 1843 proteins with high confidence scores."

# === ANNOTATION 22: protein binding (IPI, PMID:18782765) ===
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18782765
  review:
    summary: >-
      PMID:18782765 (Delille and Schrader 2008) demonstrates that hFis1 targeting to
      peroxisomes is mediated by Pex19p. PEX11B is mentioned in the context of the
      peroxisomal targeting pathway and PEX19 interactions, but the paper primarily focuses
      on hFis1-Pex19p interaction rather than PEX11B specifically.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This paper is primarily about FIS1 targeting, not PEX11B function. PEX11B is mentioned
      in context of PEX19 interactions but is not the focus. Generic protein binding
      annotation is uninformative.
    supported_by:
      - reference_id: PMID:18782765
        supporting_text: "peroxisomal targeting of hFis1 depends on Pex19p, a peroxisomal membrane protein import factor"

# === ANNOTATION 23: protein-containing complex (IDA, PMID:17408615) ===
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:17408615
  review:
    summary: >-
      PMID:17408615 (Kobayashi et al. 2007) detected ternary complexes of Fis1, Pex11pbeta,
      and DLP1 by chemical cross-linking. PEX11B forms homo-oligomers and is part of
      multi-protein complexes involved in peroxisome fission.
    action: ACCEPT
    reason: >-
      PEX11B is indeed part of protein complexes - it homo-oligomerizes and forms ternary
      complexes with FIS1 and DLP1. The annotation is supported by cross-linking experiments.
    supported_by:
      - reference_id: PMID:17408615
        supporting_text: "ternary complexes comprising Fis1, Pex11pbeta, and DLP1 were detected by chemical cross-linking"

# === ANNOTATION 24: protein binding (IPI, PMID:17408615) ===
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17408615
  review:
    summary: >-
      PMID:17408615 (Kobayashi et al. 2007) demonstrated direct binding of PEX11B to FIS1,
      involving the C-terminal region of PEX11B. This is a functionally important interaction
      for coordinating peroxisome fission. The paper also showed PEX11B self-interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction with FIS1 is biologically important and well-characterized, but
      generic protein binding is uninformative. The self-interaction is already captured by
      identical protein binding (GO:0042802) and protein homodimerization activity
      (GO:0042803). The FIS1 interaction is captured in the process annotation for
      peroxisome fission.
    supported_by:
      - reference_id: PMID:17408615
        supporting_text: "Fis1 interacted with Pex11pbeta, by direct binding apparently involving the C-terminal region of Pex11pbeta in the interaction"

# === ANNOTATION 25: peroxisome fission (IDA, PMID:17408615) ===
- term:
    id: GO:0016559
    label: peroxisome fission
  evidence_type: IDA
  original_reference_id: PMID:17408615
  review:
    summary: >-
      PMID:17408615 (Kobayashi et al. 2007) provides direct experimental evidence for
      PEX11B's role in peroxisome fission. Overexpression induces peroxisome proliferation.
      The N-terminal domain is required for homo-oligomerization and peroxisome-proliferating
      activity. PEX11B coordinates with Fis1 and DLP1 in peroxisome morphogenesis.
    action: ACCEPT
    reason: >-
      Core function. Strong experimental evidence from a targeted study demonstrating PEX11B's
      role in coordinating peroxisome fission with FIS1 and DLP1.
    supported_by:
      - reference_id: PMID:17408615
        supporting_text: "Fis1, DLP1, and Pex11p coordinately regulate peroxisome morphogenesis"
      - reference_id: PMID:17408615
        supporting_text: "the highly conserved N-terminal domain of Pex11pbeta was required for the homo-oligomerization of Pex11pbeta and indispensable for the peroxisome-proliferating activity"

# === ANNOTATION 26: protein binding (IPI, PMID:20826455) ===
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20826455
  review:
    summary: >-
      PMID:20826455 (Koch et al. 2010) established homo- and heterodimerization properties
      of PEX11 proteins and their interaction with hFis1. PEX11B interacts with PEX11G
      (heterodimerization) and FIS1.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The specific interactions (self, PEX11G, FIS1) are functionally important but already
      captured by more specific annotations (identical protein binding, protein homodimerization
      activity, protein-containing complex). Generic protein binding is uninformative.
    supported_by:
      - reference_id: PMID:20826455
        supporting_text: "We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1"

# === ANNOTATION 27: peroxisome (IDA, PMID:20826455) ===
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:20826455
  review:
    summary: >-
      PMID:20826455 (Koch et al. 2010) confirms peroxisomal localization of PEX11B through
      microscopy and functional studies. PEX11B expression leads to juxtaposed elongated
      peroxisomes (JEPs).
    action: ACCEPT
    reason: >-
      Correct localization. The more specific term peroxisomal membrane (GO:0005778) is also
      annotated, but peroxisome (GO:0005777) is acceptable as a broader compartment annotation.
    supported_by:
      - reference_id: PMID:20826455
        supporting_text: "Ectopic expression of proteins of the PEX11 family from yeast, plant or human lead to the formation of juxtaposed elongated peroxisomes (JEPs)"

# === ANNOTATION 28: peroxisome fission (IDA, PMID:20826455) ===
- term:
    id: GO:0016559
    label: peroxisome fission
  evidence_type: IDA
  original_reference_id: PMID:20826455
  review:
    summary: >-
      PMID:20826455 (Koch et al. 2010) demonstrates PEX11B's role in peroxisome membrane
      elongation and fission. Excess hFis1 is sufficient to fragment PEX11-induced JEPs,
      demonstrating that PEX11B drives the elongation step while FIS1/DRP1 drive scission.
    action: ACCEPT
    reason: >-
      Core function. Strong experimental evidence showing PEX11B as a membrane elongation
      factor that initiates the fission pathway. Complements PMID:17408615 and PMID:9792670.
    supported_by:
      - reference_id: PMID:20826455
        supporting_text: "PEX11-induced JEPs represent intermediates in the process of peroxisome membrane proliferation and that hFis1 is the limiting factor for progression"

# === ANNOTATION 29: protein-containing complex (IDA, PMID:20826455) ===
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:20826455
  review:
    summary: >-
      PMID:20826455 (Koch et al. 2010) demonstrates PEX11B forms homo- and heterodimers
      (with PEX11G) and interacts with FIS1. This multiprotein complex assembly is critical
      for coordinating peroxisome fission.
    action: ACCEPT
    reason: >-
      PEX11B forms functional complexes as demonstrated by dimerization and interaction studies.
      Consistent with PMID:17408615 cross-linking data showing ternary complexes.
    supported_by:
      - reference_id: PMID:20826455
        supporting_text: "We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1"

# === ANNOTATION 30: protein homodimerization activity (IDA, PMID:20826455) ===
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:20826455
  review:
    summary: >-
      PMID:20826455 (Koch et al. 2010) demonstrated PEX11B homodimerization. This is
      functionally important as oligomerization is required for membrane remodeling activity.
      The paper showed this using FRET-based approaches and co-immunoprecipitation.
    action: ACCEPT
    reason: >-
      Core molecular function. PEX11B homodimerization/oligomerization is essential for its
      membrane elongation activity. Well-supported by both Koch et al. 2010 and Kobayashi
      et al. 2007, and Bonekamp et al. 2013 (self-interaction study).
    supported_by:
      - reference_id: PMID:20826455
        supporting_text: "We established the homo- and heterodimerization properties of the human PEX11 proteins"
      - reference_id: PMID:17408615
        supporting_text: "the highly conserved N-terminal domain of Pex11pbeta was required for the homo-oligomerization of Pex11pbeta and indispensable for the peroxisome-proliferating activity"

# === ANNOTATION 31: regulation of peroxisome size (IDA, PMID:20826455) ===
- term:
    id: GO:0044375
    label: regulation of peroxisome size
  evidence_type: IDA
  original_reference_id: PMID:20826455
  review:
    summary: >-
      PMID:20826455 (Koch et al. 2010) demonstrated that PEX11B expression affects peroxisome
      size and morphology, specifically causing membrane elongation and formation of
      juxtaposed elongated peroxisomes (JEPs). Overexpression increased peroxisome number
      to ~405 per cell vs ~187 in controls.
    action: ACCEPT
    reason: >-
      PEX11B directly regulates peroxisome size through its membrane elongation activity.
      This is a core function. The regulation of peroxisome size is a consequence of PEX11B's
      membrane remodeling activity.
    supported_by:
      - reference_id: PMID:20826455
        supporting_text: "we propose a model for a conserved role of PEX11 proteins in peroxisome maintenance through peroxisome polarization, membrane elongation and segregation"

# === ANNOTATION 32: peroxisomal membrane (IDA, PMID:14709540) ===
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: IDA
  original_reference_id: PMID:14709540
  review:
    summary: >-
      PMID:14709540 (Jones et al. 2004) classifies PEX11B as a class 1 PMP that is imported
      to the peroxisomal membrane via PEX19. The study demonstrates PEX19-dependent targeting
      of PEX11B to the peroxisomal membrane.
    action: ACCEPT
    reason: >-
      Core localization confirmed by direct experimental observation. PEX11B is a class 1
      peroxisomal membrane protein.
    supported_by:
      - reference_id: PMID:14709540
        supporting_text: "PEX19 functions as both a chaperone and an import receptor for newly synthesized PMPs"

# === ANNOTATION 33: peroxisomal membrane (IDA, PMID:9792670) ===
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: IDA
  original_reference_id: PMID:9792670
  review:
    summary: >-
      PMID:9792670 (Schrader et al. 1998) is the foundational paper characterizing PEX11B.
      It identifies PEX11B as a peroxisomal membrane protein and demonstrates that its
      overexpression induces peroxisome proliferation through membrane elongation and division.
    action: ACCEPT
    reason: >-
      Foundational experimental evidence for PEX11B peroxisomal membrane localization.
    supported_by:
      - reference_id: PMID:9792670
        supporting_text: "identification and characterization of two novel human peroxisomal membrane proteins, PEX11alpha and PEX11beta"

# === ANNOTATION 34: peroxisome organization (IDA, PMID:9792670) ===
- term:
    id: GO:0007031
    label: peroxisome organization
  evidence_type: IDA
  original_reference_id: PMID:9792670
  review:
    summary: >-
      PMID:9792670 (Schrader et al. 1998) demonstrates PEX11B's role in peroxisome
      organization - specifically that overexpression induces peroxisome proliferation through
      elongation and division. PEX11B is implicated in constitutive control of peroxisome
      abundance.
    action: ACCEPT
    reason: >-
      Peroxisome organization is a parent term of peroxisome fission and accurately describes
      PEX11B's broader role. Supported by the foundational paper on PEX11B function.
    supported_by:
      - reference_id: PMID:9792670
        supporting_text: "PEX11beta induces peroxisome proliferation through a multistep process involving peroxisome elongation and segregation of PEX11beta from other peroxisomal membrane proteins, followed by peroxisome division"
      - reference_id: PMID:9792670
        supporting_text: "these data implicate PEX11beta in the constitutive control of peroxisome abundance"

# === ANNOTATION 35: peroxisome fission (IDA, PMID:9792670) ===
- term:
    id: GO:0016559
    label: peroxisome fission
  evidence_type: IDA
  original_reference_id: PMID:9792670
  review:
    summary: >-
      PMID:9792670 (Schrader et al. 1998) provides the original evidence that PEX11B
      mediates peroxisome proliferation through elongation followed by division. Time course
      studies demonstrated the multistep nature of this process.
    action: ACCEPT
    reason: >-
      Foundational experimental evidence for PEX11B's role in peroxisome fission. Core function.
    supported_by:
      - reference_id: PMID:9792670
        supporting_text: "PEX11beta induces peroxisome proliferation through a multistep process involving peroxisome elongation and segregation of PEX11beta from other peroxisomal membrane proteins, followed by peroxisome division"

# === ANNOTATION 36: peroxisomal membrane (ISS, GO_REF:0000024) ===
- term:
    id: GO:0005778
    label: peroxisomal membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      ISS annotation transferred from ortholog by curator judgment. Consistent with
      extensive experimental evidence for PEX11B peroxisomal membrane localization.
    action: ACCEPT
    reason: >-
      Correct. Peroxisomal membrane localization is the best-established feature of PEX11B,
      conserved across species.

# === ANNOTATION 37: peroxisome organization (ISS, GO_REF:0000024) ===
- term:
    id: GO:0007031
    label: peroxisome organization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      ISS annotation transferred from ortholog. Consistent with the well-established role
      of PEX11B in peroxisome organization across eukaryotes.
    action: ACCEPT
    reason: >-
      Correct. PEX11B's role in peroxisome organization is conserved and well-supported.

# === ANNOTATION 38: signal transduction (ISS, GO_REF:0000024) ===
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      ISS annotation for signal transduction transferred from ortholog. PEX11B is a membrane
      remodeling protein involved in peroxisome fission, not a classical signal transduction
      component. While there are recent reports linking PEX11B to PPARgamma and SIRT1
      pathways (Esmaeili et al. 2024), PEX11B itself is not a signal transduction molecule.
      It is a downstream effector of peroxisome proliferation signals, not a signal transducer.
    action: REMOVE
    reason: >-
      PEX11B is a structural/membrane-remodeling protein, not a signal transduction component.
      While peroxisome proliferation can be regulated by signaling pathways (PPARs, etc.),
      PEX11B functions as an effector of peroxisome division, not as a signal transducer itself.
      This annotation likely results from overly broad inference. PEX11B's constitutive
      expression pattern further argues against a primary signaling role (PMID:9792670).
    supported_by:
      - reference_id: PMID:9792670
        supporting_text: "Levels of PEX11beta mRNA were similar in all tissues examined and were unaffected by peroxisome-proliferating agents"

# === ANNOTATION 39: peroxisome (IDA, PMID:9922452) ===
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:9922452
  review:
    summary: >-
      PMID:9922452 (South and Gould 1999) describes peroxisome synthesis in the absence of
      preexisting peroxisomes. PEX11B is mentioned in the context of the PEX11-mediated
      division pathway. PEX11Bmyc is used as a peroxisomal membrane marker to assess
      peroxisome formation in PEX16-deficient cells.
    action: ACCEPT
    reason: >-
      PEX11B's peroxisomal localization is used as a functional readout in this study. The
      broader peroxisome term is correct, though peroxisomal membrane is more specific.
    supported_by:
      - reference_id: PMID:9922452
        supporting_text: "peroxisomes may form by either of two pathways: one that involves PEX11-mediated division of preexisting peroxisomes, and another that involves PEX16-mediated formation of peroxisomes in the absence of preexisting peroxisomes"

# === ANNOTATION 40: peroxisome (IDA, PMID:10704444) ===
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:10704444
  review:
    summary: >-
      PMID:10704444 (Sacksteder et al. 2000) demonstrates PEX11B is targeted to peroxisomes
      via PEX19. PEX11B deletion mutants were used to map the PEX19 binding/targeting region.
      Immunofluorescence confirms peroxisomal localization.
    action: ACCEPT
    reason: >-
      Correct localization. PEX11B is targeted to peroxisomes in a PEX19-dependent manner.
    supported_by:
      - reference_id: PMID:10704444
        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"

references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- 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: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:10704444
  title: PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic,
    and is required for peroxisome membrane synthesis.
  findings:
    - statement: PEX19 binds PEX11B via yeast two-hybrid and blot overlay assays
      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: C-terminal region of PEX11B (aa 211-259) is required for PEX19 interaction
      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 functions as a chaperone for newly synthesized PMPs including PEX11B
      supporting_text: "We propose that PEX19 may bind newly synthesized PMPs and facilitate their insertion into the peroxisome membrane."
- id: PMID:12096124
  title: Analysis of mammalian peroxin interactions using a non-transcription-based
    bacterial two-hybrid assay.
  findings:
    - statement: Bacterial two-hybrid confirms PEX11B-PEX19 interaction
      supporting_text: "We have used a non-transcription-based bacterial two-hybrid system to analyze the interactions among a set of 12 mammalian peroxins"
    - statement: CAAX motif of PEX19 enhances affinity for PEX11B
      supporting_text: "the CAAXmotif, and not farnesylation, of Pex19p strongly enhances its affinity for Pex11pbeta"
- id: PMID:14709540
  title: PEX19 is a predominantly cytosolic chaperone and import receptor for class
    1 peroxisomal membrane proteins.
  findings:
    - statement: PEX11B classified as a class 1 PMP imported via PEX19
      supporting_text: "PEX19 functions as both a chaperone and an import receptor for newly synthesized PMPs."
    - statement: PEX19 acts as both chaperone and import receptor
      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."
- id: PMID:17408615
  title: Fis1, DLP1, and Pex11p coordinately regulate peroxisome morphogenesis.
  findings:
    - statement: PEX11B interacts directly with FIS1 via C-terminal region
      supporting_text: "Fis1 interacted with Pex11pbeta, by direct binding apparently involving the C-terminal region of Pex11pbeta in the interaction."
    - statement: PEX11B forms homo-oligomers; N-terminal domain is required
      supporting_text: "the highly conserved N-terminal domain of Pex11pbeta was required for the homo-oligomerization of Pex11pbeta and indispensable for the peroxisome-proliferating activity"
    - statement: Ternary complexes of FIS1, PEX11B, and DLP1 detected by cross-linking
      supporting_text: "ternary complexes comprising Fis1, Pex11pbeta, and DLP1 were detected by chemical cross-linking"
    - statement: N-terminal domain required for peroxisome-proliferating activity
      supporting_text: "the highly conserved N-terminal domain of Pex11pbeta was required for the homo-oligomerization of Pex11pbeta and indispensable for the peroxisome-proliferating activity"
- id: PMID:18782765
  title: Targeting of hFis1 to peroxisomes is mediated by Pex19p.
  findings:
    - statement: hFis1 peroxisomal targeting depends on Pex19p
      supporting_text: "peroxisomal targeting of hFis1 depends on Pex19p, a peroxisomal membrane protein import factor"
    - statement: PEX11B is mentioned in context of peroxisomal targeting pathway
      supporting_text: "peroxisomal targeting of hFis1 depends on Pex19p, a peroxisomal membrane protein import factor"
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings:
    - statement: PEX11B detected in membrane fractions of NK cells by mass spectrometry
      supporting_text: "Mass spectrometric analysis identified 1843 proteins with high confidence scores."
- 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: PEX11B used as cargo protein to demonstrate mPTS binding
      supporting_text: "the structured alpha-helical domain binds PMP-targeting signal (mPTS) sequences with about 10 muM affinity"
- id: PMID:20826455
  title: PEX11 family members are membrane elongation factors that coordinate peroxisome
    proliferation and maintenance.
  findings:
    - statement: PEX11B is a membrane elongation factor
      supporting_text: "Ectopic expression of proteins of the PEX11 family from yeast, plant or human lead to the formation of juxtaposed elongated peroxisomes (JEPs),which is evocative of an evolutionary conserved function of these proteins in membrane tubulation."
    - statement: PEX11B forms homo- and heterodimers (with PEX11G)
      supporting_text: "We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1"
    - statement: PEX11B interacts with hFis1
      supporting_text: "We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1"
    - statement: Overexpression causes JEPs; excess hFis1 resolves them
      supporting_text: "We show that excess of hFis1 but not of DRP1 is sufficient to fragment JEPs into normal round-shaped organelles"
    - statement: Peroxisome number increased from ~187 to ~405 per cell with PEX11B overexpression
      supporting_text: "PEX11-induced JEPs represent intermediates in the process of peroxisome membrane proliferation and that hFis1 is the limiting factor for progression"
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings:
    - statement: High-throughput interactome mapping; PEX11B interactions detected
      supporting_text: "A proteome-scale map of the human interactome network."
- id: PMID:29997244
  title: 'LuTHy: a double-readout bioluminescence-based two-hybrid technology for
    quantitative mapping of protein-protein interactions in mammalian cells.'
  findings:
    - statement: PEX11B used as test case in LuTHy method validation
      supporting_text: "LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative mapping of protein-protein interactions in mammalian cells."
- id: PMID:31467278
  title: Maximizing binary interactome mapping with a minimal number of assays.
  findings:
    - statement: PEX11B interactions detected in systematic binary interactome mapping
      supporting_text: "Maximizing binary interactome mapping with a minimal number of assays."
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings:
    - statement: PEX11B detected as interaction partner in neurodegenerative disease interactome
      supporting_text: "Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains."
- id: PMID:37398436
  title: AI-guided pipeline for protein-protein interaction drug discovery identifies
    a SARS-CoV-2 inhibitor.
  findings:
    - statement: PEX11B used in reference interaction set for method validation
      supporting_text: "AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor."
- id: PMID:9792670
  title: Expression of PEX11beta mediates peroxisome proliferation in the absence
    of extracellular stimuli.
  findings:
    - statement: PEX11B identified as peroxisomal membrane protein
      supporting_text: "We report here the identification and characterization of two novel human peroxisomal membrane proteins, PEX11alpha and PEX11beta."
    - statement: Overexpression sufficient to induce peroxisome proliferation
      supporting_text: "Overexpression of the human PEX11beta gene alone was sufficient to induce peroxisome proliferation, demonstrating that proliferation can occur in the absence of extracellular stimuli and may be mediated by a single gene."
    - statement: Proliferation occurs through elongation then division
      supporting_text: "PEX11beta induces peroxisome proliferation through a multistep process involving peroxisome elongation and segregation of PEX11beta from other peroxisomal membrane proteins, followed by peroxisome division."
    - statement: PEX11B is constitutively expressed; not responsive to peroxisome proliferators
      supporting_text: "Levels of PEX11beta mRNA were similar in all tissues examined and were unaffected by peroxisome-proliferating agents"
    - statement: Implicated in constitutive control of peroxisome abundance
      supporting_text: "these data implicate PEX11beta in the constitutive control of peroxisome abundance"
- id: PMID:9922452
  title: Peroxisome synthesis in the absence of preexisting peroxisomes.
  findings:
    - statement: PEX11B used as peroxisomal membrane marker
      supporting_text: "Similar results were observed in cells transfected with expression vectors designed to express other human PMPs, including PEX3myc (Kammerer et al., 1998), PEX10myc (Warren et al., 1998), PEX11αmyc (Schrader et al., 1998), PEX11βmyc (Schrader et al., 1998), and PEX13myc (Gould et al., 1996) (data not shown)"
    - statement: Two pathways for peroxisome formation described including PEX11-mediated division
      supporting_text: "We propose that peroxisomes may form by either of two pathways: one that involves PEX11-mediated division of preexisting peroxisomes, and another that involves PEX16-mediated formation of peroxisomes in the absence of preexisting peroxisomes."
- id: Reactome:R-HSA-9603775
  title: PEX3:PEX19:class I PMP dissociates
  findings:
    - statement: PEX11B modeled as class I PMP released at peroxisomal membrane
      supporting_text: "The PEX19:PEX3:peroxisomal membrane protein complex dissociates, yielding cytosolic PEX19, membrane-bound PEX3, and the peroxisomal membrane protein inserted in the peroxisomal membrane"
- id: Reactome:R-HSA-9603784
  title: PEX19:class I PMP binds PEX3
  findings:
    - statement: PEX19-PEX11B complex docks at PEX3 on peroxisomal membrane
      supporting_text: "Cytosolic PEX19 bound to a peroxisomal membrane protein binds PEX3 which is located in the peroxisomal membrane and serves as a docking receptor for PEX19"
- id: Reactome:R-HSA-9603804
  title: PEX19 binds class I peroxisomal membrane proteins
  findings:
    - statement: PEX19 recognizes PEX11B as class I PMP in cytosol
      supporting_text: "In the cytosol, PEX19 binds newly synthesized class I peroxisomal membrane proteins"
core_functions:
  - description: >-
      PEX11B is the primary constitutive driver of peroxisome fission via the growth-and-division
      pathway. It directly deforms and elongates the peroxisomal membrane through its N-terminal
      amphipathic helix and homo-oligomerization. PEX11B coordinates with the fission machinery
      (FIS1, MFF, DRP1/DNM1L) to complete membrane scission. Its overexpression induces
      peroxisome proliferation; its loss causes reduced peroxisome number and elongated
      peroxisomes (PMID:9792670, PMID:17408615, PMID:20826455).
    molecular_function:
      id: GO:0042803
      label: protein homodimerization activity
    directly_involved_in:
      - id: GO:0016559
        label: peroxisome fission
      - id: GO:0044375
        label: regulation of peroxisome size
    locations:
      - id: GO:0005778
        label: peroxisomal membrane
    supported_by:
      - reference_id: PMID:9792670
        supporting_text: "PEX11beta induces peroxisome proliferation through a multistep process involving peroxisome elongation and segregation of PEX11beta from other peroxisomal membrane proteins, followed by peroxisome division"
      - reference_id: PMID:20826455
        supporting_text: "PEX11 family members are membrane elongation factors that coordinate peroxisome proliferation and maintenance"
      - reference_id: PMID:17408615
        supporting_text: "the highly conserved N-terminal domain of Pex11pbeta was required for the homo-oligomerization of Pex11pbeta and indispensable for the peroxisome-proliferating activity"