ARBA00028584 peroxisomal membrane (GO:0005778)

id: ARBA00028584
description: >-
  Assigns GO:0005778 (peroxisomal membrane) through 16 alternative condition sets covering peroxins
  (PEX2/10, PEX4, PEX11, PEX12, PEX13, PEX14 and the fungal DysF-domain peroxins), peroxisomal ABC
  transporters, PMP34 (SLC25A17), ATAD1, fatty acyl-CoA reductase, NBR1 and a Penicillium transporter
  FunFam, each with a taxon restriction.
status: COMPLETE
rule_type: ARBA
rule:
  rule_id: ARBA00028584
  condition_sets:
  - number: 1
    conditions:
    - condition_type: INTERPRO
      value: IPR006785
      curie: InterPro:IPR006785
      label: Peroxisome membrane anchor protein Pex14/PEX33, N-terminal
      negated: false
    - condition_type: INTERPRO
      value: IPR025655
      curie: InterPro:IPR025655
      label: Peroxisomal membrane protein 14
      negated: false
    - condition_type: TAXON
      value: Fungi
      curie: NCBITaxon:4751
      label: Fungi
      negated: false
    notes: >-
      UniProtKB release 2026_04: 9 reviewed entries match this set; 9 of them carry GO:0005778 or
      a descendant, 9 of those by a manual-evidence GO annotation. 2491 unreviewed entries match.
  - number: 2
    conditions:
    - condition_type: INTERPRO
      value: IPR006845
      curie: InterPro:IPR006845
      label: Pex, N-terminal
      negated: false
    - condition_type: INTERPRO
      value: IPR025654
      curie: InterPro:IPR025654
      label: Peroxisome biogenesis factor 2/10
      negated: false
    - condition_type: TAXON
      value: Ascomycota
      curie: NCBITaxon:4890
      label: Ascomycota
      negated: false
    notes: >-
      UniProtKB release 2026_04: 10 reviewed entries match this set; 10 of them carry GO:0005778 or
      a descendant, 10 of those by a manual-evidence GO annotation. 1965 unreviewed entries match.
  - number: 3
    conditions:
    - condition_type: INTERPRO
      value: IPR008733
      curie: InterPro:IPR008733
      label: Peroxisomal biogenesis factor 11
      negated: false
    - condition_type: PANTHER
      value: PTHR12652
      curie: PANTHER:PTHR12652
      label: PEROXISOMAL BIOGENESIS FACTOR 11
      negated: false
    - condition_type: TAXON
      value: Viridiplantae
      curie: NCBITaxon:33090
      label: Viridiplantae
      negated: false
    notes: >-
      UniProtKB release 2026_04: 12 reviewed entries match this set; 12 of them carry GO:0005778 or
      a descendant, 10 of those by a manual-evidence GO annotation. 1979 unreviewed entries match.
  - number: 4
    conditions:
    - condition_type: INTERPRO
      value: IPR010482
      curie: InterPro:IPR010482
      label: TECPR1-like, DysF domain
      negated: false
    - condition_type: TAXON
      value: Saccharomycetes
      curie: NCBITaxon:4891
      label: Saccharomycetes
      negated: false
    notes: >-
      UniProtKB release 2026_04: 5 reviewed entries match this set; 5 of them carry GO:0005778 or
      a descendant, 5 of those by a manual-evidence GO annotation. 261 unreviewed entries match.
  - number: 5
    conditions:
    - condition_type: FUNFAM
      value: 3.40.50.300:FF:000800
      curie: CATH.FunFam:3.40.50.300:FF:000800
      label: ATP-binding cassette sub-family D member 1
      negated: false
    - condition_type: TAXON
      value: Mammalia
      curie: NCBITaxon:40674
      label: Mammalia
      negated: false
    notes: >-
      UniProtKB release 2026_04: 6 reviewed entries match this set; 6 of them carry GO:0005778 or
      a descendant, 6 of those by a manual-evidence GO annotation. 355 unreviewed entries match.
  - number: 6
    conditions:
    - condition_type: FUNFAM
      value: 2.30.30.40:FF:000109
      curie: CATH.FunFam:2.30.30.40:FF:000109
      label: Peroxisomal biogenesis factor 13
      negated: false
    - condition_type: TAXON
      value: Chordata
      curie: NCBITaxon:7711
      label: Chordata
      negated: false
    notes: >-
      UniProtKB release 2026_04: 4 reviewed entries match this set; 4 of them carry GO:0005778 or
      a descendant, 4 of those by a manual-evidence GO annotation. 799 unreviewed entries match.
  - number: 7
    conditions:
    - condition_type: FUNFAM
      value: 1.10.8.10:FF:000033
      curie: CATH.FunFam:1.10.8.10:FF:000033
      label: Next to BRCA1 gene 1 protein
      negated: false
    - condition_type: FUNFAM
      value: 2.60.40.10:FF:000199
      curie: CATH.FunFam:2.60.40.10:FF:000199
      label: next to BRCA1 gene 1 protein-like
      negated: false
    - condition_type: FUNFAM
      value: 3.30.60.90:FF:000007
      curie: CATH.FunFam:3.30.60.90:FF:000007
      label: Next to BRCA1 gene 1 protein
      negated: false
    - condition_type: TAXON
      value: Eukaryota
      curie: NCBITaxon:2759
      label: Eukaryota
      negated: false
    notes: >-
      UniProtKB release 2026_04: 4 reviewed entries match this set; 4 of them carry GO:0005778 or
      a descendant, 2 of those by a manual-evidence GO annotation. 752 unreviewed entries match. The
      reviewed matches are NBR1 orthologues; the manual annotations are Reactome TAS.
  - number: 8
    conditions:
    - condition_type: FUNFAM
      value: 1.10.8.60:FF:000044
      curie: CATH.FunFam:1.10.8.60:FF:000044
      label: ATPase family AAA domain-containing protein 1
      negated: false
    - condition_type: FUNFAM
      value: 3.40.50.300:FF:000538
      curie: CATH.FunFam:3.40.50.300:FF:000538
      label: ATPase family AAA domain-containing protein 1
      negated: false
    - condition_type: TAXON
      value: Eukaryota
      curie: NCBITaxon:2759
      label: Eukaryota
      negated: false
    notes: >-
      UniProtKB release 2026_04: 4 reviewed entries match this set; 4 of them carry GO:0005778 or
      a descendant, 4 of those by a manual-evidence GO annotation. 314 unreviewed entries match.
  - number: 9
    conditions:
    - condition_type: FUNFAM
      value: 1.20.1560.10:FF:000036
      curie: CATH.FunFam:1.20.1560.10:FF:000036
      label: ATP-binding cassette sub-family D member 3
      negated: false
    - condition_type: FUNFAM
      value: 3.40.50.300:FF:000636
      curie: CATH.FunFam:3.40.50.300:FF:000636
      label: ATP-binding cassette sub-family D member 3
      negated: false
    - condition_type: TAXON
      value: Glires
      curie: NCBITaxon:314147
      label: Glires
      negated: false
    notes: >-
      UniProtKB release 2026_04: 2 reviewed entries match this set; 2 of them carry GO:0005778 or
      a descendant, 2 of those by a manual-evidence GO annotation. 41 unreviewed entries match.
  - number: 10
    conditions:
    - condition_type: FUNFAM
      value: 1.50.40.10:FF:000023
      curie: CATH.FunFam:1.50.40.10:FF:000023
      label: peroxisomal membrane protein PMP34 isoform X1
      negated: false
    - condition_type: FUNFAM
      value: 1.50.40.10:FF:000045
      curie: CATH.FunFam:1.50.40.10:FF:000045
      label: peroxisomal membrane protein PMP34 isoform X1
      negated: false
    - condition_type: TAXON
      value: Metazoa
      curie: NCBITaxon:33208
      label: Metazoa
      negated: false
    notes: >-
      UniProtKB release 2026_04: 2 reviewed entries match this set; 2 of them carry GO:0005778 or
      a descendant, 2 of those by a manual-evidence GO annotation. 156 unreviewed entries match.
  - number: 11
    conditions:
    - condition_type: FUNFAM
      value: 1.10.10.10:FF:000296
      curie: CATH.FunFam:1.10.10.10:FF:000296
      label: Peroxisomal membrane protein PEX14
      negated: false
    - condition_type: TAXON
      value: Muridae
      curie: NCBITaxon:10066
      label: Muridae
      negated: false
    notes: >-
      UniProtKB release 2026_04: 2 reviewed entries match this set; 2 of them carry GO:0005778 or
      a descendant, 2 of those by a manual-evidence GO annotation. 8 unreviewed entries match.
  - number: 12
    conditions:
    - condition_type: FUNFAM
      value: 1.20.1250.20:FF:000011
      curie: CATH.FunFam:1.20.1250.20:FF:000011
      label: MFS multidrug transporter, putative
      negated: false
    - condition_type: TAXON
      value: Penicillium chrysogenum species complex
      curie: NCBITaxon:254878
      label: Penicillium chrysogenum species complex
      negated: false
    notes: >-
      UniProtKB release 2026_04: 3 reviewed entries match this set; 2 of them carry GO:0005778 or
      a descendant, 2 of those by a manual-evidence GO annotation. 42 unreviewed entries match. B6HN82
      (penM) and B6HIC2 (paaT) have experimental peroxisomal membrane annotations; B6HNK5 (sorT) does
      not carry the term.
  - number: 13
    conditions:
    - condition_type: FUNFAM
      value: 2.30.30.40:FF:000128
      curie: CATH.FunFam:2.30.30.40:FF:000128
      label: Peroxisomal membrane protein (Pex13)
      negated: false
    - condition_type: TAXON
      value: Fungi
      curie: NCBITaxon:4751
      label: Fungi
      negated: false
    notes: >-
      UniProtKB release 2026_04: 4 reviewed entries match this set; 4 of them carry GO:0005778 or
      a descendant, 4 of those by a manual-evidence GO annotation. 1035 unreviewed entries match.
  - number: 14
    conditions:
    - condition_type: FUNFAM
      value: 3.30.40.10:FF:000266
      curie: CATH.FunFam:3.30.40.10:FF:000266
      label: Peroxisome assembly protein 12
      negated: false
    - condition_type: TAXON
      value: Craniata
      curie: NCBITaxon:89593
      label: Craniata
      negated: false
    notes: >-
      UniProtKB release 2026_04: 7 reviewed entries match this set; 7 of them carry GO:0005778 or
      a descendant, 7 of those by a manual-evidence GO annotation. 625 unreviewed entries match.
  - number: 15
    conditions:
    - condition_type: FUNFAM
      value: 3.40.50.720:FF:000123
      curie: CATH.FunFam:3.40.50.720:FF:000123
      label: Fatty acyl-CoA reductase
      negated: false
    - condition_type: TAXON
      value: Vertebrata
      curie: NCBITaxon:7742
      label: Vertebrata
      negated: false
    notes: >-
      UniProtKB release 2026_04: 6 reviewed entries match this set; 6 of them carry GO:0005778 or
      a descendant, 6 of those by a manual-evidence GO annotation. 1390 unreviewed entries match.
  - number: 16
    conditions:
    - condition_type: FUNFAM
      value: 3.10.110.10:FF:000044
      curie: CATH.FunFam:3.10.110.10:FF:000044
      label: protein PEROXIN-4 isoform X1
      negated: false
    - condition_type: TAXON
      value: Eukaryota
      curie: NCBITaxon:2759
      label: Eukaryota
      negated: false
    notes: >-
      UniProtKB release 2026_04: 3 reviewed entries match this set; 3 of them carry GO:0005778 or
      a descendant, 2 of those by a manual-evidence GO annotation. 577 unreviewed entries match.
  go_annotations:
  - go_id: GO:0005778
    go_label: peroxisomal membrane
    aspect: CC
  entries: []
  reviewed_protein_count: 0
  unreviewed_protein_count: 0
  created_date: '2021-10-20'
  modified_date: '2026-07-18'
  retrieved_date: '2026-11-09'
  source_condition_set_count: 16
review_summary: >-
  All 16 live condition sets were examined. They match 83 reviewed entries in total; 82 carry GO:0005778
  or a descendant, 77 by manual evidence. Fourteen sets are supported by experimental localisation
  of at least one reviewed match. Two are weaker: the NBR1 set rests on Reactome TAS annotations only,
  and the Penicillium transporter set includes sorT (B6HNK5), which has no peroxisomal annotation.
action: ACCEPT
action_rationale: >-
  The rule selects proteins that are curated to the peroxisomal membrane, almost all with experimental
  evidence. The two weaker sets are recorded in annotation_assessments; nothing checked shows either
  to be wrong. The counts are from Swiss-Prot, which is also what ARBA learns its rules from, so they
  show the condition sets are coherent rather than giving an independent error rate for unreviewed
  entries.
literature_support:
  assessment: STRONG
  notes: >-
    Peroxisomal membrane location is documented for the transporter and import-machinery families
    the rule covers.
  supported_by:
  - reference_id: PMID:22185573
    supporting_text: Recombinant and purified SLC25A17 was reconstituted into liposomes
  - reference_id: PMID:35908918
    supporting_text: >-
      ABCD1-3 are localized to peroxisomal membranes and involved in the transport of various acyl-CoAs
      from the cytosol to the peroxisomal lumen.
  - reference_id: PMID:36541703
    supporting_text: >-
      PEX13, a component of the peroxisomal matrix import system, is required to prevent the degradation
      of otherwise healthy peroxisomes.
go_specificity:
  assessment: APPROPRIATE
  notes: >-
    GO:0005778 is the cellular component term carried, with experimental evidence, by reviewed members
    of the sets (accessions in annotation_assessments).
  supported_by:
  - reference_id: PMID:35908918
    supporting_text: >-
      ABCD1-3 are localized to peroxisomal membranes and involved in the transport of various acyl-CoAs
      from the cytosol to the peroxisomal lumen.
  - reference_id: PMID:22185573
    supporting_text: >-
      In the present study we have functionally identified and characterized SLC25A17 (solute carrier
      family 25 member 17), which is the only member of the mitochondrial carrier family that has
      previously been shown to be localized in the peroxisomal membrane
annotation_assessments:
- annotation_kind: GO_TERM
  value: GO:0005778
  label: peroxisomal membrane
  assessment: CORRECT
  matched_protein_count: 83
  correct_examples:
  - P53112
  - P32800
  - Q9FZF1
  - Q06169
  - P33897
  - Q92968
  - Q8NBU5
  - P55096
  - O43808
  - Q9R0A0
  - B6HN82
  - P80667
  - O00623
  - Q8WVX9
  - Q8LGF7
  notes: >-
    Experimental annotations to GO:0005778 on reviewed matches (QuickGO, retrieved 2026-11-09). Set
    1: P53112 (PEX14), IDA, PMID:12667447. Set 2: P32800 (PEX2), IDA, PMID:35768507. Set 3: Q9FZF1
    (PEX11A), IDA, PMID:17220199. Set 4: Q06169 (PEX30), IDA, PMID:14617799. Set 5: P33897 (ABCD1),
    EXP, PMID:10777694. Set 6: Q92968 (PEX13), IDA, PMID:19197237. Set 8: Q8NBU5 (ATAD1), IDA, PMID:24843043.
    Set 9: P55096 (Abcd3), IDA, PMID:12915479. Set 10: O43808 (SLC25A17), EXP, PMID:9874197. Set 11:
    Q9R0A0 (Pex14), EXP, PMID:12488033. Set 12: B6HN82 (penM), EXP, PMID:24480587. Set 13: P80667
    (PEX13), IDA, PMID:9094717. Set 14: O00623 (PEX12), IDA, PMID:12751901. Set 15: Q8WVX9 (FAR1),
    IDA, PMID:24108123. Set 16: Q8LGF7 (PEX4), IDA, PMID:35595097. Weaker sets: set 7, Q14596 (human
    NBR1) and P97432 (mouse Nbr1) carry the term as Reactome TAS only; set 12, B6HNK5 (sorT) matches
    the set but has no peroxisomal annotation and UniProt gives its location only as Membrane (ECO:0000255).
confidence: 0.65
corrections:
- date: '2026-11-10'
  withdrawn_claim: >-
    Condition set 9 targets DECR2, which lacks transmembrane domains and is probably a matrix enzyme,
    so the set should be reviewed and the term changed to peroxisomal matrix.
  correction: >-
    The live rule has no DECR2 set. Separately, absence of a transmembrane segment does not exclude
    membrane association, and rat Decr2 carries an experimental peroxisomal membrane annotation.
  error_type: STALE_RULE_VERSION
  evidence:
  - >-
    UniProt ARBA API, ARBA00028584, modified 2026-07-18, retrieved 2026-11-09: 16 condition sets,
    none on FunFam 3.40.50.720:FF:000477.
  - >-
    QuickGO: UniProtKB:Q9Z2M4 (rat Decr2), GO:0005778, IDA, PMID:10333503, assigned by UniProt.
- date: '2026-11-10'
  withdrawn_claim: >-
    The NBR1 set should be removed because NBR1 is not a peroxisomal membrane protein; a knockdown
    result confirms that it is a pexophagy signal and not a membrane component.
  correction: >-
    The cited paper calls NBR1 the peroxisomal autophagy receptor and does not address whether it
    is at the membrane. NBR1 carries GO:0005778 as a Reactome TAS annotation in human and mouse. The
    set is weakly supported, with no experimental annotation, but removal is not justified by what
    was cited.
  error_type: UNSUPPORTED_SOURCE
  evidence:
  - >-
    QuickGO: UniProtKB:Q14596 (NBR1), GO:0005778, TAS, Reactome:R-HSA-9664867; UniProtKB:P97432 (Nbr1),
    GO:0005778, TAS, Reactome:R-MMU-9666410.
  - >-
    publications/PMID_37493040.md: 'genetic knockdown of the peroxisomal autophagy receptor NBR1 resulted
    in restoration of peroxisomal functions'.
- date: '2026-11-10'
  withdrawn_claim: >-
    IPR010482 restricted to Fungi returns 10 reviewed proteins, all established peroxisomal membrane
    proteins, and the DysF-domain peroxins are peripheral membrane proteins.
  correction: >-
    The live set is restricted to Saccharomycetes and matches five reviewed Saccharomyces cerevisiae
    peroxins, all with IDA evidence. Across Fungi the same domain also matches reviewed proteins that
    UniProt places in the endoplasmic reticulum membrane only, so the wider statement does not hold.
    UniProt describes these peroxins as multi-pass membrane proteins.
  error_type: SAMPLE_OVERGENERALISED
  evidence:
  - >-
    QuickGO: P53203 (PEX31), Q06169 (PEX30), P38292 (PEX32), GO:0005778, IDA, PMID:14617799; Q03370
    (PEX29), P38848 (PEX28), GO:0005778, IDA, PMID:12707309.
  - >-
    UniProtKB W1QL91 (Ogataea parapolymorpha PEX29) and W1QAK2 (PEX23): SUBCELLULAR LOCATION Endoplasmic
    reticulum membrane, ECO:0000269 PubMed:32665322; Multi-pass membrane protein.
  - 'UniProtKB release 2026_04: IPR010482 AND taxonomy Fungi AND reviewed returns 14 entries.'
- date: '2026-11-10'
  withdrawn_claim: >-
    The taxonomic restrictions are too narrow (PEX14 to Muridae, ABCD1 to Glires, ABCD3 to Rodentia)
    and should be broadened to Eukaryota or Vertebrata.
  correction: >-
    A narrow taxon limits how many proteins the rule reaches; it does not make any annotation wrong.
    No check was made that the FunFams stay specific outside the stated taxa. The live rule already
    has ABCD1 at Mammalia, ABCD3 at Glires, and a separate fungal PEX14 set.
  error_type: LOW_RECALL_IS_NOT_WRONG
  evidence:
  - >-
    UniProt ARBA API, ARBA00028584, modified 2026-07-18: set 5 taxon Mammalia, set 9 taxon Glires,
    set 11 taxon Muridae, set 1 (IPR006785 AND IPR025655) taxon Fungi.
- date: '2026-11-10'
  withdrawn_claim: The FunFam labels unambiguously identify the protein each set targets.
  correction: >-
    A FunFam label is the name of a representative member, not a statement of membership. The FunFam
    labelled ATP-binding cassette sub-family D member 1 also matches ABCD2.
  error_type: WRONG_IDENTIFIER_MEANING
  evidence:
  - >-
    UniProtKB release 2026_04: set 5 (FunFam 3.40.50.300:FF:000800 AND Mammalia) reviewed matches
    include Q9UBJ2 (human ABCD2) as well as P33897 (human ABCD1).
references:
- id: PMID:22185573
  title: The human gene SLC25A17 encodes a peroxisomal transporter of coenzyme A, FAD and NAD+
  findings:
  - statement: >-
      SLC25A17 is the only member of the mitochondrial carrier family localized to the peroxisomal
      membrane. It transports CoA, FAD, FMN, AMP, and to a lesser extent NAD+, PAP, and ADP into peroxisomes.
- id: PMID:35908918
  title: >-
    Substrate Specificity and the Direction of Transport in the ABC Transporters ABCD1-3 and ABCD4
  findings:
  - statement: >-
      ABCD1-3 are localized to peroxisomal membranes and transport various acyl-CoAs from the cytosol
      to the peroxisomal lumen. ABCD4 is lysosomal. Mutations in ABCD1, ABCD3, and ABCD4 cause genetic
      diseases.
- id: PMID:36541703
  title: PEX13 prevents pexophagy by regulating ubiquitinated PEX5 and peroxisomal ROS
  findings:
  - statement: >-
      PEX13 is a component of the peroxisomal matrix import system and is required to prevent degradation
      of healthy peroxisomes. Loss of PEX13 causes accumulation of ubiquitinated PEX5 on peroxisomes
      and induces pexophagy.
- id: PMID:14617799
  title: >-
    Pex30p, Pex31p, and Pex32p form a family of peroxisomal integral membrane proteins regulating
    peroxisome size and number in Saccharomyces cerevisiae
  findings:
  - statement: Reference for the IDA annotations of GO:0005778 on PEX30, PEX31 and PEX32.