ARBA00004173 mitochondrion (GO:0005739)

View original ARBA rule on UniProt

Type: ARBA
Status: COMPLETE
Action: MODIFY
Confidence: 0.75

Description

Assigns the UniProt subcellular location Mitochondrion (SL-0173) through 1,525 alternative condition sets built from CATH FunFam, InterPro and PANTHER signatures, each with a taxon condition. UniProt converts the location to GO:0005739 (mitochondrion) by GO_REF:0000044.

Analysis Summary

Condition-set counts describe the sets recorded in this review, which may omit the full rule.

0
Domain Pairs Analyzed
14
Recorded condition sets
0
Subset Relationships
0
Redundant Annotations

No domain overlap table is shown: the cached overlap analysis for this version of the review is not available. Run just analyze-rule ARBA00004173 and re-render to add it.

Review Summary

All 1,525 live condition sets were screened with two UniProtKB queries each (2026-11-10): the Swiss-Prot entries that match the whole conjunction, and how many of them have the subcellular location Mitochondrion (SL-0173). 1,524 sets match at least one Swiss-Prot entry and 1 match none. In 1,513 sets every Swiss-Prot match has the location and in 11 sets some do not (sets 43, 209, 251, 365, 378, 456, 484, 549, 718, 1084, 1384); set 1312 matches no Swiss-Prot entry. The search is at entry level and does not see locations scoped to one isoform. Summed over sets there are 18,954 set-level matches, 18,884 with the location. Sets 1 and 789 were read in detail; they and the sets with incomplete agreement are recorded in the rule block. Set 1 (cytochrome b) is sound. Three sets match plastid-encoded ATP synthase subunits whose curated location is the chloroplast thylakoid membrane: set 251 (33 of 41 Swiss-Prot matches, in rosids), set 456 (5 of 10, in Liliopsida) and set 484 (7 of 12, in Solanaceae). Set 1384 matches ATP-dependent 6-phosphofructokinases, 6 of 8 recorded as Cytoplasm, and set 1084 matches amphibian adenylosuccinate synthetase isozyme 1, 3 of 6 recorded as Cytoplasm; in both cases the Swiss-Prot location comes from a HAMAP rule, not an experiment. Set 365 also matches four apicoplast lipoyl synthases. Set 789 is defective in a different way: it requires the thiolase-type FunFam 3.40.47.10:FF:000016 together with the SCP2 FunFam 3.30.1050.10:FF:000001, but in the reviewed mouse and human entries the mitochondrial location belongs to the short SCP2 isoform, which lacks the region matched by the first FunFam, while the full-length SCPx isoform is recorded as Peroxisome only. The rule therefore gives Mitochondrion to full-length SCPx proteins such as Drosophila ScpX (Q9VJ43). In sets 43, 209, 378, 549 and 718 the entries without the location have only a generic or rule-derived location comment, which does not show the protein is absent from mitochondria. ARBA rules are mined from Swiss-Prot annotation, and precision on the 562,320 unreviewed entries the rule annotates was not measured.

Action Rationale

Specific condition sets are defective. Sets 251, 456 and 484 match chloroplast ATP synthase subunits, and set 789 transfers a location that the source entries record for a different isoform than the one the set detects. These four sets should be removed or narrowed; sets 1384, 1084 and 365 need a closer look. The remaining sets were not shown to be wrong: 1,513 of 1,525 sets agree fully with Swiss-Prot locations at entry level, so the rule as a whole is kept.

GO Annotations

GO:0005739 - mitochondrion
Aspect: C

Annotation Assessments

PARTIALLY_CORRECT OTHER SL-0173 - Mitochondrion
Matched proteins: ; incorrect:
Incorrect examples: Q9VJ43, A6MMJ2, P06286
Correct examples: P00156, P00158

Correct examples: P00156 and P00158 (cytochrome b of human and mouse) match set 1. P56757 (Arabidopsis ATP synthase subunit alpha, chloroplastic; set 251) is not listed as incorrect, because it carries GO:0005739 mitochondrion HDA PMID:22923678 (TAIR), a proteomics annotation; whether that is a real second location or organelle carry-over is not settled here. Swiss-Prot entries that match a condition set but are located in the chloroplast thylakoid membrane: A6MMJ2 (ATP synthase subunit alpha, chloroplastic; set 456), P06286 (ATP synthase subunit c, chloroplastic; set 484). ARBA does not annotate reviewed entries, so these show what the sets would assign to unreviewed orthologs. Annotated unreviewed example: Q9VJ43 (Drosophila ScpX, unreviewed) has SUBCELLULAR LOCATION Mitochondrion with evidence ECO:0000256 ARBA:ARBA00004173 and GO:0005739 IEA GO_REF:0000044; it carries FunFams 3.40.47.10:FF:000016 and 3.30.1050.10:FF:000001 and so matches set 789. P32020: location Mitochondrion scoped to Isoform SCP2 (ECO:0000269 PMID:11003606, PMID:26901662), Isoform SCPx Peroxisome (ECO:0000269 PMID:26901662). P22307: Mitochondrion scoped to Isoform SCP2 (ECO:0000269 PMID:17157249), Isoform SCPx Peroxisome.

Rule Definition

Condition Sets

Condition Set 1

3 condition(s)
Notes:

Swiss-Prot entries matching the whole conjunction: 1701; of these 1701 have the subcellular location Mitochondrion (SL-0173) (UniProtKB query, 2026-11-10). The set matches mitochondrially encoded cytochrome b, for example P00156 (human MT-CYB). In all of UniProtKB, 54,084 eukaryotic entries match both InterPro entries and 52,943 of them are encoded in the mitochondrion; one is plastid-encoded. The plastid cytochrome b6-f subunits do not match the conjunction: P56773 (Arabidopsis cytochrome b6) has IPR027387 but not IPR005798, and P56774 (Arabidopsis cytochrome b6-f complex subunit 4) has IPR005798 but not IPR027387.

Condition Set 2

6 condition(s)
Notes:

Swiss-Prot entries matching the whole conjunction: 26; 25 have the subcellular location Mitochondrion (SL-0173) at entry level and 1 do not (UniProtKB query, 2026-11-10). Those without it: 1 x ABC transporter B family member 5 (Swiss-Prot location: Membrane). Accessions: Q8T9W2.

Condition Set 3

4 condition(s)
Notes:

Swiss-Prot entries matching the whole conjunction: 75; 69 have the subcellular location Mitochondrion (SL-0173) at entry level and 6 do not (UniProtKB query, 2026-11-10). Those without it: 2 x HIG1 domain family member 1C (Swiss-Prot location: Membrane); 2 x HIG1 domain family member 1B (Swiss-Prot location: Membrane); 1 x HIG1 domain family member 2B (Swiss-Prot location: Membrane); 1 x RING-H2 finger protein ATL48 (Swiss-Prot location: Membrane). Accessions: A8MV81, Q4VC39, Q7X843, Q9P298, Q76I25, Q99JY6.

Condition Set 4

3 condition(s)
Notes:

Swiss-Prot entries matching the whole conjunction: 41; 8 have the subcellular location Mitochondrion (SL-0173) at entry level and 33 do not (UniProtKB query, 2026-11-10). Those without it: 33 x ATP synthase subunit alpha, chloroplastic (Swiss-Prot location: Plastid, chloroplast thylakoid membrane). Accessions: P56757, A4GGB2, A4QJI4, A4QKR6, A4QL04, Q09MJ3 and 27 more.

Condition Set 5

6 condition(s)
Notes:

Swiss-Prot entries matching the whole conjunction: 106; 102 have the subcellular location Mitochondrion (SL-0173) at entry level and 4 do not (UniProtKB query, 2026-11-10). Those without it: 4 x Lipoyl synthase, apicoplast (Swiss-Prot location: Plastid, apicoplast). Accessions: Q8IDQ0, A5K883, Q7RBD6, B3L8F2.

Condition Set 6

3 condition(s)
Notes:

Swiss-Prot entries matching the whole conjunction: 8; 6 have the subcellular location Mitochondrion (SL-0173) at entry level and 2 do not (UniProtKB query, 2026-11-10). Those without it: 1 x Nuclear distribution protein nudF 2 (Swiss-Prot location: Cytoplasm, cytoskeleton); 1 x Nuclear distribution protein nudF (Swiss-Prot location: Cytoplasm, cytoskeleton). Accessions: A1CF18, A2QP30.

Condition Set 7

3 condition(s)
Notes:

Swiss-Prot entries matching the whole conjunction: 10; 5 have the subcellular location Mitochondrion (SL-0173) at entry level and 5 do not (UniProtKB query, 2026-11-10). Those without it: 5 x ATP synthase subunit alpha, chloroplastic (Swiss-Prot location: Plastid, chloroplast thylakoid membrane). Accessions: A6MMJ2, Q3V549, A9L981, A9LYH0, Q3BAQ7.

Condition Set 8

3 condition(s)
Notes:

Swiss-Prot entries matching the whole conjunction: 12; 5 have the subcellular location Mitochondrion (SL-0173) at entry level and 7 do not (UniProtKB query, 2026-11-10). Those without it: 7 x ATP synthase subunit c, chloroplastic (Swiss-Prot location: Plastid, chloroplast thylakoid membrane). Accessions: P06286, Q33C51, Q3C1H2, Q8RU61, Q2MIB3, Q2MIK0 and 1 more.

Condition Set 9

4 condition(s)
Notes:

Swiss-Prot entries matching the whole conjunction: 27; 26 have the subcellular location Mitochondrion (SL-0173) at entry level and 1 do not (UniProtKB query, 2026-11-10). Those without it: 1 x ABC transporter B family member 5 (Swiss-Prot location: Membrane). Accessions: Q8T9W2.

Condition Set 10

4 condition(s)
Notes:

Swiss-Prot entries matching the whole conjunction: 10; 8 have the subcellular location Mitochondrion (SL-0173) at entry level and 2 do not (UniProtKB query, 2026-11-10). Those without it: 1 x ABC transporter B family member 28 (Swiss-Prot location: Membrane); 1 x ABC transporter B family member 1 (Swiss-Prot location: Membrane). Accessions: Q8LPQ6, Q54BU4.

Condition Set 11

5 condition(s)
Notes:

Swiss-Prot entries matching the whole conjunction: 6 (P22307, P11915, P32020, P07857, O62742, Q07598; all sterol carrier protein 2 / SCPx); an entry-level search finds the location Mitochondrion in all 6, but the search does not see isoform scoping; unreviewed matches: 1,235 (UniProtKB query, 2026-11-10). The isoform scoping was read for P32020 and P22307 only. In mouse P32020 and human P22307 the Mitochondrion location is recorded for isoform SCP2 only; isoform SCPx is recorded as Peroxisome. Isoform SCP2 of P32020 lacks residues 1-404 (VSP_018895), and the CATH-Gene3D 3.40.47.10 match of P32020 spans residues 13-405, so the isoform that carries the mitochondrial location cannot match this set. Drosophila ScpX (Q9VJ43, unreviewed) matches both FunFams and receives Mitochondrion from this rule.

Condition Set 12

3 condition(s)
Notes:

Swiss-Prot entries matching the whole conjunction: 6; 3 have the subcellular location Mitochondrion (SL-0173) at entry level and 3 do not (UniProtKB query, 2026-11-10). Those without it: 1 x Adenylosuccinate synthetase isozyme 1 A (Swiss-Prot location: Cytoplasm); 1 x Adenylosuccinate synthetase isozyme 1 B (Swiss-Prot location: Cytoplasm); 1 x Adenylosuccinate synthetase isozyme 1 (Swiss-Prot location: Cytoplasm). Accessions: Q561L1, Q68F20, Q6DIW6.

Condition Set 13

3 condition(s)
Notes:

No Swiss-Prot entry matches the whole conjunction (UniProtKB query, 2026-11-10).

Condition Set 14

5 condition(s)
Notes:

Swiss-Prot entries matching the whole conjunction: 8; 2 have the subcellular location Mitochondrion (SL-0173) at entry level and 6 do not (UniProtKB query, 2026-11-10). Those without it: 2 x ATP-dependent 6-phosphofructokinase subunit alpha (Swiss-Prot location: Cytoplasm); 2 x ATP-dependent 6-phosphofructokinase (Swiss-Prot location: Cytoplasm); 1 x ATP-dependent 6-phosphofructokinase 1 (Swiss-Prot location: Cytoplasm); 1 x ATP-dependent 6-phosphofructokinase subunit beta (Swiss-Prot location: Cytoplasm). Accessions: O94201, P78985, Q4W9B8, Q9HGZ1, C4QXA5, Q03215.

Assessments

APPROPRIATE

The rule emits the UniProt location Mitochondrion (SL-0173), which UniProt converts to GO:0005739 mitochondrion; for example Q9VJ43 carries GO:0005739 IEA GO_REF:0000044 assigned by UniProt. The term matches the location it is derived from.

References (2)

Raw YAML

View Source YAML
id: ARBA00004173
description: >-
  Assigns the UniProt subcellular location Mitochondrion (SL-0173) through 1,525 alternative condition
  sets built from CATH FunFam, InterPro and PANTHER signatures, each with a taxon condition. UniProt converts
  the location to GO:0005739 (mitochondrion) by GO_REF:0000044.
status: COMPLETE
rule_type: ARBA
rule:
  rule_id: ARBA00004173
  condition_sets:
  - number: 1
    conditions:
    - condition_type: INTERPRO
      value: IPR005798
      curie: InterPro:IPR005798
      label: Cytochrome b/b6, C-terminal
      interpro_type: DOMAIN
      negated: false
    - condition_type: INTERPRO
      value: IPR027387
      curie: InterPro:IPR027387
      label: Cytochrome b/b6-like domain superfamily
      interpro_type: HOMOLOGOUS_SUPERFAMILY
      negated: false
    - condition_type: TAXON
      value: Eukaryota
      curie: NCBITaxon:2759
      label: Eukaryota
      negated: false
    notes: >-
      Swiss-Prot entries matching the whole conjunction: 1701; of these 1701 have the subcellular location
      Mitochondrion (SL-0173) (UniProtKB query, 2026-11-10). The set matches mitochondrially encoded cytochrome
      b, for example P00156 (human MT-CYB). In all of UniProtKB, 54,084 eukaryotic entries match both
      InterPro entries and 52,943 of them are encoded in the mitochondrion; one is plastid-encoded. The
      plastid cytochrome b6-f subunits do not match the conjunction: P56773 (Arabidopsis cytochrome b6)
      has IPR027387 but not IPR005798, and P56774 (Arabidopsis cytochrome b6-f complex subunit 4) has
      IPR005798 but not IPR027387.
  - number: 43
    conditions:
    - condition_type: INTERPRO
      value: IPR003439
      curie: InterPro:IPR003439
      label: ABC transporter-like, ATP-binding domain
      interpro_type: DOMAIN
      negated: false
    - condition_type: INTERPRO
      value: IPR003593
      curie: InterPro:IPR003593
      label: AAA+ ATPase domain
      interpro_type: DOMAIN
      negated: false
    - condition_type: PANTHER
      value: PTHR24221:SF402
      curie: PANTHER:PTHR24221:SF402
      negated: false
    - condition_type: TAXON
      value: Bacteria
      curie: NCBITaxon:2
      label: Bacteria
      negated: true
    - condition_type: TAXON
      value: Archaea
      curie: NCBITaxon:2157
      label: Archaea
      negated: true
    - condition_type: TAXON
      value: Viruses
      curie: NCBITaxon:10239
      label: Viruses
      negated: true
    notes: >-
      Swiss-Prot entries matching the whole conjunction: 26; 25 have the subcellular location Mitochondrion
      (SL-0173) at entry level and 1 do not (UniProtKB query, 2026-11-10). Those without it: 1 x ABC transporter
      B family member 5 (Swiss-Prot location: Membrane). Accessions: Q8T9W2.
  - number: 209
    conditions:
    - condition_type: INTERPRO
      value: IPR007667
      curie: InterPro:IPR007667
      label: Hypoxia induced protein, domain
      interpro_type: DOMAIN
      negated: false
    - condition_type: TAXON
      value: Bacteria
      curie: NCBITaxon:2
      label: Bacteria
      negated: true
    - condition_type: TAXON
      value: Archaea
      curie: NCBITaxon:2157
      label: Archaea
      negated: true
    - condition_type: TAXON
      value: Viruses
      curie: NCBITaxon:10239
      label: Viruses
      negated: true
    notes: >-
      Swiss-Prot entries matching the whole conjunction: 75; 69 have the subcellular location Mitochondrion
      (SL-0173) at entry level and 6 do not (UniProtKB query, 2026-11-10). Those without it: 2 x HIG1
      domain family member 1C (Swiss-Prot location: Membrane); 2 x HIG1 domain family member 1B (Swiss-Prot
      location: Membrane); 1 x HIG1 domain family member 2B (Swiss-Prot location: Membrane); 1 x RING-H2
      finger protein ATL48 (Swiss-Prot location: Membrane). Accessions: A8MV81, Q4VC39, Q7X843, Q9P298,
      Q76I25, Q99JY6.
  - number: 251
    conditions:
    - condition_type: INTERPRO
      value: IPR000194
      curie: InterPro:IPR000194
      label: ATPase, F1/V1/A1 complex, alpha/beta subunit, nucleotide-binding domain
      interpro_type: DOMAIN
      negated: false
    - condition_type: INTERPRO
      value: IPR000793
      curie: InterPro:IPR000793
      label: ATP synthase, alpha subunit, C-terminal
      interpro_type: DOMAIN
      negated: false
    - condition_type: TAXON
      value: rosids
      curie: NCBITaxon:71275
      label: rosids
      negated: false
    notes: >-
      Swiss-Prot entries matching the whole conjunction: 41; 8 have the subcellular location Mitochondrion
      (SL-0173) at entry level and 33 do not (UniProtKB query, 2026-11-10). Those without it: 33 x ATP
      synthase subunit alpha, chloroplastic (Swiss-Prot location: Plastid, chloroplast thylakoid membrane).
      Accessions: P56757, A4GGB2, A4QJI4, A4QKR6, A4QL04, Q09MJ3 and 27 more.
  - number: 365
    conditions:
    - condition_type: INTERPRO
      value: IPR003698
      curie: InterPro:IPR003698
      label: Lipoyl synthase
      interpro_type: FAMILY
      negated: false
    - condition_type: INTERPRO
      value: IPR031691
      curie: InterPro:IPR031691
      label: Lipoyl synthase, N-terminal
      interpro_type: DOMAIN
      negated: false
    - condition_type: PANTHER
      value: PTHR10949:SF0
      curie: PANTHER:PTHR10949:SF0
      negated: false
    - condition_type: TAXON
      value: Bacteria
      curie: NCBITaxon:2
      label: Bacteria
      negated: true
    - condition_type: TAXON
      value: Archaea
      curie: NCBITaxon:2157
      label: Archaea
      negated: true
    - condition_type: TAXON
      value: Viruses
      curie: NCBITaxon:10239
      label: Viruses
      negated: true
    notes: >-
      Swiss-Prot entries matching the whole conjunction: 106; 102 have the subcellular location Mitochondrion
      (SL-0173) at entry level and 4 do not (UniProtKB query, 2026-11-10). Those without it: 4 x Lipoyl
      synthase, apicoplast (Swiss-Prot location: Plastid, apicoplast). Accessions: Q8IDQ0, A5K883, Q7RBD6,
      B3L8F2.
  - number: 378
    conditions:
    - condition_type: INTERPRO
      value: IPR019775
      curie: InterPro:IPR019775
      label: WD40 repeat, conserved site
      interpro_type: CONSERVED_SITE
      negated: false
    - condition_type: PANTHER
      value: PTHR22847:SF637
      curie: PANTHER:PTHR22847:SF637
      negated: false
    - condition_type: TAXON
      value: Aspergillus
      curie: NCBITaxon:5052
      label: Aspergillus
      negated: false
    notes: >-
      Swiss-Prot entries matching the whole conjunction: 8; 6 have the subcellular location Mitochondrion
      (SL-0173) at entry level and 2 do not (UniProtKB query, 2026-11-10). Those without it: 1 x Nuclear
      distribution protein nudF 2 (Swiss-Prot location: Cytoplasm, cytoskeleton); 1 x Nuclear distribution
      protein nudF (Swiss-Prot location: Cytoplasm, cytoskeleton). Accessions: A1CF18, A2QP30.
  - number: 456
    conditions:
    - condition_type: INTERPRO
      value: IPR005294
      curie: InterPro:IPR005294
      label: ATP synthase, F1 complex, alpha subunit
      interpro_type: FAMILY
      negated: false
    - condition_type: PANTHER
      value: PTHR48082:SF2
      curie: PANTHER:PTHR48082:SF2
      negated: false
    - condition_type: TAXON
      value: Liliopsida
      curie: NCBITaxon:4447
      label: Liliopsida
      negated: false
    notes: >-
      Swiss-Prot entries matching the whole conjunction: 10; 5 have the subcellular location Mitochondrion
      (SL-0173) at entry level and 5 do not (UniProtKB query, 2026-11-10). Those without it: 5 x ATP synthase
      subunit alpha, chloroplastic (Swiss-Prot location: Plastid, chloroplast thylakoid membrane). Accessions:
      A6MMJ2, Q3V549, A9L981, A9LYH0, Q3BAQ7.
  - number: 484
    conditions:
    - condition_type: INTERPRO
      value: IPR020537
      curie: InterPro:IPR020537
      label: ATP synthase, F0 complex, subunit C, DCCD-binding site
      interpro_type: BINDING_SITE
      negated: false
    - condition_type: INTERPRO
      value: IPR035921
      curie: InterPro:IPR035921
      label: F/V-ATP synthase subunit C superfamily
      interpro_type: HOMOLOGOUS_SUPERFAMILY
      negated: false
    - condition_type: TAXON
      value: Solanaceae
      curie: NCBITaxon:4070
      label: Solanaceae
      negated: false
    notes: >-
      Swiss-Prot entries matching the whole conjunction: 12; 5 have the subcellular location Mitochondrion
      (SL-0173) at entry level and 7 do not (UniProtKB query, 2026-11-10). Those without it: 7 x ATP synthase
      subunit c, chloroplastic (Swiss-Prot location: Plastid, chloroplast thylakoid membrane). Accessions:
      P06286, Q33C51, Q3C1H2, Q8RU61, Q2MIB3, Q2MIK0 and 1 more.
  - number: 549
    conditions:
    - condition_type: FUNFAM
      value: 1.20.1560.10:FF:000004
      curie: CATH.FunFam:1.20.1560.10:FF:000004
      label: ATP-binding cassette sub-family B member 7
      negated: false
    - condition_type: TAXON
      value: Bacteria
      curie: NCBITaxon:2
      label: Bacteria
      negated: true
    - condition_type: TAXON
      value: Archaea
      curie: NCBITaxon:2157
      label: Archaea
      negated: true
    - condition_type: TAXON
      value: Viruses
      curie: NCBITaxon:10239
      label: Viruses
      negated: true
    notes: >-
      Swiss-Prot entries matching the whole conjunction: 27; 26 have the subcellular location Mitochondrion
      (SL-0173) at entry level and 1 do not (UniProtKB query, 2026-11-10). Those without it: 1 x ABC transporter
      B family member 5 (Swiss-Prot location: Membrane). Accessions: Q8T9W2.
  - number: 718
    conditions:
    - condition_type: FUNFAM
      value: 3.40.50.300:FF:000403
      curie: CATH.FunFam:3.40.50.300:FF:000403
      label: ATP-binding cassette sub-family B member 8, mitochondrial
      negated: false
    - condition_type: TAXON
      value: Bacteria
      curie: NCBITaxon:2
      label: Bacteria
      negated: true
    - condition_type: TAXON
      value: Archaea
      curie: NCBITaxon:2157
      label: Archaea
      negated: true
    - condition_type: TAXON
      value: Viruses
      curie: NCBITaxon:10239
      label: Viruses
      negated: true
    notes: >-
      Swiss-Prot entries matching the whole conjunction: 10; 8 have the subcellular location Mitochondrion
      (SL-0173) at entry level and 2 do not (UniProtKB query, 2026-11-10). Those without it: 1 x ABC transporter
      B family member 28 (Swiss-Prot location: Membrane); 1 x ABC transporter B family member 1 (Swiss-Prot
      location: Membrane). Accessions: Q8LPQ6, Q54BU4.
  - number: 789
    conditions:
    - condition_type: FUNFAM
      value: 3.30.1050.10:FF:000001
      curie: CATH.FunFam:3.30.1050.10:FF:000001
      label: Putative Non-specific lipid-transfer protein
      negated: false
    - condition_type: FUNFAM
      value: 3.40.47.10:FF:000016
      curie: CATH.FunFam:3.40.47.10:FF:000016
      label: Non-specific lipid-transfer protein
      negated: false
    - condition_type: TAXON
      value: Bacteria
      curie: NCBITaxon:2
      label: Bacteria
      negated: true
    - condition_type: TAXON
      value: Archaea
      curie: NCBITaxon:2157
      label: Archaea
      negated: true
    - condition_type: TAXON
      value: Viruses
      curie: NCBITaxon:10239
      label: Viruses
      negated: true
    notes: >-
      Swiss-Prot entries matching the whole conjunction: 6 (P22307, P11915, P32020, P07857, O62742, Q07598;
      all sterol carrier protein 2 / SCPx); an entry-level search finds the location Mitochondrion in
      all 6, but the search does not see isoform scoping; unreviewed matches: 1,235 (UniProtKB query,
      2026-11-10). The isoform scoping was read for P32020 and P22307 only. In mouse P32020 and human
      P22307 the Mitochondrion location is recorded for isoform SCP2 only; isoform SCPx is recorded as
      Peroxisome. Isoform SCP2 of P32020 lacks residues 1-404 (VSP_018895), and the CATH-Gene3D 3.40.47.10
      match of P32020 spans residues 13-405, so the isoform that carries the mitochondrial location cannot
      match this set. Drosophila ScpX (Q9VJ43, unreviewed) matches both FunFams and receives Mitochondrion
      from this rule.
  - number: 1084
    conditions:
    - condition_type: FUNFAM
      value: 1.10.300.10:FF:000002
      curie: CATH.FunFam:1.10.300.10:FF:000002
      label: Adenylosuccinate synthetase, chloroplastic
      negated: false
    - condition_type: FUNFAM
      value: 3.90.170.10:FF:000001
      curie: CATH.FunFam:3.90.170.10:FF:000001
      label: Adenylosuccinate synthetase
      negated: false
    - condition_type: TAXON
      value: Amphibia
      curie: NCBITaxon:8292
      label: Amphibia
      negated: false
    notes: >-
      Swiss-Prot entries matching the whole conjunction: 6; 3 have the subcellular location Mitochondrion
      (SL-0173) at entry level and 3 do not (UniProtKB query, 2026-11-10). Those without it: 1 x Adenylosuccinate
      synthetase isozyme 1 A (Swiss-Prot location: Cytoplasm); 1 x Adenylosuccinate synthetase isozyme
      1 B (Swiss-Prot location: Cytoplasm); 1 x Adenylosuccinate synthetase isozyme 1 (Swiss-Prot location:
      Cytoplasm). Accessions: Q561L1, Q68F20, Q6DIW6.
  - number: 1312
    conditions:
    - condition_type: FUNFAM
      value: 3.40.640.10:FF:000003
      curie: CATH.FunFam:3.40.640.10:FF:000003
      label: Cysteine desulfurase IscS
      negated: false
    - condition_type: FUNFAM
      value: 3.90.1150.10:FF:000002
      curie: CATH.FunFam:3.90.1150.10:FF:000002
      label: Cysteine desulfurase IscS
      negated: false
    - condition_type: TAXON
      value: Candida/Lodderomyces clade
      curie: NCBITaxon:1535325
      label: Candida/Lodderomyces clade
      negated: false
    notes: No Swiss-Prot entry matches the whole conjunction (UniProtKB query, 2026-11-10).
  - number: 1384
    conditions:
    - condition_type: FUNFAM
      value: 3.40.50.450:FF:000010
      curie: CATH.FunFam:3.40.50.450:FF:000010
      label: ATP-dependent 6-phosphofructokinase
      negated: false
    - condition_type: FUNFAM
      value: 3.40.50.460:FF:000008
      curie: CATH.FunFam:3.40.50.460:FF:000008
      label: ATP-dependent 6-phosphofructokinase
      negated: false
    - condition_type: TAXON
      value: Bacteria
      curie: NCBITaxon:2
      label: Bacteria
      negated: true
    - condition_type: TAXON
      value: Archaea
      curie: NCBITaxon:2157
      label: Archaea
      negated: true
    - condition_type: TAXON
      value: Viruses
      curie: NCBITaxon:10239
      label: Viruses
      negated: true
    notes: >-
      Swiss-Prot entries matching the whole conjunction: 8; 2 have the subcellular location Mitochondrion
      (SL-0173) at entry level and 6 do not (UniProtKB query, 2026-11-10). Those without it: 2 x ATP-dependent
      6-phosphofructokinase subunit alpha (Swiss-Prot location: Cytoplasm); 2 x ATP-dependent 6-phosphofructokinase
      (Swiss-Prot location: Cytoplasm); 1 x ATP-dependent 6-phosphofructokinase 1 (Swiss-Prot location:
      Cytoplasm); 1 x ATP-dependent 6-phosphofructokinase subunit beta (Swiss-Prot location: Cytoplasm).
      Accessions: O94201, P78985, Q4W9B8, Q9HGZ1, C4QXA5, Q03215.
  go_annotations:
  - go_id: GO:0005739
    go_label: mitochondrion
    aspect: C
  entries: []
  reviewed_protein_count: 0
  unreviewed_protein_count: 562320
  created_date: '2020-05-12'
  modified_date: '2026-07-18'
  source_condition_set_count: 1525
  retrieved_date: '2026-11-09'
review_summary: >-
  All 1,525 live condition sets were screened with two UniProtKB queries each (2026-11-10): the Swiss-Prot
  entries that match the whole conjunction, and how many of them have the subcellular location Mitochondrion
  (SL-0173). 1,524 sets match at least one Swiss-Prot entry and 1 match none. In 1,513 sets every Swiss-Prot
  match has the location and in 11 sets some do not (sets 43, 209, 251, 365, 378, 456, 484, 549, 718,
  1084, 1384); set 1312 matches no Swiss-Prot entry. The search is at entry level and does not see locations
  scoped to one isoform. Summed over sets there are 18,954 set-level matches, 18,884 with the location.
  Sets 1 and 789 were read in detail; they and the sets with incomplete agreement are recorded in the
  rule block. Set 1 (cytochrome b) is sound. Three sets match plastid-encoded ATP synthase subunits whose
  curated location is the chloroplast thylakoid membrane: set 251 (33 of 41 Swiss-Prot matches, in rosids),
  set 456 (5 of 10, in Liliopsida) and set 484 (7 of 12, in Solanaceae). Set 1384 matches ATP-dependent
  6-phosphofructokinases, 6 of 8 recorded as Cytoplasm, and set 1084 matches amphibian adenylosuccinate
  synthetase isozyme 1, 3 of 6 recorded as Cytoplasm; in both cases the Swiss-Prot location comes from
  a HAMAP rule, not an experiment. Set 365 also matches four apicoplast lipoyl synthases. Set 789 is defective
  in a different way: it requires the thiolase-type FunFam 3.40.47.10:FF:000016 together with the SCP2
  FunFam 3.30.1050.10:FF:000001, but in the reviewed mouse and human entries the mitochondrial location
  belongs to the short SCP2 isoform, which lacks the region matched by the first FunFam, while the full-length
  SCPx isoform is recorded as Peroxisome only. The rule therefore gives Mitochondrion to full-length SCPx
  proteins such as Drosophila ScpX (Q9VJ43). In sets 43, 209, 378, 549 and 718 the entries without the
  location have only a generic or rule-derived location comment, which does not show the protein is absent
  from mitochondria. ARBA rules are mined from Swiss-Prot annotation, and precision on the 562,320 unreviewed
  entries the rule annotates was not measured.
action: MODIFY
action_rationale: >-
  Specific condition sets are defective. Sets 251, 456 and 484 match chloroplast ATP synthase subunits,
  and set 789 transfers a location that the source entries record for a different isoform than the one
  the set detects. These four sets should be removed or narrowed; sets 1384, 1084 and 365 need a closer
  look. The remaining sets were not shown to be wrong: 1,513 of 1,525 sets agree fully with Swiss-Prot
  locations at entry level, so the rule as a whole is kept.
suggested_modifications:
- >-
  Remove condition set 789 (FunFam 3.30.1050.10:FF:000001 AND FunFam 3.40.47.10:FF:000016 AND NOT Bacteria,
  Archaea, Viruses), or stop it from emitting Mitochondrion. In P32020 and P22307 the Mitochondrion location
  is scoped to isoform SCP2, which lacks residues 1-404 and so cannot match FunFam 3.40.47.10:FF:000016;
  isoform SCPx is recorded as Peroxisome.
- >-
  When rules are mined from subcellular location comments that are scoped to a named isoform, do not transfer
  the location through a signature set that the named isoform cannot match.
- >-
  Remove or narrow set 251 (IPR000194 AND IPR000793 AND rosids), set 456 (IPR005294 AND PTHR48082:SF2
  AND Liliopsida) and set 484 (IPR020537 AND IPR035921 AND Solanaceae): 33 of 41, 5 of 10 and 7 of 12
  of their Swiss-Prot matches are chloroplast ATP synthase subunits curated to the chloroplast thylakoid
  membrane (for example A6MMJ2, P06286).
- >-
  Review set 1384 (FunFams 3.40.50.450:FF:000010 AND 3.40.50.460:FF:000008): 6 of 8 Swiss-Prot matches
  are ATP-dependent 6-phosphofructokinases recorded as Cytoplasm by HAMAP rule MF_03184 (for example O94201,
  P78985). Review set 1084 (Amphibia adenylosuccinate synthetase, 3 of 6 recorded as Cytoplasm by HAMAP
  rule MF_03126) and set 365 (4 of 106 matches are apicoplast lipoyl synthases, for example Q8IDQ0).
go_specificity:
  assessment: APPROPRIATE
  notes: >-
    The rule emits the UniProt location Mitochondrion (SL-0173), which UniProt converts to GO:0005739
    mitochondrion; for example Q9VJ43 carries GO:0005739 IEA GO_REF:0000044 assigned by UniProt. The term
    matches the location it is derived from.
annotation_assessments:
- annotation_kind: OTHER
  value: SL-0173
  label: Mitochondrion
  assessment: PARTIALLY_CORRECT
  correct_examples:
  - P00156
  - P00158
  incorrect_examples:
  - Q9VJ43
  - A6MMJ2
  - P06286
  notes: >-
    Correct examples: P00156 and P00158 (cytochrome b of human and mouse) match set 1. P56757 (Arabidopsis
    ATP synthase subunit alpha, chloroplastic; set 251) is not listed as incorrect, because it carries
    GO:0005739 mitochondrion HDA PMID:22923678 (TAIR), a proteomics annotation; whether that is a real
    second location or organelle carry-over is not settled here. Swiss-Prot entries
    that match a condition set but are located in the chloroplast thylakoid membrane: A6MMJ2 (ATP synthase subunit alpha, chloroplastic; set 456),
    P06286 (ATP synthase subunit c, chloroplastic; set 484). ARBA does not annotate reviewed entries,
    so these show what the sets would assign to unreviewed orthologs. Annotated unreviewed example: Q9VJ43
    (Drosophila ScpX, unreviewed) has SUBCELLULAR LOCATION Mitochondrion with evidence ECO:0000256 ARBA:ARBA00004173
    and GO:0005739 IEA GO_REF:0000044; it carries FunFams 3.40.47.10:FF:000016 and 3.30.1050.10:FF:000001
    and so matches set 789. P32020: location Mitochondrion scoped to Isoform SCP2 (ECO:0000269 PMID:11003606,
    PMID:26901662), Isoform SCPx Peroxisome (ECO:0000269 PMID:26901662). P22307: Mitochondrion scoped
    to Isoform SCP2 (ECO:0000269 PMID:17157249), Isoform SCPx Peroxisome.
  supported_by:
  - reference_id: PMID:26901662
    supporting_text: >-
      the N-terminal mitochondrial targeting sequence is not powerful enough to localize the SCPX and
      SCP2 proteins to the mitochondria.
  - reference_id: PMID:26901662
    supporting_text: >-
      The Scp2 gene contains two transcription initiation sites, giving rise to the 58 kDa sterol carrier
      protein-x (SCPX) and 15 kDa pro-SCP2 proteins
confidence: 0.75
references:
- id: PMID:26901662
  title: >-
    Sterol Carrier Protein-2, a Nonspecific Lipid-Transfer Protein, in Intracellular Cholesterol Trafficking
    in Testicular Leydig Cells.
- id: PMID:11003606
  title: >-
    Sterol carrier protein-2 localization in endoplasmic reticulum and role in phospholipid formation.
  full_text_unavailable: true
supported_by:
- reference_id: PMID:26901662
  supporting_text: >-
    the N-terminal mitochondrial targeting sequence is not powerful enough to localize the SCPX and SCP2
    proteins to the mitochondria.
- reference_id: PMID:11003606
  supporting_text: detected SCP-2 in peroxisomes > endoplasmic reticulum > mitochondria >
corrections:
- date: '2026-11-10'
  withdrawn_claim: >-
    The broad NOT Bacteria/Archaea/Viruses taxon condition, combined with single-FunFam sets, is the principal
    false-positive generator and is exactly how the Drosophila ScpX case arises.
  correction: >-
    The ScpX case comes from a two-FunFam set and from an isoform-scoped source annotation; no taxon condition
    within eukaryotes would prevent it, and no false-positive rate was measured for any class of set.
    The taxonomic scope block was removed.
  error_type: OTHER
  evidence:
  - >-
    Live set 789: FunFam 3.30.1050.10:FF:000001 AND FunFam 3.40.47.10:FF:000016 AND NOT (Bacteria, Archaea,
    Viruses)
  - >-
    UniProtKB:P32020 SUBCELLULAR LOCATION: Mitochondrion scoped to Isoform SCP2; Isoform SCPx Peroxisome
- date: '2026-11-10'
  withdrawn_claim: >-
    About 96% of the InterPro conditions assert a mitochondrial location that InterPro curators did not
    assert.
  correction: >-
    The conditions act as conjunctions, so a single InterPro entry need not imply the location, and InterPro2GO
    maps few cellular component terms; the figure is not evidence against the rule.
  error_type: CONJUNCTION_IGNORED
  evidence:
  - >-
    Live set 1 is IPR005798 AND IPR027387 AND Eukaryota: 54,084 UniProtKB entries match, 52,943 of them
    mitochondrion-encoded (UniProtKB, 2026-11-09)
- date: '2026-11-10'
  withdrawn_claim: >-
    Single-FunFam sets whose FunFam label does not mention mitochondria, or has no resolved label, should
    be dropped.
  correction: >-
    A label is not evidence about location. Agreement with Swiss-Prot locations was measured instead.
  error_type: UNEXAMINED_RULE
  evidence:
  - >-
    717 live sets consist of one FunFam plus taxon conditions; in 715 of them every Swiss-Prot match has
    the location Mitochondrion (UniProtKB, 2026-11-10)
- date: '2026-11-10'
  withdrawn_claim: The rule annotates zero reviewed proteins, so no reviewed proteins act as controls.
  correction: >-
    The ARBA API reports a reviewed count of zero for every rule because ARBA annotates unreviewed entries;
    reviewed entries do match the condition sets.
  error_type: OTHER
  evidence:
  - >-
    1,524 of 1,525 live sets match at least one Swiss-Prot entry; 18,954 set-level Swiss-Prot matches
    in total
  - >-
    reviewedProteinCount is 0 for all 15 live ARBA rules retrieved on 2026-11-09 for this group of reviews
- date: '2026-11-10'
  withdrawn_claim: >-
    A rule with 1,490 condition sets, about 124 times the 12-set threshold of the analysis tool, cannot
    be reviewed and is overly complex.
  correction: >-
    The number of condition sets is not evidence about correctness; every set was screened. The parsimony
    and overlap blocks were removed.
  error_type: SIZE_AS_EVIDENCE
  evidence:
  - 'All 1,525 live sets screened: 1,513 agree fully with Swiss-Prot locations'
- date: '2026-11-10'
  withdrawn_claim: >-
    The rule has 1,490 condition sets and annotates 536,854 proteins; the SCPx set is number 779.
  correction: The live rule has more sets and the SCPx set is number 789.
  error_type: STALE_RULE_VERSION
  evidence:
  - >-
    https://rest.uniprot.org/arba/ARBA00004173 retrieved 2026-11-09: 1,525 condition sets, unreviewedProteinCount
    562,320, modifiedDate 2026-07-18
- date: '2026-11-10'
  withdrawn_claim: Assessments were supported by quotations from an AI-generated deep-research report.
  correction: >-
    That report is not literature; those supporting entries were removed and the two cached papers are
    cited directly.
  error_type: UNSUPPORTED_SOURCE
  evidence:
  - >-
    Previous supported_by entries cited rules/arba/ARBA00004173/ARBA00004173-deep-research-falcon.md