Rv2199c Family assigned · medium auto-curated

H37Rv Rv2199c · MTBC0 mtbc0_002335 · 139 aa · 2489390–2489809 (-) · RefSeq NP_216715.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cytochrome c oxidase polypeptide 4
MTBC0 PGAP re-annotationcytochrome c oxidase subunit 4
Revised (this work)Cytochrome c oxidase subunit 4. Pfam: Cyt_c_ox_IV (PF12270.14).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WP45 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable cytochrome c oxidase polypeptide 4
EC (curated) EC 7.1.1.9
Curated functionPart of cytochrome c oxidase, its function is unknown.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namectaF
eggNOG descriptionBelongs to the cytochrome c oxidase bacterial subunit CtaF family
Orthologous group2D9MJ
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 0 missense, 0 nonsense, 0 frameshift

pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.

Domains (Pfam, hmmscan --cut_ga)

PfamAccessioni-EvalueResiduesDescription
Cyt_c_ox_IVPF12270.14 1.9e-501–137 Cytochrome c oxidase subunit IV

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: ctaC (cytochrome C oxidase subunit II), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3043c ctaD cytochrome C oxidase cytochrome 1 999 1000 experimental:999 textmining:597
Rv2200c ctaC cytochrome C oxidase subunit II 999 1000 ctx neighborhood:882 cooccurence:611 experimental:999 textmining:902
Rv2193 ctaE cytochrome C oxidase subunit III 999 1000 ctx cooccurence:555 experimental:999 textmining:801
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 999 1000 ctx cooccurence:774 experimental:999 textmining:434
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 999 1000 ctx cooccurence:769 experimental:999 textmining:514
Rv2196 qcrB ubiquinol-cytochrome C reductase cytochrome subunit B 999 1000 ctx cooccurence:768 coexpression:533 experimental:999 textmining:490
Rv2876 transmembrane protein 999 999 experimental:999
Rv0863 hyp hypothetical protein 987 987 experimental:987
Rv3584 lpqE lipoprotein LpqE 898 895 experimental:889
Rv0432 sodC superoxide dismutase 871 872 experimental:870
Rv2468A hyp hypothetical protein 870 870 experimental:870
Rv2468c hyp hypothetical protein 829 829 experimental:747
Rv0528 transmembrane protein 763 763 ctx cooccurence:761
Rv2197c transmembrane protein 754 754 ctx neighborhood:740
Rv2345 transmembrane protein 750 751 experimental:747

STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.

Evidence

  • Legacy H37Rv annotation: cytochrome c oxidase polypeptide 4
  • MTBC0 PGAP product: cytochrome c oxidase subunit 4
  • Pfam (hmmscan --cut_ga): Cyt_c_ox_IV PF12270.14 (E=2e-50)
  • (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)

Sources

  • Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
  • Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_216715.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Cyt_c_ox_IV (PF12270.14)
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021, doi:10.1093/molbev/msab293), eggNOG 5.0 DB (Huerta-Cepas et al. 2019) — OG 2D9MJ
  • Curated reference: UniProt P9WP45 (SwissProt, reviewed; Evidence at protein level)
  • Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 72 functional partner(s); context anchor ctaC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002335|Rv2199c|
MHIEARLFEFVAAFFVVTAVLYGVLTSMFATGGVEWAGTTALALTGGMALIVATFFRFVARRLDSRPEDYEGAEISDGAGELGFFSPHSWWPIMVALSGSVAAVGIALWLPWLIAAGVAFILASAAGLVFEYYVGPEKH