ctaC Family assigned · medium auto-curated

H37Rv Rv2200c · MTBC0 mtbc0_002336 · 363 aa · 2489817–2490908 (-) · RefSeq NP_216716.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cytochrome C oxidase subunit II
MTBC0 PGAP re-annotationcytochrome c oxidase subunit II
Revised (this work)Cytochrome c oxidase subunit II. Pfam: COX2 (PF00116.27).

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

Curated reference (UniProt)

UniProt P9WP69 SwissProt · reviewed · Evidence at protein level
UniProt nameCytochrome c oxidase subunit 2
EC (curated) EC 7.1.1.9
Curated functionSubunits I and II form the functional core of the enzyme complex. Electrons originating in cytochrome c are transferred via heme a and Cu(A) to the binuclear center formed by heme a3 and Cu(B) (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namectaC
eggNOG descriptioncytochrome C oxidase (Subunit
Orthologous groupCOG1622
EC number EC 1.9.3.1
KEGG orthology K02275
KEGG pathways map00190, map01100
KEGG modules M00155
Gene Ontology (72) GO:0005575, GO:0005576, GO:0005623, GO:0005886, GO:0005887, GO:0006091, GO:0006119, GO:0006139, GO:0006163, GO:0006725, GO:0006753, GO:0006793 +60 more

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 0.189 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 3 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
COX2PF00116.27 5.2e-13235–311 Cytochrome C oxidase subunit II, periplasmic domain

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

Closest characterised functional partner: ctaD (cytochrome C oxidase cytochrome 1), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3043c ctaD cytochrome C oxidase cytochrome 1 999 1000 ctx cooccurence:773 coexpression:911 experimental:999 database:984 textmining:960
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 999 1000 ctx cooccurence:637 coexpression:401 experimental:999 textmining:850
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 999 1000 ctx cooccurence:627 coexpression:445 experimental:999 textmining:889
Rv2199c ctaF cytochrome c oxidase polypeptide 4 999 1000 ctx neighborhood:882 cooccurence:611 experimental:999 textmining:902
Rv2196 qcrB ubiquinol-cytochrome C reductase cytochrome subunit B 999 1000 ctx cooccurence:718 coexpression:857 experimental:999 textmining:846
Rv2193 ctaE cytochrome C oxidase subunit III 999 1000 ctx cooccurence:774 coexpression:866 experimental:999 database:984 textmining:968
Rv2876 transmembrane protein 999 999 experimental:999
Rv1451 ctaB protoheme IX farnesyltransferase 999 994 ctx cooccurence:770 coexpression:751 database:900 textmining:853
Rv3157 nuoM NADH-quinone oxidoreductase subunit M 979 973 coexpression:859 experimental:771
Rv3152 nuoH NADH-quinone oxidoreductase subunit H 974 967 coexpression:862 experimental:771
Rv3145 nuoA NADH-quinone oxidoreductase subunit A 950 926 coexpression:690 experimental:771
Rv2782c pepR zinc protease 930 923 experimental:919
Rv3584 lpqE lipoprotein LpqE 919 919 experimental:902
Rv1304 atpB ATP synthase subunit A 913 886 coexpression:886
Rv3147 nuoC NADH-quinone oxidoreductase subunit C 900 878 coexpression:484 experimental:773

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 subunit II
  • MTBC0 PGAP product: cytochrome c oxidase subunit II
  • Pfam (hmmscan --cut_ga): COX2 PF00116.27 (E=5e-13)
  • (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_216716.1)
  • Domains: Pfam-A via hmmscan --cut_ga — COX2 (PF00116.27)
  • 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 COG1622
  • Curated reference: UniProt P9WP69 (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 — 103 functional partner(s); context anchor ctaD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002336|Rv2200c|ctaC
MTPRGPGRLQRLSQCRPQRGSGGPARGLRQLALAAMLGALAVTVSGCSWSEALGIGWPEGITPEAHLNRELWIGAVIASLAVGVIVWGLIFWSAVFHRKKNTDTELPRQFGYNMPLELVLTVIPFLIISVLFYFTVVVQEKMLQIAKDPEVVIDITSFQWNWKFGYQRVNFKDGTLTYDGADPERKRAMVSKPEGKDKYGEELVGPVRGLNTEDRTYLNFDKVETLGTSTEIPVLVLPSGKRIEFQMASADVIHAFWVPEFLFKRDVMPNPVANNSVNVFQIEEITKTGAFVGHCAEMCGTYHSMMNFEVRVVTPNDFKAYLQQRIDGKTNAEALRAINQPPLAVTTHPFDTRRGELAPQPVG