qcrA Resolved · high
H37Rv Rv2195 · MTBC0 mtbc0_002331 ·
429 aa · 2484399–2485688 (+) ·
RefSeq NP_216711.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ubiquinol-cytochrome C reductase rieske iron-sulfur subunit |
|---|---|
| MTBC0 PGAP re-annotation | ubiquinol-cytochrome c reductase iron-sulfur subunit |
| Revised (this work) | QcrA, the Rieske iron-sulfur protein of the cytochrome bcc (bc1) complex of the respiratory chain. RefSeq leaves this locus uncharacterised, but Rv2195 is qcrA, part of the qcrCAB operon (with qcrB/Rv2196, the target of telacebec/Q203). Resistance to QcrB inhibitors can arise via QcrA mutations in the stigmatellin pocket (Lupien 2020), and qcrA is an essential, human-homolog-free drug target (Cloete 2016). |
Curated reference (UniProt)
| UniProt |
P9WH23
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Cytochrome bc1 complex Rieske iron-sulfur subunit |
| Curated function | Iron-sulfur subunit of the cytochrome bc1 complex, an essential component of the respiratory electron transport chain required for ATP synthesis. The bc1 complex catalyzes the oxidation of menaquinol and the reduction of cytochrome c in the respiratory chain. The bc1 complex operates through a Q-cycle mechanism that couples electron transfer to generation of the proton gradient that drives ATP synthesis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | qcrA |
| eggNOG description | c reductase, iron-sulfur subunit |
| Orthologous group | COG0723 |
| KEGG orthology |
K03890
|
| KEGG pathways |
map00190, map01100
|
| KEGG modules |
M00151
|
| Gene Ontology (16) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0005887, GO:0008150, GO:0016020, GO:0016021, GO:0030312, GO:0031224, GO:0031226, GO:0040007 +4 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 | 0.977 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: qcrC (ubiquinol-cytochrome C reductase cytochrome subunit C), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2194 qcrC |
ubiquinol-cytochrome C reductase cytochrome subunit C | 999 | 1000 ctx | neighborhood:881 cooccurence:773 coexpression:929 experimental:999 database:900 textmining:965 |
Rv2196 qcrB |
ubiquinol-cytochrome C reductase cytochrome subunit B | 999 | 1000 ctx | neighborhood:881 cooccurence:772 coexpression:983 experimental:999 database:984 textmining:909 |
Rv2199c ctaF |
cytochrome c oxidase polypeptide 4 | 999 | 1000 ctx | cooccurence:769 experimental:999 textmining:514 |
Rv2193 ctaE |
cytochrome C oxidase subunit III | 999 | 1000 ctx | neighborhood:822 cooccurence:506 coexpression:928 experimental:999 textmining:935 |
Rv2200c ctaC |
cytochrome C oxidase subunit II | 999 | 1000 ctx | cooccurence:627 coexpression:445 experimental:999 textmining:889 |
Rv3043c ctaD |
cytochrome C oxidase cytochrome 1 | 999 | 1000 | coexpression:663 experimental:999 textmining:809 |
Rv2876 |
transmembrane protein | 999 | 999 | experimental:999 |
Rv0432 sodC |
superoxide dismutase | 997 | 997 | experimental:997 |
Rv2782c pepR |
zinc protease | 997 | 996 | coexpression:710 experimental:928 database:844 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 987 | 986 | coexpression:812 experimental:922 |
Rv3149 nuoE |
NADH-quinone oxidoreductase subunit E | 987 | 984 | coexpression:803 experimental:922 |
Rv3148 nuoD |
NADH-quinone oxidoreductase subunit D | 985 | 981 | coexpression:808 experimental:904 |
Rv3147 nuoC |
NADH-quinone oxidoreductase subunit C | 979 | 976 | coexpression:746 experimental:908 |
Rv3151 nuoG |
NADH-quinone oxidoreductase subunit G | 978 | 975 | coexpression:683 experimental:923 |
Rv3150 nuoF |
NADH-quinone oxidoreductase subunit F | 977 | 974 | coexpression:671 experimental:925 |
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
- Rieske Fe-S subunit of cytochrome bcc; qcrCAB operon (Lupien 2020, PMID 31971990)
- QcrA mutations confer cross-resistance to QcrB inhibitors (stigmatellin pocket)
- Essential respiratory drug target without human homolog
- Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)
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_216711.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
COG0723 - Curated reference: UniProt P9WH23 (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 —
203 functional partner(s); context anchor
qcrC - Primary literature: Lupien A, Foo CS, Savina S, Vocat A, Piton J, Monakhova N, Benjak A, Lamprecht DA, Steyn AJC, Pethe K, Makarov VA, Cole ST (2020). New 2-Ethylthio-4-methylaminoquinazoline derivatives inhibiting two subunits of cytochrome bc1 in Mycobacterium tuberculosis PLoS Pathog 16(1):e1008270. doi:10.1371/journal.ppat.1008270 PMID:31971990
Ancestral MTBC0 protein sequence
>mtbc0_002331|Rv2195|qcrA MSRADDDAVGVPPTCGGRSDEEERRIVPGPNPQDGAKDGAKATAVPREPDEAALAAMSNQELLALGGKLDGVRIAYKEPRWPVEGTKAEKRAERSVAVWLLLGGVFGLALLLIFLFWPWEFKAADGESDFIYSLTTPLYGLTFGLSILSIAIGAVLYQKRFIPEEISIQERHDGASREIDRKTVVANLTDAFEGSTIRRRKLIGLSFGVGMGAFGLGTLVAFAGGLIKNPWKPVVPTAEGKKAVLWTSGWTPRYQGETIYLARATGTEDGPPFIKMRPEDMDAGGMETVFPWRESDGDGTTVESHHKLQEIAMGIRNPVMLIRIKPSDLGRVVKRKGQESFNFGEFFAFTKVCSHLGCPSSLYEQQSYRILCPCHQSQFDALHFAKPIFGPAARALAQLPITIDTDGYLVANGDFVEPVGPAFWERTTT