cydA Family assigned · medium auto-curated

H37Rv Rv1623c · MTBC0 - · 485 aa · 1824430–1825887 (-) · RefSeq YP_177824.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cytochrome D ubiquinol oxidase subunit I CydA
MTBC0 PGAP re-annotation
Revised (this work)Cytochrome D ubiquinol oxidase subunit I CydA. Pfam: Cyt_bd_oxida_I (PF01654.23).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt L7N662 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable integral membrane cytochrome D ubiquinol oxidase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namecydA
eggNOG descriptionubiquinol oxidase (Subunit I)
Orthologous groupCOG1271
EC number EC 1.10.3.14
KEGG orthology K00425
KEGG pathways map00190, map01100, map02020
KEGG modules M00153

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 0.4 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 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_bd_oxida_IPF01654.23 1.1e-1566–460 Cytochrome bd terminal oxidase subunit I

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

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv1622c cydB cytochrome D ubiquinol oxidase subunit II CydB 999 1000 ctx neighborhood:841 cooccurence:774 coexpression:976 experimental:999 database:540 textmining:966
Rv1621c cydD cytochrome biosyntheisis ABC transporter ATP-binding protein/permease CydD 999 991 ctx neighborhood:731 cooccurence:746 coexpression:877 textmining:918
Rv1620c cydC cytochrome biosyntheisis ABC transporter ATP-binding protein/permease CydC 998 974 ctx neighborhood:756 cooccurence:497 coexpression:807 textmining:934
Rv1624c membrane protein 781 781 ctx neighborhood:768
Rv1625c cya adenylate cyclase 534 534 ctx neighborhood:527
Rv3601c panD aspartate 1-decarboxylase 494 446 coexpression:446
Rv0558 menH demethylmenaquinone methyltransferase 495 435 ctx cooccurence:421
Rv0389 purT phosphoribosylglycinamide formyltransferase PurT 411 389
Rv3239c transmembrane transport protein 417 335
Rv3728 membrane protein 414 332
Rv1854c ndh NADH dehydrogenase 505 266
Rv1161 narG nitrate reductase subunit alpha 545 160 textmining:481
Rv1736c narX nitrate reductase-like protein NarX 428 160
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 473 138 textmining:414
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 476 120 textmining:429

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): cytochrome D ubiquinol oxidase subunit I CydA
  • Pfam (hmmscan --cut_ga): Cyt_bd_oxida_I PF01654.23 (E=1e-156)
  • (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 YP_177824.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Cyt_bd_oxida_I (PF01654.23)
  • 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 COG1271
  • Curated reference: UniProt L7N662 (TrEMBL, unreviewed; 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 — 29 functional partner(s); context anchor cydB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1623c|cydA
MNVVDISRWQFGITTVYHFIFVPLTIGLAPLIAVMQTLWVVTDNPAWYRLTKFFGKLFLINFAIGVATGIVQEFQFGMNWSEYSRFVGDVFGAPLAMEGLAAFFFESTFIGLWIFGWNRLPRLVHLACIWIVAIAVNVSAFFIIAANSFMQHPVGAHYNPTTGRAELSSIVVLLTNNTAQAAFTHTVSGALLTAGTFVAAVSAWWLVRSSTTHADSDTQAMYRPATILGCWVALAATAGLLFTGDHQGKLMFQQQPMKMASAESLCDTQTDPNFSVLTVGRQNNCDSLTRVIEVPYVLPFLAEGRISGVTLQGIRDLQQEYQQRFGPNDYRPNLFVTYWSFRMMIGLMAIPVLFALIALWLTRGGQIPNQRWFSWLALLTMPAPFLANSAGWVFTEMGRQPWVVVPNPTGDQLVRLTVKAGVSDHSATVVATSLLMFTLVYAVLAVIWCWLLKRYIVEGPLEHDAEPAAHGAPRDDEVAPLSFAY