Rv1456c Resolved · high auto-curated

H37Rv Rv1456c · MTBC0 mtbc0_001558 · 310 aa · 1651245–1652177 (-) · RefSeq NP_215972.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)antibiotic ABC transporter permease
MTBC0 PGAP re-annotationheme A synthase
Revised (this work)Heme A synthase. Pfam: COX15-CtaA (PF02628.21).

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

Curated reference (UniProt)

UniProt O53148 TrEMBL · unreviewed · Predicted
UniProt nameProbable unidentified antibiotic-transport integral membrane ABC transporter

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred namectaA
eggNOG descriptioncytochrome oxidase assembly
Orthologous groupCOG1612
KEGG orthology K02259
KEGG pathways map00190, map00860, map01100, map01110, map02020, map04714
KEGG modules M00154

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) 1 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
COX15-CtaAPF02628.21 4.0e-1017–291 Cytochrome oxidase assembly protein

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

Closest characterised functional partner: ctaB (protoheme IX farnesyltransferase), high confidence from genomic context alone (score 990 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1451 ctaB protoheme IX farnesyltransferase 996 990 ctx cooccurence:440 coexpression:664 experimental:471 database:900 textmining:646
Rv1457c antibiotic ABC transporter permease 998 989 ctx neighborhood:767 cooccurence:568 database:900 textmining:870
Rv1458c antibiotic ABC transporter ATP-binding protein 996 978 ctx neighborhood:746 database:900 textmining:865
Rv2235 transmembrane protein 927 905 ctx cooccurence:495 coexpression:674 experimental:425
Rv1459c mptB alpha-(1->6)-mannopyranosyltransferase 957 784 ctx neighborhood:699 textmining:810
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 828 762 ctx cooccurence:703
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 828 756 ctx cooccurence:728
Rv2196 qcrB ubiquinol-cytochrome C reductase cytochrome subunit B 748 710 ctx cooccurence:697
Rv1460 sufR transcriptional regulator 662 662 ctx neighborhood:662
Rv2199c ctaF cytochrome c oxidase polypeptide 4 658 658 ctx cooccurence:656
Rv1462 sufD hyp hypothetical protein 601 601 ctx neighborhood:600
Rv1463 sufC ABC transporter ATP-binding protein 601 601 ctx neighborhood:600
Rv2200c ctaC cytochrome C oxidase subunit II 693 600 ctx cooccurence:494
Rv1464 csd cysteine desulfurase 587 587 ctx neighborhood:586
Rv1466 hyp hypothetical protein 586 586 ctx neighborhood:585

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: antibiotic ABC transporter permease
  • MTBC0 PGAP product: heme A synthase
  • Pfam (hmmscan --cut_ga): COX15-CtaA PF02628.21 (E=4e-10)
  • (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_215972.1)
  • Domains: Pfam-A via hmmscan --cut_ga — COX15-CtaA (PF02628.21)
  • 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 COG1612
  • Curated reference: UniProt O53148 (TrEMBL, unreviewed; Predicted)
  • 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 — 41 functional partner(s); context anchor ctaB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001558|Rv1456c|
MPYDRAVSPSLRVQRVIAAIVILTQGGIAVTGAIVRVTASGLGCPTWPQCFPGSFTPVVVAEVPRVHQAVEFGNRMVTFAVVIAAALAVLVVTRARRRTEVLAYAWLMPVSTVVQAMIGGITVRTGLLWWTVAIHLLASMTMVWLAVLLYVKIGQPDDGVVHELVVSPLRALTALSALNLAAVLVTGTLVTAAGPHAGDRSPSRTVPRLKVEITTLVHMHSSLLVAYLALLIGLGFGLLAVGATRAILVRLAVLLALVATQAAVGTTQYFTGVPAALVAIHVAGAAAVTAATAALWASMGERAQPQPLQR