Rv1218c Family assigned · medium auto-curated

H37Rv Rv1218c · MTBC0 mtbc0_001306 · 311 aa · 1370240–1371175 (-) · RefSeq NP_215734.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)tetronasin ABC transporter ATP-binding protein
MTBC0 PGAP re-annotationmultidrug efflux ABC transporter ATP-binding protein
Revised (this work)Multidrug efflux ABC transporter ATP-binding protein. Pfam: ABC_tran (PF00005.34), AAA_21 (PF13304.13), DrrA1-3_C (PF13732.13).

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

Curated reference (UniProt)

UniProt O86311 SwissProt · reviewed · Evidence at protein level
UniProt nameMultidrug efflux system ATP-binding protein Rv1218c
EC (curated) EC 7.6.2.-
Curated functionProbably part of the ABC transporter complex Rv1217c-Rv1218c involved in the resistance to a wide range of structurally unrelated drugs. Could be involved in the efflux of substrates belonging to the diverse chemical classes of novobiocins, biarylpiperazines, pyridines, bisanilinopyrimidines, pyrroles and, to a smaller extent, pyrazolones. Probably responsible for energy coupling to the transport system (Probable).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category V Defense mechanisms
eggNOG descriptionABC transporter
Orthologous groupCOG1131
KEGG orthology K01990
KEGG modules M00254

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 0.691 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 4 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
ABC_tranPF00005.34 6.5e-2825–163 ABC transporter
AAA_21PF13304.13 1.1e-07133–194 AAA domain, putative AbiEii toxin, Type IV TA system
DrrA1-3_CPF13732.13 3.7e-07217–295 ATP-binding protein DrrA1-3-like, C-terminal domain

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

Closest characterised functional partner: Rv1217c (tetronasin ABC transporter integral membrane protein), high confidence from genomic context alone (score 995 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1217c tetronasin ABC transporter integral membrane protein 999 995 ctx neighborhood:881 cooccurence:774 coexpression:830 textmining:875
Rv1219c raaS transcriptional regulator 981 908 ctx neighborhood:882 textmining:803
Rv2397c cysA1 sulfate ABC transporter ATP-binding protein CysA 900 900 ctx fusion:900
Rv1216c integral membrane protein 901 831 ctx neighborhood:801 textmining:438
Rv1686c ABC transporter permease 917 745 ctx cooccurence:564 coexpression:408 textmining:689
Rv1215c hyp hypothetical protein 900 726 ctx neighborhood:725 textmining:650
Rv1272c drug ABC transporter ATP-binding protein 800 706 database:536
Rv2938 drrC daunorubicin ABC transporter permease DrrC 801 691 ctx cooccurence:473 coexpression:405
Rv1273c drug ABC transporter ATP-binding protein 755 690 database:536
Rv1348 irtA iron ABC transporter ATP-binding protein/permease IrtA 638 615 database:536
Rv1349 irtB iron ABC transporter ATP-binding protein/permease IrtB 631 615 database:536
Rv0194 multidrug ABC transporter ATPase/permease 657 612 database:536
Rv2937 drrB daunorubicin ABC transporter permease DrrB 819 575 coexpression:405 textmining:593
Rv1311 atpC ATP synthase subunit epsilon 549 550 experimental:444
Rv2832c ugpC sn-glycerol-3-phosphate ABC transporter ATP-binding protein UgpC 533 533 ctx fusion:532

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: tetronasin ABC transporter ATP-binding protein
  • MTBC0 PGAP product: multidrug efflux ABC transporter ATP-binding protein
  • Pfam (hmmscan --cut_ga): ABC_tran PF00005.34 (E=7e-28), AAA_21 PF13304.13 (E=1e-07), DrrA1-3_C PF13732.13 (E=4e-07)
  • (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_215734.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ABC_tran (PF00005.34), AAA_21 (PF13304.13), DrrA1-3_C (PF13732.13)
  • 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 COG1131
  • Curated reference: UniProt O86311 (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 — 47 functional partner(s); context anchor Rv1217c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001306|Rv1218c|
MSADNHQVPIEIRGLTKHFGSVRALDGLDLTVREGEVHGFLGPNGAGKSTTLRILLGLVKADGGSVRLLGGDPWTDAVDLHRHIAYVPGDVTLWPSLTGGETIDLLARMRGGIDNARRAELIERFGLDPTKKARTYSKGNRQKVSLISALSSHATLLLLDEPSSGLDPLMENVFQQCIGEARQRGVTVLLSSHILAETEALCEKVTIIRAGKTVESGSLDALRHLSRTSIKAEMIGDPGDLSRIKGVEDISIEGTTVRAQVDSESLRELIQVLGHAGVRSLVSQPPTLEELFLRHYSLGPEVAAEQQVATP