Rv1258c Resolved · high auto-curated

H37Rv Rv1258c · MTBC0 mtbc0_001347 · 419 aa · 1414525–1415784 (-) · RefSeq NP_215774.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)multidrug-efflux transporter
MTBC0 PGAP re-annotationMFS transporter
Revised (this work)MFS transporter. Pfam: MFS_1 (PF07690.22), MFS_3 (PF05977.20).

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

Curated reference (UniProt)

UniProt P9WJX9 SwissProt · reviewed · Evidence at protein level
UniProt nameMultidrug efflux pump Tap
Curated functionEfflux pump that contributes to intrinsic antibiotic resistance. The pump uses the electrochemical gradient as a source of energy (By similarity). Confers resistance to rifampicin. Confers low-level resistance to tetracycline and to several aminoglycosides, including streptomycin, gentamicin, 2'-N-ethylnetilmicin and 6'-N-ethylnetilmicin.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
eggNOG descriptionMajor facilitator superfamily
Orthologous groupCOG2271
Gene Ontology (12) GO:0003674, GO:0005215, GO:0006810, GO:0008150, GO:0015562, GO:0022857, GO:0042221, GO:0046677, GO:0050896, GO:0051179, GO:0051234, GO:0055085

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) pseudogene candidate

pN/pS 0.968 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 5 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 24.23% of strains (35184) · clonal

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
MFS_1PF07690.22 2.5e-3112–363 Major Facilitator Superfamily
MFS_3PF05977.20 1.3e-1812–414 Transmembrane secretion effector

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

Closest characterised functional partner: Rv1257c (oxidoreductase), high confidence from genomic context alone (score 912 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1257c oxidoreductase 911 912 ctx neighborhood:881
Rv2416c eis enhanced intracellular survival protein 898 845 coexpression:845
Rv1260 oxidoreductase 774 766 ctx neighborhood:760
Rv0339c iniR transcriptional regulator 691 690 ctx cooccurence:688
Rv0538 membrane protein 639 626 ctx cooccurence:624
Rv1259 udgB uracil DNA glycosylase 595 595 ctx neighborhood:585
Rv0343 iniC iIsoniazid inductible protein IniC 595 595 ctx cooccurence:586
Rv1255c HTH-type transcriptional regulator 572 573 ctx neighborhood:570
Rv0342 iniA isoniazid inductible protein IniA 569 569 ctx cooccurence:568
Rv2164c hyp hypothetical protein 548 548 ctx cooccurence:547
Rv1256c cyp130 cytochrome P450 Cyp130 535 535 ctx neighborhood:527
Rv3835 hyp hypothetical protein 533 532 ctx cooccurence:532
Rv2843 hyp hypothetical protein 499 500 ctx cooccurence:495
Rv0097 oxidoreductase 487 488 ctx cooccurence:486
Rv1648 transmembrane protein 487 488 ctx cooccurence:486

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: multidrug-efflux transporter
  • MTBC0 PGAP product: MFS transporter
  • Pfam (hmmscan --cut_ga): MFS_1 PF07690.22 (E=3e-31), MFS_3 PF05977.20 (E=1e-18)
  • (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_215774.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MFS_1 (PF07690.22), MFS_3 (PF05977.20)
  • 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 COG2271
  • Curated reference: UniProt P9WJX9 (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 — 49 functional partner(s); context anchor Rv1257c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001347|Rv1258c|
MRNSNRGPAFLILFATLMAAAGDGVSIVAFPWLVLQREGSAGQASIVASATMLPLLFATLVAGTAVDYFGRRRVSMVADALSGAAVAGVPLVAWGYGGDAVNVLVLAVLAALAAAFGPAGMTARDSMLPEAAARAGWSLDRINGAYEAILNLAFIVGPAIGGLMIATVGGITTMWITATAFGLSILAIAALQLEGAGKPHHTSRPQGLVSGIAEGLRFVWNLRVLRTLGMIDLTVTALYLPMESVLFPKYFTDHQQPVQLGWALMAIAGGGLVGALGYAVLAIRVPRRVTMSTAVLTLGLASMVIAFLPPLPVIMVLCAVVGLVYGPIQPIYNYVIQTRAAQHLRGRVVGVMTSLAYAAGPLGLLLAGPLTDAAGLHATFLALALPIVCTGLVAIRLPALRELDLAPQADIDRPVGSAQ