mftR Family assigned · medium auto-curated

H37Rv Rv0691c · MTBC0 mtbc0_000731 · 198 aa · 795156–795752 (-) · RefSeq NP_215205.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)mycofactocin biosynthesis transcriptional regulator MftR
MTBC0 PGAP re-annotationmycofactocin system transcriptional regulator
Revised (this work)Mycofactocin system transcriptional regulator. Pfam: TetR_N (PF00440.30), TetR_C_14 (PF17754.7).

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

Curated reference (UniProt)

UniProt P9WMB7 SwissProt · reviewed · Evidence at protein level
UniProt namePutative mycofactocin biosynthesis transcriptional regulator MftR
Curated functionMay regulate a gene cluster involved in mycofactocin expression. Mycofactocin is a conserved polypeptide that might serve as an electron carrier.

UniProt still lists this protein as Putative mycofactocin biosynthesis transcriptional regulator MftR; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namemftR
eggNOG descriptionTranscriptional regulator
Orthologous groupCOG1309
Gene Ontology (41) GO:0000976, GO:0001067, GO:0003674, GO:0003676, GO:0003677, GO:0003690, GO:0003700, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737 +29 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 0.218 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 2 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
TetR_NPF00440.30 2.4e-1319–60 Bacterial regulatory proteins, tetR family
TetR_C_14PF17754.7 5.8e-4185–193 MftR C-terminal domain

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

Closest characterised functional partner: Rv3830c (TetR family transcriptional regulator), high confidence from genomic context alone (score 908 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3830c TetR family transcriptional regulator 908 908 ctx cooccurence:420 coexpression:848
Rv0692 mftB mycofactocin system protein MftB 980 902 ctx neighborhood:603 cooccurence:762 textmining:812
Rv0693 mftC mycofactocin radical SAM maturase MftC 961 893 ctx neighborhood:602 cooccurence:741 textmining:658
Rv3183 higA3 transcriptional regulator 882 882 coexpression:850
Rv0690c hyp hypothetical protein 882 882 ctx neighborhood:882
Rv3167c TetR family transcriptional regulator 882 879 coexpression:857
Rv0212c nadR transcriptional regulator NadR 869 863 coexpression:863
Rv1151c cobB NAD-dependent protein deacylase 866 861 coexpression:861
Rv1267c embR transcriptional regulator EmbR 863 860 coexpression:860
Rv3736 AraC/XylS family transcriptional regulator 862 860 coexpression:860
Rv3263 DNA methylase 860 860 coexpression:860
Rv1675c cmr HTH-type transcriptional regulator Cmr 860 860 coexpression:860
Rv3840 transcriptional regulator 860 860 coexpression:860
Rv1359 transcriptional regulator 860 860 coexpression:860
Rv1674c transcriptional regulator 863 858 coexpression:858

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: mycofactocin biosynthesis transcriptional regulator MftR
  • MTBC0 PGAP product: mycofactocin system transcriptional regulator
  • Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=2e-13), TetR_C_14 PF17754.7 (E=6e-41)
  • (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_215205.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TetR_N (PF00440.30), TetR_C_14 (PF17754.7)
  • 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 COG1309
  • Curated reference: UniProt P9WMB7 (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 — 93 functional partner(s); context anchor Rv3830c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000731|Rv0691c|mftR
MPHESRVGRRRSTTPHHISDVAIELFAAHGFTDVSVDDIARAAGIARRTLFRYYASKNAIPWGDFSTHLAQLQGLLDNIDSRIQLRDALRAALLAFNTFDESETIRHRKRMRVILQTPELQAYSMTMYAGWREVIAKFVARRSGGKTTDFMPQTVAWTMLGVALSAYEHWLRDESVSLTEALGAAFDVVGAGLDRLNQ