smtB Family assigned · medium auto-curated

H37Rv Rv2358 · MTBC0 mtbc0_002510 · 135 aa · 2665439–2665846 (+) · RefSeq NP_216874.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)HTH-type transcriptional regulator SmtB
MTBC0 PGAP re-annotationmetalloregulator ArsR/SmtB family transcription factor
Revised (this work)Metalloregulator ArsR/SmtB family transcription factor. Pfam: HTH_20 (PF12840.14), HTH_5 (PF01022.27).

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

Curated reference (UniProt)

UniProt P9WMI5 SwissProt · reviewed · Evidence at protein level
UniProt nameHTH-type transcriptional repressor SmtB
Curated functionTranscriptional regulator involved in zinc homeostasis. Represses the expression of the smtB-zur operon in the absence of zinc. Could act as the metal sensor that controls the expression of zur in response to zinc availability.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namesmtB
eggNOG descriptiontranscriptional
Orthologous groupCOG0640
KEGG orthology K22298
Gene Ontology (32) GO:0001067, GO:0003674, GO:0003676, GO:0003677, GO:0005488, GO:0006355, GO:0008150, GO:0009889, GO:0010035, GO:0010038, GO:0010043, GO:0010468 +20 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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 1 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
HTH_20PF12840.14 2.4e-0655–103 Helix-turn-helix domain
HTH_5PF01022.27 5.0e-1558–102 Bacterial regulatory protein, arsR family

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

Closest characterised functional partner: zur (zinc uptake regulation protein), high confidence from genomic context alone (score 907 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2359 zur zinc uptake regulation protein 965 907 ctx neighborhood:882 textmining:639
Rv2642 ArsR family transcriptional regulator 565 566 ctx cooccurence:564
Rv2357c glyS glycine--tRNA ligase 565 565 ctx neighborhood:565
Rv1994c cmtR HTH-type transcriptional regulator CmtR 797 433 ctx cooccurence:429 textmining:658
Rv0081 HTH-type transcriptional regulator 664 432 ctx cooccurence:432 textmining:433
Rv1674c transcriptional regulator 501 309
Rv3270 ctpC manganese/zinc-exporting P-type ATPase 406 293
Rv1469 ctpD cobalt/nickel-exporting P-type ATPase 408 260
Rv3744 nmtR HTH-type transcriptional regulator NmtR 408 234
Rv2788 sirR transcriptional repressor SirR 455 226
Rv2711 ideR iron-dependent repressor and activator IdeR 413 209
Rv2641 cadI cadmium inducible protein CadI 658 84 textmining:643
Rv2025c cation efflux system protein 719 78 textmining:708

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: HTH-type transcriptional regulator SmtB
  • MTBC0 PGAP product: metalloregulator ArsR/SmtB family transcription factor
  • Pfam (hmmscan --cut_ga): HTH_20 PF12840.14 (E=2e-06), HTH_5 PF01022.27 (E=5e-15)
  • (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_216874.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_20 (PF12840.14), HTH_5 (PF01022.27)
  • 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 COG0640
  • Curated reference: UniProt P9WMI5 (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 — 13 functional partner(s); context anchor zur
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002510|Rv2358|smtB
MVTSPSTPTAAHEDVGADEVGGHQHPADRFAECPTFPAPPPREILDAAGELLRALAAPVRIAIVLQLRESQRCVHELVDALHVPQPLVSQHLKILKAAGVVTGERSGREVLYRLADHHLAHIVLDAVAHAGEDAI