Rv0324 Family assigned · medium auto-curated

H37Rv Rv0324 · MTBC0 mtbc0_000345 · 226 aa · 394675–395355 (+) · RefSeq NP_214838.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transcriptional regulator
MTBC0 PGAP re-annotationmetalloregulator ArsR/SmtB family transcription factor
Revised (this work)Metalloregulator ArsR/SmtB family transcription factor. Pfam: HTH_5 (PF01022.27), HTH_IclR (PF09339.17), Rhodanese (PF00581.26).

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

Curated reference (UniProt)

UniProt O08446 SwissProt · reviewed · Evidence at protein level
UniProt nameHTH-type transcriptional regulator Rv0324
Curated functionPart of a regulatory network that coordinates tolerance to the antitubercular drug bedaquiline.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptionRhodanese-like domain
Orthologous groupCOG0607

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, 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
HTH_5PF01022.27 2.3e-0626–69 Bacterial regulatory protein, arsR family
HTH_IclRPF09339.17 1.9e-0527–70 IclR helix-turn-helix domain
RhodanesePF00581.26 5.6e-20121–210 Rhodanese-like domain

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

Closest characterised functional partner: arsC (arsenic-transport integral membrane protein ArsC), high confidence from genomic context alone (score 729 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0326 hyp hypothetical protein 823 816 ctx neighborhood:775
Rv0325 hyp hypothetical protein 799 791 ctx neighborhood:786
Rv2643 arsC arsenic-transport integral membrane protein ArsC 805 729 ctx neighborhood:479
Rv3846 sodA superoxide dismutase 660 622 experimental:573
Rv0323c hyp hypothetical protein 601 601 ctx neighborhood:596
Rv2367c ybeY endoribonuclease 585 586 experimental:573
Rv3456c rplQ 50S ribosomal protein L17 531 531 experimental:466
Rv3443c rplM 50S ribosomal protein L13 515 516 experimental:453
Rv0710 rpsQ 30S ribosomal protein S17 506 506 experimental:476
Rv2442c rplU 50S ribosomal protein L21 499 499 experimental:466
Rv0640 rplK 50S ribosomal protein L11 491 492 experimental:461
Rv0715 rplX 50S ribosomal protein L24 506 491 experimental:453
Rv0701 rplC 50S ribosomal protein L3 490 490 experimental:450
Rv0723 rplO 50S ribosomal protein L15 480 481 experimental:453
Rv2234 ptpA protein-tyrosine-phosphatase 495 448

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: transcriptional regulator
  • MTBC0 PGAP product: metalloregulator ArsR/SmtB family transcription factor
  • Pfam (hmmscan --cut_ga): HTH_5 PF01022.27 (E=2e-06), HTH_IclR PF09339.17 (E=2e-05), Rhodanese PF00581.26 (E=6e-20)
  • (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_214838.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_5 (PF01022.27), HTH_IclR (PF09339.17), Rhodanese (PF00581.26)
  • 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 COG0607
  • Curated reference: UniProt O08446 (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 — 40 functional partner(s); context anchor arsC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000345|Rv0324|
MAGQSDRKAALLDQVARVGKALANGRRLQILDLLAQGERAVEAIATATGMNLTTASANLQALKSGGLVEARREGTRQYYRIAGEDVARLFALVQVVADEHLADVAVAAADVLGSPEDAITRAELLRRREAGEVTLVDVRPHEEYQAGHIPGAINIPIAELADRLAELAGDRDIVAYCRGAYCVMAPDAVRIARDAGREVKRLDDGMLEWRLAGLPVDEGAPVGHGD