Rv3095 Family assigned · medium auto-curated

H37Rv Rv3095 · MTBC0 mtbc0_003289 · 158 aa · 3485337–3485813 (+) · RefSeq NP_217611.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)HTH-type transcriptional regulator
MTBC0 PGAP re-annotationhelix-turn-helix domain-containing protein
Revised (this work)Helix-turn-helix domain-containing protein. Pfam: HxlR (PF01638.24), 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 P9WMG3 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized HTH-type transcriptional regulator Rv3095

UniProt still lists this protein as Uncharacterized HTH-type transcriptional regulator Rv3095; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptionHxlR-like helix-turn-helix
Orthologous groupCOG1733

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 0.362 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 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
HxlRPF01638.24 5.1e-2821–108 HxlR-like helix-turn-helix
HTH_5PF01022.27 9.5e-0529–67 Bacterial regulatory protein, arsR family

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

Closest characterised functional partner: Rv3093c (oxidoreductase), high confidence from genomic context alone (score 899 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3093c oxidoreductase 898 899 ctx neighborhood:636 coexpression:733
Rv3094c hyp hypothetical protein 984 886 ctx neighborhood:783 coexpression:494 textmining:870
Rv3092c integral membrane protein 877 877 ctx neighborhood:507 coexpression:761
Rv3096 hyp hypothetical protein 670 671 ctx neighborhood:652
Rv2405 hyp hypothetical protein 555 555 coexpression:554
Rv1931c transcriptional regulator 468 468 ctx cooccurence:465
Rv0659c mazF2 toxin MazF2 421 422 coexpression:422
Rv0456A mazF1 toxin MazF1 416 417 coexpression:417
Rv2801c mazF9 mRNA interferase MazF9 416 417 coexpression:417
Rv1102c mazF3 mRNA interferase MazF3 416 417 coexpression:417
Rv1942c mazF5 toxin MazF5 414 415 coexpression:415
Rv1991c mazF6 mRNA interferase MazF6 414 415 coexpression:415
Rv1495 mazF4 mRNA interferase MazF4 412 413 coexpression:413
Rv2063A mazF7 mRNA interferase MazF7 412 413 coexpression:413
Rv3098A PemK-like protein 412 413 coexpression:413

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
  • MTBC0 PGAP product: helix-turn-helix domain-containing protein
  • Pfam (hmmscan --cut_ga): HxlR PF01638.24 (E=5e-28), HTH_5 PF01022.27 (E=1e-04)
  • (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_217611.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HxlR (PF01638.24), 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 COG1733
  • Curated reference: UniProt P9WMG3 (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 — 34 functional partner(s); context anchor Rv3093c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003289|Rv3095|
MAVSDLSHRFEGESVGRALELVGERWTLLILREAFFGVRRFGQLARNLGIPRPTLSSRLRMLVEVGLFDRVPYSSDPERHEYRLTEAGRDLFAAIVVLMQWGDEYLPRPEGPPIKLRHHTCGEHADPRLICTHCGEEITARNVTPEPGPGFKAKLASS