MTBC Gene Atlas

Rv2370c Family assigned · medium auto-curated

H37Rv Rv2370c · MTBC0 mtbc0_002522 · 437 aa · 2674438–2675751 (-) · RefSeq NP_216886.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationPucR family transcriptional regulator
Revised (this work)PucR family transcriptional regulator. Pfam: GGDEF_2 (PF17853.7), HTH_30 (PF13556.13).

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

Curated reference (UniProt)

UniProt O05828 TrEMBL · unreviewed · Inferred from homology
UniProt nameTranscriptional activator protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
T Signal transduction mechanisms
eggNOG descriptiontranscriptional
Orthologous groupCOG2508

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 1.236 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 6 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.25% of strains (367) · 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
GGDEF_2PF17853.7 6.2e-16187–295 GGDEF-like domain
HTH_30PF13556.13 2.2e-11342–395 PucR C-terminal helix-turn-helix domain

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

Closest characterised functional partner: Rv2366c (transmembrane protein), high confidence from genomic context alone (score 773 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2365c hyp hypothetical protein 800 799 ctx neighborhood:773
Rv2369c hyp hypothetical protein 779 779 ctx neighborhood:773
Rv2366c transmembrane protein 774 773 ctx neighborhood:773
Rv2368c phoH1 phosphate starvation-inducible protein PhoH 774 773 ctx neighborhood:773
Rv2367c ybeY endoribonuclease 774 773 ctx neighborhood:773
Rv2364c era GTPase Era 568 568 ctx neighborhood:568
Rv2371 PE_PGRS40 PE-PGRS family protein PE_PGRS40 533 532 ctx neighborhood:532
Rv2098c PE_PGRS36 PE-PGRS family protein PE_PGRS36; Rv2098c, (MTCY49.38c), len: 434 aa. PE_PGRS36,Member of the Mycobacterium tuberculosis PE family, PGRS sub 473 473 ctx cooccurence:467
Rv3726 dehydrogenase 438 438 ctx cooccurence:433
Rv2945c lppX lipoprotein LppX 406 406 ctx cooccurence:406
Rv3680 anion transporter ATPase 885 154 textmining:870
Rv3696c glpK glycerol kinase 662 47 textmining:660
Rv3679 anion transporter ATPase 870 45 textmining:870
Rv1509 hyp hypothetical protein 870 44 textmining:870

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: hypothetical protein
  • MTBC0 PGAP product: PucR family transcriptional regulator
  • Pfam (hmmscan --cut_ga): GGDEF_2 PF17853.7 (E=6e-16), HTH_30 PF13556.13 (E=2e-11)
  • (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_216886.1)
  • Domains: Pfam-A via hmmscan --cut_ga — GGDEF_2 (PF17853.7), HTH_30 (PF13556.13)
  • 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 COG2508
  • Curated reference: UniProt O05828 (TrEMBL, unreviewed; Inferred from homology)
  • 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 — 14 functional partner(s); context anchor Rv2366c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002522|Rv2370c|
MVLPKPTPRGRELIRQAAKVALHPTPEWLDELDRATLAAHPSIAADPALATVVSRANRSHLIHFATANLRKPGQPVPANLGPDPLRMARDLVRRGLDASALDVYRVGQNVAWQRWTEIAFGLTTDPQELHELLTLPFRSASEFIDATLAGLAAQMQLEYDELTRDVHAEHRRIVELILDGAPISRQSAEAKLGYPLDRSHTAAIIWYDDPDDNQNHLDHTARAFGRALGCPQPLIAVASAATRWVWVSDAATLDTDRIHQVLDHAPHARIAVGTTARGIDGFRRSHRDALATQRMLARLRSQQRLAFFADIHMIAVLTENPDSAADFITSTLGDLESASPQLLTTVLTYINEQCNASRAAHVLHTHRNTLLRRLETAQRLLPRPLDHTIIQVAVAISALQWRGSQTSDPVETPVEGITSPPPESLGRRRSRLAQLER