Rv2250c Family assigned · medium auto-curated

H37Rv Rv2250c · MTBC0 mtbc0_002392 · 189 aa · 2550946–2551515 (-) · RefSeq NP_216766.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)HTH-type transcriptional regulator
MTBC0 PGAP re-annotationTetR/AcrR family transcriptional regulator
Revised (this work)TetR/AcrR family transcriptional regulator. Pfam: TetR_N (PF00440.30).

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

Curated reference (UniProt)

UniProt P9WMC5 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized HTH-type transcriptional regulator Rv2250c

UniProt still lists this protein as Uncharacterized HTH-type transcriptional regulator Rv2250c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
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 0.363 · 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
TetR_NPF00440.30 1.0e-1115–58 Bacterial regulatory proteins, tetR family

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

Closest characterised functional partner: glpD1 (glycerol-3-phosphate dehydrogenase), high confidence from genomic context alone (score 930 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2249c glpD1 glycerol-3-phosphate dehydrogenase 930 930 ctx neighborhood:882
Rv2250A Possible flavoprotein; Rv2250A, len: 139 aa. Conserved hypothetical protein, possibly flavoprotein. Similar to N-terminus of SCF91.28c|AL132 890 890 ctx neighborhood:600 cooccurence:727
Rv2252 dagK diacylglycerol kinase 798 799 ctx neighborhood:743
Rv2251 flavoprotein 794 794 ctx neighborhood:600 cooccurence:480
Rv0330c hyp hypothetical protein 733 733 coexpression:733
Rv2253 hyp hypothetical protein 596 597 ctx neighborhood:594
Rv3830c TetR family transcriptional regulator 491 476 ctx cooccurence:450
Rv0767c HTH-type transcriptional regulator 437 438
Rv0275c transcriptional regulator 587 416 ctx cooccurence:408
Rv1776c transcriptional regulator 410 410
Rv2991 hyp hypothetical protein 405 405
Rv0494 HTH-type transcriptional regulator 421 404 coexpression:403
Rv1014c pth peptidyl-tRNA hydrolase 400 401
Rv0825c hyp hypothetical protein 400 400 ctx cooccurence:400
Rv3066 DeoR family transcriptional regulator 486 378

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: TetR/AcrR family transcriptional regulator
  • Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=1e-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_216766.2)
  • Domains: Pfam-A via hmmscan --cut_ga — TetR_N (PF00440.30)
  • 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 P9WMC5 (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 — 20 functional partner(s); context anchor glpD1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002392|Rv2250c|
MLSMSNDRADTGGRILRAAASCVVDYGVDRVTLAEIARRAGVSRPTVYRRWPDTRSIMASMLTSHIADVLREVPLDGDDREALVKQIVAVADRLRGDDLIMSVMHSELARVYITERLGTSQQVLIEGLAARLTVAQRSGSVRSGDARRLATMVLLIAQSTIQSADIVDSILDSAALATELTHALNGYLC