Rv3295 Family assigned · medium auto-curated

H37Rv Rv3295 · MTBC0 mtbc0_003503 · 221 aa · 3698146–3698811 (+) · RefSeq NP_217812.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)TetR family 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 P96900 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable transcriptional regulatory protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptionTranscriptional regulator
Orthologous groupCOG1309

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 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 4.9e-1517–63 Bacterial regulatory proteins, tetR family

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

Closest characterised functional partner: lhr (ATP-dependent helicase), high confidence from genomic context alone (score 820 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3296 lhr ATP-dependent helicase 820 820 ctx neighborhood:818
Rv3297 nei endonuclease VIII 819 819 ctx neighborhood:818
Rv3294c hyp hypothetical protein 610 609 ctx neighborhood:605
Rv0210 hyp hypothetical protein 607 607 ctx cooccurence:607
Rv3293 pcd piperideine-6-carboxylic acid dehydrogenase 562 553 ctx neighborhood:544
Rv1182 papA3 acyltransferase papA3 492 493 ctx cooccurence:488
Rv3405c HTH-type transcriptional regulator 482 483 ctx cooccurence:478
Rv3291c lrpA transcriptional regulator LrpA 492 477 ctx neighborhood:469
Rv1978 hyp hypothetical protein 476 477 ctx cooccurence:415
Rv0169 mce1A Mce family protein Mce1A 464 464
Rv3824c papA1 acyltransferase 452 453 ctx cooccurence:451
Rv1006 hyp hypothetical protein 433 433
Rv3148 nuoD NADH-quinone oxidoreductase subunit D 422 423 coexpression:423
Rv2035 hyp hypothetical protein 417 417 ctx cooccurence:417
Rv3033 hyp hypothetical protein 410 411 ctx cooccurence:407

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: TetR family transcriptional regulator
  • MTBC0 PGAP product: TetR/AcrR family transcriptional regulator
  • Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (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_217812.1)
  • 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 P96900 (TrEMBL, unreviewed; 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 — 22 functional partner(s); context anchor lhr
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003503|Rv3295|
MATARRRLSPQDRRAELLALGAEVFGKRPYDEVRIDEIAERAGVSRALMYHYFPDKRAFFAAVVKDEADRLYAATNKAPAPGMTMFEEIRTGVLAYMAYHQQNPEAAWAAYVGLGRSDPVLLGIDDEAKNRQMEHIMSRIAEVVSGIDRDNTLDPEVERDLRVIIHGWLAFTFELCRQRIMDPSTDAERLADACAHALLDAISRLPQIPAELADAMATARM