Rv3173c Family assigned · medium auto-curated

H37Rv Rv3173c · MTBC0 mtbc0_003372 · 200 aa · 3566291–3566893 (-) · RefSeq NP_217689.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)TetR/Acr family transcriptional regulator
MTBC0 PGAP re-annotationhelix-turn-helix domain-containing protein
Revised (this work)Helix-turn-helix domain-containing protein. 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 O53323 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable transcriptional regulatory protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptionBacterial regulatory proteins, tetR family
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 0.355 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 2 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 8.0e-1722–67 Bacterial regulatory proteins, tetR family

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

Closest characterised functional partner: Rv3174 (short-chain dehydrogenase/reductase), medium confidence from genomic context alone (score 672 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3174 short-chain dehydrogenase/reductase 672 672 ctx neighborhood:598
Rv3172c hyp hypothetical protein 588 588 ctx neighborhood:583
Rv3175 amidase 538 539 ctx neighborhood:532
Rv1014c pth peptidyl-tRNA hydrolase 400 401
Rv0377 HTH-type transcriptional regulator 518 350
Rv0067c transcriptional regulator 519 336
Rv3833 AraC family transcriptional regulator 475 293
Rv2034 ArsR family HTH-type transcriptional repressor 438 275
Rv2640c ArsR family transcriptional regulator 569 227 textmining:466
Rv1110 lytB2 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 461 85 textmining:436
Rv2711 ideR iron-dependent repressor and activator IdeR 472 81 textmining:450
Rv1657 argR arginine repressor 436 63 textmining:423
Rv0465c ramB HTH-type transcriptional regulator 491 52 textmining:486
Rv0712 hyp hypothetical protein 523 50 textmining:519
Rv3096 hyp hypothetical protein 440 47 textmining:437

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/Acr family transcriptional regulator
  • MTBC0 PGAP product: helix-turn-helix domain-containing protein
  • Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=8e-17)
  • (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_217689.1)
  • 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 O53323 (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 — 18 functional partner(s); context anchor Rv3174
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003372|Rv3173c|
MPPVTRTTEPPRRGGRGARQRILKAAAELFYCEGINATGVELIANKASVSKRTLYQHFPSKSALVEEYLRGLRQAAGEADKMPKASNATPRERLLALFDRPNRGDGRMRGCPFHNAAVEAAGEMPGVERIVHSHKRDYIKGLARLAREAGAAHPRSLGNQLAVLFEGAAALSTSLDDAGPWAHARAAAEVLIDQATARPV