Rv0330c Family assigned · medium auto-curated

H37Rv Rv0330c · MTBC0 mtbc0_000350 · 246 aa · 398670–399410 (-) · RefSeq NP_214844.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
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 O07254 TrEMBL · unreviewed · Predicted
UniProt nameHTH tetR-type domain-containing 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 0.945 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 5 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 7.9e-1213–59 Bacterial regulatory proteins, tetR family

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

Closest characterised functional partner: Rv2209 (integral membrane protein), high confidence from genomic context alone (score 764 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0329c hyp hypothetical protein 863 863 ctx neighborhood:846
Rv2209 integral membrane protein 764 764 ctx cooccurence:763
Rv0355c PPE8 PPE family protein PPE8 761 761 ctx cooccurence:761
Rv1004c membrane protein 760 761 ctx cooccurence:759
Rv3347c PPE55 PPE family protein PPE55 759 759 ctx cooccurence:759
Rv2490c PE_PGRS43 PE-PGRS family protein PE_PGRS43 759 759 ctx cooccurence:759
Rv3350c PPE56 PPE family protein PPE56 758 758 ctx cooccurence:758
Rv1452c PE_PGRS28 PE-PGRS family protein PE_PGRS28 756 756 ctx cooccurence:756
Rv2293c hyp hypothetical protein 755 756 ctx cooccurence:723
Rv0304c PPE5 PPE family protein PPE5 751 751 ctx cooccurence:751
Rv2337c hyp hypothetical protein 750 750 ctx cooccurence:750
Rv0494 HTH-type transcriptional regulator 755 749 coexpression:748
Rv1651c PE_PGRS30 PE-PGRS family protein PE_PGRS30 749 749 ctx cooccurence:749
Rv3343c PPE54 PPE family protein PPE54 748 749 ctx cooccurence:747
Rv1917c PPE34 PPE family protein PPE34 748 748 ctx cooccurence:745

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: helix-turn-helix domain-containing protein
  • Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=8e-12)
  • (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_214844.1)
  • 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 O07254 (TrEMBL, unreviewed; Predicted)
  • 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 — 120 functional partner(s); context anchor Rv2209
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000350|Rv0330c|
MARSIPADRFSAIVAASARVFIAHGYQRTQVQDVADALALAKGTLYGYAQGKAALFAAAVRYGDAQEALPLASELPVAAPVAGEIAAVVSARLAGEVTDMRLTHALRATLPPGATTGDARAELAGIVTDLYSRLARHRIALKLVDRCAPELPDLAEVWFGTGRNAQVDAVQAYLVHRERAGLLILPGPAPMVARTIVELCALWAVHLHFDPSPEPWSIVQPGVIDDDAIAATLAEFVVRATTASSD