Rv0474 Family assigned · medium auto-curated

H37Rv Rv0474 · MTBC0 mtbc0_000499 · 140 aa · 568386–568808 (+) · RefSeq NP_214988.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)HTH-type transcriptional regulator
MTBC0 PGAP re-annotationhelix-turn-helix transcriptional regulator
Revised (this work)Helix-turn-helix transcriptional regulator. Pfam: HTH_31 (PF13560.13), HTH_3 (PF01381.29).

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

Curated reference (UniProt)

UniProt P9WMH9 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized HTH-type transcriptional regulator Rv0474

UniProt still lists this protein as Uncharacterized HTH-type transcriptional regulator Rv0474; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptiontranscriptional
Orthologous groupCOG1396
Gene Ontology (11) GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0030312, GO:0044424, GO:0044444, GO:0044464, GO:0071944

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 0.128 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 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
HTH_31PF13560.13 1.4e-1122–78 Helix-turn-helix domain
HTH_3PF01381.29 5.2e-1526–79 Helix-turn-helix

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

Closest characterised functional partner: hbhA (heparin binding hemagglutinin HbhA), high confidence from genomic context alone (score 720 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2185c TB16.3 hyp hypothetical protein 772 764 ctx cooccurence:763
Rv0854 hyp hypothetical protein 763 755 ctx cooccurence:754
Rv0857 hyp hypothetical protein 752 753 ctx cooccurence:749
Rv0475 hbhA heparin binding hemagglutinin HbhA 720 720 ctx neighborhood:711
Rv0476 transmembrane protein 709 709 ctx neighborhood:661
Rv0487 hyp hypothetical protein 687 688 ctx cooccurence:682
Rv3197 ABC transporter ATP-binding protein 677 678 ctx cooccurence:673
Rv0502 hyp hypothetical protein 676 677 ctx cooccurence:672
Rv0477 hyp hypothetical protein 671 668 ctx neighborhood:661
Rv3679 anion transporter ATPase 665 665 ctx cooccurence:663
Rv0478 deoC 2-deoxyribose-5-phosphate aldolase 655 655 ctx neighborhood:647
Rv0473 transmembrane protein 634 634 ctx neighborhood:632
Rv3916c hyp hypothetical protein 602 603 ctx cooccurence:597
Rv3680 anion transporter ATPase 546 547 ctx cooccurence:542
Rv3233c Rv3233c, (MTCY20B11.08c), len: 196 aa. Possible triacylglycerol synthase (See Daniel et al., 2004), similar to C-terminus of Q9RIU8|SCM11.13 506 507 ctx cooccurence:501

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: helix-turn-helix transcriptional regulator
  • Pfam (hmmscan --cut_ga): HTH_31 PF13560.13 (E=1e-11), HTH_3 PF01381.29 (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_214988.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_31 (PF13560.13), HTH_3 (PF01381.29)
  • 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 COG1396
  • Curated reference: UniProt P9WMH9 (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 — 25 functional partner(s); context anchor hbhA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000499|Rv0474|
MSSEEKLAAKVSTKASDVASDIGSFIRSQRETAHVSMRQLAERSGVSNPYLSQVERGLRKPSADVLSQIAKALRVSAEVLYVRAGILEPSETSQVRDAIITDTAITERQKQILLDIYASFTHQNEATREECPSDPTPTDD