Rv2175c Family assigned · medium auto-curated

H37Rv Rv2175c · MTBC0 - · 146 aa · 2437446–2437886 (-) · RefSeq NP_216691.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)DNA-binding protein
MTBC0 PGAP re-annotation
Revised (this work)DNA-binding protein. Pfam: Rv2175c_wHTH (PF21531.4), Rv2175c_C (PF18367.7).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt O53509 SwissProt · reviewed · Evidence at protein level
UniProt nameDNA-binding protein Rv2175c
Curated functionBinds DNA at low salt concentrations.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptiontranscriptional regulator
Orthologous group2E0H9
Gene Ontology (38) GO:0003674, GO:0003676, GO:0003677, GO:0005488, GO:0006464, GO:0006468, GO:0006793, GO:0006796, GO:0006807, GO:0008150, GO:0008152, GO:0009987 +26 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 1.092 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 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
Rv2175c_wHTHPF21531.4 3.1e-2615–71 DNA-binding protein Rv2175c, wHTH domain
Rv2175c_CPF18367.7 3.8e-2878–145 Rv2175c C-terminal domain of unknown function

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

Closest characterised functional partner: pknL (serine/threonine-protein kinase PknL), high confidence from genomic context alone (score 788 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2788 sirR transcriptional repressor SirR 797 797 coexpression:797
Rv2176 pknL serine/threonine-protein kinase PknL 957 788 ctx neighborhood:787 textmining:808
Rv1773c transcriptional regulator 734 734 coexpression:734
Rv1151c cobB NAD-dependent protein deacylase 733 733 coexpression:733
Rv0603 hyp hypothetical protein 732 732 coexpression:732
Rv1725c hyp hypothetical protein 730 730 coexpression:730
Rv0880 HTH-type transcriptional regulator 730 730 coexpression:730
Rv1027c kdpE transcriptional regulator KdpE 729 729 coexpression:729
Rv3736 AraC/XylS family transcriptional regulator 729 729 coexpression:729
Rv0691c mftR mycofactocin biosynthesis transcriptional regulator MftR 726 716 coexpression:716
Rv3840 transcriptional regulator 716 716 coexpression:716
Rv3488 hyp hypothetical protein 615 615 coexpression:615
Rv3263 DNA methylase 615 615 coexpression:615
Rv2488c LuxR family transcriptional regulator 615 615 coexpression:615
Rv3328c sigJ ECF RNA polymerase sigma factor SigJ 580 580 coexpression:580

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): DNA-binding protein
  • Pfam (hmmscan --cut_ga): Rv2175c_wHTH PF21531.4 (E=3e-26), Rv2175c_C PF18367.7 (E=4e-28)
  • (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_216691.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Rv2175c_wHTH (PF21531.4), Rv2175c_C (PF18367.7)
  • 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 2E0H9
  • Curated reference: UniProt O53509 (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 — 36 functional partner(s); context anchor pknL
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2175c|
MPGRAPGSTLARVGSIPAGDDVLDPDEPTYDLPRVAELLGVPVSKVAQQLREGHLVAVRRAGGVVIPQVFFTNSGQVVKSLPGLLTILHDGGYRDTEIMRWLFTPDPSLTITRDGSRDAVSNARPVDALHAHQAREVVRRAQAMAY