clgR Family assigned · medium auto-curated

H37Rv Rv2745c · MTBC0 mtbc0_002922 · 112 aa · 3080608–3080946 (-) · RefSeq NP_217261.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transcriptional regulator ClgR
MTBC0 PGAP re-annotationtranscriptional regulator ClgR
Revised (this work)Transcriptional regulator ClgR. Pfam: HTH_31 (PF13560.13), HTH_3 (PF01381.29), HTH_25 (PF13413.13).

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

Curated reference (UniProt)

UniProt P9WMH7 SwissProt · reviewed · Evidence at protein level
UniProt nameTranscriptional regulator ClgR
Curated functionKey stress-response regulator that plays an important role in multiple regulatory networks in response to different stress conditions. Involved in preservation of envelope integrity and tolerance to surface stress. Essential for macrophage infection and facilitates intracellular growth of M.tuberculosis. Controls the expression of several protease and chaperone systems, including clpP1, clpP2, clpC1, ptrB, Rv1043c, acr2, clpB, Rv3269 and the clgR-pspA-rv2743c-rv2742c region. Also plays an essential role in RecA/LexA-independent DNA repair mechanism by inducing expression of DNA repair genes in.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred nameclgR
eggNOG descriptiontranscriptional
Orthologous groupCOG1396
Gene Ontology (125) GO:0002682, GO:0002683, GO:0003674, GO:0003676, GO:0003677, GO:0005488, GO:0006109, GO:0006355, GO:0006950, GO:0006979, GO:0008150, GO:0009266 +113 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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.15% of strains (215) · clonal

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 2.6e-0910–63 Helix-turn-helix domain
HTH_3PF01381.29 1.2e-1013–65 Helix-turn-helix
HTH_25PF13413.13 2.2e-0513–45 Helix-turn-helix domain

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

Closest characterised functional partner: rbpA (RNA polymerase-binding protein RbpA), high confidence from genomic context alone (score 716 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2744c 35kd_ag hyp hypothetical protein 973 925 ctx neighborhood:759 coexpression:703 textmining:665
Rv2710 sigB RNA polymerase sigma factor SigB 809 717 coexpression:716
Rv2050 rbpA RNA polymerase-binding protein RbpA 765 716 ctx cooccurence:643
Rv2699c hyp hypothetical protein 714 715 ctx cooccurence:711
Rv2746c pgsA3 CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase 658 658 ctx neighborhood:656
Rv2743c hyp hypothetical protein 950 635 ctx neighborhood:616 textmining:870
Rv2708c hyp hypothetical protein 634 635 ctx cooccurence:627
Rv1830 HTH-type transcriptional regulator 644 630 ctx cooccurence:623
Rv2413c hyp hypothetical protein 613 613 ctx cooccurence:612
Rv2146c transmembrane protein 599 599 ctx cooccurence:595
Rv3195 hyp hypothetical protein 592 592 ctx cooccurence:592
Rv2256c hyp hypothetical protein 586 586 ctx cooccurence:569
Rv1423 whiA transcriptional regulator WhiA 607 584 ctx cooccurence:580
Rv2901c hyp hypothetical protein 571 571 ctx cooccurence:565
Rv3260c whiB2 transcriptional regulator WhiB2 568 568 ctx cooccurence:562

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: transcriptional regulator ClgR
  • MTBC0 PGAP product: transcriptional regulator ClgR
  • Pfam (hmmscan --cut_ga): HTH_31 PF13560.13 (E=3e-09), HTH_3 PF01381.29 (E=1e-10), HTH_25 PF13413.13 (E=2e-05)
  • (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_217261.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_31 (PF13560.13), HTH_3 (PF01381.29), HTH_25 (PF13413.13)
  • 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 P9WMH7 (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 — 48 functional partner(s); context anchor rbpA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002922|Rv2745c|clgR
MAALVREVVGDVLRGARMSQGRTLREVSDSARVSLGYLSEIERGRKEPSSELLSAICTALQLPLSVVLIDAGERMARQERLARATPAGRATGATIDASTKVVIAPVVSLAVA