cmr Family assigned · medium auto-curated

H37Rv Rv1675c · MTBC0 mtbc0_001783 · 244 aa · 1912256–1912990 (-) · RefSeq NP_216191.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)HTH-type transcriptional regulator Cmr
MTBC0 PGAP re-annotationHTH-type transcriptional regulator Cmr
Revised (this work)HTH-type transcriptional regulator Cmr. Pfam: cNMP_binding (PF00027.36), HTH_Crp_2 (PF13545.13).

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

Curated reference (UniProt)

UniProt P9WMH5 SwissProt · reviewed · Evidence at protein level
UniProt nameHTH-type transcriptional regulator Cmr
Curated functionPositively regulates the expression of at least groEL2. Cyclic AMP does not affect transcription in vitro.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptiontranscriptional
Orthologous groupCOG0664
KEGG orthology K21884
Gene Ontology (25) GO:0003674, GO:0003676, GO:0003677, GO:0005488, GO:0006355, GO:0008150, GO:0009889, GO:0010468, GO:0010556, GO:0019219, GO:0019222, GO:0031323 +13 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 1.448 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 4 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.17% of strains (248) · 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
cNMP_bindingPF00027.36 1.8e-1960–146 Cyclic nucleotide-binding domain
HTH_Crp_2PF13545.13 3.9e-11179–241 Crp-like helix-turn-helix domain

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

Closest characterised functional partner: Rv1674c (transcriptional regulator), high confidence from genomic context alone (score 903 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2488c LuxR family transcriptional regulator 935 932 coexpression:856 experimental:440
Rv1674c transcriptional regulator 918 903 ctx neighborhood:420 coexpression:839
Rv1359 transcriptional regulator 898 895 coexpression:833
Rv0602c tcrA two component DNA binding transcriptional regulator TcrA 877 870 coexpression:854
Rv1189 sigI ECF RNA polymerase sigma factor SigI 870 865 coexpression:845
Rv2282c LysR family HTH-type transcriptional regulator 869 862 coexpression:862
Rv3736 AraC/XylS family transcriptional regulator 865 860 coexpression:860
Rv1931c transcriptional regulator 861 860 coexpression:860
Rv3840 transcriptional regulator 860 860 coexpression:860
Rv1267c embR transcriptional regulator EmbR 860 860 coexpression:860
Rv0691c mftR mycofactocin biosynthesis transcriptional regulator MftR 860 860 coexpression:860
Rv3167c TetR family transcriptional regulator 859 859 coexpression:859
Rv1190 hyp hypothetical protein 851 851 coexpression:850
Rv0603 hyp hypothetical protein 850 850 coexpression:850
Rv3263 DNA methylase 848 848 coexpression:848

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 Cmr
  • MTBC0 PGAP product: HTH-type transcriptional regulator Cmr
  • Pfam (hmmscan --cut_ga): cNMP_binding PF00027.36 (E=2e-19), HTH_Crp_2 PF13545.13 (E=4e-11)
  • (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_216191.1)
  • Domains: Pfam-A via hmmscan --cut_ga — cNMP_binding (PF00027.36), HTH_Crp_2 (PF13545.13)
  • 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 COG0664
  • Curated reference: UniProt P9WMH5 (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 — 161 functional partner(s); context anchor Rv1674c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001783|Rv1675c|cmr
MADRSVRPLRHLVHAVTGGQPPSEAQVRQAAWIARCVGRGGSAPLHRDDVSALAETLQAKEFAPGAVVFHADQTADGVWIVRHGLIELAVGSRRRRAVVNILHPGDVDGDIPLLLEMPMVYTGRALTQATCLFLDRQAFERLLATHPAIARRWLSSVAQRVSTAQIRLMGMLGRPLPAQVAQLLLDEAIDARIELAQRTLAAMLGAQRPSINKILKEFERDRLITVGYAVIEITDQHGLRARAQ