devR Resolved · high auto-curated

H37Rv Rv3133c · MTBC0 mtbc0_003330 · 217 aa · 3520627–3521280 (-) · RefSeq NP_217649.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)two component transcriptional regulator DevR
MTBC0 PGAP re-annotationtwo-component system response regulator DevR
Revised (this work)Two-component system response regulator DevR. Pfam: Response_reg (PF00072.31), GerE (PF00196.26).

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

Curated reference (UniProt)

UniProt P9WMF9 SwissProt · reviewed · Evidence at protein level
UniProt nameDNA-binding transcriptional activator DevR/DosR
Curated functionMember of the two-component regulatory system DevR/DevS (also called DosR/DosS) involved in onset of the dormancy response. Regulates an approximately 48-member regulon. When phosphorylated binds and activates the promoter of DevR regulon genes in response to hypoxia. The presence of target DNA increases stability of phospho-DevR in vitro. Activates its own transcription under hypoxic but not aerobic conditions, probably binds as a dimer to tandem binding sites within the devR and hspX promoters. Accepts a phosphate group from DevS (DosS) and from DosT. Does not regulate transcription of dosT.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namedevR
eggNOG descriptionRegulator
Orthologous groupCOG2197
KEGG orthology K07695
KEGG pathways map02020
KEGG modules M00482
Gene Ontology (90) GO:0001666, GO:0003674, GO:0003676, GO:0003677, GO:0003700, GO:0005488, GO:0005575, GO:0005576, GO:0005615, GO:0005618, GO:0005622, GO:0005623 +78 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 0.362 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 1 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
Response_regPF00072.31 1.9e-234–115 Response regulator receiver domain
GerEPF00196.26 5.8e-18149–204 Bacterial regulatory proteins, luxR family

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

Closest characterised functional partner: devS (two component sensor histidine kinase DevS), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3132c devS two component sensor histidine kinase DevS 999 1000 ctx neighborhood:882 cooccurence:769 coexpression:895 experimental:544 database:900 textmining:963
Rv3134c universal stress protein 991 954 ctx neighborhood:744 coexpression:805 textmining:818
Rv2027c dosT two component sensor histidine kinase DosT 993 883 ctx cooccurence:767 textmining:946
Rv0845 narS sensor histidine kinase NarS 884 853 ctx cooccurence:726
Rv2005c universal stress protein 866 849 coexpression:848
Rv0569 hyp hypothetical protein 900 832 coexpression:810 textmining:433
Rv1736c narX nitrate reductase-like protein NarX 905 805 coexpression:799 textmining:535
Rv2029c pfkB 6-phosphofructokinase PfkB 901 805 coexpression:734 textmining:515
Rv2623 TB31.7 universal stress protein 932 802 coexpression:772 textmining:671
Rv1997 ctpF cation transporter ATPase F 869 779 coexpression:762 textmining:435
Rv2625c rip3 zinc metalloprotease Rip3 880 765 coexpression:765 textmining:512
Rv2028c universal stress protein 910 752 coexpression:703 textmining:652
Rv2004c hyp hypothetical protein 834 733 coexpression:732 textmining:404
Rv2629 hyp hypothetical protein 794 732 coexpression:732
Rv0195 two component transcriptional regulator 780 704 ctx cooccurence:703

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: two component transcriptional regulator DevR
  • MTBC0 PGAP product: two-component system response regulator DevR
  • Pfam (hmmscan --cut_ga): Response_reg PF00072.31 (E=2e-23), GerE PF00196.26 (E=6e-18)
  • (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_217649.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Response_reg (PF00072.31), GerE (PF00196.26)
  • 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 COG2197
  • Curated reference: UniProt P9WMF9 (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 — 77 functional partner(s); context anchor devS
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003330|Rv3133c|devR
MVKVFLVDDHEVVRRGLVDLLGADPELDVVGEAGSVAEAMARVPAARPDVAVLDVRLPDGNGIELCRDLLSRMPDLRCLILTSYTSDEAMLDAILAGASGYVVKDIKGMELARAVKDVGAGRSLLDNRAAAALMAKLRGAAEKQDPLSGLTDQERTLLGLLSEGLTNKQIADRMFLAEKTVKNYVSRLLAKLGMERRTQAAVFATELKRSRPPGDGP