devS Resolved · high auto-curated

H37Rv Rv3132c · MTBC0 mtbc0_003329 · 578 aa · 3518894–3520630 (-) · RefSeq NP_217648.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)two component sensor histidine kinase DevS
MTBC0 PGAP re-annotationtwo-component system sensor histidine kinase DevS
Revised (this work)Two-component system sensor histidine kinase DevS. Pfam: GAF_2 (PF13185.13), GAF (PF01590.33), GAF_3 (PF13492.13), HisKA_3 (PF07730.20), HATPase_c (PF02518.32).

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

Curated reference (UniProt)

UniProt P9WGK3 SwissProt · reviewed · Evidence at protein level
UniProt nameOxygen sensor histidine kinase response regulator DevS/DosS
EC (curated) EC 2.7.13.3
Curated functionMember of the two-component regulatory system DevR/DevS (DosR/DosS) involved in onset of the dormancy response. Regulates an approximately 48-member regulon. Required for full induction of the DevR (DosR) regulon; acts later than DosT to positively regulate expression of the DevR regulon during adaptation to anaerobiosis. Characterized as an oxygen sensor; O(2) acts as a switch, with O(2)-bound Fe(2+) protein inactive in autophosphorylation. Has also been suggested to act as a redox sensor, or perhaps as a dual oxygen/redox sensor. Autophosphorylates under anaerobic but not aerobic conditions,.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namedevS
eggNOG descriptionthe two-component regulatory system DevR DevS (DosR DosS) involved in onset of the dormancy response. May act as a
Orthologous groupCOG2203
EC number EC 2.7.13.3
KEGG orthology K07682
KEGG pathways map02020
KEGG modules M00482
Gene Ontology (71) GO:0000166, GO:0000287, GO:0003674, GO:0003824, GO:0004672, GO:0005488, GO:0005524, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006464 +59 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 0.722 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 8 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
GAF_2PF13185.13 4.2e-1662–200 GAF domain
GAFPF01590.33 4.1e-1663–200 GAF domain
GAF_3PF13492.13 1.7e-07320–368 GAF domain
HisKA_3PF07730.20 5.9e-13387–447 Histidine kinase
HATPase_cPF02518.32 2.9e-12491–576 Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase

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

Closest characterised functional partner: devR (two component transcriptional regulator DevR), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3133c devR two component transcriptional regulator DevR 999 1000 ctx neighborhood:882 cooccurence:769 coexpression:895 experimental:544 database:900 textmining:963
Rv3134c universal stress protein 989 946 ctx neighborhood:744 coexpression:730 textmining:809
Rv0569 hyp hypothetical protein 904 870 coexpression:803
Rv2005c universal stress protein 850 838 coexpression:833
Rv1736c narX nitrate reductase-like protein NarX 871 819 coexpression:799
Rv2624c universal stress protein 845 814 coexpression:744
Rv2004c hyp hypothetical protein 822 811 coexpression:805
Rv2028c universal stress protein 888 809 coexpression:748 textmining:440
Rv0570 nrdZ vitamin B12-dependent ribonucleoside-diphosphate reductase 827 807 coexpression:806
Rv2629 hyp hypothetical protein 797 797 coexpression:797
Rv1997 ctpF cation transporter ATPase F 829 795 coexpression:793
Rv0844c narL nitrate/nitrite response transcriptional regulator NarL 877 792 ctx cooccurence:612 textmining:437
Rv2029c pfkB 6-phosphofructokinase PfkB 840 781 coexpression:774
Rv0571c hyp hypothetical protein 772 772 coexpression:759
Rv2006 otsB1 trehalose-6-phosphate phosphatase OtsB 782 756 coexpression:740

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 sensor histidine kinase DevS
  • MTBC0 PGAP product: two-component system sensor histidine kinase DevS
  • Pfam (hmmscan --cut_ga): GAF_2 PF13185.13 (E=4e-16), GAF PF01590.33 (E=4e-16), GAF_3 PF13492.13 (E=2e-07), HisKA_3 PF07730.20 (E=6e-13), HATPase_c PF02518.32 (E=3e-12)
  • (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_217648.1)
  • Domains: Pfam-A via hmmscan --cut_ga — GAF_2 (PF13185.13), GAF (PF01590.33), GAF_3 (PF13492.13), HisKA_3 (PF07730.20), HATPase_c (PF02518.32)
  • 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 COG2203
  • Curated reference: UniProt P9WGK3 (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 — 58 functional partner(s); context anchor devR
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003329|Rv3132c|devS
MTTGGLVDENDGAAMRPLRHTLSQLRLHELLVEVQDRVEQIVEGRDRLDGLVEAMLVVTAGLDLEATLRAIVHSATSLVDARYGAMEVHDRQHRVLHFVYEGIDEETVRRIGHLPKGLGVIGLLIEDPKPLRLDDVSAHPASIGFPPYHPPMRTFLGVPVRVRDESFGTLYLTDKTNGQPFSDDDEVLVQALAAAAGIAVANARLYQQAKARQSWIEATRDIATELLSGTEPATVFRLVAAEALKLTAADAALVAVPVDEDMPAADVGELLVIETVGSAVASTVGRTIPVAGAVLREVFVNGIPRRVDRVDLEGLDELADAGPALLLPLRARGTVAGVVVVLSQGGPGAFTDEQLEMMAAFADQAALAWQLATSQRRMRELDVLTDRDRIARDLHDHVIQRLFAIGLALQGAVPHERNPEVQQRLSDVVDDLQDVIQEIRTTIYDLHGASQGITRLRQRIDAAVAQFADSGLRTSVQFVGPLSVVDSALADQAEAVVREAVSNAVRHAKASTLTVRVKVDDDLCIEVTDNGRGLPDEFTGSGLTNLRQRAEQAGGEFTLASVPGASGTVLRWSAPLSQ