Rv1985c Family assigned · medium auto-curated

H37Rv Rv1985c · MTBC0 mtbc0_002109 · 303 aa · 2252604–2253515 (-) · RefSeq NP_216501.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)HTH-type transcriptional regulator
MTBC0 PGAP re-annotationArgP/LysG family DNA-binding transcriptional regulator
Revised (this work)ArgP/LysG family DNA-binding transcriptional regulator. Pfam: HTH_1 (PF00126.34), LysR_substrate (PF03466.26).

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

Curated reference (UniProt)

UniProt P9WMF5 SwissProt · reviewed · Evidence at protein level
UniProt nameHTH-type transcriptional regulator LysG
Curated functionPositively regulates the expression of the exporter LysE and represses its own expression. Activity requires the presence of a coinducer, lysine or histidine. Acts by binding to lysG-lysE promoter region. Also up-regulates the expression of ppsB, ppsC and ppsD, by binding to the upstream region of ppsB.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred nameiciA
eggNOG descriptionTranscriptional regulator
Orthologous groupCOG0583
KEGG orthology K05596
Gene Ontology (47) GO:0001130, GO:0003674, GO:0003676, GO:0003677, GO:0003688, GO:0003690, GO:0003700, GO:0005488, GO:0006275, GO:0006355, GO:0008150, GO:0008156 +35 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 0.356 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 2 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.44% of strains (639) · 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_1PF00126.34 8.1e-1810–65 Bacterial regulatory helix-turn-helix protein, lysR family
LysR_substratePF03466.26 4.5e-1095–263 LysR substrate binding domain

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

Closest characterised functional partner: lysE (amino acid transporter), high confidence from genomic context alone (score 905 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1986 lysE amino acid transporter 973 905 ctx neighborhood:595 cooccurence:774 textmining:727
Rv3736 AraC/XylS family transcriptional regulator 872 865 coexpression:840
Rv3167c TetR family transcriptional regulator 853 851 coexpression:833
Rv0691c mftR mycofactocin biosynthesis transcriptional regulator MftR 847 845 coexpression:826
Rv3183 higA3 transcriptional regulator 850 844 coexpression:844
Rv3263 DNA methylase 836 836 coexpression:836
Rv1776c transcriptional regulator 863 833 coexpression:812
Rv1674c transcriptional regulator 841 831 coexpression:828
Rv3855 ethR HTH-type transcriptional repressor EthR 833 831 coexpression:810
Rv3830c TetR family transcriptional regulator 829 827 coexpression:805
Rv3840 transcriptional regulator 833 826 coexpression:826
Rv1725c hyp hypothetical protein 831 825 coexpression:824
Rv1931c transcriptional regulator 828 822 coexpression:822
Rv0653c transcriptional regulator 825 822 coexpression:800
Rv3055 TetR family transcriptional regulator 825 822 coexpression:800

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
  • MTBC0 PGAP product: ArgP/LysG family DNA-binding transcriptional regulator
  • Pfam (hmmscan --cut_ga): HTH_1 PF00126.34 (E=8e-18), LysR_substrate PF03466.26 (E=4e-10)
  • (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_216501.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_1 (PF00126.34), LysR_substrate (PF03466.26)
  • 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 COG0583
  • Curated reference: UniProt P9WMF5 (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 — 81 functional partner(s); context anchor lysE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002109|Rv1985c|
MVDPQLDGPQLAALAAVVELGSFDAAAERLHVTPSAVSQRIKSLEQQVGQVLVVREKPCRATTAGIPLLRLAAQTALLESEALAEMGGNASLKRTRITIAVNADSMATWFSAVFDGLGDVLLDVRIEDQDHSARLLREGVAMGAVTTERNPVPGCRVHPLGEMRYLPVASRPFVQRHLSDGFTAAAAAKAPSLAWNRDDGLQDMLVRKAFRRAITRPTHFVPTTEGFTAAARAGLGWGMFPEKLAASPLADGSFVRVCDIHLDVPLYWQCWKLDSPIIARITDTVRAAASGLYRGQQRRRRPG