Rv2488c Family assigned · medium auto-curated

H37Rv Rv2488c · MTBC0 - · 1137 aa · 2797467–2800880 (-) · RefSeq NP_217004.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)LuxR family transcriptional regulator
MTBC0 PGAP re-annotation
Revised (this work)LuxR family transcriptional regulator. Pfam: HTH_77 (PF25872.1), GerE (PF00196.26).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt O53213 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable transcriptional regulatory protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptioninvolved in signal transduction (via phosphorylation) involved in transcriptional regulatory mechanism and in the regulation of secondary metabolites catalytic activity ATP a protein ADP a phosphoprotein
Orthologous groupCOG2114

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 0.814 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 10 synonymous, 21 missense, 1 nonsense, 3 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 17.38% of strains (25238) · convergent

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_77PF25872.1 4.8e-09487–557 Winged helix-turn-helix domain
GerEPF00196.26 1.3e-151070–1122 Bacterial regulatory proteins, luxR family

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

Closest characterised functional partner: embR (transcriptional regulator EmbR), high confidence from genomic context alone (score 931 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1675c cmr HTH-type transcriptional regulator Cmr 935 932 coexpression:856 experimental:440
Rv1267c embR transcriptional regulator EmbR 935 931 ctx fusion:454 coexpression:859
Rv1027c kdpE transcriptional regulator KdpE 893 881 coexpression:861
Rv1931c transcriptional regulator 885 879 coexpression:857
Rv1189 sigI ECF RNA polymerase sigma factor SigI 868 860 coexpression:829
Rv1359 transcriptional regulator 846 847 coexpression:805
Rv1725c hyp hypothetical protein 851 846 coexpression:846
Rv1190 hyp hypothetical protein 847 846 coexpression:845
Rv3840 transcriptional regulator 845 843 coexpression:843
Rv3736 AraC/XylS family transcriptional regulator 850 842 coexpression:841
Rv3164c moxR3 methanol dehydrogenase transcriptional regulator MoxR 839 840 coexpression:836
Rv3263 DNA methylase 839 839 coexpression:839
Rv3328c sigJ ECF RNA polymerase sigma factor SigJ 846 837 coexpression:804
Rv0691c mftR mycofactocin biosynthesis transcriptional regulator MftR 844 837 coexpression:836
Rv3167c TetR family transcriptional regulator 844 836 coexpression:806

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): LuxR family transcriptional regulator
  • Pfam (hmmscan --cut_ga): HTH_77 PF25872.1 (E=5e-09), GerE PF00196.26 (E=1e-15)
  • (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_217004.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_77 (PF25872.1), 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 COG2114
  • Curated reference: UniProt O53213 (TrEMBL, unreviewed; 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 — 120 functional partner(s); context anchor embR
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2488c|
MDRRPRDFEQSRRRCRCNALRAGSMLASMSKIHPGVDVVPVDWSADGVSELVPTGTVTLLLADIEGATHLPGSQLDTTAIAKLDRTLTELVREHRGVCPVEQGEGDSFLVAFARASDAVACALGLQRAPLAPIRLRIGMHTGEVSSPDEGNCVGPTIDRTARLRELAHGGQTVLSGTTSDLVADLLPKDAWLNDLGTYRLDDLPRPERVVQLCHPDLHNAFPPLRTRKVVGAHCLPAQLTRLVGRVDEVAQVRGLLDVKRWVTLTGVGGVGKTRLATQVASAVADGYPDGVWYVNLAPITDPALVPIAAARVLGLPDQPGRSTVDTIVRRIGDRRMLVVLDNCEHLLDGCAALIVALLGACPALRVLATSREPIAVAGEQIWRVPPLGHGEAIELFTDRAREARPELEITADNLALVTEICHRLDGIPLAIELAASRVRALALTEIVDSLHDRFRLLTGGSRIAVRRQQTMRASVDWSHALLTGPEQVLFRRLAVFPSGFDLDGAQAAAAGGDVQRYEVVDLLSLLADKSLVVTDDSDGRTRYRLLETVRQYALEKLRESGDADAVRARHRDHYAAVAAGLDAPSVAGHERRLNQAELEIDNLRAAFAFSRENGDTGHALLLASCLQPLWRARGRLQEGLAWFAAALADHDAHPAGADPGLYARALADRALIDAVAGITDRLDDAQKALAIARDIEDPALLARALTACGGVAAYNADLARPWLAEAVGLARAVGDKWRLAEVLAWQAYVGFAGEGDPGATRAAGEEARSLADEIGDAFLSRSCRWALAAANLWQGNLEAAVGLSREVIGESDAAHDMVSSCAGQACLAHALAHRGDTEAAAAAQASIDTAVGLSPVLSGSACSALVFATLAAGDVAAAEHARESATRFFGASAAAIINDPTSSAQISCARGDLNAAHRLADGAASITRGVHRARALTTRCRIEIAQGDRHRAERDAHDALGVAASIGAYLWVPDILECLASVMADAGSNREAVRLFGAADAARGRMGAVRFGIYQAGCNSSLATLRKSMGDSEFDDAWAEGTALSIDEAIAYAQRGRGARKRPTSGWGALTPTELEVALLVGEGLSNKEIGVRLFISPRTVHSHLTHVYTKLGLSSRLQLAQQAARRGESERGPSRP