Rv2884 Family assigned · medium auto-curated

H37Rv Rv2884 · MTBC0 - · 252 aa · 3193393–3194151 (+) · RefSeq NP_217400.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transcriptional regulator
MTBC0 PGAP re-annotation
Revised (this work)Transcriptional regulator. Pfam: GlnR_1st (PF21695.4), Trans_reg_C (PF00486.35).

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 I6X5M3 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable transcriptional regulatory protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
T Signal transduction mechanisms
eggNOG descriptionTranscriptional regulatory protein, C terminal
Orthologous groupCOG0745

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) 4 synonymous, 4 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
GlnR_1stPF21695.4 4.3e-3321–130 Transcription regulator GlnR, N-terminal domain
Trans_reg_CPF00486.35 7.8e-25161–232 Transcriptional regulatory protein, C terminal

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

Closest characterised functional partner: Rv0600c (two component sensor kinase HK1), high confidence from genomic context alone (score 872 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0600c two component sensor kinase HK1 877 872 ctx cooccurence:710
Rv1032c trcS two component sensor histidine kinase TrcS 806 795 ctx cooccurence:526
Rv3764c tcrY two component sensor kinase TcrY 798 786 ctx cooccurence:504
Rv0490 senX3 two component sensor histidine kinase SenX3 865 781 ctx cooccurence:617 textmining:410
Rv1027c kdpE transcriptional regulator KdpE 739 740 ctx cooccurence:725
Rv0982 mprB two component histidine-protein kinase/phosphatase MprB 738 729
Rv0902c prrB two component sensor histidine kinase PrrB 730 719
Rv0758 phoR two component system response sensor kinase PhoR 800 716 ctx cooccurence:500
Rv0601c two component sensor kinase HK2 672 660
Rv3245c mtrB two component sensory histidine kinase MtrB 644 597
Rv3365c hyp hypothetical protein 593 578
Rv2998A Rv2998A, len: 67 aa. Probable conserved hypothetical protein, (possibly gene fragment), highly similar to central part of two-component sens 592 577
Rv2883c pyrH uridylate kinase 560 547 ctx neighborhood:484
Rv3645 transmembrane protein 547 519
Rv1028c kdpD sensor protein KdpD 564 512 experimental:417

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): transcriptional regulator
  • Pfam (hmmscan --cut_ga): GlnR_1st PF21695.4 (E=4e-33), Trans_reg_C PF00486.35 (E=8e-25)
  • (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_217400.1)
  • Domains: Pfam-A via hmmscan --cut_ga — GlnR_1st (PF21695.4), Trans_reg_C (PF00486.35)
  • 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 COG0745
  • Curated reference: UniProt I6X5M3 (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 — 39 functional partner(s); context anchor Rv0600c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2884|
MPTGPTTGKWHPHEVWRYLLEVLLLTDEADLESALPELESFAQSVQRAPLDDPGAAKGADADVAIIDARADLAAARRVCRRLTTSAPALAVVAVVAPANFVAVDGDWIFDDVLLNAAGGAELQARLRLAITRRRSTLAGTLQFGDLVLHPASYTASLGDRDLGLTLTEFKLMNFLVQHAGRAFTRTRLMREVWGYECHGRIRTVDVHVRRLRAKLGAEHESMIDTVRGVGYMAVTPPQPRWIISESILNRCK