Rv2324 Family assigned · medium auto-curated

H37Rv Rv2324 · MTBC0 mtbc0_002472 · 148 aa · 2621083–2621529 (+) · RefSeq NP_216840.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)AsnC family transcriptional regulator
MTBC0 PGAP re-annotationLrp/AsnC family transcriptional regulator
Revised (this work)Lrp/AsnC family transcriptional regulator. Pfam: HTH_AsnC-type (PF13404.13), HTH_24 (PF13412.13), AsnC_trans_reg (PF01037.29).

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

Curated reference (UniProt)

UniProt P71888 SwissProt · reviewed · Evidence at protein level
UniProt nameHTH-type transcriptional regulator Rv2324
Curated functionTranscriptional regulator involved in growth, DNA replication and damage control. Plays a crucial role in regulating survival and growth of M.tuberculosis. Could function as a global regulator in both the latent/persistent and active phases of growth. Binds to its own promoter region and to promoters of multiple metabolic genes, such as serB2, lat, ald and roc operon. In vitro, interacts with intrinsically curved and non-curved DNA molecules, and with both supercoiled and linear DNA, with higher affinity for supercoiled DNA. Binds to DNA recombination, replication and repair intermediates.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptiontranscriptional
Orthologous groupCOG1522

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 0.653 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 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
HTH_AsnC-typePF13404.13 3.5e-154–44 AsnC-type helix-turn-helix domain
HTH_24PF13412.13 1.9e-144–51 Winged helix-turn-helix DNA-binding
AsnC_trans_regPF01037.29 4.0e-1768–147 Lrp/AsnC ligand binding domain

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

Closest characterised functional partner: Rv2319c (universal stress protein), medium confidence from genomic context alone (score 615 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2323c hyp hypothetical protein 943 710 ctx neighborhood:618 textmining:813
Rv1725c hyp hypothetical protein 692 690 coexpression:690
Rv2621c transcriptional regulator 656 655 coexpression:655
Rv2319c universal stress protein 713 615 ctx neighborhood:613
Rv2320c rocE cationic amino acid transporter permease RocE 650 613 ctx neighborhood:606
Rv2322c rocD1 Rv2322c, (MTCY3G12.12), len: 221 aa. Probable rocD1,ornithine aminotransferase, highly similar to N-terminal region of other ornithine amino 597 594 ctx neighborhood:590
Rv2321c rocD2 Rv2321c, (MTCY3G12.13), len: 181 aa. Probable rocD2,ornithine aminotransferase, highly similar to C-terminal region of other ornithine amino 684 593 ctx neighborhood:590
Rv3291c lrpA transcriptional regulator LrpA 531 532 coexpression:415
Rv1985c lysG HTH-type transcriptional regulator 502 474 coexpression:474
Rv3183 higA3 transcriptional regulator 463 441 coexpression:441
Rv3167c TetR family transcriptional regulator 426 409 coexpression:409
Rv0339c iniR transcriptional regulator 425 404
Rv3736 AraC/XylS family transcriptional regulator 434 402
Rv3066 DeoR family transcriptional regulator 554 398
Rv0792c transcriptional regulator 414 386

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: AsnC family transcriptional regulator
  • MTBC0 PGAP product: Lrp/AsnC family transcriptional regulator
  • Pfam (hmmscan --cut_ga): HTH_AsnC-type PF13404.13 (E=4e-15), HTH_24 PF13412.13 (E=2e-14), AsnC_trans_reg PF01037.29 (E=4e-17)
  • (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_216840.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_AsnC-type (PF13404.13), HTH_24 (PF13412.13), AsnC_trans_reg (PF01037.29)
  • 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 COG1522
  • Curated reference: UniProt P71888 (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 — 26 functional partner(s); context anchor Rv2319c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002472|Rv2324|
MDRLDDTDERILAELAEHARATFAEIGHKVSLSAPAVKRRVDRMLESGVIKGFTTVVDRNALGWNTEAYVQIFCHGRIAPDQLRAAWVNIPEVVSAATVTGTSDAILHVLAHDMRHLEAALERIRSSADVERSESTVVLSNLIDRMPP