lsr2 Resolved · high auto-curated

H37Rv Rv3597c · MTBC0 mtbc0_003816 · 112 aa · 4064685–4065023 (-) · RefSeq NP_218114.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)iron-regulated H-NS-like protein
MTBC0 PGAP re-annotationhistone-like nucleoid-structuring protein Lsr2
Revised (this work)Histone-like nucleoid-structuring protein Lsr2. Pfam: Lsr2 (PF11774.15), Lsr2_DNA-bd (PF23359.2).

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

Curated reference (UniProt)

UniProt P9WIP7 SwissProt · reviewed · Evidence at protein level
UniProt nameNucleoid-associated protein Lsr2
Curated functionDNA-bridging protein that has both architectural and regulatory roles. Influences the organization of chromatin and gene expression by binding non-specifically to DNA, with a preference for AT-rich sequences, and bridging distant DNA segments. Binds in the minor groove of AT-rich DNA. Represses expression of multiple genes involved in a broad range of cellular processes, including major virulence factors or antibiotic-induced genes, such as iniBAC or efpA, and genes important for adaptation of changing O(2) levels. May also activate expression of some gene. May coordinate global gene regulatio.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namelsr2
eggNOG descriptionpathogenesis
Orthologous group2C4MW
Gene Ontology (82) GO:0000302, GO:0003674, GO:0003676, GO:0003677, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886 +70 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 0.698 · 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
Lsr2PF11774.15 1.2e-281–59 Lsr2 dimerization domain
Lsr2_DNA-bdPF23359.2 2.0e-1976–111 Lsr2 DNA-binding domain

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

Closest characterised functional partner: clpC1 (ATP-dependent protease ATP-binding subunit ClpC), high confidence from genomic context alone (score 724 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3596c clpC1 ATP-dependent protease ATP-binding subunit ClpC 724 724 ctx neighborhood:721
Rv3601c panD aspartate 1-decarboxylase 703 704 ctx neighborhood:702
Rv3602c panC pantothenate synthetase 703 703 ctx neighborhood:702
Rv3600c coaX type III pantothenate kinase 703 703 ctx neighborhood:702
Rv3603c hyp hypothetical protein 702 702 ctx neighborhood:702
Rv3604c transmembrane protein 663 650 ctx neighborhood:645
Rv3610c ftsH zinc metalloprotease FtsH 687 620 ctx neighborhood:561
Rv3598c lysS lysine--tRNA ligase 607 607 ctx neighborhood:606
Rv3607c folB dihydroneopterin aldolase 596 596 ctx neighborhood:593
Rv3605c hyp hypothetical protein 596 596 ctx neighborhood:596
Rv2256c hyp hypothetical protein 590 591 ctx cooccurence:575
Rv3608c folP1 dihydropteroate synthase 579 578 ctx neighborhood:577
Rv0786c hyp hypothetical protein 546 546 ctx cooccurence:546
Rv2239c hyp hypothetical protein 543 543 ctx cooccurence:539
Rv0498 hyp hypothetical protein 523 523 ctx cooccurence:520

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: iron-regulated H-NS-like protein
  • MTBC0 PGAP product: histone-like nucleoid-structuring protein Lsr2
  • Pfam (hmmscan --cut_ga): Lsr2 PF11774.15 (E=1e-28), Lsr2_DNA-bd PF23359.2 (E=2e-19)
  • (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_218114.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Lsr2 (PF11774.15), Lsr2_DNA-bd (PF23359.2)
  • 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 2C4MW
  • Curated reference: UniProt P9WIP7 (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 — 56 functional partner(s); context anchor clpC1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003816|Rv3597c|lsr2
MAKKVTVTLVDDFDGSGAADETVEFGLDGVTYEIDLSTKNATKLRGDLKQWVAAGRRVGGRRRGRSGSGRGRGAIDREQSAAIREWARRNGHNVSTRGRIPADVIDAYHAAT