lpqR Family assigned · medium auto-curated

H37Rv Rv0838 · MTBC0 mtbc0_000893 · 256 aa · 937871–938641 (+) · RefSeq NP_215353.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)lipoprotein LpqR
MTBC0 PGAP re-annotationM15 family metallopeptidase
Revised (this work)M15 family metallopeptidase. Pfam: Peptidase_M15 (PF01427.23).

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

Curated reference (UniProt)

UniProt O53850 TrEMBL · unreviewed · Evidence at protein level
UniProt nameD-alanyl-D-alanine dipeptidase
EC (curated) EC 3.4.13.22
Curated functionCatalyzes hydrolysis of the D-alanyl-D-alanine dipeptide.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namelpqR
eggNOG descriptionCatalyzes hydrolysis of the D-alanyl-D-alanine dipeptide
Orthologous groupCOG2173
EC number EC 3.4.13.22
KEGG orthology K08641
KEGG pathways map01502, map02020
KEGG modules M00651

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 0.89 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 4 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.17% of strains (250) · 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
Peptidase_M15PF01427.23 5.3e-8563–255 D-ala-D-ala dipeptidase

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

Closest characterised functional partner: lpqI (lipoprotein LpqI), medium confidence from genomic context alone (score 454 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0839 hyp hypothetical protein 781 781 ctx neighborhood:780
Rv0237 lpqI lipoprotein LpqI 454 454 ctx fusion:452
Rv0315 beta-1,3-glucanase 665 316 textmining:531
Rv2981c ddlA D-alanine--D-alanine ligase 520 182 textmining:438
Rv1493 mutB methylmalonyl-CoA mutase large subunit 453 77 textmining:432
Rv0175 Mce associated membrane protein 550 46 textmining:548
Rv1252c lprE lipoprotein LprE 401 46
Rv3491 hyp hypothetical protein 805 44 textmining:805
Rv0852 fadD16 hyp hypothetical protein 680 42 textmining:680

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: lipoprotein LpqR
  • MTBC0 PGAP product: M15 family metallopeptidase
  • Pfam (hmmscan --cut_ga): Peptidase_M15 PF01427.23 (E=5e-85)
  • (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_215353.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M15 (PF01427.23)
  • 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 COG2173
  • Curated reference: UniProt O53850 (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 — 9 functional partner(s); context anchor lpqI
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000893|Rv0838|lpqR
MRLIGRLRLLMVGLVVICGACACDRVSAGRWSESPSATSWPVRPVNTTTPSGPVPPVSEAARAAGLVDVRGVVPDAAIDLRYATANNFTGTQLYPPGARCLVHESMAEGLAAAAAVLRPHGQVLVFWDCYRPHDVQVRMFDVVPNPAWVARPGKYAHSHEAGRSVDVTFASAQRQCPSVRRSGELCLADMGTDFDDFSSRATAFATQGVSAEAQANRAHLRAAMQAGGLTVYSGEWWHFDGPGAGVDRPILEVPVD