lpqL Family assigned · medium auto-curated

H37Rv Rv0418 · MTBC0 mtbc0_000439 · 500 aa · 506861–508363 (+) · RefSeq NP_214932.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)lipoprotein aminopeptidase LpqL
MTBC0 PGAP re-annotationM28 family metallopeptidase
Revised (this work)M28 family metallopeptidase. Pfam: PA (PF02225.28), Peptidase_M28 (PF04389.23), Peptidase_M20 (PF01546.34).

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

Curated reference (UniProt)

UniProt P96264 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable lipoprotein aminopeptidase LpqL
EC (curated) EC 3.4.11.1
Curated functionAn aminopeptidase; acts on free N-terminal amino groups with a very strong preference for Leu in the first position.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namelpqL
eggNOG descriptionPeptidase, M28
Orthologous groupCOG2234
Gene Ontology (7) GO:0005575, GO:0005576, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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 1.028 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 6 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
PAPF02225.28 7.0e-19140–229 PA domain
Peptidase_M28PF04389.23 2.9e-47252–472 Peptidase family M28
Peptidase_M20PF01546.34 1.1e-05269–339 Peptidase family M20/M25/M40

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

Closest characterised functional partner: lpqM (lipoprotein peptidase LpqM), high confidence from genomic context alone (score 782 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0419 lpqM lipoprotein peptidase LpqM 883 782 ctx neighborhood:745 textmining:486
Rv1104 Rv1104, (MTV017.57), len: 229 aa. Possible para-nitrobenzyl esterase (fragment; possibly first part). Similar to the N-terminal domain of ma 713 698 database:587
Rv1105 Rv1105, (MTV017.58), len: 171 aa. Possible para-nitrobenzyl esterase (fragment; possibly second part). Similar to C-terminal domain of many 711 696 database:587
Rv2045c lipT carboxylesterase LipT 711 696 database:587
Rv0416 thiS sulfur carrier protein ThiS 622 622 ctx neighborhood:467
Rv3372 otsB2 trehalose 6-phosphate phosphatase 611 609 database:584
Rv2006 otsB1 trehalose-6-phosphate phosphatase OtsB 611 608 database:584
Rv2124c metH methionine synthase 614 584 database:572
Rv3841 bfrB bacterioferritin BfrB 593 577 database:415
Rv0342 iniA isoniazid inductible protein IniA 596 575 database:569
Rv1488 hyp hypothetical protein 568 568 database:508
Rv3147 nuoC NADH-quinone oxidoreductase subunit C 568 568 database:562
Rv3090 hyp hypothetical protein 566 567 database:508
Rv3418c groES chaperonin GroES 564 565 database:561
Rv1305 atpE ATP synthase subunit C 581 564 database:561

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 aminopeptidase LpqL
  • MTBC0 PGAP product: M28 family metallopeptidase
  • Pfam (hmmscan --cut_ga): PA PF02225.28 (E=7e-19), Peptidase_M28 PF04389.23 (E=3e-47), Peptidase_M20 PF01546.34 (E=1e-05)
  • (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_214932.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PA (PF02225.28), Peptidase_M28 (PF04389.23), Peptidase_M20 (PF01546.34)
  • 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 COG2234
  • Curated reference: UniProt P96264 (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 — 123 functional partner(s); context anchor lpqM
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000439|Rv0418|lpqL
MVNKSRMMPAVLAVAVVVAFLTTGCIRWSTQSRPVVNGPAAAEFAVALRNRVSTDAMMAHLSKLQDIANANDGTRAVGTPGYQASVDYVVNTLRNSGFDVQTPEFSARVFKAEKGVVTLGGNTVEARALEYSLGTPPDGVTGPLVAAPADDSPGCSPSDYDRLPVSGAVVLVDRGVCPFAQKEDAAAQRGAVALIIADNIDEQAMGGTLGANTDVKIPVVSVTKSVGFQLRGQSGPTTVKLTASTQSFKARNVIAQTKTGSSANVVMAGAHLDSVPEGPGINDNGSGVAAVLETAVQLGNSPHVSNAVRFAFWGAEEFGLIGSRNYVESLDIDALKGIALYLNFDMLASPNPGYFTYDGDQSLPLDARGQPVVPEGSAGIERTFVAYLKMAGKTAQDTSFDGRSDYDGFTLAGIPSGGLFSGAEVKKSAEQAELWGGTADEPFDPNYHQKTDTLDHIDRTALGINGAGVAYAVGLYAQDLGGPNGVPVMADRTRHLIAKP