lprL Family assigned · medium auto-curated

H37Rv Rv0593 · MTBC0 - · 402 aa · 692024–693232 (+) · RefSeq NP_215107.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)Mce family lipoprotein LprL
MTBC0 PGAP re-annotation
Revised (this work)Mce family lipoprotein LprL. Pfam: MlaD (PF02470.26), Mce4_CUP1 (PF11887.14).

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 I6Y461 TrEMBL · unreviewed · Predicted
UniProt namePossible Mce-family lipoprotein LprL

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namelprL
eggNOG descriptionVirulence factor Mce family protein
Orthologous groupCOG1463
KEGG orthology K02067
KEGG pathways map02010
KEGG modules M00210, M00669, M00670

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) pseudogene candidate

pN/pS 1.43 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 8.53% of strains (12382) · 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
MlaDPF02470.26 3.0e-1468–139 MlaD protein
Mce4_CUP1PF11887.14 1.2e-09145–313 Cholesterol uptake porter CUP1 of Mce4, putative

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

Closest characterised functional partner: mce2D (Mce family protein Mce2D), high confidence from genomic context alone (score 988 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0592 mce2D Mce family protein Mce2D 998 988 ctx neighborhood:782 cooccurence:774 coexpression:778 textmining:887
Rv0588 yrbE2B hyp hypothetical protein 971 969 ctx neighborhood:781 cooccurence:769
Rv0587 yrbE2A hyp hypothetical protein 968 968 ctx neighborhood:781 cooccurence:756
Rv0594 mce2F Mce family protein Mce2F 992 956 ctx neighborhood:801 cooccurence:774 textmining:830
Rv0589 mce2A Mce family protein Mce2A 990 949 ctx neighborhood:783 cooccurence:774 textmining:822
Rv0590 mce2B Mce-family protein Mce2B; Rv0590, (MTCY19H5.32c), len: 275 aa. Mce2B; belongs to 24-membered Mycobacterium tuberculosis Mce protein family ( 965 949 ctx neighborhood:781 cooccurence:772
Rv0591 mce2C Mce family protein Mce2C 942 899 ctx neighborhood:785 textmining:446
Rv0655 mkl ABC transporter ATP-binding protein 917 885 ctx cooccurence:761 experimental:431
Rv0168 yrbE1B membrane protein 880 873 ctx cooccurence:769
Rv1965 yrbE3B integral membrane protein 879 872 ctx cooccurence:766
Rv3500c yrbE4B integral membrane protein 878 870 ctx cooccurence:770
Rv3501c yrbE4A integral membrane protein 873 869 ctx cooccurence:762
Rv0167 yrbE1A membrane protein 872 868 ctx cooccurence:759
Rv1964 yrbE3A integral membrane protein 880 866 ctx cooccurence:753
Rv0170 mce1B Mce family protein Mce1B 807 796 ctx cooccurence:773

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): Mce family lipoprotein LprL
  • Pfam (hmmscan --cut_ga): MlaD PF02470.26 (E=3e-14), Mce4_CUP1 PF11887.14 (E=1e-09)
  • (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_215107.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MlaD (PF02470.26), Mce4_CUP1 (PF11887.14)
  • 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 COG1463
  • Curated reference: UniProt I6Y461 (TrEMBL, unreviewed; Predicted)
  • 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 — 47 functional partner(s); context anchor mce2D
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0593|lprL
MRCGVSAGSANGKPNRWTLRCGVSAGHRGSVFLLAVLLAPVVLTSCTWRGIANVPLPVGRGMGPDRMTIYVQMPDTLALNTNSRVRVADVWVGTVRDISLRNWIATLTLELEPTVRLPANATAKIGQTSLLGTQHVELAAPPIPSPQPLKSGDTIGLKNSSAYPTVERTLASVALILTGGGIVNLDVIQTEILNILDGHAGQIREFLERLATFTAELNNQRGDLTRAIDSTNQLLTIIANRNDTLDRVLTDVPPLIEHFADTGQLFADATESLGRFSEVANRALAATRPNLHQTLQSLQRPLRQLERASPYVVGALKLGLTAPFNIDEVPNVIRGDYVNVSATFDVTLSALDNALLSGTGISGMLRALEQAWGRDPDTMIPDVRYTPNPNDAPGGPLVERAE