lppL Family assigned · medium
H37Rv Rv2138 · MTBC0 mtbc0_002271 ·
358 aa · 2424593–2425669 (+) ·
RefSeq NP_216654.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipoprotein LppL |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | PkwA-like protein (WD40-repeat / Ser-Thr-kinase-associated fold). RefSeq leaves it 'hypothetical protein'. |
Curated reference (UniProt)
| UniProt |
O06237
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable conserved lipoprotein LppL |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | lppL |
| eggNOG description | amine dehydrogenase activity |
| Orthologous group | COG3391 |
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 | 2.285 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0556 (transmembrane protein), high confidence from genomic context alone (score 771 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3212 hyp |
hypothetical protein | 792 | 782 ctx | cooccurence:769 |
Rv0556 |
transmembrane protein | 771 | 771 ctx | cooccurence:770 |
Rv1081c |
membrane protein | 768 | 769 ctx | cooccurence:767 |
Rv0996 |
transmembrane protein | 883 | 767 ctx | cooccurence:766 textmining:519 |
Rv2743c hyp |
hypothetical protein | 765 | 765 ctx | cooccurence:765 |
Rv0431 |
tuberculin-like peptide | 759 | 759 ctx | cooccurence:758 |
Rv1109c hyp |
hypothetical protein | 752 | 752 ctx | cooccurence:750 |
Rv0513 |
transmembrane protein | 749 | 749 ctx | cooccurence:743 |
Rv2360c hyp |
hypothetical protein | 741 | 742 ctx | cooccurence:740 |
Rv0383c ttfA hyp |
hypothetical protein | 748 | 739 ctx | cooccurence:738 |
Rv2091c |
membrane protein | 739 | 739 ctx | cooccurence:738 |
Rv0817c lmeA hyp |
hypothetical protein | 738 | 739 ctx | cooccurence:737 |
Rv2732c |
transmembrane protein | 737 | 738 ctx | cooccurence:737 |
Rv3004 cfp6 |
low molecular weight protein antigen 6 | 736 | 736 ctx | cooccurence:736 |
Rv1632c hyp |
hypothetical protein | 735 | 736 ctx | cooccurence:734 |
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
- Foldseek vs AFDB-SwissProt: Ser/Thr kinase PkwA, TM 0.66, E 7e-12
- Structural homology vs AlphaFold-Swiss-Prot (Foldseek; 542k curated SwissProt structures), project 'Still unknown gene function' phase13, 2026-06-10. Fold/family-level, not a demonstrated function.
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_216654.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
COG3391 - Curated reference: UniProt O06237 (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 —
141 functional partner(s); context anchor
Rv0556 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002271|Rv2138|lppL MLTGNKPAVQRRFIGLLMLSVLVAGCSSNPLANFAPGYPPTIEPAQPAVSPPTSQDPAGAVRPLSGHPRAALFDNGTRQLVALRPGADSAAPASIMVFDDVHVAPRVIFLPGPAAALTSDDHGTAFLAARGGYFVADLSSGHTARVNVADAAHTDFTAIARRSDGKLVLGSADGAVYTLAKNPAVDPASGAATVASRTKIFARVDALVTQGNTTVVLDRGQTSVTTIGADGHAQQALRAGQGATTMAADPLGRVLIADTRGGQLLVYGVDPLILRQAYPVRQAPYGLAGSRELAWVSQTASNTVIGYDLTTGIPVEKVRYPTVQQPNSLAFDETSDTLYVVSGSGAGVQVIEHAAGTR