lppI Family assigned · medium
H37Rv Rv2046 · MTBC0 mtbc0_002179 ·
218 aa · 2319882–2320538 (+) ·
RefSeq NP_216562.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipoprotein LppI |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Conserved lipoprotein LppI; interacts physically and site-specifically with the virulence-associated lipid-transport protein LprG (at the entrance to its lipid-binding pocket), implicating it in outer-membrane lipid assembly/transport. Substrate/precise activity unfixed. |
Curated reference (UniProt)
| UniProt |
O53489
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable lipoprotein LppI |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Preferred name | lppI |
|---|---|
| Orthologous group | 2B0HC |
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 | 0.728 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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: lipT (carboxylesterase LipT), medium confidence from genomic context alone (score 679 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2045c lipT |
carboxylesterase LipT | 678 | 679 ctx | neighborhood:674 |
Rv2044c hyp |
hypothetical protein | 483 | 482 ctx | neighborhood:480 |
Rv2116 lppK |
lipoprotein LppK | 591 | 44 | textmining:590 |
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
- Lipoprotein; site-specific interactor of LprG (lipid transport / outer-membrane biogenesis) (Touchette 2017, PMID 28276676)
- Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)
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_216562.1)
- 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
2B0HC - Curated reference: UniProt O53489 (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 —
3 functional partner(s); context anchor
lipT - Primary literature: Touchette MH, Van Vlack ER, Bai L, Kim J, Cognetta AB 3rd, Previti ML, Backus KM, Martin DW, Cravatt BF, Seeliger JC (2017). A Screen for Protein-Protein Interactions in Live Mycobacteria Reveals a Functional Link between the Virulence-Associated Lipid Transporter LprG and the Mycolyltransferase Antigen 85A ACS Infect Dis 3(5):336-348. doi:10.1021/acsinfecdis.6b00179 PMID:28276676
Ancestral MTBC0 protein sequence
>mtbc0_002179|Rv2046|lppI MRIAALVAVSLLIAGCSREVGGDVGQSQTIAPPAPAPSAAPSTPPAAGAPITTIVSWIEAGHPVDPAAYHVATRDGVTTQLGDDVAFSASSGTVACMTDARHTSGTLACLVRLANPPPRPETAYGEWKGGWVDFDGIHLQVGSARADPGPFVYGNGPELANGDTLSIGDYRCRSYQAGLFCVNYAHQSAVRFASAGIEPFGCLKPAPPPDGVGVAFGC