lppM Resolved · high auto-curated
H37Rv Rv2171 · MTBC0 mtbc0_002305 ·
227 aa · 2458958–2459641 (+) ·
RefSeq NP_216687.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipoprotein LppM |
|---|---|
| MTBC0 PGAP re-annotation | lipoprotein LppM |
| Revised (this work) | Lipoprotein LppM. Pfam: LppM (PF21946.2). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53505
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Protein LppM |
| Curated function | A putative lipoprotein that seems to be specialized for the initial steps of macrophage infection. A non-acylated fragment (residues 26-185) binds phosphatidyl-myo-inositol mannosides (PIMs). Limits, in a TLR2-dependent fashion, bacterial uptake by host (mouse); this effect may be mediated by nonacylated fragment 26-185. Plays a TLR2-dependent role in host phagosome maturation arrest. Plays a TLR2-independent role in chemokine production during the first 24 hours of mouse infection. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Preferred name | lppM |
|---|---|
| Orthologous group | 2E8DR |
| Gene Ontology (54) |
GO:0002682, GO:0002683, GO:0005575, GO:0005618, GO:0005623, GO:0008150, GO:0009605, GO:0009607, GO:0030312, GO:0031347, GO:0031348, GO:0035821 +42 more
|
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 | 0.6 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 5 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
LppM | PF21946.2 | 1.7e-53 | 27–178 | LppM domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2170 (GCN5-like N-acetyltransferase), high confidence from genomic context alone (score 776 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2170 |
GCN5-like N-acetyltransferase | 775 | 776 ctx | neighborhood:775 |
Rv2732c |
transmembrane protein | 763 | 763 ctx | cooccurence:762 |
Rv3205c hyp |
hypothetical protein | 754 | 755 ctx | cooccurence:745 |
Rv0010c |
membrane protein | 735 | 735 ctx | cooccurence:734 |
Rv1100 hyp |
hypothetical protein | 720 | 720 ctx | cooccurence:720 |
Rv0358 hyp |
hypothetical protein | 716 | 717 ctx | cooccurence:716 |
Rv0556 |
transmembrane protein | 713 | 714 ctx | cooccurence:713 |
Rv3850 hyp |
hypothetical protein | 705 | 706 ctx | cooccurence:704 |
Rv1109c hyp |
hypothetical protein | 694 | 695 ctx | cooccurence:694 |
Rv0431 |
tuberculin-like peptide | 686 | 687 ctx | cooccurence:684 |
Rv3755c hyp |
hypothetical protein | 676 | 676 ctx | cooccurence:676 |
Rv1638A hyp |
hypothetical protein | 665 | 665 ctx | cooccurence:664 |
Rv2446c |
integral membrane protein | 659 | 659 ctx | cooccurence:658 |
Rv3212 hyp |
hypothetical protein | 659 | 659 ctx | cooccurence:648 |
Rv3839 hyp |
hypothetical protein | 655 | 655 ctx | cooccurence:655 |
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 LppM
- MTBC0 PGAP product: lipoprotein LppM
- Pfam (hmmscan --cut_ga): LppM PF21946.2 (E=2e-53)
- (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_216687.1)
- Domains: Pfam-A via hmmscan --cut_ga — LppM (PF21946.2)
- 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
2E8DR - Curated reference: UniProt O53505 (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 —
93 functional partner(s); context anchor
Rv2170 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002305|Rv2171|lppM MARTRRRGMLAIAMLLMLVPLATGCLRVRASITISPDDLVSGEIIAAAKPKNSKDTGPALDGDVPFSQKVAVSNYDSDGYVGSQAVFSDLTFAELPQLANMNSDAAGVNLSLRRNGNIVILEGRADLTSVSDPDADVELTVAFPAAVTSTNGDRIEPEVVQWKLKPGVVSTMSAQARYTDPNTRSFTGAGIWLGIAAFAAAGVVAVLAWIDRDRSPRLTASGDPPTS