lppN Family assigned · medium
H37Rv Rv2270 · MTBC0 mtbc0_002412 ·
175 aa · 2570803–2571330 (+) ·
RefSeq NP_216786.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipoprotein LppN |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Lipoprotein LppN of the mycobacterial cell envelope; peptides derived from it bind alveolar epithelial (A549) and monocyte-derived (U937) cells and inhibit mycobacterial entry in vitro, implicating it in host-cell adhesion/invasion. Precise molecular function unfixed. |
Curated reference (UniProt)
| UniProt |
P9WK73
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | Putative lipoprotein LppN |
| Curated function | Probably involved in bacterial recognition and uptake by its host (human). |
UniProt still lists this protein as Putative lipoprotein LppN; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Preferred name | lppN |
|---|---|
| Orthologous group | 29VFP |
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 | 4.344 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 12 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.57% of strains (831) · 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cyp128 (cytochrome P450 Cyp128), medium confidence from genomic context alone (score 570 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2271 hyp |
hypothetical protein | 577 | 577 ctx | neighborhood:576 |
Rv2269c hyp |
hypothetical protein | 573 | 573 ctx | neighborhood:561 |
Rv2268c cyp128 |
cytochrome P450 Cyp128 | 570 | 570 ctx | neighborhood:550 |
Rv2267c stf3 hyp |
hypothetical protein | 556 | 557 ctx | neighborhood:550 |
Rv2272 |
transmembrane protein | 415 | 416 ctx | neighborhood:412 |
Rv2273 |
transmembrane protein | 414 | 414 ctx | neighborhood:412 |
Rv1968 mce3C |
Mce family protein Mce3C | 526 | 55 | textmining:519 |
Rv1970 lprM |
Mce family lipoprotein LprM | 516 | 54 | textmining:510 |
Rv1973 |
Mce associated membrane protein | 633 | 51 | textmining:630 |
Rv1351 hyp |
hypothetical protein | 810 | 47 | textmining:809 |
Rv1899c lppD |
lipoprotein LppD | 723 | 47 | textmining:722 |
Rv1911c lppC |
lipoprotein LppC | 652 | 47 | textmining:650 |
Rv3905c esxF |
ESAT-6 like protein EsxF | 570 | 47 | textmining:568 |
Rv3904c esxE |
ESAT-6 like protein EsxE | 508 | 47 | textmining:505 |
Rv0431 |
tuberculin-like peptide | 652 | 44 | textmining:651 |
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
- Cell-envelope lipoprotein; binding peptides inhibit mycobacterial entry (adhesion) (Ocampo 2014, PMID 25041568)
- 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_216786.1)
- 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
29VFP - Curated reference: UniProt P9WK73 (SwissProt, reviewed; Inferred from homology)
- 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 —
19 functional partner(s); context anchor
cyp128 - Primary literature: Ocampo M, Curtidor H, Vanegas M, Patarroyo MA, Patarroyo ME (2014). Specific interaction between Mycobacterium tuberculosis lipoprotein-derived peptides and target cells inhibits mycobacterial entry in vitro Chem Biol Drug Des 84(6):626-41. doi:10.1111/cbdd.12365 PMID:25041568
Ancestral MTBC0 protein sequence
>mtbc0_002412|Rv2270|lppN MRLPGRHVLYALSAVTMLAACSSNGARGGIASTNMNPTNPPATAETATVSPTPAPQSARTETWINLQVGDCLADLPPADLSRITVTIVDCATAHSAEVYLRAPVAVDAAVVSMANRDCAAGFAPYTGQSVDTSPYSVAYLIDSHQDRTGADPTPSTVICLLQPANGQLLTGSARR