lppR Family assigned · medium auto-curated
H37Rv Rv2403c · MTBC0 mtbc0_002559 ·
251 aa · 2724782–2725537 (-) ·
RefSeq NP_216919.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipoprotein LppR |
|---|---|
| MTBC0 PGAP re-annotation | sensor domain-containing protein |
| Revised (this work) | Sensor domain-containing protein. Pfam: PknH_C (PF14032.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P71740
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable conserved lipoprotein LppR |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | lppR |
| eggNOG description | PknH-like extracellular domain |
| Orthologous group | 2AEV2 |
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 | 2.541 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 6 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.24% of strains (343) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
PknH_C | PF14032.13 | 5.6e-40 | 42–246 | PknH-like extracellular domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lepA (GTP-binding protein LepA), high confidence from genomic context alone (score 900 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2404c lepA |
GTP-binding protein LepA | 899 | 900 ctx | neighborhood:881 |
Rv2405 hyp |
hypothetical protein | 621 | 622 ctx | neighborhood:620 |
Rv0399c lpqK |
lipoprotein LpqK | 658 | 53 | textmining:654 |
Rv1857 modA |
molybdate ABC transporter substrate-binding lipoprotein ModA | 519 | 49 | textmining:515 |
Rv0237 lpqI |
lipoprotein LpqI | 644 | 47 | textmining:643 |
Rv1016c lpqT |
lipoprotein LpqT | 561 | 47 | textmining:559 |
Rv0418 lpqL |
lipoprotein aminopeptidase LpqL | 482 | 47 | textmining:479 |
Rv3044 fecB |
FeIII-dicitrate-binding periplasmic lipoprotein | 442 | 47 | textmining:439 |
Rv1228 lpqX |
lipoprotein LpqX | 655 | 46 | textmining:654 |
Rv3244c lpqB |
lipoprotein LpqB | 645 | 46 | textmining:644 |
Rv0419 lpqM |
lipoprotein peptidase LpqM | 630 | 46 | textmining:628 |
Rv1166 lpqW |
monoacyl phosphatidylinositol tetramannoside-binding protein LpqW | 434 | 44 | textmining:433 |
Rv2138 lppL |
lipoprotein LppL | 544 | 41 | textmining:544 |
Rv3576 lppH |
lipoprotein LppH | 516 | 41 | textmining:516 |
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 LppR
- MTBC0 PGAP product: sensor domain-containing protein
- Pfam (hmmscan --cut_ga): PknH_C PF14032.13 (E=6e-40)
- (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_216919.1)
- Domains: Pfam-A via hmmscan --cut_ga — PknH_C (PF14032.13)
- 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
2AEV2 - Curated reference: UniProt P71740 (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 —
14 functional partner(s); context anchor
lepA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002559|Rv2403c|lppR MTNRWRWVVPLFAVFLAAGCTTTTTGKAGLAPNAVPRPLMGSLIQRVPLDGAALSTLLNQPFQALPPFPPVFGGSDSLGDSDVSARPADCVGVGYLTQRNVYRSVEVKSVARVSWRHDGSSVKVDDVDEGVVALPSAAAADDLFARFSAQWKECDGTTLTVPASAFGQRSITDVRVADSVVAATVSLRRGTHSILASVPQARAVGVRGNCVVEVAVTFFGITHPSDQGSADISTSAVDIAHAMMDRISELS