lppA Family assigned · medium auto-curated
H37Rv Rv2543 · MTBC0 mtbc0_002709 ·
219 aa · 2889358–2890017 (+) ·
RefSeq NP_217059.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipoprotein LppA |
|---|---|
| MTBC0 PGAP re-annotation | LppA family lipoprotein |
| Revised (this work) | LppA family lipoprotein. Pfam: LppA (PF16708.11). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WK81
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative lipoprotein LppA |
UniProt still lists this protein as Putative lipoprotein LppA; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | lppB |
| eggNOG description | Lipoprotein confined to pathogenic Mycobacterium |
| Orthologous group | 2ATJU |
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 | 0.229 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 7 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.10% of strains (145) · 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 |
|---|---|---|---|---|
LppA | PF16708.11 | 1.7e-43 | 40–194 | Lipoprotein confined to pathogenic Mycobacterium |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lppB (lipoprotein LppB), high confidence from genomic context alone (score 944 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2544 lppB |
lipoprotein LppB | 945 | 944 ctx | neighborhood:801 coexpression:732 |
Rv2545 vapB18 |
antitoxin VapB18 | 783 | 783 ctx | neighborhood:781 |
Rv2546 vapC18 |
ribonuclease VapC18 | 546 | 546 ctx | neighborhood:543 |
Rv2542 hyp |
hypothetical protein | 526 | 526 ctx | neighborhood:523 |
Rv2548 vapC19 |
ribonuclease VapC19 | 464 | 464 ctx | neighborhood:458 |
Rv2547 vapB19 |
antitoxin VapB19 | 461 | 461 ctx | neighborhood:458 |
Rv1872c lldD2 |
L-lactate dehydrogenase | 413 | 54 | textmining:406 |
Rv3648c cspA |
cold shock protein A | 406 | 51 | textmining:400 |
Rv1224 tatB |
Sec-independent protein translocase protein TatB | 464 | 50 | textmining:460 |
Rv3429 PPE59 |
PPE family protein PPE59 | 460 | 47 | textmining:457 |
Rv1446c opcA |
OXPP cycle protein OpcA | 475 | 45 | textmining:473 |
Rv3892c PPE69 |
PPE family protein PPE69 | 435 | 45 | textmining:433 |
Rv0648 |
alpha-mannosidase | 631 | 44 | textmining:630 |
Rv2178c aroG |
phospho-2-dehydro-3-deoxyheptonate aldolase AroG | 560 | 43 | textmining:559 |
Rv3564 fadE33 |
acyl-CoA dehydrogenase FadE33 | 407 | 42 | textmining:407 |
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 LppA
- MTBC0 PGAP product: LppA family lipoprotein
- Pfam (hmmscan --cut_ga): LppA PF16708.11 (E=2e-43)
- (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_217059.1)
- Domains: Pfam-A via hmmscan --cut_ga — LppA (PF16708.11)
- 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
2ATJU - Curated reference: UniProt P9WK81 (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 —
22 functional partner(s); context anchor
lppB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002709|Rv2543|lppA MIAPQPISRTLPRWQRIVALTMIGISTALIGGCTMDHNPDTSRRLTGEQKIQLIDSMRNKGSYEAARERLTATARIIADRVSAAIPGQTWKFDDDPNIQQSDRNGALCDKLTADIARRPIANSVMFGATFSAEDFKIAANIVREEAAKYGATTESSLFNESAKRDYDVQGNGYEFRLLQIKFATLNITGDCFLLQKVLDLPAGQLPPEPPIWPTTSTPH