lprA Resolved · high auto-curated
H37Rv Rv1270c · MTBC0 mtbc0_001360 ·
244 aa · 1427997–1428731 (-) ·
RefSeq NP_215786.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipoprotein LprA |
|---|---|
| MTBC0 PGAP re-annotation | TLR2 agonist LprA |
| Revised (this work) | TLR2 agonist LprA. Pfam: LppX_LprAFG (PF07161.20). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WK55
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Lipoprotein LprA |
| Curated function | Constitutes a host TLR2 agonist (toll-like receptor), shown experimentally for human and mouse. In host cells full-length (acylated) protein acts as a TLR2 agonist, inducing human and murine macrophages to produce cytokines, inducing murine dendritic cell maturation and cytokine production and inhibiting antibody processing in murine macrophages. Binds diacylated phosphatidyl-myo-inositol mannosides (PIMs). Does not induce murine macrophage apoptosis or necrosis. Non-acylated protein does not act as a TLR2 agonist. Requires only host TLR2 as receptors to elicit host response in mouse, although. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | lprA |
| eggNOG description | LppX_LprAFG lipoprotein |
| Orthologous group | 2DQVM |
| KEGG orthology |
K14954, K14955
|
| KEGG pathways |
map05152
|
| Gene Ontology (52) |
GO:0003674, GO:0005102, GO:0005488, GO:0005515, GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0009605, GO:0009607 +40 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 | 0.867 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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 |
|---|---|---|---|---|
LppX_LprAFG | PF07161.20 | 1.4e-70 | 45–239 | LppX_LprAFG lipoprotein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: papA5 (phthiocerol/phthiodiolone dimycocerosyl transferase), medium confidence from genomic context alone (score 661 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0493c hyp |
hypothetical protein | 680 | 681 ctx | cooccurence:676 |
Rv1269c hyp |
hypothetical protein | 668 | 669 ctx | neighborhood:669 |
Rv2939 papA5 |
phthiocerol/phthiodiolone dimycocerosyl transferase | 660 | 661 ctx | cooccurence:660 |
Rv2365c hyp |
hypothetical protein | 632 | 632 ctx | cooccurence:632 |
Rv3909 hyp |
hypothetical protein | 566 | 566 ctx | cooccurence:565 |
Rv0538 |
membrane protein | 556 | 557 ctx | cooccurence:554 |
Rv2608 PPE42 |
PPE family protein PPE42 | 545 | 546 ctx | cooccurence:540 |
Rv3413c rsdA |
anti-sigma-D factor RsdA | 529 | 529 ctx | cooccurence:529 |
Rv3415c hyp |
hypothetical protein | 525 | 525 ctx | cooccurence:525 |
Rv1111c hyp |
hypothetical protein | 502 | 502 ctx | cooccurence:495 |
Rv2695 hyp |
hypothetical protein | 479 | 480 ctx | cooccurence:473 |
Rv3788 hyp |
hypothetical protein | 477 | 478 ctx | cooccurence:454 |
Rv0676c mmpL5 |
transmembrane transport protein MmpL5 | 475 | 476 ctx | cooccurence:475 |
Rv1271c hyp |
hypothetical protein | 469 | 468 ctx | neighborhood:468 |
Rv1963c mce3R |
transcriptional repressor Mce3R | 468 | 468 ctx | cooccurence:465 |
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 LprA
- MTBC0 PGAP product: TLR2 agonist LprA
- Pfam (hmmscan --cut_ga): LppX_LprAFG PF07161.20 (E=1e-70)
- (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_215786.1)
- Domains: Pfam-A via hmmscan --cut_ga — LppX_LprAFG (PF07161.20)
- 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
2DQVM - Curated reference: UniProt P9WK55 (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 —
72 functional partner(s); context anchor
papA5 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001360|Rv1270c|lprA MKHPPCSVVAAATAILAVVLAIGGCSTEGDAGKASDTAATASNGDAAMLLKQATDAMRKVTGMHVRLAVTGDVPNLRVTKLEGDISNTPQTVATGSATLLVGNKSEDAKFVYVDGHLYSDLGQPGTYTDFGNGASIYNVSVLLDPNKGLANLLANLKDASVAGSQQADGVATTKITGNSSADDIATLAGSRLTSEDVKTVPTTVWIASDGSSHLVQIQIAPTKDTSVTLTMSDWGKQVTATKPV