lspA Resolved · high auto-curated
H37Rv Rv1539 · MTBC0 mtbc0_001646 ·
202 aa · 1752053–1752661 (+) ·
RefSeq NP_216055.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lipoprotein signal peptidase |
|---|---|
| MTBC0 PGAP re-annotation | signal peptidase II |
| Revised (this work) | Signal peptidase II. Pfam: Peptidase_A8 (PF01252.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WK99
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Lipoprotein signal peptidase |
| EC (curated) |
EC 3.4.23.36
|
| Curated function | This protein specifically catalyzes the removal of signal peptides from prolipoproteins. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesisU Intracellular trafficking, secretion and vesicular transport
|
|---|---|
| Preferred name | lspA |
| eggNOG description | This protein specifically catalyzes the removal of signal peptides from prolipoproteins |
| Orthologous group | COG0597 |
| EC number |
EC 3.4.23.36
|
| KEGG orthology |
K03101
|
| KEGG pathways |
map03060
|
| Gene Ontology (28) |
GO:0006464, GO:0006497, GO:0006807, GO:0008150, GO:0008152, GO:0009058, GO:0009059, GO:0009405, GO:0009987, GO:0019538, GO:0034645, GO:0036211 +16 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 | 0.194 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 1 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 |
|---|---|---|---|---|
Peptidase_A8 | PF01252.24 | 3.0e-32 | 39–178 | Signal peptidase (SPase) II |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1540 (RNA pseudouridine synthase), high confidence from genomic context alone (score 910 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1540 |
RNA pseudouridine synthase | 909 | 910 ctx | neighborhood:881 |
Rv1538c ansA |
L-aparaginase | 809 | 789 ctx | neighborhood:788 |
Rv2838c rbfA |
ribosome-binding factor RbfA | 640 | 617 | coexpression:412 |
Rv1536 ileS |
isoleucine--tRNA ligase | 583 | 537 | coexpression:473 |
Rv2154c ftsW |
lipid II flippase FtsW | 497 | 466 | |
Rv1614 lgt |
prolipoprotein diacylglyceryl transferase | 833 | 458 ctx | cooccurence:407 textmining:706 |
Rv1709 scpA |
segregation and condensation protein ScpA | 465 | 441 | |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 433 | 433 | coexpression:400 |
Rv1112 ychF |
GTP-binding protein | 422 | 423 | coexpression:422 |
Rv1225c hyp |
hypothetical protein | 409 | 410 | |
Rv3423c alr |
alanine racemase | 406 | 407 | |
Rv1692 |
phosphatase | 406 | 406 | |
Rv2157c murF |
UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase | 411 | 378 | |
Rv1407 fmu |
16S rRNA m5C967 methyltransferase | 401 | 373 | |
Rv1710 scpB |
segregation and condensation protein ScpB | 481 | 323 |
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 signal peptidase
- MTBC0 PGAP product: signal peptidase II
- Pfam (hmmscan --cut_ga): Peptidase_A8 PF01252.24 (E=3e-32)
- (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_216055.1)
- Domains: Pfam-A via hmmscan --cut_ga — Peptidase_A8 (PF01252.24)
- 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
COG0597 - Curated reference: UniProt P9WK99 (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 —
34 functional partner(s); context anchor
Rv1540 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001646|Rv1539|lspA MPDEPTGSADPLTSTEEAGGAGEPNAPAPPRRLRMLLSVAVVVLTLDIVTKVVAVQLLPPGQPVSIIGDTVTWTLVRNSGAAFSMATGYTWVLTLIATGVVVGIFWMGRRLVSPWWALGLGMILGGAMGNLVDRFFRAPGPLRGHVVDFLSVGWWPVFNVADPSVVGGAILLVILSIFGFDFDTVGRRHADGDTVGRRKADG