sppA Resolved · high auto-curated
H37Rv Rv0724 · MTBC0 - ·
623 aa · 815663–817534 (+) ·
RefSeq NP_215238.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | protease IV SppA |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Protease IV SppA. Pfam: Peptidase_S49 (PF01343.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P95072
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible protease IV SppA |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperonesU Intracellular trafficking, secretion and vesicular transport
|
|---|---|
| Preferred name | sppA |
| eggNOG description | signal peptide peptidase SppA, 67K type |
| Orthologous group | COG0616 |
| KEGG orthology |
K04773, K04774
|
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 | 0.296 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 8 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.17% of strains (252) · 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 |
|---|---|---|---|---|
Peptidase_S49 | PF01343.24 | 1.1e-51 | 403–554 | Peptidase family S49 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rpsE (30S ribosomal protein S5), high confidence from genomic context alone (score 724 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0721 rpsE |
30S ribosomal protein S5 | 724 | 724 ctx | neighborhood:676 |
Rv0723 rplO |
50S ribosomal protein L15 | 688 | 688 ctx | neighborhood:685 |
Rv0722 rpmD |
50S ribosomal protein L30 | 677 | 677 ctx | neighborhood:675 |
Rv0719 rplF |
50S ribosomal protein L6 | 630 | 630 ctx | neighborhood:628 |
Rv0720 rplR |
50S ribosomal protein L18 | 630 | 630 ctx | neighborhood:628 |
Rv0718 rpsH |
30S ribosomal protein S8 | 575 | 576 ctx | neighborhood:573 |
Rv1227c |
transmembrane protein | 452 | 453 | coexpression:436 |
Rv1226c |
transmembrane protein | 443 | 443 | coexpression:429 |
Rv3278c |
transmembrane protein | 436 | 437 | coexpression:423 |
Rv0176 |
Mce associated transmembrane protein | 624 | 202 | textmining:549 |
Rv0233 nrdB |
ribonucleoside-diphosphate reductase subunit beta NrdB | 574 | 158 | textmining:515 |
Rv3869 eccB1 |
ESX-1 secretion system protein EccB | 425 | 120 | |
Rv2182c |
1-acylglycerol-3-phosphate O-acyltransferase | 416 | 113 | |
Rv3328c sigJ |
ECF RNA polymerase sigma factor SigJ | 450 | 88 | textmining:423 |
Rv0251c hsp |
heat shock protein | 464 | 86 | textmining:438 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): protease IV SppA
- Pfam (hmmscan --cut_ga): Peptidase_S49 PF01343.24 (E=1e-51)
- (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_215238.1)
- Domains: Pfam-A via hmmscan --cut_ga — Peptidase_S49 (PF01343.24)
- 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
COG0616 - Curated reference: UniProt P95072 (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 —
30 functional partner(s); context anchor
rpsE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0724|sppA MPIFGGFCVCSRALGGRWVRWVNMVAFLPSIPVVEDLRALVGRVDTARHHGVPNGCVLEFNLRSVPPETTGFDPLTVLTGGGRPMALRDAVAAIHRAAEDPRVAGLIARVQLPPSPAGAVQELREAIAAFSAVKPSLAWAETYPGTLSYYLASAFGEVWMQPSGSVGLVGFATNATFLRDALHKAGIEAQFVARGEYKSAANLFTEDGFTDAHREAVTRMLDSLQDQVWQAVAKSRNIGVDALDELADRAPLLRDDAVTCGLIDRIGFRDQAYARMAELVGVEKGSPESSGSQTSPDEKPPRMYLARYASSARPRLTPPVPSIPGRRSKPTIAVVTLEGPIVNGRGGPQFLPLGPSSAGGDTIAAALREVAADDSVSAIVLRVDSPGGSVTASETIWREVARARDRGKPVVASMGAVAASGGYYVSMGADAIVANPGTITGSIGVITGKLVVRDLKDRLGVGSDAVRTNANADAWSIDAPFTPDQQAHREAEADLFYSDFVERVAEGRKMTTDAVDVVARGRVWTGADALDRGLVDELGGLRTAVRRAKVLAGLDEDTEVRIVSYPGSSLWDMVRPRPSSRPAAASLPDAMGALLARSIVGIVEQVEQTLSGASVLWLGESRL