pepA Family assigned · medium auto-curated
H37Rv Rv0125 · MTBC0 mtbc0_000136 ·
355 aa · 151494–152561 (+) ·
RefSeq NP_214639.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | serine protease PepA |
|---|---|
| MTBC0 PGAP re-annotation | S1C family serine protease |
| Revised (this work) | S1C family serine protease. Pfam: Trypsin_2 (PF13365.13), Trypsin (PF00089.33), PDZ (PF00595.30), PDZ_2 (PF13180.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O07175
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable serine protease PepA |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | pepA |
| eggNOG description | serine protease |
| Orthologous group | COG0265 |
| KEGG orthology |
K08372
|
| KEGG pathways |
map02020
|
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 | 0.308 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 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 |
|---|---|---|---|---|
Trypsin_2 | PF13365.13 | 1.3e-25 | 79–222 | Trypsin-like peptidase domain |
Trypsin | PF00089.33 | 5.4e-11 | 79–243 | Trypsin |
PDZ | PF00595.30 | 2.8e-06 | 267–319 | PDZ domain |
PDZ_2 | PF13180.13 | 5.3e-12 | 269–336 | PDZ domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: treS (trehalose synthase/amylase TreS), high confidence from genomic context alone (score 797 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2115c mpa |
proteasome-associated ATPase | 824 | 813 | experimental:551 database:594 |
Rv0126 treS |
trehalose synthase/amylase TreS | 806 | 797 ctx | neighborhood:768 |
Rv3696c glpK |
glycerol kinase | 767 | 753 | experimental:402 database:589 |
Rv0127 mak |
maltokinase | 701 | 701 ctx | neighborhood:698 |
Rv1334 mec |
[CysO | 708 | 698 | database:576 |
Rv2109c prcA |
proteasome subunit alpha | 637 | 620 | database:562 |
Rv2110c prcB |
proteasome subunit beta | 709 | 618 | database:562 |
Rv2555c alaS |
alanine--tRNA ligase | 625 | 612 | database:586 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 649 | 604 | |
Rv2048c pks12 |
polyketide synthase | 648 | 602 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 648 | 602 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 647 | 600 | |
Rv1527c pks5 |
polyketide synthase | 647 | 600 | |
Rv0128 |
transmembrane protein | 595 | 595 ctx | neighborhood:593 |
Rv1293 lysA |
diaminopimelate decarboxylase | 590 | 591 | database:588 |
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: serine protease PepA
- MTBC0 PGAP product: S1C family serine protease
- Pfam (hmmscan --cut_ga): Trypsin_2 PF13365.13 (E=1e-25), Trypsin PF00089.33 (E=5e-11), PDZ PF00595.30 (E=3e-06), PDZ_2 PF13180.13 (E=5e-12)
- (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_214639.1)
- Domains: Pfam-A via hmmscan --cut_ga — Trypsin_2 (PF13365.13), Trypsin (PF00089.33), PDZ (PF00595.30), PDZ_2 (PF13180.13)
- 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
COG0265 - Curated reference: UniProt O07175 (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 —
233 functional partner(s); context anchor
treS - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000136|Rv0125|pepA MSNSRRRSLRWSWLLSVLAAVGLGLATAPAQAAPPALSQDRFADFPALPLDPSAMVAQVGPQVVNINTKLGYNNAVGAGTGIVIDPNGVVLTNNHVIAGATDINAFSVGSGQTYGVDVVGYDRTQDVAVLQLRGAGGLPSAAIGGGVAVGEPVVAMGNSGGQGGTPRAVPGRVVALGQTVQASDSLTGAEETLNGLIQFDAAIQPGDSGGPVVNGLGQVVGMNTAASDNFQLSQGGQGFAIPIGQAMAIAGQIRSGGGSPTVHIGPTAFLGLGVVDNNGNGARVQRVVGSAPAASLGISTGDVITAVDGAPINSATAMADALNGHHPGDVISVTWQTKSGGTRTGNVTLAEGPPA