pepD Resolved · high auto-curated
H37Rv Rv0983 · MTBC0 mtbc0_001054 ·
464 aa · 1106402–1107796 (+) ·
RefSeq NP_215498.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | serine protease PepD |
|---|---|
| MTBC0 PGAP re-annotation | serine protease PepD |
| Revised (this work) | Serine protease PepD. Pfam: Trypsin (PF00089.33), Trypsin_2 (PF13365.13), 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 |
O53896
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Serine protease PepD |
| EC (curated) |
EC 3.4.21.107
|
| Curated function | Required for virulence. Acts both as a protease, which degrades and/or refolds damaged substrate targets, and as a chaperone. Plays an important role in the stress response network mediated through the two-component regulatory system MprAB and SigE signaling networks. May utilize its PDZ domain to recognize and process misfolded proteins at the cell membrane, leading to activation of the MprAB and SigE signaling pathways and subsequent establishment of a positive feedback loop that facilitates bacterial adaptation. Interacts with and potentially cleaves several proteins, including the 35 kDa a. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | pepD |
| eggNOG description | COG0265 Trypsin-like serine proteases, typically periplasmic, contain C-terminal PDZ domain |
| 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 | 0.204 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 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 | PF00089.33 | 7.1e-16 | 180–359 | Trypsin |
Trypsin_2 | PF13365.13 | 2.1e-32 | 181–331 | Trypsin-like peptidase domain |
PDZ | PF00595.30 | 6.7e-06 | 373–444 | PDZ domain |
PDZ_2 | PF13180.13 | 7.4e-10 | 378–446 | PDZ domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: moaB2 (pterin-4-alpha-carbinolamine dehydratase), high confidence from genomic context alone (score 982 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0984 moaB2 |
pterin-4-alpha-carbinolamine dehydratase | 981 | 982 ctx | neighborhood:881 coexpression:853 |
Rv0982 mprB |
two component histidine-protein kinase/phosphatase MprB | 941 | 939 ctx | neighborhood:702 coexpression:805 |
Rv2115c mpa |
proteasome-associated ATPase | 831 | 821 | experimental:551 database:594 |
Rv0563 htpX |
protease HtpX | 819 | 810 | coexpression:804 |
Rv0981 mprA |
two-component response regulator MrpA | 790 | 776 ctx | neighborhood:683 |
Rv2710 sigB |
RNA polymerase sigma factor SigB | 788 | 771 | coexpression:710 |
Rv2711 ideR |
iron-dependent repressor and activator IdeR | 761 | 762 | coexpression:757 |
Rv3837c |
phosphoglycerate mutase | 760 | 761 | coexpression:757 |
Rv2051c ppm1 |
polyprenol-monophosphomannose synthase | 769 | 759 | coexpression:730 |
Rv3696c glpK |
glycerol kinase | 767 | 753 | experimental:402 database:589 |
Rv2053c fxsA |
transmembrane protein FxsA | 740 | 741 | coexpression:732 |
Rv1334 mec |
[CysO | 721 | 712 | database:576 |
Rv2109c prcA |
proteasome subunit alpha | 645 | 628 | database:562 |
Rv2110c prcB |
proteasome subunit beta | 643 | 626 | database:562 |
Rv2555c alaS |
alanine--tRNA ligase | 639 | 626 | database:586 |
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 PepD
- MTBC0 PGAP product: serine protease PepD
- Pfam (hmmscan --cut_ga): Trypsin PF00089.33 (E=7e-16), Trypsin_2 PF13365.13 (E=2e-32), PDZ PF00595.30 (E=7e-06), PDZ_2 PF13180.13 (E=7e-10)
- (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_215498.1)
- Domains: Pfam-A via hmmscan --cut_ga — Trypsin (PF00089.33), Trypsin_2 (PF13365.13), 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 O53896 (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 —
246 functional partner(s); context anchor
moaB2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001054|Rv0983|pepD MAKLARVVGLVQEEQPSDMTNHPRYSPPPQQPGTPGYAQGQQQTYSQQFDWRYPPSPPPQPTQYRQPYEALGGTRPGLIPGVIPTMTPPPGMVRQRPRAGMLAIGAVTIAVVSAGIGGAAASLVGFNRAPAGPSGGPVAASAAPSIPAANMPPGSVEQVAAKVVPSVVMLETDLGRQSEEGSGIILSAEGLILTNNHVIAAAAKPPLGSPPPKTTVTFSDGRTAPFTVVGADPTSDIAVVRVQGVSGLTPISLGSSSDLRVGQPVLAIGSPLGLEGTVTTGIVSALNRPVSTTGEAGNQNTVLDAIQTDAAINPGNSGGALVNMNAQLVGVNSAIATLGADSADAQSGSIGLGFAIPVDQAKRIADELISTGKASHASLGVQVTNDKDTPGAKIVEVVAGGAAANAGVPKGVVVTKVDDRPINSADALVAAVRSKAPGATVALTFQDPSGGSRTVQVTLGKAEQ