pepR Family assigned · medium auto-curated
H37Rv Rv2782c · MTBC0 mtbc0_002961 ·
438 aa · 3111460–3112776 (-) ·
RefSeq NP_217298.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | zinc protease |
|---|---|
| MTBC0 PGAP re-annotation | pitrilysin family protein |
| Revised (this work) | Pitrilysin family protein. Pfam: Peptidase_M16 (PF00675.26), Peptidase_M16_C (PF05193.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHT5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized zinc protease Rv2782c |
| EC (curated) |
EC 3.4.24.-
|
UniProt still lists this protein as Uncharacterized zinc protease Rv2782c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | pepR |
| eggNOG description | Belongs to the peptidase M16 family |
| Orthologous group | COG0612 |
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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 | 2.56 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 14 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_M16 | PF00675.26 | 8.6e-37 | 25–171 | Insulinase (Peptidase family M16) |
Peptidase_M16_C | PF05193.27 | 4.4e-42 | 179–354 | Peptidase M16 inactive domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gpsI (bifunctional guanosine pentaphosphate synthetase/polyribonucleotide nucleotidyltransferase), high confidence from genomic context alone (score 941 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2195 qcrA |
ubiquinol-cytochrome C reductase rieske iron-sulfur subunit | 997 | 996 | coexpression:710 experimental:928 database:844 |
Rv2196 qcrB |
ubiquinol-cytochrome C reductase cytochrome subunit B | 989 | 989 | experimental:928 database:844 |
Rv3150 nuoF |
NADH-quinone oxidoreductase subunit F | 977 | 974 | coexpression:701 experimental:917 |
Rv3151 nuoG |
NADH-quinone oxidoreductase subunit G | 974 | 971 | coexpression:665 experimental:916 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 973 | 971 | coexpression:652 experimental:915 |
Rv3149 nuoE |
NADH-quinone oxidoreductase subunit E | 969 | 968 | coexpression:638 experimental:915 |
Rv3148 nuoD |
NADH-quinone oxidoreductase subunit D | 963 | 956 | coexpression:595 experimental:895 |
Rv0310c hyp |
hypothetical protein | 956 | 950 | coexpression:409 experimental:919 |
Rv3147 nuoC |
NADH-quinone oxidoreductase subunit C | 947 | 942 | coexpression:489 experimental:891 |
Rv2783c gpsI |
bifunctional guanosine pentaphosphate synthetase/polyribonucleotide nucleotidyltransferase | 945 | 941 ctx | neighborhood:882 |
Rv3146 nuoB |
NADH-quinone oxidoreductase subunit B | 938 | 933 | experimental:894 |
Rv2200c ctaC |
cytochrome C oxidase subunit II | 930 | 923 | experimental:919 |
Rv2193 ctaE |
cytochrome C oxidase subunit III | 926 | 922 | experimental:915 |
Rv3043c ctaD |
cytochrome C oxidase cytochrome 1 | 929 | 920 | experimental:917 |
Rv3157 nuoM |
NADH-quinone oxidoreductase subunit M | 892 | 886 | experimental:882 |
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: zinc protease
- MTBC0 PGAP product: pitrilysin family protein
- Pfam (hmmscan --cut_ga): Peptidase_M16 PF00675.26 (E=9e-37), Peptidase_M16_C PF05193.27 (E=4e-42)
- (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_217298.1)
- Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M16 (PF00675.26), Peptidase_M16_C (PF05193.27)
- 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
COG0612 - Curated reference: UniProt P9WHT5 (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 —
135 functional partner(s); context anchor
gpsI - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002961|Rv2782c|pepR MPRRSPADPAAALAPRRTTLPGGLRVVTEFLPAVHSASVGVWVGVGSRDEGATVAGAAHFLEHLLFKSTPTRSAVDIAQAMDAVGGELNAFTAKEHTCYYAHVLGSDLPLAVDLVADVVLNGRCAADDVEVERDVVLEEIAMRDDDPEDALADMFLAALFGDHPVGRPVIGSAQSVSVMTRAQLQSFHLRRYTPERMVVAAAGNVDHDGLVALVREHFGSRLVRGRRPVAPRKGTGRVNGSPRLTLVSRDAEQTHVSLGIRTPGRGWEHRWALSVLHTALGGGLSSRLFQEVRETRGLAYSVYSALDLFADSGALSVYAACLPERFADVMRVTADVLESVARDGITEAECGIAKGSLRGGLVLGLEDSSSRMSRLGRSELNYGKHRSIEHTLRQIEQVTVEEVNAVARHLLSRRYGAAVLGPHGSKRSLPQQLRAMVG