Rv0457c Family assigned · medium auto-curated

H37Rv Rv0457c · MTBC0 mtbc0_000481 · 673 aa · 550951–552972 (-) · RefSeq NP_214971.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)peptidase
MTBC0 PGAP re-annotationprolyl oligopeptidase family protein
Revised (this work)Prolyl oligopeptidase family protein. Pfam: Peptidase_S9_N (PF02897.22), Peptidase_S9 (PF00326.28).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt O07178 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable peptidase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
eggNOG descriptionProlyl oligopeptidase
Orthologous groupCOG1505
EC number EC 3.4.21.26
KEGG orthology K01322
KEGG pathways map04614

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 1.33 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 6 missense, 2 nonsense, 2 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 17.54% of strains (25465) · convergent

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)

PfamAccessioni-EvalueResiduesDescription
Peptidase_S9_NPF02897.22 3.6e-2310–391 Prolyl oligopeptidase, N-terminal beta-propeller domain
Peptidase_S9PF00326.28 1.9e-42470–671 Prolyl oligopeptidase family

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: Rv0458 (aldehyde dehydrogenase), high confidence from genomic context alone (score 775 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0458 aldehyde dehydrogenase 783 775 ctx neighborhood:763
Rv0459 hyp hypothetical protein 772 772 ctx neighborhood:772
Rv0781 ptrBa Rv0781, (MTCY369.25), len: 236 aa. Probable ptrBa,first part of protease II, equivalent to N-terminus of NP_302455.1|NC_002677 protease II f 767 759 ctx fusion:518 cooccurence:469
Rv0460 hyp hypothetical protein 708 709 ctx neighborhood:708
Rv0456c echA2 enoyl-CoA hydratase EchA2 683 683 ctx neighborhood:681
Rv0461 transmembrane protein 681 681 ctx neighborhood:680
Rv0455c hyp hypothetical protein 635 636 ctx neighborhood:635
Rv0456A mazF1 toxin MazF1 589 589 ctx neighborhood:588
Rv0456B mazE1 antitoxin MazE1 587 588 ctx neighborhood:588
Rv0463 membrane protein 488 489 ctx neighborhood:487
Rv0198c zmp1 zinc metalloprotease 669 486 ctx cooccurence:444
Rv0462 lpdC dihydrolipoamide dehydrogenase 465 465 ctx neighborhood:462
Rv0782 ptrBb Rv0782, (MTCY369.26), len: 552 aa. Probable ptrBb,second part of protease II, equivalent to C-terminus of NP_302455.1|NC_002677 protease II 568 340
Rv1284 canA beta-carbonic anhydrase 439 55 textmining:431
Rv3588c canB carbonic anhydrase 512 41 textmining:512

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: peptidase
  • MTBC0 PGAP product: prolyl oligopeptidase family protein
  • Pfam (hmmscan --cut_ga): Peptidase_S9_N PF02897.22 (E=4e-23), Peptidase_S9 PF00326.28 (E=2e-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_214971.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_S9_N (PF02897.22), Peptidase_S9 (PF00326.28)
  • 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 COG1505
  • Curated reference: UniProt O07178 (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 — 15 functional partner(s); context anchor Rv0458
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000481|Rv0457c|
MTFEPAPDGADPYLWLEDVTGAEALDWVRARNKPTTAAFCDAEFERMRVEALEVLDTDARIPYVNRRGNYLYNFWRDAANPRGLWRRTTLDSYRTDSPGWDVLIDVDELGRADDQKWVWGGAGVIEPDYTRALIGLSPGGSDASIVREFDMLTREFVEDGFQLPPAKSQITWEDPDTVLLGTDFGGDSLTTSGYPRVIKRWRRGKPLADAETIFEGAGTDVRVNASADRTPGFERTLLGRALDFWNEEVYELRGSELIRIEAPTDASVSIHRDWLLIELRTDWTVATTRYTAGSLLAAEYDEFLAGSAELQVVFEPDEHTALYQYAWTRDRLLIVTLADVASRVEIATPGSWRREPLSGIPAATNTVIVSADSHGDEFFLDSSGFDTPSRLMRGTDDGRLAEIKSAPAFFDAENMAVTQYFATSDDGTSIPYFVVRRTDADNPGPTLLNGYGGFETSRTPTYDGVLGRLWLARGGTYALANIRGGGEYGPGWHTQAMREGRDKVAQDFAAVATDLVTRGITTAEQLGARGGSNGGLLMGIMLTGYPEKFGALVCDVPLLDMKRYHLLLAGASWMAEYGDPDNPDDWKFISEYSPYQNISANRKYPPVLMTTSTRDDRVHPGHARKMTAALQAAGHPVWYYENIEGGHAGAADNAQIAFKSALSFAFLWRMLAG