pepC Family assigned · medium auto-curated

H37Rv Rv0800 · MTBC0 mtbc0_000849 · 433 aa · 896385–897686 (+) · RefSeq NP_215315.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)M18 family aminopeptidase
MTBC0 PGAP re-annotationM18 family aminopeptidase
Revised (this work)M18 family aminopeptidase. Pfam: Peptidase_M18 (PF02127.21).

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

Curated reference (UniProt)

UniProt P9WHT1 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable M18 family aminopeptidase 2
EC (curated) EC 3.4.11.-

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nameapeB
eggNOG descriptionM18 family aminopeptidase 2
Orthologous groupCOG1362
EC number EC 3.4.11.21
KEGG orthology K01267
Gene Ontology (36) GO:0003674, GO:0003824, GO:0004177, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006508, GO:0006518, GO:0006807 +24 more

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 0.633 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 7 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)

PfamAccessioni-EvalueResiduesDescription
Peptidase_M18PF02127.21 4.2e-14511–425 Aminopeptidase I zinc metalloprotease (M18)

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

Closest characterised functional partner: purL (phosphoribosylformylglycinamidine synthase 2), medium confidence from genomic context alone (score 548 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0801 hyp hypothetical protein 873 874 ctx neighborhood:872
Rv0798c cfp29 hyp hypothetical protein 794 794 ctx neighborhood:788
Rv0799c hyp hypothetical protein 791 791 ctx neighborhood:788
Rv0803 purL phosphoribosylformylglycinamidine synthase 2 547 548 ctx neighborhood:544
Rv2461c clpP1 ATP-dependent CLP protease proteolytic subunit 1 560 104 textmining:530
Rv3011c gatA glutamyl-tRNA(GLN) amidotransferase subunit A 421 55 textmining:413

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: M18 family aminopeptidase
  • MTBC0 PGAP product: M18 family aminopeptidase
  • Pfam (hmmscan --cut_ga): Peptidase_M18 PF02127.21 (E=4e-145)
  • (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_215315.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M18 (PF02127.21)
  • 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 COG1362
  • Curated reference: UniProt P9WHT1 (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 — 6 functional partner(s); context anchor purL
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000849|Rv0800|pepC
MAATAHGLCEFIDASPSPFHVCATVAGRLLGAGYRELREADRWPDKPGRYFTVRAGSLVAWNAEQSGHTQVPFRIVGAHTDSPNLRVKQHPDRLVAGWHVVALQPYGGVWLHSWLDRDLGISGRLSVRDGTGVSHRLVRIDDPILRVPQLAIHLAEDRKSLTLDPQRHINAVWGVGERVESFVGYVAQRAGVAAADVLAADLMTHDLTPSALIGASVNGTASLLSAPRLDNQASCYAGMEALLAVDVDSASSGFVPVLAIFDHEEVGSASGHGAQSDLLSSVLERIVLAAGGTREDFLRRLTTSMLASADMAHATHPNYPDRHEPSHPIEVNAGPVLKVHPNLRYATDGRTAAAFALACQRAGVPMQRYEHRADLPCGSTIGPLAAARTGIPTVDVGAAQLAMHSARELMGAHDVAAYSAALQAFLSAELSEA