pepB Resolved · high auto-curated
H37Rv Rv2213 · MTBC0 mtbc0_002349 ·
515 aa · 2504495–2506042 (+) ·
RefSeq NP_216729.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cytosol aminopeptidase |
|---|---|
| MTBC0 PGAP re-annotation | leucyl aminopeptidase |
| Revised (this work) | Leucyl aminopeptidase. Pfam: Peptidase_M17_N (PF02789.24), Peptidase_M17 (PF00883.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHT3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable cytosol aminopeptidase |
| EC (curated) |
EC 3.4.11.1, EC 3.4.11.10
|
| Curated function | Presumably involved in the processing and regular turnover of intracellular proteins. Catalyzes the removal of unsubstituted N-terminal amino acids from various peptides (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | pepA |
| eggNOG description | Presumably involved in the processing and regular turnover of intracellular proteins. Catalyzes the removal of unsubstituted N-terminal amino acids from various peptides |
| Orthologous group | COG0260 |
| EC number |
EC 3.4.11.1
|
| KEGG orthology |
K01255
|
| KEGG pathways |
map00480, map01100
|
| Gene Ontology (8) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, 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 | 0.583 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 8 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_M17_N | PF02789.24 | 2.3e-21 | 45–157 | Cytosol aminopeptidase family, N-terminal domain |
Peptidase_M17 | PF00883.27 | 1.4e-114 | 193–504 | Cytosol aminopeptidase family, catalytic domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2212 (adenylyl cyclase), high confidence from genomic context alone (score 874 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2467 pepN |
aminopeptidase PepN | 941 | 924 | database:900 |
Rv0773c ggtA |
bifunctional cephalosporin acylase/gamma-glutamyltranspeptidase | 928 | 919 | database:900 |
Rv2394 ggtB |
gamma-glutamyltranspeptidase precursor GgtB | 912 | 901 | database:900 |
Rv3704c gshA |
glutamate--cysteine ligase | 900 | 901 | database:900 |
Rv0433 |
carboxylate-amine ligase | 900 | 901 | database:900 |
Rv2212 |
adenylyl cyclase | 880 | 874 ctx | neighborhood:872 |
Rv2211c gcvT |
aminomethyltransferase | 861 | 856 ctx | neighborhood:785 |
Rv2334 cysK1 |
O-acetylserine sulfhydrylase | 837 | 828 | database:800 |
Rv3684 |
lyase | 835 | 826 | database:800 |
Rv2294 |
cystathionine beta-lyase | 816 | 817 | database:800 |
Rv1093 glyA1 |
serine hydroxymethyltransferase | 831 | 815 | database:800 |
Rv0075 |
aminotransferase | 811 | 812 | database:800 |
Rv0070c glyA2 |
serine hydroxymethyltransferase | 826 | 811 | database:800 |
Rv0761c adhB |
alcohol dehydrogenase B | 796 | 784 | coexpression:756 |
Rv2299c htpG |
chaperone protein HtpG | 733 | 734 | coexpression:732 |
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: cytosol aminopeptidase
- MTBC0 PGAP product: leucyl aminopeptidase
- Pfam (hmmscan --cut_ga): Peptidase_M17_N PF02789.24 (E=2e-21), Peptidase_M17 PF00883.27 (E=1e-114)
- (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_216729.1)
- Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M17_N (PF02789.24), Peptidase_M17 (PF00883.27)
- 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
COG0260 - Curated reference: UniProt P9WHT3 (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 —
27 functional partner(s); context anchor
Rv2212 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002349|Rv2213|pepB MTTEPGYLSPSVAVATSMPKRGVGAAVLIVPVVSTGEEDRPGAVVASAEPFLRADTVAEIEAGLRALDATGASDQVHRLAVPSLPVGSVLTVGLGKPRREWPADTIRCAAGVAARALNSSEAVITTLAELPGDGICSATVEGLILGSYRFSAFRSDKTAPKDAGLRKITVLCCAKDAKKRALHGAAVATAVATARDLVNTPPSHLFPAEFAKRAKTLSESVGLDVEVIDEKALKKAGYGGVIGVGQGSSRPPRLVRLIHRGSRLAKNPQKAKKVALVGKGITFDTGGISIKPAASMHHMTSDMGGAAAVIATVTLAARLRLPIDVIATVPMAENMPSATAQRPGDVLTQYGGTTVEVLNTDAEGRLILADAIVRACEDKPDYLIETSTLTGAQTVALGTRIPGVMGSDEFRDRVAAISQRVGENGWPMPLPDDLKDDLKSTVADLANVSGQRFAGMLVAGVFLREFVAESVDWAHIDVAGPAYNTGSAWGYTPKGATGVPTRTMFAVLEDIAKNG