pepN Resolved · high auto-curated
H37Rv Rv2467 · MTBC0 - ·
861 aa · 2768986–2771571 (+) ·
RefSeq YP_177885.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | aminopeptidase PepN |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Aminopeptidase PepN. Pfam: Peptidase_M1_N (PF17900.7), Peptidase_M1 (PF01433.27), ERAP1_C (PF11838.15). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
L7N655
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Aminopeptidase N |
| EC (curated) |
EC 3.4.11.2
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | pepN |
| eggNOG description | aminopeptidase N |
| Orthologous group | COG0308 |
| EC number |
EC 3.4.11.2
|
| KEGG orthology |
K01256, K08776
|
| KEGG pathways |
map00480, map01100
|
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 | 0.34 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 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_M1_N | PF17900.7 | 6.6e-17 | 111–189 | Peptidase M1 N-terminal domain |
Peptidase_M1 | PF01433.27 | 4.1e-58 | 233–444 | Peptidase family M1 domain |
ERAP1_C | PF11838.15 | 2.2e-50 | 531–850 | ERAP1-like C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: nei1 (DNA glycosylase), high confidence from genomic context alone (score 715 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2213 pepB |
cytosol aminopeptidase | 941 | 924 | database:900 |
Rv0773c ggtA |
bifunctional cephalosporin acylase/gamma-glutamyltranspeptidase | 907 | 902 | database:900 |
Rv0433 |
carboxylate-amine ligase | 910 | 901 | database:900 |
Rv2394 ggtB |
gamma-glutamyltranspeptidase precursor GgtB | 907 | 901 | database:900 |
Rv3704c gshA |
glutamate--cysteine ligase | 900 | 901 | database:900 |
Rv1093 glyA1 |
serine hydroxymethyltransferase | 844 | 825 | database:800 |
Rv0070c glyA2 |
serine hydroxymethyltransferase | 842 | 823 | database:800 |
Rv2294 |
cystathionine beta-lyase | 809 | 809 | database:800 |
Rv2334 cysK1 |
O-acetylserine sulfhydrylase | 814 | 805 | database:800 |
Rv3684 |
lyase | 813 | 804 | database:800 |
Rv0075 |
aminotransferase | 801 | 802 | database:800 |
Rv2464c nei1 |
DNA glycosylase | 715 | 715 ctx | neighborhood:701 |
Rv2465c rpiB |
ribose-5-phosphate isomerase B | 740 | 712 ctx | neighborhood:708 |
Rv1830 |
HTH-type transcriptional regulator | 660 | 660 ctx | cooccurence:653 |
Rv2466c hyp |
hypothetical protein | 638 | 638 ctx | neighborhood:633 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): aminopeptidase PepN
- Pfam (hmmscan --cut_ga): Peptidase_M1_N PF17900.7 (E=7e-17), Peptidase_M1 PF01433.27 (E=4e-58), ERAP1_C PF11838.15 (E=2e-50)
- (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 YP_177885.1)
- Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M1_N (PF17900.7), Peptidase_M1 (PF01433.27), ERAP1_C (PF11838.15)
- 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
COG0308 - Curated reference: UniProt L7N655 (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 —
87 functional partner(s); context anchor
nei1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2467|pepN MALPNLTRDQAVERAALITVDSYQIILDVTDGNGAPGERTFRSTTTVVFDALPGADTVIDISAHTVRRASLNDQDLDVSGYDEAAGIPLRGLAQRNVVVVDADCHYSNTGEGLHRFVDPVDGETYLYSQFETADAKRMFACFDQPDLKATFDVRVTAPAHWKVISNGAPLAAANGVHTFATTPRMSTYLVALIAGPYAAWTDTYIDDHGEIPLGIYCRASLAEYMDAERLFTQTKQGFGFYHKHFGLPYAFGKYDQLFVPEFNAGAMENAGAVTFLEDYVFRSKVTRASYERRAETVLHEMAHMWFGDLVTMTWWDDLWLNESFATFASVLCQSEATEFTEAWTTFATVEKSWAYRQDQLPSTHPIAADIPDLAAVEVNFDGITYAKGASVLKQLVAYVGLERFLAGLRDYFRTHAFGNASFDDLLAALEKASGRDLSNWGEQWLKTTGLNTLRPDFEVDAEGRFTRFAVTQSGAAPGAGETRVHRLAVGIYDDDGSKSSGKLVRVHREELDVSGPITNVPALVGVSRGKLILVNDDDLTYCSLRLDERSLQTALDRIADIAEPLPRTLVWSAAWEMTREAELRARDFVSLVSGGVHAETEVGVAQRLLLQAQTALGCYAEPGWARERGWPQFADRLLELAREAEPGSDHQLAYINSLCSSVLSPRHVQTLGALLEGEPAACGLAGLAVDTDLRWRIVTALATAGAIDADGPETPRIDAEVQRDPTAAGKRHAAQARAARPQFVVKDEAFTTVVEDDTLANATGRAMIAGIAAPGQGELLKPFARRYFQAIPGVWARRSSEVAQSVVIGLYPHWDISEQGITAAEEFLSDPEVPPALRRLVLEGQAAVQRSLRARNFDADG