pepE Family assigned · medium auto-curated
H37Rv Rv2089c · MTBC0 mtbc0_002223 ·
375 aa · 2374821–2375948 (-) ·
RefSeq NP_216605.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dipeptidase PepE |
|---|---|
| MTBC0 PGAP re-annotation | Xaa-Pro peptidase family protein |
| Revised (this work) | Xaa-Pro peptidase family protein. Pfam: Creatinase_N (PF01321.25), Peptidase_M24 (PF00557.30). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHS7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable dipeptidase PepE |
| EC (curated) |
EC 3.4.13.-
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | pepE |
| eggNOG description | Belongs to the peptidase M24B family |
| Orthologous group | COG0006 |
| EC number |
EC 3.4.13.9
|
| KEGG orthology |
K01271, K01274
|
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 | 0.272 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 5 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.54% of strains (777) · clonal |
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 |
|---|---|---|---|---|
Creatinase_N | PF01321.25 | 5.2e-06 | 14–146 | Creatinase/Prolidase N-terminal domain |
Peptidase_M24 | PF00557.30 | 5.7e-66 | 154–356 | Metallopeptidase family M24 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2090 (5'-3' exonuclease), high confidence from genomic context alone (score 799 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2090 |
5'-3' exonuclease | 807 | 799 ctx | neighborhood:788 |
Rv2438c nadE |
glutamine-dependent NAD(+) synthetase | 616 | 616 | database:497 |
Rv0730 |
GCN5-like N-acetyltransferase | 627 | 605 ctx | neighborhood:544 |
Rv0480c |
amidohydrolase | 559 | 559 | database:497 |
Rv2996c serA1 |
D-3-phosphoglycerate dehydrogenase | 538 | 538 | |
Rv3336c trpS |
tryptophan--tRNA ligase | 519 | 498 | |
Rv0194 |
multidrug ABC transporter ATPase/permease | 506 | 489 | |
Rv2534c efp |
elongation factor P | 497 | 451 | |
Rv1972 |
Mce associated membrane protein | 466 | 445 | |
Rv2218 lipA |
lipoyl synthase | 443 | 443 | database:424 |
Rv0728c serA2 |
D-3-phosphoglycerate dehydrogenase SerA | 442 | 442 | |
Rv1843c guaB1 |
inosine-5'-monophosphate dehydrogenase | 427 | 427 | |
Rv1362c |
membrane protein | 447 | 425 | |
Rv2390c hyp |
hypothetical protein | 442 | 419 | |
Rv1104 |
Rv1104, (MTV017.57), len: 229 aa. Possible para-nitrobenzyl esterase (fragment; possibly first part). Similar to the N-terminal domain of ma | 439 | 417 |
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: dipeptidase PepE
- MTBC0 PGAP product: Xaa-Pro peptidase family protein
- Pfam (hmmscan --cut_ga): Creatinase_N PF01321.25 (E=5e-06), Peptidase_M24 PF00557.30 (E=6e-66)
- (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_216605.1)
- Domains: Pfam-A via hmmscan --cut_ga — Creatinase_N (PF01321.25), Peptidase_M24 (PF00557.30)
- 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
COG0006 - Curated reference: UniProt P9WHS7 (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 —
49 functional partner(s); context anchor
Rv2090 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002223|Rv2089c|pepE MGSRRFDAEVYARRLALAAAATADAGLAGLVITPGYDLCYLIGSRAETFERLTALVLPAAGAPAVVLPRLELAALKQSAAAELGLRVCDWVDGDDPYGLVSAVLGGAPVATAVTDSMPALHMLPLADALGVLPVLATDVLRRLRMVKEETEIDALRKAGAAIDRVHARVPEFLVPGRTEADVAADIAEAIVAEGHSEVAFVIVGSGPHGADPHHGYSDRELREGDIVVVDIGGTYGPGYHSDSTRTYSIGEPDSDVAQSYSMLQRAQRAAFEAIRPGVTAEQVDAAARDVLAEAGLAEYFVHRTGHGIGLCVHEEPYIVAGNDLVLVPGMAFSIEPGIYFPGRWGARIEDIVIVTEDGAVSVNNCPHELIVVPVS