pip Family assigned · medium auto-curated
H37Rv Rv0840c · MTBC0 mtbc0_000895 ·
286 aa · 939608–940468 (-) ·
RefSeq NP_215355.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | proline iminopeptidase |
|---|---|
| MTBC0 PGAP re-annotation | proline-specific peptidase family protein |
| Revised (this work) | Proline-specific peptidase family protein. Pfam: Abhydrolase_1 (PF00561.27), Abhydrolase_6 (PF12697.14). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6Y8X0
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Proline iminopeptidase |
| EC (curated) |
EC 3.4.11.5
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | pip |
| eggNOG description | Belongs to the peptidase S33 family |
| Orthologous group | COG0596 |
| EC number |
EC 3.4.11.5, EC 3.5.1.101
|
| KEGG orthology |
K01259, K18457
|
| KEGG pathways |
map00330
|
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 | 0.958 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 3 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.13% of strains (186) · 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 |
|---|---|---|---|---|
Abhydrolase_1 | PF00561.27 | 3.8e-19 | 24–270 | alpha/beta hydrolase fold |
Abhydrolase_6 | PF12697.14 | 2.7e-18 | 25–273 | Alpha/beta hydrolase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0841 (transmembrane protein), medium confidence from genomic context alone (score 454 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0500 proC |
pyrroline-5-carboxylate reductase | 903 | 903 | database:900 |
Rv1188 |
proline dehydrogenase | 901 | 902 | database:900 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 529 | 501 | experimental:441 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 528 | 500 | experimental:441 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 527 | 500 | experimental:441 |
Rv2048c pks12 |
polyketide synthase | 527 | 500 | experimental:441 |
Rv1527c pks5 |
polyketide synthase | 526 | 499 | experimental:441 |
Rv2946c pks1 |
polyketide synthase | 488 | 458 | |
Rv0841 |
transmembrane protein | 454 | 454 ctx | neighborhood:429 |
Rv1661 pks7 |
polyketide synthase | 451 | 426 | |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 451 | 426 | |
Rv1663 pks17 |
polyketide synthase | 435 | 414 | |
Rv0405 pks6 |
membrane bound polyketide synthase | 644 | 275 | textmining:530 |
Rv0640 rplK |
50S ribosomal protein L11 | 440 | 205 | |
Rv0908 ctpE |
metal cation transporter ATPase E | 670 | 143 | textmining:631 |
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: proline iminopeptidase
- MTBC0 PGAP product: proline-specific peptidase family protein
- Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=4e-19), Abhydrolase_6 PF12697.14 (E=3e-18)
- (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_215355.1)
- Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_1 (PF00561.27), Abhydrolase_6 (PF12697.14)
- 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
COG0596 - Curated reference: UniProt I6Y8X0 (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 —
25 functional partner(s); context anchor
Rv0841 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000895|Rv0840c|pip MEGTIAVPGGRVWFQRIGGGPGRPLLVVHGGPGLPHNYLAPLRRLSDEREVIFWDQLGCGNSACPSDVDLWTMNRSVAEMATVAEALALTRFHIFSHSWGGMLAQQYVLDKAPDAVSLTIANSTASIPEFSASLVSLKSCLDVATRSAIDRHEAAGTTHSAEYQAAIRTWNETYLCRTRPWPRELTEAFANMGTEIFETMFGPSDFRIVGNVRDWDVVDRLADIAVPTLLVVGRFDECSPEHMREMQGRIAGSRLEFFESSSHMPFIEEPARFDRVMREFLRLHDI