ppiA Resolved · high auto-curated
H37Rv Rv0009 · MTBC0 - ·
182 aa · 12468–13016 (+) ·
RefSeq NP_214523.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | iron-regulated peptidyl-prolyl cis-trans isomerase PpiA |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Iron-regulated peptidyl-prolyl cis-trans isomerase PpiA. Pfam: Pro_isomerase (PF00160.27). |
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 |
P9WHW3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Peptidyl-prolyl cis-trans isomerase A |
| EC (curated) |
EC 5.2.1.8
|
| Curated function | PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | ppiA |
| eggNOG description | PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides |
| Orthologous group | COG0652 |
| EC number |
EC 5.2.1.8
|
| KEGG orthology |
K03767, K03768
|
| KEGG pathways |
map01503, map04217
|
| Gene Ontology (43) |
GO:0000413, GO:0003674, GO:0003755, GO:0003824, GO:0005575, GO:0005576, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886 +31 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 | 0.132 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 2 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 |
|---|---|---|---|---|
Pro_isomerase | PF00160.27 | 3.5e-48 | 18–180 | Cyclophilin type peptidyl-prolyl cis-trans isomerase/CLD |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2048c pks12 |
polyketide synthase | 926 | 919 | experimental:910 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 926 | 919 | experimental:910 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 925 | 919 | experimental:910 |
Rv1527c pks5 |
polyketide synthase | 925 | 918 | experimental:910 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 925 | 918 | experimental:910 |
Rv3211 rhlE |
ATP-dependent RNA helicase RhlE | 880 | 873 | experimental:473 database:626 |
Rv2299c htpG |
chaperone protein HtpG | 886 | 872 | experimental:465 database:655 |
Rv0714 rplN |
50S ribosomal protein L14 | 861 | 857 | coexpression:410 experimental:768 |
Rv1253 deaD |
ATP-dependent RNA helicase DeaD | 861 | 853 | experimental:473 database:626 |
Rv0682 rpsL |
30S ribosomal protein S12 | 854 | 847 | coexpression:782 |
Rv1663 pks17 |
polyketide synthase | 842 | 835 | experimental:821 |
Rv0704 rplB |
50S ribosomal protein L2 | 838 | 832 | coexpression:710 experimental:445 |
Rv0715 rplX |
50S ribosomal protein L24 | 831 | 832 | experimental:779 |
Rv0640 rplK |
50S ribosomal protein L11 | 837 | 831 | experimental:777 |
Rv3443c rplM |
50S ribosomal protein L13 | 838 | 829 | experimental:768 |
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): iron-regulated peptidyl-prolyl cis-trans isomerase PpiA
- Pfam (hmmscan --cut_ga): Pro_isomerase PF00160.27 (E=3e-48)
- (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_214523.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pro_isomerase (PF00160.27)
- 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
COG0652 - Curated reference: UniProt P9WHW3 (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 — 226 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0009|ppiA MADCDSVTNSPLATATATLHTNRGDIKIALFGNHAPKTVANFVGLAQGTKDYSTQNASGGPSGPFYDGAVFHRVIQGFMIQGGDPTGTGRGGPGYKFADEFHPELQFDKPYLLAMANAGPGTNGSQFFITVGKTPHLNRRHTIFGEVIDAESQRVVEAISKTATDGNDRPTDPVVIESITIS