prcA Family assigned · medium auto-curated
H37Rv Rv2109c · MTBC0 mtbc0_002241 ·
248 aa · 2396246–2396992 (-) ·
RefSeq NP_216625.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | proteasome subunit alpha |
|---|---|
| MTBC0 PGAP re-annotation | proteasome subunit alpha |
| Revised (this work) | Proteasome subunit alpha. Pfam: Proteasome (PF00227.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHU1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Proteasome subunit alpha |
| Curated function | Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. The M.tuberculosis proteasome is able to cleave oligopeptides not only after hydrophobic but also after basic, acidic and small neutral residues. In complex with the ATPase Mpa, degrades protein targets conjugated to a prokaryotic ubiquitin-like protein (Pup). Among the identified substrates of the M.tuberculosis proteasome are the pupylated FabD, PanB and Mpa proteins. One function of the proteasome is to contribute to M.tuberculosis ability to resist killing by host macrophages,. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | prcA |
| eggNOG description | Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation |
| Orthologous group | COG0638 |
| EC number |
EC 3.4.25.1
|
| KEGG orthology |
K03432
|
| KEGG pathways |
map03050
|
| KEGG modules |
M00342, M00343
|
| Gene Ontology (55) |
GO:0000502, GO:0003674, GO:0003824, GO:0004175, GO:0004298, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005839, GO:0005886, GO:0006508 +43 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 | 0.334 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 5 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 |
|---|---|---|---|---|
Proteasome | PF00227.32 | 8.4e-22 | 26–204 | Proteasome subunit |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: prcB (proteasome subunit beta), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2110c prcB |
proteasome subunit beta | 999 | 1000 ctx | neighborhood:881 cooccurence:774 coexpression:751 experimental:999 database:900 textmining:948 |
Rv2115c mpa |
proteasome-associated ATPase | 999 | 1000 ctx | cooccurence:757 experimental:999 database:662 textmining:657 |
Rv2111c pup |
ubiquitin-like protein Pup | 998 | 997 ctx | neighborhood:881 cooccurence:750 experimental:898 textmining:684 |
Rv3780 bpa hyp |
hypothetical protein | 981 | 976 ctx | cooccurence:766 experimental:900 |
Rv2112c dop |
pup deamidase/depupylase | 979 | 939 ctx | neighborhood:766 cooccurence:739 textmining:673 |
Rv2097c pafA |
proteasome accessory factor PafA | 985 | 934 ctx | neighborhood:539 fusion:473 cooccurence:744 textmining:782 |
Rv1334 mec |
[CysO | 937 | 929 | experimental:786 database:662 |
Rv3696c glpK |
glycerol kinase | 936 | 928 | experimental:791 database:662 |
Rv3868 eccA1 |
ESX-1 secretion system protein EccA1 | 760 | 746 | experimental:406 database:537 |
Rv0282 eccA3 |
ESX-3 secretion system protein EccA | 756 | 742 | experimental:406 database:537 |
Rv0435c |
ATPase | 756 | 741 | experimental:406 database:537 |
Rv3884c eccA2 |
ESX-2 secretion system protein EccA | 754 | 739 | experimental:406 database:537 |
Rv2555c alaS |
alanine--tRNA ligase | 651 | 652 | database:601 |
Rv0983 pepD |
serine protease PepD | 645 | 628 | database:562 |
Rv1223 htrA |
serine protease HtrA | 645 | 628 | database:562 |
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: proteasome subunit alpha
- MTBC0 PGAP product: proteasome subunit alpha
- Pfam (hmmscan --cut_ga): Proteasome PF00227.32 (E=8e-22)
- (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_216625.1)
- Domains: Pfam-A via hmmscan --cut_ga — Proteasome (PF00227.32)
- 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
COG0638 - Curated reference: UniProt P9WHU1 (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 —
65 functional partner(s); context anchor
prcB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002241|Rv2109c|prcA MSFPYFISPEQAMRERSELARKGIARAKSVVALAYAGGVLFVAENPSRSLQKISELYDRVGFAAAGKFNEFDNLRRGGIQFADTRGYAYDRRDVTGRQLANVYAQTLGTIFTEQAKPYEVELCVAEVAHYGETKPPELYRITYDGSIADEPHFVVMGGTTEPIANALKESYAENASLTDALGIAVAALRAGSADTSGGDQPTLGVASLEVAVLDANRPRRAFRRITGSALQALLVDQESPQSDGESSG