rraA Resolved · high auto-curated
H37Rv Rv3853 · MTBC0 mtbc0_004086 ·
157 aa · 4349605–4350078 (+) ·
RefSeq NP_218370.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | RNase E regulator RraA |
|---|---|
| MTBC0 PGAP re-annotation | ribonuclease E activity regulator RraA |
| Revised (this work) | Ribonuclease E activity regulator RraA. Pfam: RraA-like (PF03737.22). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WGY3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative 4-hydroxy-4-methyl-2-oxoglutarate aldolase |
| EC (curated) |
EC 4.1.1.112, EC 4.1.3.17
|
| Curated function | Catalyzes the aldol cleavage of 4-hydroxy-4-methyl-2-oxoglutarate (HMG) into 2 molecules of pyruvate. Also contains a secondary oxaloacetate (OAA) decarboxylase activity due to the common pyruvate enolate transition state formed following C-C bond cleavage in the retro-aldol and decarboxylation reactions (By similarity). |
UniProt still lists this protein as Putative 4-hydroxy-4-methyl-2-oxoglutarate aldolase; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | rraA |
| eggNOG description | Catalyzes the aldol cleavage of 4-hydroxy-4-methyl-2- oxoglutarate (HMG) into 2 molecules of pyruvate. Also contains a secondary oxaloacetate (OAA) decarboxylase activity due to the common pyruvate enolate transition state formed following C-C bond cleavage in the retro-aldol and decarboxylation reactions |
| Orthologous group | COG0684 |
| KEGG orthology |
K02553
|
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 | 0.118 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 1 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 |
|---|---|---|---|---|
RraA-like | PF03737.22 | 1.1e-43 | 8–156 | Aldolase/RraA |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hns (histone-like protein Hns), high confidence from genomic context alone (score 879 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3852 hns |
histone-like protein Hns | 879 | 879 ctx | neighborhood:861 |
Rv3850 hyp |
hypothetical protein | 752 | 753 ctx | neighborhood:751 |
Rv3851 |
membrane protein | 528 | 528 ctx | neighborhood:523 |
Rv0467 icl1 |
isocitrate lyase | 540 | 524 | |
Rv3849 espR |
ESX-1 transcriptional regulator EspR | 516 | 516 ctx | neighborhood:514 |
Rv3846 sodA |
superoxide dismutase | 470 | 470 | |
Rv3211 rhlE |
ATP-dependent RNA helicase RhlE | 494 | 444 | experimental:438 |
Rv1253 deaD |
ATP-dependent RNA helicase DeaD | 489 | 440 | experimental:438 |
Rv1869c |
reductase | 409 | 410 | coexpression:408 |
Rv0688 |
ferredoxin reductase | 409 | 409 | coexpression:407 |
Rv0252 nirB |
nitrite reductase large subunit NirB | 406 | 407 | coexpression:405 |
Rv0985c mscL |
large-conductance ion mechanosensitive channel | 429 | 406 | coexpression:406 |
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: RNase E regulator RraA
- MTBC0 PGAP product: ribonuclease E activity regulator RraA
- Pfam (hmmscan --cut_ga): RraA-like PF03737.22 (E=1e-43)
- (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_218370.1)
- Domains: Pfam-A via hmmscan --cut_ga — RraA-like (PF03737.22)
- 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
COG0684 - Curated reference: UniProt P9WGY3 (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 —
12 functional partner(s); context anchor
hns - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004086|Rv3853|rraA MAISFRPTADLVDDIGPDVRSCDLQFRQFGGRSQFAGPISTVRCFQDNALLKSVLSQPSAGGVLVIDGAGSLHTALVGDVIAELARSTGWTGLIVHGAVRDAAALRGIDIGIKALGTNPRKSTKTGAGERDVEITLGGVTFVPGDIAYSDDDGIIVV