ilvX Family assigned · medium auto-curated
H37Rv Rv3509c · MTBC0 mtbc0_003724 ·
515 aa · 3962055–3963602 (-) ·
RefSeq NP_218026.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acetohydroxyacid synthase large subunit |
|---|---|
| MTBC0 PGAP re-annotation | acetolactate synthase large subunit |
| Revised (this work) | Acetolactate synthase large subunit. Pfam: TPP_enzyme_N (PF02776.24), TPP_enzyme_C (PF02775.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53554
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative acetolactate synthase large subunit IlvX |
| EC (curated) |
EC 2.2.1.6
|
| Curated function | Catalyzes the conversion of 2 pyruvate molecules into acetolactate in the first common step of the biosynthetic pathway of the branched-amino acids such as leucine, isoleucine, and valine. |
UniProt still lists this protein as Putative acetolactate synthase large subunit IlvX; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolismH Coenzyme transport and metabolism
|
|---|---|
| Preferred name | ilvX |
| eggNOG description | Thiamine pyrophosphate enzyme, C-terminal TPP binding domain |
| Orthologous group | COG0028 |
| EC number |
EC 2.2.1.6
|
| KEGG orthology |
K01652
|
| KEGG pathways |
map00290, map00650, map00660, map00770, map01100, map01110, map01130, map01210, map01230
|
| KEGG modules |
M00019, M00570
|
| Gene Ontology (38) |
GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0006082, GO:0006520, GO:0006549, GO:0006573, GO:0006807, GO:0008150, GO:0008152 +26 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 | 0.381 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 6 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 |
|---|---|---|---|---|
TPP_enzyme_N | PF02776.24 | 5.8e-30 | 1–108 | Thiamine pyrophosphate enzyme, N-terminal TPP binding domain |
TPP_enzyme_C | PF02775.27 | 6.0e-30 | 374–508 | Thiamine pyrophosphate enzyme, C-terminal TPP binding domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3002c ilvN |
acetolactate synthase small subunit | 995 | 992 | coexpression:648 experimental:704 database:900 textmining:490 |
Rv3001c ilvC |
ketol-acid reductoisomerase | 980 | 964 | coexpression:540 database:900 textmining:479 |
Rv2995c leuB |
3-isopropylmalate dehydrogenase | 960 | 948 | coexpression:409 database:900 |
Rv1559 ilvA |
threonine dehydratase IlvA | 957 | 935 | database:900 |
Rv3470c ilvB2 |
acetolactate synthase large subunit | 990 | 926 | database:900 textmining:870 |
Rv3710 leuA |
2-isopropylmalate synthase | 950 | 919 | database:872 textmining:414 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 935 | 915 | database:900 |
Rv3003c ilvB1 |
acetolactate synthase large subunit IlvB | 943 | 911 | database:900 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB | 911 | 906 | database:900 |
Rv1820 ilvG |
acetolactate synthase large subunit IlvG | 937 | 901 | database:900 |
Rv0694 mftD |
mycofactocin system heme/flavin oxidoreductase MftD | 904 | 899 | database:893 |
Rv1872c lldD2 |
L-lactate dehydrogenase | 904 | 899 | database:893 |
Rv3510c hyp |
hypothetical protein | 882 | 882 ctx | neighborhood:881 |
Rv2332 mez |
malate oxidoreductase | 854 | 844 | database:800 |
Rv1617 pykA |
pyruvate kinase | 851 | 836 | database:800 |
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: acetohydroxyacid synthase large subunit
- MTBC0 PGAP product: acetolactate synthase large subunit
- Pfam (hmmscan --cut_ga): TPP_enzyme_N PF02776.24 (E=6e-30), TPP_enzyme_C PF02775.27 (E=6e-30)
- (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_218026.1)
- Domains: Pfam-A via hmmscan --cut_ga — TPP_enzyme_N (PF02776.24), TPP_enzyme_C (PF02775.27)
- 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
COG0028 - Curated reference: UniProt O53554 (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 — 162 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003724|Rv3509c|ilvX MNGAQALINTLVDGGVDVCFANPGTSEMHFVAALDAVPRMRGMLTLFEGVATGAADGYARIAGRPAAVLLHLGPGLGNGLANLHNARRARVPMVVVVGDHATYHKKYDAPLESDIDAVAGTVSGWVRRTEAAADVGADAEAAIAASRSGSQIATLILPADVCWSDGAHAAAGVPAQAAAAPVDVGPVAGVLRSGEPAMMLIGGDATRGPGLTAAARIVQATGARWLCETFPTCLERGAGIPAVERLAYFAEGAAAQLDGVKHLVLAGARSPVSFFAYPGMPSDLVPAGCEVHVLAEPGGAADALAALADEVAPGTVAPVAGASRPQLPTGDLTSVSAADVVGALLPERAIVVDESNTCGVLLPQATAGAPAHDWLTLTGGAIGYGIPAAVGAAVAAPDRPVLCLESDGSAMYTISGLWSQARENLDVTTVIYNNGAYDILRIELQRVGAGSDPGPKALDLLDISRPTMDFVKIAEGMGVPARRVTTCEEFADALRAAFAEPGPHLIDVVVPSLVG