ilvC Resolved · high auto-curated
H37Rv Rv3001c · MTBC0 mtbc0_003190 ·
333 aa · 3380894–3381895 (-) ·
RefSeq NP_217517.3
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ketol-acid reductoisomerase |
|---|---|
| MTBC0 PGAP re-annotation | ketol-acid reductoisomerase |
| Revised (this work) | Ketol-acid reductoisomerase. Pfam: KARI_N (PF07991.19), 2-Hacid_dh_C (PF02826.26), NAD_binding_2 (PF03446.22), KARI_C (PF01450.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKJ7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Ketol-acid reductoisomerase |
| EC (curated) |
EC 1.1.1.86
|
| Curated function | Involved in the biosynthesis of branched-chain amino acids (BCAA). Catalyzes an alkyl-migration followed by a ketol-acid reduction of (S)-2-acetolactate (S2AL) to yield (R)-2,3-dihydroxy-isovalerate. In the isomerase reaction, S2AL is rearranged via a Mg-dependent methyl migration to produce 3-hydroxy-3-methyl-2-ketobutyrate (HMKB). In the reductase reaction, this 2-ketoacid undergoes a metal-dependent reduction by NADPH to yield (R)-2,3-dihydroxy-isovalerate. It is also able to use 3-hydroxypyruvate (HP). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolismH Coenzyme transport and metabolism
|
|---|---|
| Preferred name | ilvC |
| eggNOG description | Involved in the biosynthesis of branched-chain amino acids (BCAA). Catalyzes an alkyl-migration followed by a ketol- acid reduction of (S)-2-acetolactate (S2AL) to yield (R)-2,3- dihydroxy-isovalerate. In the isomerase reaction, S2AL is rearranged via a Mg-dependent methyl migration to produce 3- hydroxy-3-methyl-2-ketobutyrate (HMKB). In the reductase reaction, this 2-ketoacid undergoes a metal-dependent reduction by NADPH to yield (R)-2,3-dihydroxy-isovalerate |
| Orthologous group | COG0059 |
| EC number |
EC 1.1.1.86
|
| KEGG orthology |
K00053
|
| KEGG pathways |
map00290, map00770, map01100, map01110, map01130, map01210, map01230
|
| KEGG modules |
M00019, M00570
|
| Gene Ontology (21) |
GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0008150, GO:0008152, GO:0008677, GO:0016020 +9 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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 0 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 |
|---|---|---|---|---|
KARI_N | PF07991.19 | 2.1e-69 | 12–175 | Acetohydroxy acid isomeroreductase, NADPH-binding domain |
2-Hacid_dh_C | PF02826.26 | 1.1e-06 | 12–84 | D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain |
NAD_binding_2 | PF03446.22 | 5.0e-05 | 16–101 | NAD binding domain of 6-phosphogluconate dehydrogenase |
KARI_C | PF01450.26 | 1.8e-58 | 181–324 | Ketol-acid reductoisomerase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ilvN (acetolactate synthase small subunit), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3002c ilvN |
acetolactate synthase small subunit | 999 | 1000 ctx | neighborhood:823 cooccurence:719 coexpression:951 database:900 textmining:938 |
Rv3003c ilvB1 |
acetolactate synthase large subunit IlvB | 999 | 997 ctx | neighborhood:732 cooccurence:766 coexpression:618 database:900 textmining:813 |
Rv0189c ilvD |
dihydroxy-acid dehydratase | 998 | 995 ctx | cooccurence:733 coexpression:791 database:900 textmining:802 |
Rv3470c ilvB2 |
acetolactate synthase large subunit | 988 | 987 ctx | cooccurence:735 coexpression:537 database:900 |
Rv1820 ilvG |
acetolactate synthase large subunit IlvG | 991 | 975 ctx | cooccurence:463 coexpression:540 database:900 textmining:670 |
Rv3509c ilvX |
acetohydroxyacid synthase large subunit | 980 | 964 | coexpression:540 database:900 textmining:479 |
Rv2987c leuD |
3-isopropylmalate dehydratase small subunit | 970 | 905 | coexpression:848 textmining:707 |
Rv2995c leuB |
3-isopropylmalate dehydrogenase | 972 | 904 | coexpression:837 textmining:725 |
Rv2988c leuC |
3-isopropylmalate dehydratase large subunit | 958 | 903 | coexpression:852 textmining:588 |
Rv3710 leuA |
2-isopropylmalate synthase | 937 | 777 | coexpression:699 textmining:731 |
Rv3469c mhpE |
4-hydroxy-2-oxovalerate aldolase MhpE | 765 | 740 | coexpression:691 |
Rv1295 thrC |
threonine synthase | 795 | 712 | coexpression:636 |
Rv3534c hsaF |
4-hydroxy-2-oxovalerate aldolase | 733 | 704 | coexpression:693 |
Rv1559 ilvA |
threonine dehydratase IlvA | 900 | 699 | coexpression:526 textmining:682 |
Rv0118c oxcA |
oxalyl-CoA decarboxylase OxcA | 775 | 691 | coexpression:538 |
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: ketol-acid reductoisomerase
- MTBC0 PGAP product: ketol-acid reductoisomerase
- Pfam (hmmscan --cut_ga): KARI_N PF07991.19 (E=2e-69), 2-Hacid_dh_C PF02826.26 (E=1e-06), NAD_binding_2 PF03446.22 (E=5e-05), KARI_C PF01450.26 (E=2e-58)
- (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_217517.3)
- Domains: Pfam-A via hmmscan --cut_ga — KARI_N (PF07991.19), 2-Hacid_dh_C (PF02826.26), NAD_binding_2 (PF03446.22), KARI_C (PF01450.26)
- 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
COG0059 - Curated reference: UniProt P9WKJ7 (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 —
79 functional partner(s); context anchor
ilvN - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003190|Rv3001c|ilvC MFYDDDADLSIIQGRKVGVIGYGSQGHAHSLSLRDSGVQVRVGLKQGSRSRPKVEEQGLDVDTPAEVAKWADVVMVLAPDTAQAEIFAGDIEPNLKPGDALFFGHGLNVHFGLIKPPADVAVAMVAPKGPGHLVRRQFVDGKGVPCLVAVEQDPRGDGLALALSYAKAIGGTRAGVIKTTFKDETETDLFGEQTVLCGGTEELVKAGFEVMVEAGYPAELAYFEVLHELKLIVDLMYEGGLARMYYSVSDTAEFGGYLSGPRVIDAGTKERMRDILREIQDGSFVHKLVADVEGGNKQLEELRRQNAEHPIEVVGKKLRDLMSWVDRPITETA