UniProtKB - P05793 (ILVC_ECOLI)
Ketol-acid reductoisomerase (NADP(+))
ilvC
Functioni
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. Also able to use 2-ketopantoate, 2-ketoisovalerate, 2-ketovalerate, 2-ketobutyrate, 3-hydroxypyruvate, 3-hydroxy-2-ketobutyrate and pyruvate (PubMed:15654896).
4 PublicationsCatalytic activityi
- (2R)-2,3-dihydroxy-3-methylbutanoate + NADP+ = (2S)-2-acetolactate + H+ + NADPHUniRule annotation4 PublicationsEC:1.1.1.86UniRule annotation4 Publications
- (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP+ = (S)-2-ethyl-2-hydroxy-3-oxobutanoate + H+ + NADPHUniRule annotationEC:1.1.1.86UniRule annotation
Cofactori
Activity regulationi
Kineticsi
- KM=0.04 mM for NADPH1 Publication
- KM=0.042 mM for NADP1 Publication
- KM=0.073 mM for NADPH1 Publication
- KM=0.17 mM for 2-ketopantoate (at pH 8 and 37 degrees Celsius)1 Publication
- KM=0.206 mM for NADH1 Publication
- KM=0.21 mM for 3-hydroxy-2-ketobutyrate (at pH 8 and 37 degrees Celsius)1 Publication
- KM=0.25 mM for 2-acetolactate (at pH 8 and 37 degrees Celsius)1 Publication
- KM=0.27 mM for 3-hydroxy-3-methyl-2-ketobutyrate (at pH 8 and 37 degrees Celsius)1 Publication
- KM=0.42 mM for magnesium (with S2AL and NADPH as substrates)1 Publication
- KM=1.08 mM for NADH1 Publication
- KM=1.54 mM for pyruvate (at pH 8 and 37 degrees Celsius)1 Publication
- KM=2.96 mM for 3-hydroxypyruvate (at pH 8 and 37 degrees Celsius)1 Publication
- KM=3.15 mM for 2-ketovalerate (at pH 8 and 37 degrees Celsius)1 Publication
- KM=4.56 mM for 2-ketobutyrate (at pH 8 and 37 degrees Celsius)1 Publication
- KM=6.91 mM for 2-ketoisovalerate (at pH 8 and 37 degrees Celsius)1 Publication
- Vmax=5.421 µmol/min/mg enzyme with 3-hydroxypyruvate as substrate (at pH 8 and 37 degrees Celsius)1 Publication
- Vmax=3.541 µmol/min/mg enzyme with 3-hydroxy-3-methyl-2-ketobutyrate as substrate (at pH 8 and 37 degrees Celsius)1 Publication
- Vmax=2.25 µmol/min/mg enzyme with 2-acetolactate as substrate (at pH 8 and 37 degrees Celsius)1 Publication
- Vmax=0.599 µmol/min/mg enzyme with 3-hydroxy-2-ketobutyrate as substrate (at pH 8 and 37 degrees Celsius)1 Publication
- Vmax=0.196 µmol/min/mg enzyme with 2-ketopantoate as substrate (at pH 8 and 37 degrees Celsius)1 Publication
- Vmax=0.184 µmol/min/mg enzyme with 2-ketoisovalerate as substrate (at pH 8 and 37 degrees Celsius)1 Publication
- Vmax=0.168 µmol/min/mg enzyme with 2-ketobutyrate as substrate (at pH 8 and 37 degrees Celsius)1 Publication
- Vmax=0.05 µmol/min/mg enzyme with 2-ketovalerate as substrate (at pH 8 and 37 degrees Celsius)1 Publication
- Vmax=0.021 µmol/min/mg enzyme with pyruvate as substrate (at pH 8 and 37 degrees Celsius)1 Publication
: L-isoleucine biosynthesis Pathwayi
This protein is involved in step 2 of the subpathway that synthesizes L-isoleucine from 2-oxobutanoate.UniRule annotation1 Publication This subpathway is part of the pathway L-isoleucine biosynthesis, which is itself part of Amino-acid biosynthesis.View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-isoleucine from 2-oxobutanoate, the pathway L-isoleucine biosynthesis and in Amino-acid biosynthesis.
Pathwayi: L-valine biosynthesis
This protein is involved in step 2 of the subpathway that synthesizes L-valine from pyruvate.UniRule annotation1 Publication This subpathway is part of the pathway L-valine biosynthesis, which is itself part of Amino-acid biosynthesis.View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-valine from pyruvate, the pathway L-valine biosynthesis and in Amino-acid biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 68 | NADPUniRule annotation1 Publication | 1 | |
Binding sitei | 76 | NADPUniRule annotation1 Publication1 Publication | 1 | |
Binding sitei | 78 | NADPUniRule annotation1 Publication | 1 | |
Active sitei | 132 | UniRule annotation | 1 | |
Binding sitei | 158 | NADP; via amide nitrogenUniRule annotation | 1 | |
Metal bindingi | 217 | Magnesium 1UniRule annotation1 Publication | 1 | |
Metal bindingi | 217 | Magnesium 2UniRule annotation1 Publication | 1 | |
Metal bindingi | 221 | Magnesium 1UniRule annotation | 1 | |
Metal bindingi | 389 | Magnesium 2UniRule annotation1 Publication | 1 | |
Metal bindingi | 393 | Magnesium 2UniRule annotation1 Publication | 1 | |
Binding sitei | 414 | SubstrateUniRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 45 – 48 | NADPUniRule annotation1 Publication | 4 | |
Nucleotide bindingi | 108 – 110 | NADPUniRule annotation1 Publication | 3 |
GO - Molecular functioni
- identical protein binding Source: EcoCyc
- ketol-acid reductoisomerase activity Source: UniProtKB
- magnesium ion binding Source: UniProtKB
- NADP binding Source: UniProtKB
GO - Biological processi
- isoleucine biosynthetic process Source: EcoCyc
- valine biosynthetic process Source: EcoCyc
Keywordsi
Molecular function | Oxidoreductase |
Biological process | Amino-acid biosynthesis, Branched-chain amino acid biosynthesis |
Ligand | Magnesium, Metal-binding, NADP |
Enzyme and pathway databases
BioCyci | EcoCyc:KETOLREDUCTOISOM-MONOMER |
BRENDAi | 1.1.1.383, 2026 1.1.1.86, 2026 |
SABIO-RKi | P05793 |
UniPathwayi | UPA00047;UER00056 UPA00049;UER00060 |
Names & Taxonomyi
Protein namesi | Recommended name: Ketol-acid reductoisomerase (NADP(+))1 PublicationUniRule annotation (EC:1.1.1.86UniRule annotation4 Publications)Short name: KARI1 PublicationUniRule annotation Alternative name(s): Acetohydroxy-acid isomeroreductase1 PublicationUniRule annotation Short name: AHIR1 PublicationUniRule annotation Alpha-keto-beta-hydroxylacyl reductoisomeraseUniRule annotation Ketol-acid reductoisomerase type 21 PublicationUniRule annotation Ketol-acid reductoisomerase type II1 PublicationUniRule annotation |
Gene namesi | Name:ilvCUniRule annotation Ordered Locus Names:b3774, JW3747 |
Organismi | Escherichia coli (strain K12) |
Taxonomic identifieri | 83333 [NCBI] |
Taxonomic lineagei | Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacterales › Enterobacteriaceae › Escherichia › |
Proteomesi |
|
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Cytosol
- cytosol Source: EcoCyc
Other locations
- protein-containing complex Source: EcoCyc
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 68 | R → D: Inversion of cofactor specificity from NADPH to NADH; when associated with L-69, V-75 and D-76. 1 Publication | 1 | |
Mutagenesisi | 68 | R → Q: 18-fold decrease of the catalytic efficiency and 3-fold decrease of the affinity for NADPH. 1 Publication | 1 | |
Mutagenesisi | 69 | K → L: Does not significantly alter the affinity for NADPH. Slight increase of the catalytic efficiency. Inversion of cofactor specificity from NADPH to NADH; when associated with D-68, V-75 and D-76. 1 Publication | 1 | |
Mutagenesisi | 71 | A → S: 7- and 2.5-fold increase of the reductoisomerase activity with NADH and NADPH, respectively. 1 Publication | 1 | |
Mutagenesisi | 75 | K → Q: 13-fold decrease of the catalytic efficiency and 3-fold increase of the affinity for NADPH. 1 Publication | 1 | |
Mutagenesisi | 75 | K → V: Inversion of cofactor specificity from NADPH to NADH; when associated with D-68, L-69 and D-76. 1 Publication | 1 | |
Mutagenesisi | 76 | R → D: 3-fold increase of the reductoisomerase activity with NADH and slight decrease of the reductoisomerase activity with NADPH. 1 Publication | 1 | |
Mutagenesisi | 76 | R → D: Strong increase of catalytic efficiency and 2.5-fold increase of the affinity for NADH. 4-fold decrease of the catalytic efficiency and strong decrease of the affinity for NADPH. Inversion of cofactor specificity from NADPH to NADH; when associated with D-68, L-69 and V-75. 1 Publication | 1 | |
Mutagenesisi | 76 | R → Q: 20-fold decrease of the catalytic efficiency and 5-fold decrease of the affinity for NADPH. 1 Publication | 1 | |
Mutagenesisi | 78 | S → D: 12-fold increase of the reductoisomerase activity with NADH and slight decrease of the reductoisomerase activity with NADPH. 1 Publication | 1 | |
Mutagenesisi | 110 | Q → V or A: 12- and 2-fold increase of the reductoisomerase activity with NADH and NADPH, respectively. 1 Publication | 1 | |
Mutagenesisi | 132 | H → K: Loss of reductoisomerase activity. 1 Publication | 1 | |
Mutagenesisi | 132 | H → Q: Loss of reductoisomerase activity. The reductase activity with 3-hydroxypyruvate and HMKB is nearly normal, and the isomerase activity decreases 24-fold. 1 Publication | 1 | |
Mutagenesisi | 155 | K → E or Q: Loss of reductoisomerase activity. 1 Publication | 1 | |
Mutagenesisi | 155 | K → R: Loss of reductoisomerase activity. The reductase activity with 3-hydroxypyruvate and HMKB is nearly normal, and the isomerase activity decreases 40-fold. 1 Publication | 1 | |
Mutagenesisi | 213 | E → D: Loss of reductoisomerase activity. 1.5-fold decrease of the reductase activity with 3-hydroxypyruvate and the isomerase activity decreases 48-fold. 1 Publication | 1 | |
Mutagenesisi | 217 | D → E or N: Loss of reductoisomerase activity. 1 Publication | 1 | |
Mutagenesisi | 221 | E → D or Q: Loss of reductoisomerase activity. 1 Publication | 1 | |
Mutagenesisi | 389 | E → D: Loss of reductoisomerase activity. 1.5-fold decrease of the reductase activity with 3-hydroxypyruvate and the isomerase activity decreases 4-fold. 1 Publication | 1 | |
Mutagenesisi | 389 | E → Q: Loss of reductoisomerase activity. 1 Publication | 1 | |
Mutagenesisi | 393 | E → D: Loss of reductoisomerase activity. The reductase activity with HMKB is nearly normal. 1 Publication | 1 | |
Mutagenesisi | 414 | S → A: Loss of reductoisomerase activity. The isomerase activity decreases 15-fold. 1 Publication | 1 | |
Mutagenesisi | 414 | S → T: Loss of reductoisomerase activity. The isomerase activity decreases 24-fold. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL2366462 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed1 Publication | |||
ChainiPRO_0000151309 | 2 – 491 | Ketol-acid reductoisomerase (NADP(+))Add BLAST | 490 |
Proteomic databases
jPOSTi | P05793 |
PaxDbi | P05793 |
PRIDEi | P05793 |
2D gel databases
SWISS-2DPAGEi | P05793 |
Expressioni
Inductioni
Interactioni
Subunit structurei
Homotetramer.
2 PublicationsGO - Molecular functioni
- identical protein binding Source: EcoCyc
Protein-protein interaction databases
BioGRIDi | 4263331, 21 interactors 852586, 1 interactor |
IntActi | P05793, 4 interactors |
STRINGi | 511145.b3774 |
Chemistry databases
BindingDBi | P05793 |
Structurei
Secondary structure
3D structure databases
SMRi | P05793 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P05793 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 15 – 208 | KARI N-terminal RossmannPROSITE-ProRule annotation1 PublicationAdd BLAST | 194 | |
Domaini | 209 – 344 | KARI C-terminal knotted 1PROSITE-ProRule annotation1 PublicationAdd BLAST | 136 | |
Domaini | 345 – 484 | KARI C-terminal knotted 2PROSITE-ProRule annotation1 PublicationAdd BLAST | 140 |
Sequence similaritiesi
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | COG0059, Bacteria |
HOGENOMi | CLU_551905_0_0_6 |
InParanoidi | P05793 |
PhylomeDBi | P05793 |
Family and domain databases
Gene3Di | 1.10.1040.10, 1 hit |
HAMAPi | MF_00435, IlvC, 1 hit |
InterProi | View protein in InterPro IPR008927, 6-PGluconate_DH-like_C_sf IPR013328, 6PGD_dom2 IPR013023, KARI IPR000506, KARI_C IPR013116, KARI_N IPR036291, NAD(P)-bd_dom_sf |
PANTHERi | PTHR21371, PTHR21371, 2 hits |
Pfami | View protein in Pfam PF01450, IlvC, 2 hits PF07991, IlvN, 1 hit |
SUPFAMi | SSF48179, SSF48179, 2 hits SSF51735, SSF51735, 1 hit |
TIGRFAMsi | TIGR00465, ilvC, 1 hit |
PROSITEi | View protein in PROSITE PS51851, KARI_C, 2 hits PS51850, KARI_N, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MANYFNTLNL RQQLAQLGKC RFMGRDEFAD GASYLQGKKV VIVGCGAQGL
60 70 80 90 100
NQGLNMRDSG LDISYALRKE AIAEKRASWR KATENGFKVG TYEELIPQAD
110 120 130 140 150
LVINLTPDKQ HSDVVRTVQP LMKDGAALGY SHGFNIVEVG EQIRKDITVV
160 170 180 190 200
MVAPKCPGTE VREEYKRGFG VPTLIAVHPE NDPKGEGMAI AKAWAAATGG
210 220 230 240 250
HRAGVLESSF VAEVKSDLMG EQTILCGMLQ AGSLLCFDKL VEEGTDPAYA
260 270 280 290 300
EKLIQFGWET ITEALKQGGI TLMMDRLSNP AKLRAYALSE QLKEIMAPLF
310 320 330 340 350
QKHMDDIISG EFSSGMMADW ANDDKKLLTW REETGKTAFE TAPQYEGKIG
360 370 380 390 400
EQEYFDKGVL MIAMVKAGVE LAFETMVDSG IIEESAYYES LHELPLIANT
410 420 430 440 450
IARKRLYEMN VVISDTAEYG NYLFSYACVP LLKPFMAELQ PGDLGKAIPE
460 470 480 490
GAVDNGQLRD VNEAIRSHAI EQVGKKLRGY MTDMKRIAVA G
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 251 | E → K in AAA24029 (PubMed:3003115).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M11689 Genomic DNA Translation: AAA24029.1 M87049 Genomic DNA Translation: AAA67577.1 U00096 Genomic DNA Translation: AAC76779.1 AP009048 Genomic DNA Translation: BAE77523.1 |
PIRi | A65181, ISECKR |
RefSeqi | NP_418222.1, NC_000913.3 WP_000024939.1, NZ_SSZK01000025.1 |
Genome annotation databases
EnsemblBacteriai | AAC76779; AAC76779; b3774 BAE77523; BAE77523; BAE77523 |
GeneIDi | 948286 |
KEGGi | ecj:JW3747 eco:b3774 |
PATRICi | fig|511145.12.peg.3891 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M11689 Genomic DNA Translation: AAA24029.1 M87049 Genomic DNA Translation: AAA67577.1 U00096 Genomic DNA Translation: AAC76779.1 AP009048 Genomic DNA Translation: BAE77523.1 |
PIRi | A65181, ISECKR |
RefSeqi | NP_418222.1, NC_000913.3 WP_000024939.1, NZ_SSZK01000025.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1YRL | X-ray | 2.60 | A/B/C/D | 1-491 | [»] | |
3ULK | X-ray | 2.30 | A/B | 1-491 | [»] | |
SMRi | P05793 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 4263331, 21 interactors 852586, 1 interactor |
IntActi | P05793, 4 interactors |
STRINGi | 511145.b3774 |
Chemistry databases
BindingDBi | P05793 |
ChEMBLi | CHEMBL2366462 |
2D gel databases
SWISS-2DPAGEi | P05793 |
Proteomic databases
jPOSTi | P05793 |
PaxDbi | P05793 |
PRIDEi | P05793 |
Genome annotation databases
EnsemblBacteriai | AAC76779; AAC76779; b3774 BAE77523; BAE77523; BAE77523 |
GeneIDi | 948286 |
KEGGi | ecj:JW3747 eco:b3774 |
PATRICi | fig|511145.12.peg.3891 |
Organism-specific databases
EchoBASEi | EB0490 |
Phylogenomic databases
eggNOGi | COG0059, Bacteria |
HOGENOMi | CLU_551905_0_0_6 |
InParanoidi | P05793 |
PhylomeDBi | P05793 |
Enzyme and pathway databases
UniPathwayi | UPA00047;UER00056 UPA00049;UER00060 |
BioCyci | EcoCyc:KETOLREDUCTOISOM-MONOMER |
BRENDAi | 1.1.1.383, 2026 1.1.1.86, 2026 |
SABIO-RKi | P05793 |
Miscellaneous databases
EvolutionaryTracei | P05793 |
PROi | PR:P05793 |
Family and domain databases
Gene3Di | 1.10.1040.10, 1 hit |
HAMAPi | MF_00435, IlvC, 1 hit |
InterProi | View protein in InterPro IPR008927, 6-PGluconate_DH-like_C_sf IPR013328, 6PGD_dom2 IPR013023, KARI IPR000506, KARI_C IPR013116, KARI_N IPR036291, NAD(P)-bd_dom_sf |
PANTHERi | PTHR21371, PTHR21371, 2 hits |
Pfami | View protein in Pfam PF01450, IlvC, 2 hits PF07991, IlvN, 1 hit |
SUPFAMi | SSF48179, SSF48179, 2 hits SSF51735, SSF51735, 1 hit |
TIGRFAMsi | TIGR00465, ilvC, 1 hit |
PROSITEi | View protein in PROSITE PS51851, KARI_C, 2 hits PS51850, KARI_N, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ILVC_ECOLI | |
Accessioni | P05793Primary (citable) accession number: P05793 Secondary accession number(s): Q2M883 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1988 |
Last sequence update: | January 23, 2007 | |
Last modified: | February 23, 2022 | |
This is version 190 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families