Catalytic (large) subunit of mitochondrial acetohydroxyacid synthase (AHAS; acetolactate synthase, EC 2.2.1.6) of Saccharomyces cerevisiae. Ilv2 is a thiamine diphosphate-, Mg2+- and FAD-dependent enzyme that decarboxylates pyruvate and condenses the resulting hydroxyethyl-ThDP intermediate with a second pyruvate (giving 2-acetolactate, the precursor of valine and leucine) or with 2-oxobutanoate (giving 2-aceto-2-hydroxybutanoate, the precursor of isoleucine). This is the first common step of branched-chain amino acid biosynthesis and occurs in the mitochondrial matrix. Ilv2 is active alone but is stimulated several-fold by the regulatory small subunit Ilv6, which also confers valine feedback inhibition that is reversed by MgATP. Ilv2 is the target of sulfonylurea herbicides (the SMR1 allele confers sulfometuron resistance), and crystal structures of the yeast enzyme with these inhibitors have been determined.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000287 magnesium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based Mg2+ binding. AHAS binds one Mg2+ per subunit to anchor thiamine diphosphate; correct but a cofactor property. Reason: Cofactor binding is a real property of the enzyme but is a means to the catalytic activity rather than a distinct function; retained as non-core. Supporting Evidence: file:yeast/ILV2/ILV2-uniprot.txt Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250}; |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic catalytic activity from InterPro IPR011766 (ThDP enzyme C-terminal domain). True but uninformative; the specific activity is acetolactate synthase activity. Reason: Replace the root catalytic term with the specific, experimentally supported activity. Proposed replacements: acetolactate synthase activity Supporting Evidence: PMID:10213630 Reconstitution studies showed that the ilv6 protein stimulates the catalytic activity of the ilv2 protein by up to 7-fold file:yeast/ILV2/ILV2-uniprot.txt Catalytic subunit of mitochondrial acetolactate synthase, |
| GO:0003984 acetolactate synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA of the family-defining AHAS catalytic activity; Ilv2 lies within the AHAS large-subunit clade and has direct experimental support (purified recombinant Ilv2 is active). Core function. Supporting Evidence: PMID:10213630 Reconstitution studies showed that the ilv6 protein stimulates the catalytic activity of the ilv2 protein by up to 7-fold file:yeast/ILV2/ILV2-uniprot.txt Catalytic subunit of mitochondrial acetolactate synthase, |
| GO:0003984 acetolactate synthase activity | IDA PMID:10213630 Expression, purification, characterization, and reconstituti... | ACCEPT | Summary: Direct demonstration: recombinant Ilv2 purified from E. coli is catalytically active and is stimulated by Ilv6 on reconstitution. Core function. Supporting Evidence: PMID:10213630 Reconstitution studies showed that the ilv6 protein stimulates the catalytic activity of the ilv2 protein by up to 7-fold file:yeast/ILV2/ILV2-uniprot.txt Catalytic subunit of mitochondrial acetolactate synthase, |
| GO:0003984 acetolactate synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic EC/RHEA mapping (EC 2.2.1.6; RHEA:25249 and RHEA:27654) consistent with experimental data. Core function. Supporting Evidence: PMID:10213630 Reconstitution studies showed that the ilv6 protein stimulates the catalytic activity of the ilv2 protein by up to 7-fold file:yeast/ILV2/ILV2-uniprot.txt Catalytic subunit of mitochondrial acetolactate synthase, |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: Mitochondrial proteome HDA; consistent with the N-terminal transit peptide and mitochondrial site of the first BCAA steps. Supporting Evidence: PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. file:yeast/ILV2/ILV2-uniprot.txt Catalytic subunit of mitochondrial acetolactate synthase, |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Mitochondrial proteome HDA (multidimensional separation study); consistent with known mitochondrial location of AHAS. Supporting Evidence: PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics. file:yeast/ILV2/ILV2-uniprot.txt Catalytic subunit of mitochondrial acetolactate synthase, |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Quantitative mitochondrial proteome HDA; consistent with known mitochondrial location. Supporting Evidence: PMID:24769239 Quantitative variations of the mitochondrial proteome and phosphoproteome during fermentative and respiratory growth in Saccharomyces cerevisiae. file:yeast/ILV2/ILV2-uniprot.txt Catalytic subunit of mitochondrial acetolactate synthase, |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (mitochondrion); correct. Supporting Evidence: file:yeast/ILV2/ILV2-uniprot.txt Catalytic subunit of mitochondrial acetolactate synthase, |
| GO:0005739 mitochondrion | NAS PMID:16390333 Mutations in the regulatory subunit of yeast acetohydroxyaci... | ACCEPT | Summary: Author statement in an AHAS regulatory-subunit study; the yeast AHAS holoenzyme is mitochondrial. Supporting Evidence: file:yeast/ILV2/ILV2-uniprot.txt Catalytic subunit of mitochondrial acetolactate synthase, PMID:10213630 YCL009c was shown to be expressed in yeast and the protein localized in mitochondria where it undergoes removal of a transit peptide targeting sequence. |
| GO:0005948 acetolactate synthase complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for membership of the AHAS (Ilv2-Ilv6) complex; supported experimentally by reconstitution. Supporting Evidence: PMID:16390333 This heterotetrameric enzyme is composed of a larger subunit that contains the catalytic machinery and a smaller subunit that plays a regulatory role. PMID:10213630 Under optimal conditions for reconstitution, a dissociation constant for the subunits of 70 +/- 7 nM was determined. |
| GO:0005948 acetolactate synthase complex | IDA PMID:10213630 Expression, purification, characterization, and reconstituti... | ACCEPT | Summary: Reconstitution of the Ilv2-Ilv6 complex from purified subunits with a measurable subunit dissociation constant. Supporting Evidence: PMID:16390333 This heterotetrameric enzyme is composed of a larger subunit that contains the catalytic machinery and a smaller subunit that plays a regulatory role. PMID:10213630 Under optimal conditions for reconstitution, a dissociation constant for the subunits of 70 +/- 7 nM was determined. |
| GO:0005948 acetolactate synthase complex | IPI PMID:16390333 Mutations in the regulatory subunit of yeast acetohydroxyaci... | ACCEPT | Summary: Physical association of Ilv2 with Ilv6 in the heterotetrameric AHAS holoenzyme. Supporting Evidence: PMID:16390333 This heterotetrameric enzyme is composed of a larger subunit that contains the catalytic machinery and a smaller subunit that plays a regulatory role. PMID:10213630 Under optimal conditions for reconstitution, a dissociation constant for the subunits of 70 +/- 7 nM was determined. |
| GO:0009082 branched-chain amino acid biosynthetic process | IDA PMID:16390333 Mutations in the regulatory subunit of yeast acetohydroxyaci... | ACCEPT | Summary: Ilv2 catalyses the first common step of isoleucine, leucine and valine biosynthesis. Core process. Supporting Evidence: PMID:16390333 Isoleucine, leucine and valine are synthesized via a common pathway in which the first reaction is catalysed by AHAS (acetohydroxyacid synthase; EC 2.2.1.6). PMID:10213630 Reconstitution studies showed that the ilv6 protein stimulates the catalytic activity of the ilv2 protein by up to 7-fold |
| GO:0009082 branched-chain amino acid biosynthetic process | IDA PMID:2406721 Protein N-myristoylation in Escherichia coli: reconstitution... | ACCEPT | Summary: The cached reference (PMID:2406721) is a protein N-myristoylation study whose abstract does not mention ILV2 or BCAA biosynthesis; the curator may have used full-text content we cannot see (or this may be a reference mis-mapping). Because the process is unambiguously correct for Ilv2, the annotation is accepted on independent evidence and the reference is flagged for checking. Supporting Evidence: PMID:16390333 Isoleucine, leucine and valine are synthesized via a common pathway in which the first reaction is catalysed by AHAS (acetohydroxyacid synthase; EC 2.2.1.6). |
| GO:0009082 branched-chain amino acid biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (ARBA/InterPro) annotation consistent with experimental data. Core process. Supporting Evidence: PMID:16390333 Isoleucine, leucine and valine are synthesized via a common pathway in which the first reaction is catalysed by AHAS (acetohydroxyacid synthase; EC 2.2.1.6). |
| GO:0009082 branched-chain amino acid biosynthetic process | IMP PMID:2406721 Protein N-myristoylation in Escherichia coli: reconstitution... | ACCEPT | Summary: As for the IDA row from the same reference: the cached abstract of PMID:2406721 does not mention ILV2, but the process is unambiguously correct and is accepted on independent evidence; reference flagged. Supporting Evidence: PMID:16390333 Isoleucine, leucine and valine are synthesized via a common pathway in which the first reaction is catalysed by AHAS (acetohydroxyacid synthase; EC 2.2.1.6). |
| GO:0009099 L-valine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA; acetolactate formation is step 1 of valine biosynthesis. Supporting Evidence: PMID:16390333 Isoleucine, leucine and valine are synthesized via a common pathway in which the first reaction is catalysed by AHAS (acetohydroxyacid synthase; EC 2.2.1.6). file:yeast/ILV2/ILV2-uniprot.txt -!- PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from |
| GO:0009099 L-valine biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway mapping (UPA00049, L-valine biosynthesis step 1/4); correct. Supporting Evidence: PMID:16390333 Isoleucine, leucine and valine are synthesized via a common pathway in which the first reaction is catalysed by AHAS (acetohydroxyacid synthase; EC 2.2.1.6). |
| GO:0030976 thiamine pyrophosphate binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based ThDP binding; AHAS is a ThDP-dependent enzyme and ThDP is seen in the yeast AHAS crystal structures. Reason: Cofactor binding is a real property of the enzyme but is a means to the catalytic activity rather than a distinct function; retained as non-core. Supporting Evidence: PMID:15709745 In addition to thiamin diphosphate, AHAS requires FAD for activity. |
| GO:0050660 flavin adenine dinucleotide binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA for FAD binding. AHAS requires FAD (a non-redox structural cofactor) for activity; correct. Reason: Cofactor binding is a real property of the enzyme but is a means to the catalytic activity rather than a distinct function; retained as non-core. Supporting Evidence: PMID:15709745 In addition to thiamin diphosphate, AHAS requires FAD for activity. |
| GO:0050660 flavin adenine dinucleotide binding | IDA PMID:15709745 Elucidating the specificity of binding of sulfonylurea herbi... | KEEP AS NON CORE | Summary: Crystal structures of yeast AHAS show bound FAD in a bent conformation; direct evidence for FAD binding. Reason: Cofactor binding is a real property of the enzyme but is a means to the catalytic activity rather than a distinct function; retained as non-core. Supporting Evidence: PMID:15709745 In addition to thiamin diphosphate, AHAS requires FAD for activity. PMID:15709745 Here we report that the isoalloxazine ring has a bent conformation that would account for its ability to accept electrons from the hydroxyethyl intermediate. |
| GO:0050660 flavin adenine dinucleotide binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based FAD binding; consistent with structural data. Reason: Cofactor binding is a real property of the enzyme but is a means to the catalytic activity rather than a distinct function; retained as non-core. Supporting Evidence: PMID:15709745 In addition to thiamin diphosphate, AHAS requires FAD for activity. |
| GO:1901705 L-isoleucine biosynthetic process | IC PMID:16390333 Mutations in the regulatory subunit of yeast acetohydroxyaci... | NEW | Summary: Ilv2 itself catalyses step 1 of isoleucine biosynthesis (pyruvate + 2-oxobutanoate -> 2-aceto-2-hydroxybutanoate), so it performs a step of this process. The downstream yeast enzymes ILV5, ILV3, BAT1 and BAT2 already carry GO:1901705 (YeastPathways RCA), and the AHAS complex (ComplexPortal) does too, but the catalytic subunit itself lacks it, apparently because YeastPathways assigns the reaction to the complex. Reason: Ilv2 performs the catalytic chemistry of the first isoleucine-pathway step; comparator enzymes for the other steps in yeast carry this term. Supporting Evidence: PMID:16390333 Isoleucine, leucine and valine are synthesized via a common pathway in which the first reaction is catalysed by AHAS (acetohydroxyacid synthase; EC 2.2.1.6). file:yeast/ILV2/ILV2-uniprot.txt -!- PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L- |
Loading supporting content…
Download this section (compressed HTML)Acetolactate synthase; catalyses the first common step in isoleucine and valine biosynthesis and is the target of several classes of inhibitors, localizes to the mitochondria; expression of the gene is under general amino acid control
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)