LAT1 (YNL071W; also PDA2/ODP2) encodes the dihydrolipoyllysine-residue acetyltransferase (E2, EC 2.3.1.12) of the mitochondrial pyruvate dehydrogenase (PDH) complex. Lat1p carries a covalently bound lipoyl cofactor on its N-terminal lipoyl domain. Its C-terminal catalytic domain transfers the acetyl group from acetyl-dihydrolipoyl-E2 to coenzyme A, forming acetyl-CoA (written in the reverse direction in UniProt). The catalytic domain self-assembles into a 60-mer pentagonal-dodecahedral core. E1 (Pda1p/Pdb1p) binds to this core, and E3 (Lpd1p) binds through the E3-binding protein Pdx1p. The complex sits in the mitochondrial matrix and converts pyruvate to acetyl-CoA and CO2, linking glycolysis to the TCA cycle. LAT1 deletion abolishes the replicative life span extension induced by calorie restriction, and Lat1 overexpression extends life span in a respiration-dependent, Sir2-independent manner.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004742 dihydrolipoyllysine-residue acetyltransferase activity | EXP PMID:7030741 Pyruvate dehydrogenase complex from baker's yeast. 2. Molecu... | ACCEPT | Summary: EXP from Kresze & Ronft 1981: the baker's yeast PDH complex was resolved into E1, E2 (lipoate acetyltransferase) and E3, and the isolated enzymes reassociated with full activity. UniProt cites this paper for the E2 reaction. Core MF. Supporting Evidence: PMID:7030741 E2 was isolated by gel filtration of the complex in the presence of 2 M KBr PMID:7030741 The isolated enzymes reassociated spontaneously to give pyruvate dehydrogenase overall activity. file:yeast/LAT1/LAT1-uniprot.txt Reaction=N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + acetyl-CoA = |
| GO:0004742 dihydrolipoyllysine-residue acetyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN002351721) to dihydrolipoyllysine-residue acetyltransferase activity. Correct; LAT1 is the PDH E2 of yeast, and its own experimental annotations are among the descendant evidence. Supporting Evidence: PMID:2271545 It exhibited catalytic activity (acetyl transfer from [1-14C]acetyl-CoA to dihydrolipoamide) very similar to that of wild-type E2p. |
| GO:0004742 dihydrolipoyllysine-residue acetyltransferase activity | IDA PMID:2271545 Overexpression and mutagenesis of the catalytic domain of di... | ACCEPT | Summary: IDA from Niu et al. 1990: the recombinant Lat1p inner-core (catalytic) domain catalysed acetyl transfer from acetyl-CoA to dihydrolipoamide like wild-type E2, and Asp-431 mutations reduced kcat. Direct evidence for the core MF. Supporting Evidence: PMID:2271545 It exhibited catalytic activity (acetyl transfer from [1-14C]acetyl-CoA to dihydrolipoamide) very similar to that of wild-type E2p. PMID:2271545 These findings demonstrate that the active site of E2p from S. cerevisiae resides in the inner core domain, i.e., catalytic domain, and that this domain alone can undergo self-assembly. |
| GO:0004742 dihydrolipoyllysine-residue acetyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA, InterPro IPR006257, RHEA:17017, EC 2.3.1.12). Correct. Supporting Evidence: file:yeast/LAT1/LAT1-uniprot.txt Reaction=N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + acetyl-CoA = |
| GO:0004742 dihydrolipoyllysine-residue acetyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PYRUVDEHYD-PWY) enables E2 activity, EC 2.3.1.12. Correct. Supporting Evidence: file:yeast/LAT1/LAT1-uniprot.txt Reaction=N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + acetyl-CoA = |
| GO:0005739 mitochondrion | HDA PMID:11914276 Subcellular localization of the yeast proteome. | ACCEPT | Summary: High-throughput localization of LAT1p to mitochondria in the Drawid/Snyder genome-scale epitope-tag immunolocalization screen. Correct but less specific than the experimentally supported sub-mitochondrial location. Lat1p is a matrix enzyme. Supporting Evidence: PMID:11914276 By high-throughput immunolocalization of tagged gene products, we have determined the subcellular localization of 2744 yeast proteins. |
| GO:0005739 mitochondrion | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: Huh et al. 2003 GFP-fusion screen placed Lat1p in mitochondria; UniProt cites this study for the matrix location. Correct. Supporting Evidence: PMID:14562095 Here we describe the construction and analysis of a collection of yeast strains expressing full-length, chromosomally tagged green fluorescent protein fusion proteins. file:yeast/LAT1/LAT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: High-throughput localization of LAT1p to mitochondria in the Sickmann et al. 2003 MS proteome of highly purified mitochondria. Correct but less specific than the experimentally supported sub-mitochondrial location. Supporting Evidence: PMID:14576278 The proteins of highly pure yeast mitochondria were separated by several independent methods and analyzed by tandem MS. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: High-throughput localization of LAT1p to mitochondria in the PROMITO multidimensional MS survey of purified yeast mitochondria (Reinders et al. 2006). Correct but less specific than the experimentally supported sub-mitochondrial location. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified by use of multidimensional LC-MS/MS |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: High-throughput localization of LAT1p to mitochondria in the carbon-source quantitative mitochondrial proteome/phosphoproteome study (Renvoise et al. 2014). Correct but less specific than the experimentally supported sub-mitochondrial location. Supporting Evidence: PMID:24769239 we performed an overall quantitative proteomic and phosphoproteomic study of isolated mitochondria extracted from yeast grown on fermentative (glucose or galactose) and respiratory (lactate) media |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN000568044) is_active_in mitochondrion. Correct. Supporting Evidence: file:yeast/LAT1/LAT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IDA PMID:18180296 Yeast pyruvate dehydrogenase complex is regulated by a conce... | ACCEPT | Summary: IDA (Gey et al. 2008), which studied the mitochondrial PDH complex and its associated kinases and phosphatases. Correct. Supporting Evidence: PMID:18180296 two additional mitochondrial proteins, Pkp2p (Ygl059wp) and Ppp2p (Ycr079wp), are engaged in the regulation of this complex by affecting the phosphorylation state of Pda1p |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SL-0170 mapping to mitochondrial matrix. Correct and the most specific location. Supporting Evidence: file:yeast/LAT1/LAT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA from PYRUVDEHYD-PWY placing LAT1p 'is_active_in cytosol'. This is wrong: the yeast PDH complex is a mitochondrial-matrix assembly, and LAT1p carries a mitochondrial presequence and is found in purified mitochondria. The pathway-to-GO-CAM conversion seems to have given the reaction a default cytosolic compartment. Reason: Contradicted by the experimentally established mitochondrial-matrix location of the PDH complex. Supporting Evidence: file:yeast/LAT1/LAT1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix PMID:7589446 PDC activity in isolated yeast mitochondria could be inactivated in an ATP-dependent fashion |
| GO:0006086 pyruvate decarboxylation to acetyl-CoA | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN000568044) to pyruvate decarboxylation to acetyl-CoA. Correct core process. Supporting Evidence: PMID:7947791 The E3BP-E3 complex combined rapidly with a pyruvate dehydrogenase (E1)-dihydrolipoamide acetyltransferase (E2) subcomplex (E1-E2 subcomplex) to reconstitute a functional PDH complex, with pyruvate oxidation activity similar to that of PDH complex from bakers' yeast. |
| GO:0006086 pyruvate decarboxylation to acetyl-CoA | IDA PMID:7947791 Expression, purification, and characterization of the dihydr... | ACCEPT | Summary: IDA from Maeng et al. 1994: an E1-E2 subcomplex (E2 = Lat1p) plus E3BP-E3 reconstituted a PDH complex with pyruvate oxidation activity like the native complex. Supports the core process. Supporting Evidence: PMID:7947791 The E3BP-E3 complex combined rapidly with a pyruvate dehydrogenase (E1)-dihydrolipoamide acetyltransferase (E2) subcomplex (E1-E2 subcomplex) to reconstitute a functional PDH complex, with pyruvate oxidation activity similar to that of PDH complex from bakers' yeast. |
| GO:0006086 pyruvate decarboxylation to acetyl-CoA | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IPR045257, PDH E2 family) to the PDH process. Correct. Supporting Evidence: file:yeast/LAT1/LAT1-uniprot.txt FUNCTION: The pyruvate dehydrogenase complex catalyzes the overall |
| GO:0006086 pyruvate decarboxylation to acetyl-CoA | NAS PMID:18180296 Yeast pyruvate dehydrogenase complex is regulated by a conce... | ACCEPT | Summary: NAS (Gey et al. 2008) to the PDH process. Correct; redundant with IDA/IBA. Supporting Evidence: PMID:18180296 The activity of yeast pyruvate dehydrogenase complex is regulated by reversible phosphorylation. |
| GO:0006086 pyruvate decarboxylation to acetyl-CoA | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA to the PDH process. Correct. Supporting Evidence: file:yeast/LAT1/LAT1-uniprot.txt Reaction=N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + acetyl-CoA = |
| GO:0009060 aerobic respiration | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA IEA to aerobic respiration. In GO, pyruvate decarboxylation to acetyl-CoA is part_of aerobic respiration, so this is a correct but broader ancestor of the core process. Supporting Evidence: PMID:7947791 The E3BP-E3 complex combined rapidly with a pyruvate dehydrogenase (E1)-dihydrolipoamide acetyltransferase (E2) subcomplex (E1-E2 subcomplex) to reconstitute a functional PDH complex, with pyruvate oxidation activity similar to that of PDH complex from bakers' yeast. |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO to generic acyltransferase activity. Correct but uninformative. Reason: Replace with the specific E2 activity. Proposed replacements: dihydrolipoyllysine-residue acetyltransferase activity Supporting Evidence: file:yeast/LAT1/LAT1-uniprot.txt Reaction=N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + acetyl-CoA = |
| GO:0045254 pyruvate dehydrogenase complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN000568044) part_of PDH complex. Correct. Supporting Evidence: PMID:9038189 Dihydrolipoamide acyltransferase (E2), a catalytic and structural component of the three functional classes of multienzyme complexes that catalyze the oxidative decarboxylation of alpha-keto acids, forms the central core to which the other components attach. |
| GO:0045254 pyruvate dehydrogenase complex | IDA PMID:2007123 Disruption and mutagenesis of the Saccharomyces cerevisiae P... | ACCEPT | Summary: IDA (Lawson et al. 1991): PDH complex purified from pdx1 mutant contained E1 alpha/beta and the E2 (Lat1p) core. Correct. Supporting Evidence: PMID:2007123 The PDH complex isolated from the mutant cells contained pyruvate dehydrogenase (E1 alpha + E1 beta) and dihydrolipoamide acetyltransferase (E2) but lacked protein X and dihydrolipoamide dehydrogenase (E3). |
| GO:0045254 pyruvate dehydrogenase complex | IDA PMID:9038189 On the unique structural organization of the Saccharomyces c... | ACCEPT | Summary: IDA (Stoops et al. 1997): cryo-EM of the yeast 60-mer E2 core (Lat1p), the scaffold of the PDH complex. Correct. Supporting Evidence: PMID:9038189 Dihydrolipoamide acyltransferase (E2), a catalytic and structural component of the three functional classes of multienzyme complexes that catalyze the oxidative decarboxylation of alpha-keto acids, forms the central core to which the other components attach. PMID:9038189 The tE2 core is a pentagonal dodecahedron consisting of 20 cone-shaped trimers interconnected by 30 bridges. |
| GO:0045254 pyruvate dehydrogenase complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IPR006257, IPR045257) part_of PDH complex. Correct. Supporting Evidence: PMID:9038189 Dihydrolipoamide acyltransferase (E2), a catalytic and structural component of the three functional classes of multienzyme complexes that catalyze the oxidative decarboxylation of alpha-keto acids, forms the central core to which the other components attach. |
| GO:0045254 pyruvate dehydrogenase complex | IPI PMID:18180296 Yeast pyruvate dehydrogenase complex is regulated by a conce... | ACCEPT | Summary: IPI (Gey et al. 2008) part_of PDH complex, from co-isolation of complex components with the regulatory kinases/phosphatases. Correct. Supporting Evidence: PMID:18180296 Both proteins are associated with the complex. |
| GO:1902493 acetyltransferase complex | IEA GO_REF:0000117 | MODIFY | Summary: ARBA IEA to 'acetyltransferase complex'. The PDH complex is classified under it, so this is a correct but less specific parent. Reason: Use the specific complex term. Proposed replacements: pyruvate dehydrogenase complex Supporting Evidence: PMID:9038189 Dihydrolipoamide acyltransferase (E2), a catalytic and structural component of the three functional classes of multienzyme complexes that catalyze the oxidative decarboxylation of alpha-keto acids, forms the central core to which the other components attach. |
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Download this section (compressed HTML)Dihydrolipoamide acetyltransferase component (E2) of the PDC; the pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA; metabolic longevity factor required for calorie restriction-mediated life span extension
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