ID ODPA_MOUSE Reviewed; 390 AA. AC P35486; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 02-SEP-2026, entry version 195. DE RecName: Full=Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial {ECO:0000250|UniProtKB:P08559}; DE EC=1.2.4.1 {ECO:0000269|PubMed:11708858, ECO:0000269|PubMed:20841503}; DE AltName: Full=PDHE1-A type I; DE Flags: Precursor; GN Name=Pdha1 {ECO:0000250|UniProtKB:P08559}; Synonyms=Pdha-1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1581363; DOI=10.1016/0167-4781(92)90102-6; RA Fitzgerald G.F., Hutchison W.M., Dahl H.-H.M.; RT "Isolation and characterisation of the mouse pyruvate dehydrogenase E1 RT alpha genes."; RL Biochim. Biophys. Acta 1131:83-90(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Mammary gland; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP PROTEIN SEQUENCE OF 46-58; 120-127; 133-141; 159-182; 216-244; 246-263; RP 268-274; 278-321; 324-343 AND 379-385, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC STRAIN=C57BL/6J; TISSUE=Brain, and Hippocampus; RA Lubec G., Klug S., Kang S.U.; RL Submitted (APR-2007) to UniProtKB. RN [4] RP DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=11708858; DOI=10.1006/mgme.2001.3249; RA Johnson M.T., Mahmood S., Hyatt S.L., Yang H.S., Soloway P.D., Hanson R.W., RA Patel M.S.; RT "Inactivation of the murine pyruvate dehydrogenase (Pdha1) gene and its RT effect on early embryonic development."; RL Mol. Genet. Metab. 74:293-302(2001). RN [5] RP DISRUPTION PHENOTYPE. RX PubMed=17314311; DOI=10.1095/biolreprod.106.059899; RA Johnson M.T., Freeman E.A., Gardner D.K., Hunt P.A.; RT "Oxidative metabolism of pyruvate is required for meiotic maturation of RT murine oocytes in vivo."; RL Biol. Reprod. 77:2-8(2007). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232 AND SER-293, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17208939; DOI=10.1074/mcp.m600218-mcp200; RA Lee J., Xu Y., Chen Y., Sprung R., Kim S.C., Xie S., Zhao Y.; RT "Mitochondrial phosphoproteome revealed by an improved IMAC method and RT MS/MS/MS."; RL Mol. Cell. Proteomics 6:669-676(2007). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232; SER-293; SER-295 AND RP SER-300, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [8] RP DISRUPTION PHENOTYPE. RX PubMed=18586888; DOI=10.1152/ajpheart.00363.2008; RA Sidhu S., Gangasani A., Korotchkina L.G., Suzuki G., Fallavollita J.A., RA Canty J.M. Jr., Patel M.S.; RT "Tissue-specific pyruvate dehydrogenase complex deficiency causes cardiac RT hypertrophy and sudden death of weaned male mice."; RL Am. J. Physiol. 295:H946-H952(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-301, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=18034455; DOI=10.1021/pr0701254; RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.; RT "Large-scale identification and evolution indexing of tyrosine RT phosphorylation sites from murine brain."; RL J. Proteome Res. 7:311-318(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18630941; DOI=10.1021/pr800223m; RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.; RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity RT chromatography adsorbent for phosphoproteome analysis."; RL J. Proteome Res. 7:3957-3967(2008). RN [11] RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-232; SER-293 AND SER-300. RX PubMed=19341700; DOI=10.1016/j.ab.2009.03.040; RA Rardin M.J., Wiley S.E., Naviaux R.K., Murphy A.N., Dixon J.E.; RT "Monitoring phosphorylation of the pyruvate dehydrogenase complex."; RL Anal. Biochem. 389:157-164(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [13] RP DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=20841503; DOI=10.1152/ajpendo.00339.2010; RA Srinivasan M., Choi C.S., Ghoshal P., Pliss L., Pandya J.D., Hill D., RA Cline G., Patel M.S.; RT "Beta-cell-specific pyruvate dehydrogenase deficiency impairs glucose- RT stimulated insulin secretion."; RL Am. J. Physiol. 299:E910-E917(2010). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232; SER-293; SER-295 AND RP SER-300, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [15] RP ACETYLATION AT LYS-336, AND MUTAGENESIS OF LYS-336. RX PubMed=23835326; DOI=10.2337/db12-1650; RA Jing E., O'Neill B.T., Rardin M.J., Kleinridders A., Ilkeyeva O.R., RA Ussar S., Bain J.R., Lee K.Y., Verdin E.M., Newgard C.B., Gibson B.W., RA Kahn C.R.; RT "Sirt3 regulates metabolic flexibility of skeletal muscle through RT reversible enzymatic deacetylation."; RL Diabetes 62:3404-3417(2013). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-313, SUCCINYLATION [LARGE SCALE RP ANALYSIS] AT LYS-63; LYS-244; LYS-277; LYS-313 AND LYS-385, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast, and Liver; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-63; LYS-244; LYS-267 AND LYS-321, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=23576753; DOI=10.1073/pnas.1302961110; RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.; RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria RT identifies substrates of SIRT3 in metabolic pathways."; RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013). CC -!- FUNCTION: Together with PDHB forms the heterotetrameric E1 subunit of CC the pyruvate dehydrogenase (PDH) complex. The PDH complex catalyzes the CC overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby CC links cytoplasmic glycolysis and the mitochondrial tricarboxylic acid CC (TCA) cycle. It contains multiple copies of three enzymatic components: CC pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) CC and dihydrolipoamide dehydrogenase (E3) (By similarity). The E1 subunit CC catalyzes both the thiamine pyrophosphate (TPP)-dependent CC decarboxylation of pyruvate and the reductive acetylation of a lipoyl CC group covalently linked to the lipoyl-bearing domains of E2 CC (PubMed:11708858, PubMed:20841503). {ECO:0000250|UniProtKB:P08559, CC ECO:0000269|PubMed:11708858, ECO:0000269|PubMed:20841503}. CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + pyruvate + H(+) = N(6)- CC [(R)-S(8)-acetyldihydrolipoyl]-L-lysyl-[protein] + CO2; CC Xref=Rhea:RHEA:19189, Rhea:RHEA-COMP:10474, Rhea:RHEA-COMP:10478, CC ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:83099, ChEBI:CHEBI:83111; EC=1.2.4.1; CC Evidence={ECO:0000269|PubMed:11708858, ECO:0000269|PubMed:20841503}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19190; CC Evidence={ECO:0000269|PubMed:11708858, ECO:0000269|PubMed:20841503}; CC -!- COFACTOR: CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937; CC Evidence={ECO:0000250|UniProtKB:P08559}; CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P08559}; CC -!- ACTIVITY REGULATION: Pyruvate dehydrogenase activity is inhibited by CC phosphorylation of PDHA1; it is reactivated by dephosphorylation. CC {ECO:0000250|UniProtKB:P08559}. CC -!- SUBUNIT: Heterotetramer of two PDHA1 and two PDHB subunits. The CC heterotetramer interacts with DLAT, and is part of the multimeric CC pyruvate dehydrogenase (PDH) complex that contains multiple copies of CC pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, CC E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to CC an inner core composed of about 48 DLAT and 12 PDHX molecules. CC {ECO:0000250|UniProtKB:P08559}. CC -!- INTERACTION: CC P35486; Q9QXS1: Plec; NbExp=2; IntAct=EBI-773613, EBI-774583; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000269|PubMed:19341700}. CC -!- TISSUE SPECIFICITY: In all tissues, but in very low amount in testis. CC -!- PTM: Phosphorylation at Ser-232, Ser-293 and Ser-300 by PDK family CC kinases inactivates the enzyme; for this phosphorylation at a single CC site is sufficient. Phosphorylation at Ser-293 interferes with access CC to active site, and thereby inactivates the enzyme. Dephosphorylation CC at all three sites, i.e. at Ser-232, Ser-293 and Ser-300, is required CC for reactivation (By similarity). {ECO:0000250|UniProtKB:P26284}. CC -!- PTM: Acetylation alters the phosphorylation pattern. Deacetylated by CC SIRT3. {ECO:0000269|PubMed:19341700, ECO:0000269|PubMed:23835326}. CC -!- DISRUPTION PHENOTYPE: Complete embryonic lethality. Normal embryonic CC development ceases about 9.5 dpc. Conditional gene disruption in the CC heart causes death shortly after weaning in male mice fed normal chow, CC while mice on high fat diet survive, but develop left ventricular CC hypertrophy, due to impaired glucose and energy metabolism in the CC heart. Likewise, conditional gene disruption in pancreas islet beta CC cells disrupts normal insulin secretion in response to glucose stimuli, CC while conditional gene disruption in oocytes causes reduced ATP levels CC and thereby prevents normal meiosis during oocyte maturation. CC {ECO:0000269|PubMed:11708858, ECO:0000269|PubMed:17314311, CC ECO:0000269|PubMed:18586888, ECO:0000269|PubMed:20841503}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M76727; AAA53046.1; -; mRNA. DR EMBL; BC007142; AAH07142.1; -; mRNA. DR CCDS; CCDS41195.1; -. DR PIR; S23506; S23506. DR RefSeq; NP_032836.1; NM_008810.3. DR AlphaFoldDB; P35486; -. DR SMR; P35486; -. DR BioGRID; 202090; 52. DR ComplexPortal; CPX-377; Pyruvate dehydrogenase E1 heterotetramer. DR FunCoup; P35486; 1441. DR IntAct; P35486; 49. DR MINT; P35486; -. DR STRING; 10090.ENSMUSP00000033662; -. DR GlyGen; P35486; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P35486; -. DR MetOSite; P35486; -. DR PhosphoSitePlus; P35486; -. DR SwissPalm; P35486; -. DR REPRODUCTION-2DPAGE; P35486; -. DR jPOST; P35486; -. DR PaxDb; 10090-ENSMUSP00000033662; -. DR PeptideAtlas; P35486; -. DR ProteomicsDB; 293926; -. DR Pumba; P35486; -. DR Antibodypedia; 24225; 718 antibodies from 41 providers. DR DNASU; 18597; -. DR Ensembl; ENSMUST00000033662.9; ENSMUSP00000033662.9; ENSMUSG00000031299.11. DR GeneID; 18597; -. DR KEGG; mmu:18597; -. DR UCSC; uc009utc.1; mouse. DR AGR; MGI:97532; -. DR CTD; 5160; -. DR MGI; MGI:97532; Pdha1. DR VEuPathDB; HostDB:ENSMUSG00000031299; -. DR eggNOG; KOG0225; Eukaryota. DR GeneTree; ENSGT00530000063174; -. DR HOGENOM; CLU_029393_5_2_1; -. DR InParanoid; P35486; -. DR OMA; LGYEMPC; -. DR OrthoDB; 10256198at2759; -. DR PhylomeDB; P35486; -. DR BRENDA; 1.2.1.104; 3474. DR BRENDA; 1.2.4.1; 3474. DR Reactome; R-MMU-204174; Regulation of pyruvate dehydrogenase (PDH) complex. DR Reactome; R-MMU-5362517; Signaling by Retinoic Acid. DR Reactome; R-MMU-9837999; Mitochondrial protein degradation. DR Reactome; R-MMU-9861559; PDH complex synthesizes acetyl-CoA from PYR. DR BioGRID-ORCS; 18597; 11 hits in 80 CRISPR screens. DR CD-CODE; CE726F99; Postsynaptic density. DR PRO; PR:P35486; -. DR Proteomes; UP000000589; Chromosome X. DR RNAct; P35486; protein. DR Bgee; ENSMUSG00000031299; Expressed in heart right ventricle and 285 other cell types or tissues. DR ExpressionAtlas; P35486; baseline and differential. DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:MGI. DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; ISO:GO_Central. DR GO; GO:0032991; C:protein-containing complex; IMP:MGI. DR GO; GO:0045254; C:pyruvate dehydrogenase complex; ISS:UniProtKB. DR GO; GO:0004739; F:pyruvate dehydrogenase (acetyl-transferring) activity; IMP:MGI. DR GO; GO:0006086; P:pyruvate decarboxylation to acetyl-CoA; IMP:MGI. DR CDD; cd02000; TPP_E1_PDC_ADC_BCADC; 1. DR FunFam; 3.40.50.970:FF:000020; Pyruvate dehydrogenase E1 component subunit alpha, mitochondrial; 1. DR Gene3D; 3.40.50.970; -; 1. DR InterPro; IPR001017; DH_E1. DR InterPro; IPR050642; PDH_E1_Alpha_Subunit. DR InterPro; IPR017597; Pyrv_DH_E1_asu_subgrp-y. DR InterPro; IPR029061; THDP-binding. DR NCBIfam; TIGR03182; PDH_E1_alph_y; 1. DR PANTHER; PTHR11516:SF51; PYRUVATE DEHYDROGENASE E1 COMPONENT SUBUNIT ALPHA, SOMATIC FORM, MITOCHONDRIAL; 1. DR PANTHER; PTHR11516; PYRUVATE DEHYDROGENASE E1 COMPONENT, ALPHA SUBUNIT BACTERIAL AND ORGANELLAR; 1. DR Pfam; PF00676; E1_dh; 1. DR SUPFAM; SSF52518; Thiamin diphosphate-binding fold (THDP-binding); 1. PE 1: Evidence at protein level; KW Acetylation; Carbohydrate metabolism; Direct protein sequencing; KW Glucose metabolism; Magnesium; Metal-binding; Mitochondrion; KW Oxidoreductase; Phosphoprotein; Pyruvate; Reference proteome; KW Thiamine pyrophosphate; Transit peptide; Tricarboxylic acid cycle. FT TRANSIT 1..29 FT /note="Mitochondrion" FT /evidence="ECO:0000250" FT CHAIN 30..390 FT /note="Pyruvate dehydrogenase E1 component subunit alpha, FT somatic form, mitochondrial" FT /id="PRO_0000020442" FT BINDING 92 FT /ligand="pyruvate" FT /ligand_id="ChEBI:CHEBI:15361" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 118 FT /ligand="pyruvate" FT /ligand_id="ChEBI:CHEBI:15361" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 118 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /ligand_note="ligand shared with beta subunit" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 119 FT /ligand="pyruvate" FT /ligand_id="ChEBI:CHEBI:15361" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 119 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /ligand_note="ligand shared with beta subunit" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 157 FT /ligand="pyruvate" FT /ligand_id="ChEBI:CHEBI:15361" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 165 FT /ligand="pyruvate" FT /ligand_id="ChEBI:CHEBI:15361" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 165 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /ligand_note="ligand shared with beta subunit" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 167 FT /ligand="pyruvate" FT /ligand_id="ChEBI:CHEBI:15361" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 167 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /ligand_note="ligand shared with beta subunit" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 196 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 196 FT /ligand="pyruvate" FT /ligand_id="ChEBI:CHEBI:15361" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 196 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /ligand_note="ligand shared with beta subunit" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 197 FT /ligand="pyruvate" FT /ligand_id="ChEBI:CHEBI:15361" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 197 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /ligand_note="ligand shared with beta subunit" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 198 FT /ligand="pyruvate" FT /ligand_id="ChEBI:CHEBI:15361" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 198 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /ligand_note="ligand shared with beta subunit" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 225 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 225 FT /ligand="pyruvate" FT /ligand_id="ChEBI:CHEBI:15361" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 225 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /ligand_note="ligand shared with beta subunit" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 227 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 227 FT /ligand="pyruvate" FT /ligand_id="ChEBI:CHEBI:15361" FT /evidence="ECO:0000250|UniProtKB:P08559" FT BINDING 292 FT /ligand="thiamine diphosphate" FT /ligand_id="ChEBI:CHEBI:58937" FT /ligand_note="ligand shared with beta subunit" FT /evidence="ECO:0000250|UniProtKB:P08559" FT MOD_RES 63 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23576753" FT MOD_RES 63 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 232 FT /note="Phosphoserine; by PDK1" FT /evidence="ECO:0000269|PubMed:19341700, FT ECO:0007744|PubMed:17208939, ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 244 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23576753" FT MOD_RES 244 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 267 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23576753" FT MOD_RES 277 FT /note="N6-succinyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 293 FT /note="Phosphoserine; by PDK1, PDK2, PDK3 and PDK4" FT /evidence="ECO:0000269|PubMed:19341700, FT ECO:0007744|PubMed:17208939, ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079" FT MOD_RES 295 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 300 FT /note="Phosphoserine; by PDK1, PDK2, PDK3 and PDK4" FT /evidence="ECO:0000269|PubMed:19341700, FT ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:21183079" FT MOD_RES 301 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:18034455" FT MOD_RES 313 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 313 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 321 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23576753" FT MOD_RES 336 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:23835326" FT MOD_RES 385 FT /note="N6-succinyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MUTAGEN 336 FT /note="K->Q,R: Decreases phosphorylation at S-232 and S-300 FT but does not affect activity or substrate metabolism." FT /evidence="ECO:0000269|PubMed:23835326" SQ SEQUENCE 390 AA; 43232 MW; 40898944CE8E0A03 CRC64; MRKMLAAVSR VLAGSAQKPA SRVLVASRNF ANDATFEIKK CDLHRLEEGP PVTTVLTRED GLKYYRMMQT VRRMELKADQ LYKQKIIRGF CHLCDGQEAC CVGLEAGINP TDHLITAYRA HGFTFTRGLP VRAILAELTG RRGGCAKGKG GSMHMYAKNF YGGNGIVGAQ VPLGAGIALA CKYNGKDEVC LTLYGDGAAN QGQIFEAYNM AALWKLPCIF ICENNRYGMG TSVERAAAST DYYKRGDFIP GLRVDGMDIL CVREATKFAA AYCRSGKGPI LMELQTYRYH GHSMSDPGVS YRTREEIQEV RSKSDPIMLL KDRMVNSNLA SVEELKEIDV EVRKEIEDAA QFATADPEPP LEELGYHIYS SDPPFEVRGA NQWIKFKSVS //