ID PDK1_HUMAN Reviewed; 436 AA. AC Q15118; B2R6T1; B7Z937; D3DPD8; E9PD65; Q308M4; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 24-JAN-2024, entry version 202. DE RecName: Full=[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial; DE EC=2.7.11.2; DE AltName: Full=Pyruvate dehydrogenase kinase isoform 1; DE Short=PDH kinase 1; DE Flags: Precursor; GN Name=PDK1; Synonyms=PDHK1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND RP TISSUE SPECIFICITY. RC TISSUE=Liver; RX PubMed=7499431; DOI=10.1074/jbc.270.48.28989; RA Gudi R., Bowker-Kinley M.M., Kedishvili N.Y., Zhao Y., Popov K.M.; RT "Diversity of the pyruvate dehydrogenase kinase gene family in humans."; RL J. Biol. Chem. 270:28989-28994(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Li H., Nong W., Zhou G., Ke R., Shen C., Zhong G., Zheng Z., Liang M., RA Tang Z., Huang B., Lin L., Yang S.; RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Skin; 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 [7] RP FUNCTION. RX PubMed=18541534; DOI=10.1074/jbc.m801765200; RA McFate T., Mohyeldin A., Lu H., Thakar J., Henriques J., Halim N.D., Wu H., RA Schell M.J., Tsang T.M., Teahan O., Zhou S., Califano J.A., Jeoung N.H., RA Harris R.A., Verma A.; RT "Pyruvate dehydrogenase complex activity controls metabolic and malignant RT phenotype in cancer cells."; RL J. Biol. Chem. 283:22700-22708(2008). RN [8] RP INDUCTION BY HYPOXIA. RX PubMed=21763680; DOI=10.1016/j.ajpath.2011.05.050; RA Lu C.W., Lin S.C., Chien C.W., Lin S.C., Lee C.T., Lin B.W., Lee J.C., RA Tsai S.J.; RT "Overexpression of pyruvate dehydrogenase kinase 3 increases drug RT resistance and early recurrence in colon cancer."; RL Am. J. Pathol. 179:1405-1414(2011). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT RP TYR-136; TYR-243 AND TYR-244. RX PubMed=22195962; DOI=10.1016/j.molcel.2011.10.015; RA Hitosugi T., Fan J., Chung T.W., Lythgoe K., Wang X., Xie J., Ge Q., RA Gu T.L., Polakiewicz R.D., Roesel J.L., Chen G.Z., Boggon T.J., Lonial S., RA Fu H., Khuri F.R., Kang S., Chen J.; RT "Tyrosine phosphorylation of mitochondrial pyruvate dehydrogenase kinase 1 RT is important for cancer metabolism."; RL Mol. Cell 44:864-877(2011). RN [11] RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER PHE-28, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [12] RP ROLE IN HYPOXIC TUMOR SURVIVAL. RX PubMed=27505672; DOI=10.1016/j.ccell.2016.07.004; RA Chae Y.C., Vaira V., Caino M.C., Tang H.Y., Seo J.H., Kossenkov A.V., RA Ottobrini L., Martelli C., Lucignani G., Bertolini I., Locatelli M., RA Bryant K.G., Ghosh J.C., Lisanti S., Ku B., Bosari S., Languino L.R., RA Speicher D.W., Altieri D.C.; RT "Mitochondrial Akt regulation of hypoxic tumor reprogramming."; RL Cancer Cell 30:257-272(2016). RN [13] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 30-436 IN COMPLEX WITH THE RP INHIBITORS AZD7545 AND DICHLOROACETATE, FUNCTION, SUBUNIT, CATALYTIC RP ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=17683942; DOI=10.1016/j.str.2007.07.001; RA Kato M., Li J., Chuang J.L., Chuang D.T.; RT "Distinct structural mechanisms for inhibition of pyruvate dehydrogenase RT kinase isoforms by AZD7545, dichloroacetate, and radicicol."; RL Structure 15:992-1004(2007). RN [14] RP VARIANT [LARGE SCALE ANALYSIS] THR-412. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Kinase that plays a key role in regulation of glucose and CC fatty acid metabolism and homeostasis via phosphorylation of the CC pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate CC dehydrogenase activity, and thereby regulates metabolite flux through CC the tricarboxylic acid cycle, down-regulates aerobic respiration and CC inhibits the formation of acetyl-coenzyme A from pyruvate. Plays an CC important role in cellular responses to hypoxia and is important for CC cell proliferation under hypoxia. Protects cells against apoptosis in CC response to hypoxia and oxidative stress. {ECO:0000269|PubMed:17683942, CC ECO:0000269|PubMed:18541534, ECO:0000269|PubMed:22195962, CC ECO:0000269|PubMed:7499431}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[pyruvate dehydrogenase E1 alpha subunit] = ADP CC + H(+) + O-phospho-L-seryl-[pyruvate dehydrogenase E1 alpha subunit]; CC Xref=Rhea:RHEA:23052, Rhea:RHEA-COMP:13689, Rhea:RHEA-COMP:13690, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.2; CC Evidence={ECO:0000269|PubMed:17683942, ECO:0000269|PubMed:22195962, CC ECO:0000269|PubMed:7499431}; CC -!- ACTIVITY REGULATION: Activity is enhanced by binding to the pyruvate CC dehydrogenase subunit DLAT. Inhibited by AZD7545; this compound CC interferes with DLAT binding and thereby inhibits kinase activity. CC Inhibited by dichloroacetate and radicicol. CC {ECO:0000269|PubMed:17683942}. CC -!- SUBUNIT: Homodimer, and heterodimer with PDK2. Interacts with the CC pyruvate dehydrogenase complex subunit DLAT, and is part of the CC multimeric pyruvate dehydrogenase complex that contains multiple copies CC of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase CC (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). CC {ECO:0000269|PubMed:17683942}. CC -!- INTERACTION: CC Q15118; P05067: APP; NbExp=3; IntAct=EBI-7016221, EBI-77613; CC Q15118; P08559: PDHA1; NbExp=2; IntAct=EBI-7016221, EBI-715747; CC Q15118; Q16513: PKN2; NbExp=6; IntAct=EBI-7016221, EBI-2511350; CC Q15118-1; P31749-1: AKT1; NbExp=2; IntAct=EBI-12562315, EBI-12562306; CC Q15118-1; P31751-1: AKT2; NbExp=2; IntAct=EBI-12562315, EBI-12562336; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000269|PubMed:22195962}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q15118-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15118-2; Sequence=VSP_055172; CC -!- TISSUE SPECIFICITY: Expressed predominantly in the heart. Detected at CC lower levels in liver, skeletal muscle and pancreas. CC {ECO:0000269|PubMed:7499431}. CC -!- INDUCTION: Up-regulated via the HIF1A signaling pathway in response to CC hypoxia. {ECO:0000269|PubMed:21763680}. CC -!- PTM: Phosphorylated by constitutively activated ABL1, FGFR1, FLT3 and CC JAK2 (in vitro), and this may also occur in cancer cells that express CC constitutively activated ABL1, FGFR1, FLT3 and JAK2. Phosphorylation at CC Tyr-243 and Tyr-244 strongly increases kinase activity, while CC phosphorylation at Tyr-136 has a lesser effect. CC {ECO:0000269|PubMed:22195962}. CC -!- MISCELLANEOUS: Exposure of cancer cells to severe hypoxia induces CC translocation of AKT to the mitochondrion, leading to AKT-mediated CC phosphorylation of PDK1 at Thr-346 which supports tumor cell survival CC and proliferation during hypoxia. {ECO:0000269|PubMed:27505672}. CC -!- SIMILARITY: Belongs to the PDK/BCKDK protein kinase family. CC {ECO:0000305}. 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; L42450; AAC42009.1; -; mRNA. DR EMBL; DQ234350; ABB29979.1; -; mRNA. DR EMBL; AK304388; BAH14173.1; -; mRNA. DR EMBL; AK312700; BAG35578.1; -; mRNA. DR EMBL; AC018712; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC093818; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471058; EAX11173.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11174.1; -; Genomic_DNA. DR EMBL; BC039158; AAH39158.1; -; mRNA. DR CCDS; CCDS2250.1; -. [Q15118-1] DR CCDS; CCDS63059.1; -. [Q15118-2] DR PIR; I55465; I55465. DR RefSeq; NP_001265478.1; NM_001278549.1. [Q15118-2] DR RefSeq; NP_002601.1; NM_002610.4. [Q15118-1] DR PDB; 2Q8F; X-ray; 2.03 A; A=30-436. DR PDB; 2Q8G; X-ray; 1.90 A; A=30-436. DR PDB; 2Q8H; X-ray; 2.00 A; A=30-436. DR PDBsum; 2Q8F; -. DR PDBsum; 2Q8G; -. DR PDBsum; 2Q8H; -. DR AlphaFoldDB; Q15118; -. DR SMR; Q15118; -. DR BioGRID; 111189; 353. DR DIP; DIP-29497N; -. DR IntAct; Q15118; 285. DR MINT; Q15118; -. DR STRING; 9606.ENSP00000376352; -. DR BindingDB; Q15118; -. DR ChEMBL; CHEMBL4766; -. DR DrugBank; DB07403; 4-[(3-CHLORO-4-{[(2R)-3,3,3-TRIFLUORO-2-HYDROXY-2-METHYLPROPANOYL]AMINO}PHENYL)SULFONYL]-N,N-DIMETHYLBENZAMIDE. DR DrugBank; DB08809; Dichloroacetic acid. DR DrugCentral; Q15118; -. DR GuidetoPHARMACOLOGY; 2915; -. DR GlyGen; Q15118; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q15118; -. DR PhosphoSitePlus; Q15118; -. DR SwissPalm; Q15118; -. DR BioMuta; PDK1; -. DR DMDM; 3183117; -. DR CPTAC; CPTAC-2843; -. DR CPTAC; CPTAC-2889; -. DR EPD; Q15118; -. DR jPOST; Q15118; -. DR MassIVE; Q15118; -. DR MaxQB; Q15118; -. DR PaxDb; 9606-ENSP00000376352; -. DR PeptideAtlas; Q15118; -. DR ProteomicsDB; 19593; -. DR ProteomicsDB; 60444; -. [Q15118-1] DR Pumba; Q15118; -. DR Antibodypedia; 4312; 735 antibodies from 40 providers. DR DNASU; 5163; -. DR Ensembl; ENST00000282077.8; ENSP00000282077.3; ENSG00000152256.14. [Q15118-1] DR Ensembl; ENST00000392571.6; ENSP00000376352.2; ENSG00000152256.14. [Q15118-2] DR Ensembl; ENST00000410055.5; ENSP00000386985.1; ENSG00000152256.14. [Q15118-1] DR GeneID; 5163; -. DR KEGG; hsa:5163; -. DR MANE-Select; ENST00000282077.8; ENSP00000282077.3; NM_002610.5; NP_002601.1. DR UCSC; uc002uhs.5; human. [Q15118-1] DR AGR; HGNC:8809; -. DR CTD; 5163; -. DR DisGeNET; 5163; -. DR GeneCards; PDK1; -. DR HGNC; HGNC:8809; PDK1. DR HPA; ENSG00000152256; Low tissue specificity. DR MIM; 602524; gene. DR neXtProt; NX_Q15118; -. DR OpenTargets; ENSG00000152256; -. DR PharmGKB; PA33154; -. DR VEuPathDB; HostDB:ENSG00000152256; -. DR eggNOG; KOG0787; Eukaryota. DR GeneTree; ENSGT01030000234646; -. DR HOGENOM; CLU_023861_1_1_1; -. DR InParanoid; Q15118; -. DR OMA; AGHHISM; -. DR OrthoDB; 3058550at2759; -. DR PhylomeDB; Q15118; -. DR TreeFam; TF314918; -. DR BRENDA; 2.7.11.2; 2681. DR PathwayCommons; Q15118; -. DR Reactome; R-HSA-204174; Regulation of pyruvate dehydrogenase (PDH) complex. DR Reactome; R-HSA-5362517; Signaling by Retinoic Acid. DR SignaLink; Q15118; -. DR SIGNOR; Q15118; -. DR BioGRID-ORCS; 5163; 9 hits in 1202 CRISPR screens. DR ChiTaRS; PDK1; human. DR EvolutionaryTrace; Q15118; -. DR GeneWiki; Pyruvate_dehydrogenase_lipoamide_kinase_isozyme_1; -. DR GenomeRNAi; 5163; -. DR Pharos; Q15118; Tchem. DR PRO; PR:Q15118; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q15118; Protein. DR Bgee; ENSG00000152256; Expressed in secondary oocyte and 182 other cell types or tissues. DR ExpressionAtlas; Q15118; baseline and differential. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005967; C:mitochondrial pyruvate dehydrogenase complex; IEA:Ensembl. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB. DR GO; GO:0004740; F:pyruvate dehydrogenase (acetyl-transferring) kinase activity; IDA:UniProtKB. DR GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB. DR GO; GO:0006006; P:glucose metabolic process; TAS:ProtInc. DR GO; GO:0097411; P:hypoxia-inducible factor-1alpha signaling pathway; IMP:UniProtKB. DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IMP:UniProtKB. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0010510; P:regulation of acetyl-CoA biosynthetic process from pyruvate; TAS:Reactome. DR GO; GO:0010906; P:regulation of glucose metabolic process; IMP:UniProtKB. DR CDD; cd16929; HATPase_PDK-like; 1. DR Gene3D; 1.20.140.20; Alpha-ketoacid/pyruvate dehydrogenase kinase, N-terminal domain; 1. DR Gene3D; 3.30.565.10; Histidine kinase-like ATPase, C-terminal domain; 1. DR InterPro; IPR036784; AK/P_DHK_N_sf. DR InterPro; IPR018955; BCDHK/PDK_N. DR InterPro; IPR039028; BCKD/PDK. DR InterPro; IPR003594; HATPase_C. DR InterPro; IPR036890; HATPase_C_sf. DR InterPro; IPR005467; His_kinase_dom. DR PANTHER; PTHR11947:SF14; [PYRUVATE DEHYDROGENASE (ACETYL-TRANSFERRING)] KINASE ISOZYME 1, MITOCHONDRIAL; 1. DR PANTHER; PTHR11947; PYRUVATE DEHYDROGENASE KINASE; 1. DR Pfam; PF10436; BCDHK_Adom3; 1. DR Pfam; PF02518; HATPase_c; 1. DR SMART; SM00387; HATPase_c; 1. DR SUPFAM; SSF69012; alpha-ketoacid dehydrogenase kinase, N-terminal domain; 1. DR SUPFAM; SSF55874; ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase; 1. DR PROSITE; PS50109; HIS_KIN; 1. DR Genevisible; Q15118; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Kinase; Mitochondrion; KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase; KW Transit peptide. FT TRANSIT 1..28 FT /note="Mitochondrion" FT /evidence="ECO:0000255, ECO:0007744|PubMed:25944712" FT CHAIN 29..436 FT /note="[Pyruvate dehydrogenase (acetyl-transferring)] FT kinase isozyme 1, mitochondrial" FT /id="PRO_0000023437" FT DOMAIN 163..393 FT /note="Histidine kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107" FT BINDING 279..286 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 318 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 337..338 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 354..359 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT MOD_RES 136 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000269|PubMed:22195962" FT MOD_RES 243 FT /note="Phosphotyrosine; by FGFR1, ABL1, FLT3 and JAK2" FT /evidence="ECO:0000269|PubMed:22195962" FT MOD_RES 244 FT /note="Phosphotyrosine; by FGFR1" FT /evidence="ECO:0000269|PubMed:22195962" FT MOD_RES 405 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BFP9" FT VAR_SEQ 137 FT /note="D -> ERPRRTWLQVSSLCCMACKMI (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.2" FT /id="VSP_055172" FT VARIANT 134 FT /note="A -> T (in dbSNP:rs35661499)" FT /id="VAR_050477" FT VARIANT 412 FT /note="N -> T (in dbSNP:rs34250425)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042295" FT CONFLICT 8 FT /note="R -> L (in Ref. 2; ABB29979)" FT /evidence="ECO:0000305" FT CONFLICT 96 FT /note="L -> R (in Ref. 3; BAH14173)" FT /evidence="ECO:0000305" FT CONFLICT 363 FT /note="R -> C (in Ref. 2; ABB29979)" FT /evidence="ECO:0000305" FT HELIX 42..50 FT /evidence="ECO:0007829|PDB:2Q8G" FT HELIX 59..67 FT /evidence="ECO:0007829|PDB:2Q8G" FT HELIX 72..94 FT /evidence="ECO:0007829|PDB:2Q8G" FT HELIX 99..102 FT /evidence="ECO:0007829|PDB:2Q8G" FT HELIX 105..122 FT /evidence="ECO:0007829|PDB:2Q8G" FT STRAND 125..127 FT /evidence="ECO:0007829|PDB:2Q8G" FT HELIX 132..148 FT /evidence="ECO:0007829|PDB:2Q8G" FT TURN 149..151 FT /evidence="ECO:0007829|PDB:2Q8G" FT HELIX 152..166 FT /evidence="ECO:0007829|PDB:2Q8G" FT HELIX 171..202 FT /evidence="ECO:0007829|PDB:2Q8G" FT STRAND 219..224 FT /evidence="ECO:0007829|PDB:2Q8G" FT HELIX 225..244 FT /evidence="ECO:0007829|PDB:2Q8G" FT STRAND 250..259 FT /evidence="ECO:0007829|PDB:2Q8G" FT STRAND 265..268 FT /evidence="ECO:0007829|PDB:2Q8G" FT HELIX 270..291 FT /evidence="ECO:0007829|PDB:2Q8G" FT TURN 293..295 FT /evidence="ECO:0007829|PDB:2Q8G" FT STRAND 301..307 FT /evidence="ECO:0007829|PDB:2Q8G" FT STRAND 309..318 FT /evidence="ECO:0007829|PDB:2Q8G" FT HELIX 325..328 FT /evidence="ECO:0007829|PDB:2Q8G" FT HELIX 329..332 FT /evidence="ECO:0007829|PDB:2Q8G" FT TURN 334..337 FT /evidence="ECO:0007829|PDB:2Q8G" FT STRAND 352..354 FT /evidence="ECO:0007829|PDB:2Q8H" FT HELIX 358..368 FT /evidence="ECO:0007829|PDB:2Q8G" FT STRAND 372..378 FT /evidence="ECO:0007829|PDB:2Q8G" FT TURN 379..381 FT /evidence="ECO:0007829|PDB:2Q8G" FT STRAND 382..392 FT /evidence="ECO:0007829|PDB:2Q8G" FT TURN 393..395 FT /evidence="ECO:0007829|PDB:2Q8G" FT HELIX 405..411 FT /evidence="ECO:0007829|PDB:2Q8G" SQ SEQUENCE 436 AA; 49244 MW; D14CD594E0EA45A2 CRC64; MRLARLLRGA ALAGPGPGLR AAGFSRSFSS DSGSSPASER GVPGQVDFYA RFSPSPLSMK QFLDFGSVNA CEKTSFMFLR QELPVRLANI MKEISLLPDN LLRTPSVQLV QSWYIQSLQE LLDFKDKSAE DAKAIYDFTD TVIRIRNRHN DVIPTMAQGV IEYKESFGVD PVTSQNVQYF LDRFYMSRIS IRMLLNQHSL LFGGKGKGSP SHRKHIGSIN PNCNVLEVIK DGYENARRLC DLYYINSPEL ELEELNAKSP GQPIQVVYVP SHLYHMVFEL FKNAMRATME HHANRGVYPP IQVHVTLGNE DLTVKMSDRG GGVPLRKIDR LFNYMYSTAP RPRVETSRAV PLAGFGYGLP ISRLYAQYFQ GDLKLYSLEG YGTDAVIYIK ALSTDSIERL PVYNKAAWKH YNTNHEADDW CVPSREPKDM TTFRSA //