PDK1_HUMAN
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 03-AUG-2022, entry version 194.
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}.
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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; 330.
DR DIP; DIP-29497N; -.
DR IntAct; Q15118; 281.
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 iPTMnet; Q15118; -.
DR PhosphoSitePlus; Q15118; -.
DR BioMuta; PDK1; -.
DR DMDM; 3183117; -.
DR EPD; Q15118; -.
DR jPOST; Q15118; -.
DR MassIVE; Q15118; -.
DR MaxQB; Q15118; -.
DR PaxDb; Q15118; -.
DR PeptideAtlas; Q15118; -.
DR PRIDE; Q15118; -.
DR ProteomicsDB; 19593; -.
DR ProteomicsDB; 60444; -. [Q15118-1]
DR Antibodypedia; 4312; 692 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 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; IGCIDSM; -.
DR OrthoDB; 1242599at2759; -.
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 1114 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 180 other tissues.
DR ExpressionAtlas; Q15118; baseline and differential.
DR Genevisible; Q15118; HS.
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:0006468; P:protein phosphorylation; IBA:GO_Central.
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 Gene3D; 1.20.140.20; -; 1.
DR Gene3D; 3.30.565.10; -; 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; PTHR11947; 1.
DR Pfam; PF10436; BCDHK_Adom3; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR SUPFAM; SSF69012; SSF69012; 1.
DR PROSITE; PS50109; HIS_KIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Carbohydrate metabolism;
KW Glucose metabolism; Kinase; Mitochondrion; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase; 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
