PDK2_HUMAN
ID PDK2_HUMAN Reviewed; 407 AA.
AC Q15119; A8K3A7; B3KNW0; Q6P515; Q9BS05;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 06-JUN-2002, sequence version 2.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial;
DE EC=2.7.11.2;
DE AltName: Full=Pyruvate dehydrogenase kinase isoform 2;
DE Short=PDH kinase 2;
DE Short=PDKII;
DE Flags: Precursor;
GN Name=PDK2; Synonyms=PDHK2;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-342.
RC TISSUE=Lung, Prostate, and 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 [6]
RP INDUCTION BY INSULIN, AND FUNCTION.
RX PubMed=9787110; DOI=10.1006/mgme.1998.2748;
RA Majer M., Popov K.M., Harris R.A., Bogardus C., Prochazka M.;
RT "Insulin downregulates pyruvate dehydrogenase kinase (PDK) mRNA: potential
RT mechanism contributing to increased lipid oxidation in insulin-resistant
RT subjects.";
RL Mol. Genet. Metab. 65:181-186(1998).
RN [7]
RP SUBUNIT, AND INTERACTION WITH DLAT.
RX PubMed=12816949; DOI=10.1074/jbc.m212733200;
RA Hiromasa Y., Roche T.E.;
RT "Facilitated interaction between the pyruvate dehydrogenase kinase isoform
RT 2 and the dihydrolipoyl acetyltransferase.";
RL J. Biol. Chem. 278:33681-33693(2003).
RN [8]
RP CATALYTIC ACTIVITY, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=15491150; DOI=10.1021/bi049488x;
RA Bao H., Kasten S.A., Yan X., Roche T.E.;
RT "Pyruvate dehydrogenase kinase isoform 2 activity limited and further
RT inhibited by slowing down the rate of dissociation of ADP.";
RL Biochemistry 43:13432-13441(2004).
RN [9]
RP CATALYTIC ACTIVITY, INTERACTION WITH DLAT, SUBUNIT, AND ACTIVITY
RP REGULATION.
RX PubMed=16517984; DOI=10.1074/jbc.m513514200;
RA Hiromasa Y., Hu L., Roche T.E.;
RT "Ligand-induced effects on pyruvate dehydrogenase kinase isoform 2.";
RL J. Biol. Chem. 281:12568-12579(2006).
RN [10]
RP FUNCTION.
RX PubMed=17222789; DOI=10.1016/j.ccr.2006.10.020;
RA Bonnet S., Archer S.L., Allalunis-Turner J., Haromy A., Beaulieu C.,
RA Thompson R., Lee C.T., Lopaschuk G.D., Puttagunta L., Bonnet S., Harry G.,
RA Hashimoto K., Porter C.J., Andrade M.A., Thebaud B., Michelakis E.D.;
RT "A mitochondria-K+ channel axis is suppressed in cancer and its
RT normalization promotes apoptosis and inhibits cancer growth.";
RL Cancer Cell 11:37-51(2007).
RN [11]
RP INDUCTION BY PPARD.
RX PubMed=17669420; DOI=10.1016/j.jmb.2007.06.091;
RA Degenhardt T., Saramaki A., Malinen M., Rieck M., Vaisanen S., Huotari A.,
RA Herzig K.H., Muller R., Carlberg C.;
RT "Three members of the human pyruvate dehydrogenase kinase gene family are
RT direct targets of the peroxisome proliferator-activated receptor
RT beta/delta.";
RL J. Mol. Biol. 372:341-355(2007).
RN [12]
RP CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION, INTERACTION WITH DLAT,
RP AND SUBUNIT.
RX PubMed=19833728; DOI=10.1074/jbc.m109.065557;
RA Li J., Kato M., Chuang D.T.;
RT "Pivotal role of the C-terminal DW-motif in mediating inhibition of
RT pyruvate dehydrogenase kinase 2 by dichloroacetate.";
RL J. Biol. Chem. 284:34458-34467(2009).
RN [13]
RP FUNCTION, AND INDUCTION BY CIGARETTE SMOKE EXTRACT AND REACTIVE OXYGEN
RP SPECIES.
RX PubMed=21283817; DOI=10.1371/journal.pone.0016207;
RA Sun W., Chang S.S., Fu Y., Liu Y., Califano J.A.;
RT "Chronic CSE treatment induces the growth of normal oral keratinocytes via
RT PDK2 upregulation, increased glycolysis and HIF1alpha stabilization.";
RL PLoS ONE 6:E16207-E16207(2011).
RN [14]
RP FUNCTION.
RX PubMed=22123926; DOI=10.1158/0008-5472.can-11-1215;
RA Contractor T., Harris C.R.;
RT "p53 negatively regulates transcription of the pyruvate dehydrogenase
RT kinase Pdk2.";
RL Cancer Res. 72:560-567(2012).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 16-407 IN COMPLEX WITH ATP AND THE
RP INHIBITORS AZD7545; NOV3R; PFZ3 AND DICHLOROACETATE.
RX PubMed=16401071; DOI=10.1021/bi051402s;
RA Knoechel T.R., Tucker A.D., Robinson C.M., Phillips C., Taylor W.,
RA Bungay P.J., Kasten S.A., Roche T.E., Brown D.G.;
RT "Regulatory roles of the N-terminal domain based on crystal structures of
RT human pyruvate dehydrogenase kinase 2 containing physiological and
RT synthetic ligands.";
RL Biochemistry 45:402-415(2006).
RN [17]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-342.
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 the 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. Inhibition
CC of pyruvate dehydrogenase decreases glucose utilization and increases
CC fat metabolism. Mediates cellular responses to insulin. Plays an
CC important role in maintaining normal blood glucose levels and in
CC metabolic adaptation to nutrient availability. Via its regulation of
CC pyruvate dehydrogenase activity, plays an important role in maintaining
CC normal blood pH and in preventing the accumulation of ketone bodies
CC under starvation. Plays a role in the regulation of cell proliferation
CC and in resistance to apoptosis under oxidative stress. Plays a role in
CC p53/TP53-mediated apoptosis. {ECO:0000269|PubMed:17222789,
CC ECO:0000269|PubMed:19833728, ECO:0000269|PubMed:21283817,
CC ECO:0000269|PubMed:22123926, ECO:0000269|PubMed:7499431,
CC ECO:0000269|PubMed:9787110}.
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:15491150, ECO:0000269|PubMed:16517984,
CC ECO:0000269|PubMed:19833728, ECO:0000269|PubMed:7499431};
CC -!- ACTIVITY REGULATION: Activity is enhanced by binding to the pyruvate
CC dehydrogenase subunit DLAT. Inhibited by ADP and pyruvate; these
CC compounds interfere with DLAT binding and thereby inhibit kinase
CC activity. Inhibited by dichloroacetate. Inhibited by AZD7545; this
CC compound interferes with DLAT binding and thereby inhibits kinase
CC activity. {ECO:0000269|PubMed:15491150, ECO:0000269|PubMed:16517984,
CC ECO:0000269|PubMed:19833728}.
CC -!- SUBUNIT: Homodimer, and heterodimer with PDK1. 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:12816949, ECO:0000269|PubMed:15491150,
CC ECO:0000269|PubMed:16401071, ECO:0000269|PubMed:16517984,
CC ECO:0000269|PubMed:19833728}.
CC -!- INTERACTION:
CC Q15119; P42858: HTT; NbExp=10; IntAct=EBI-726271, EBI-466029;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15119-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15119-2; Sequence=VSP_042549;
CC -!- TISSUE SPECIFICITY: Expressed in many tissues, with the highest level
CC in heart and skeletal muscle, intermediate levels in brain, kidney,
CC pancreas and liver, and low levels in placenta and lung.
CC {ECO:0000269|PubMed:7499431}.
CC -!- INDUCTION: Down-regulated by insulin. Up-regulated by reactive oxygen
CC species and cigarette smoke extract. Up-regulated by PPARD.
CC {ECO:0000269|PubMed:17669420, ECO:0000269|PubMed:21283817,
CC ECO:0000269|PubMed:9787110}.
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; L42451; AAC42010.1; -; mRNA.
DR EMBL; AK055119; BAG51472.1; -; mRNA.
DR EMBL; AK290522; BAF83211.1; -; mRNA.
DR EMBL; AC002401; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471109; EAW94642.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94644.1; -; Genomic_DNA.
DR EMBL; BC005811; AAH05811.1; -; mRNA.
DR EMBL; BC040478; AAH40478.1; -; mRNA.
DR EMBL; BC063137; AAH63137.1; -; mRNA.
DR CCDS; CCDS11559.1; -. [Q15119-1]
DR CCDS; CCDS56039.1; -. [Q15119-2]
DR PIR; I70159; I70159.
DR RefSeq; NP_001186827.1; NM_001199898.1. [Q15119-2]
DR RefSeq; NP_001186828.1; NM_001199899.1. [Q15119-2]
DR RefSeq; NP_002602.2; NM_002611.4. [Q15119-1]
DR PDB; 2BTZ; X-ray; 2.20 A; A=16-407.
DR PDB; 2BU2; X-ray; 2.40 A; A=16-407.
DR PDB; 2BU5; X-ray; 2.35 A; A=16-407.
DR PDB; 2BU6; X-ray; 2.40 A; A=16-407.
DR PDB; 2BU7; X-ray; 2.40 A; A=16-407.
DR PDB; 2BU8; X-ray; 2.50 A; A=16-407.
DR PDB; 4MP2; X-ray; 1.75 A; A=9-407.
DR PDB; 4MP7; X-ray; 1.80 A; A=9-407.
DR PDB; 4MPC; X-ray; 1.70 A; A=9-407.
DR PDB; 4MPE; X-ray; 1.95 A; A=9-407.
DR PDB; 4MPN; X-ray; 1.75 A; A=9-407.
DR PDB; 4V25; X-ray; 2.60 A; A=1-407.
DR PDB; 4V26; X-ray; 2.49 A; A=1-407.
DR PDB; 5J6A; X-ray; 2.04 A; A=9-407.
DR PDB; 5J71; X-ray; 1.65 A; A=9-407.
DR PDB; 5M4K; X-ray; 2.60 A; A=1-407.
DR PDB; 5M4M; X-ray; 2.40 A; A=1-407.
DR PDB; 5M4N; X-ray; 2.60 A; A=1-407.
DR PDB; 5M4P; X-ray; 2.30 A; A=1-407.
DR PDB; 6LIL; X-ray; 1.93 A; A/B=6-386.
DR PDB; 6LIN; X-ray; 2.67 A; A/B/C/D=6-386.
DR PDB; 6LIO; X-ray; 1.76 A; A/B=6-386.
DR PDB; 6TMP; X-ray; 2.08 A; AAA=14-407.
DR PDB; 6TMQ; X-ray; 2.11 A; AAA=14-407.
DR PDB; 6TMZ; X-ray; 2.71 A; AAA=14-407.
DR PDB; 6TN0; X-ray; 1.91 A; AAA=14-407.
DR PDB; 6TN2; X-ray; 1.77 A; AAA=14-407.
DR PDB; 7EA0; X-ray; 2.34 A; A=16-407.
DR PDB; 7EAS; X-ray; 1.97 A; A=16-407.
DR PDB; 7EBH; X-ray; 1.96 A; A=16-407.
DR PDB; 7VBU; X-ray; 1.89 A; A=16-407.
DR PDB; 7VBV; X-ray; 2.21 A; A/B=16-407.
DR PDB; 7VBX; X-ray; 2.60 A; A=16-407.
DR PDBsum; 2BTZ; -.
DR PDBsum; 2BU2; -.
DR PDBsum; 2BU5; -.
DR PDBsum; 2BU6; -.
DR PDBsum; 2BU7; -.
DR PDBsum; 2BU8; -.
DR PDBsum; 4MP2; -.
DR PDBsum; 4MP7; -.
DR PDBsum; 4MPC; -.
DR PDBsum; 4MPE; -.
DR PDBsum; 4MPN; -.
DR PDBsum; 4V25; -.
DR PDBsum; 4V26; -.
DR PDBsum; 5J6A; -.
DR PDBsum; 5J71; -.
DR PDBsum; 5M4K; -.
DR PDBsum; 5M4M; -.
DR PDBsum; 5M4N; -.
DR PDBsum; 5M4P; -.
DR PDBsum; 6LIL; -.
DR PDBsum; 6LIN; -.
DR PDBsum; 6LIO; -.
DR PDBsum; 6TMP; -.
DR PDBsum; 6TMQ; -.
DR PDBsum; 6TMZ; -.
DR PDBsum; 6TN0; -.
DR PDBsum; 6TN2; -.
DR PDBsum; 7EA0; -.
DR PDBsum; 7EAS; -.
DR PDBsum; 7EBH; -.
DR PDBsum; 7VBU; -.
DR PDBsum; 7VBV; -.
DR PDBsum; 7VBX; -.
DR AlphaFoldDB; Q15119; -.
DR SMR; Q15119; -.
DR BioGRID; 111190; 27.
DR IntAct; Q15119; 27.
DR MINT; Q15119; -.
DR STRING; 9606.ENSP00000420927; -.
DR BindingDB; Q15119; -.
DR ChEMBL; CHEMBL3861; -.
DR DrugBank; DB08609; (2R)-N-{4-[Ethyl(phenyl)sulfamoyl]-2-methylphenyl}-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide.
DR DrugBank; DB08608; 4-({(2R,5S)-2,5-DIMETHYL-4-[(2R)-3,3,3-TRIFLUORO-2-HYDROXY-2-METHYLPROPANOYL]PIPERAZIN-1-YL}CARBONYL)BENZONITRILE.
DR DrugBank; DB08610; N-(2-AMINOETHYL)-2-{3-CHLORO-4-[(4-ISOPROPYLBENZYL)OXY]PHENYL} ACETAMIDE.
DR DrugCentral; Q15119; -.
DR GuidetoPHARMACOLOGY; 2142; -.
DR iPTMnet; Q15119; -.
DR PhosphoSitePlus; Q15119; -.
DR BioMuta; PDK2; -.
DR DMDM; 21431820; -.
DR EPD; Q15119; -.
DR jPOST; Q15119; -.
DR MassIVE; Q15119; -.
DR MaxQB; Q15119; -.
DR PaxDb; Q15119; -.
DR PeptideAtlas; Q15119; -.
DR PRIDE; Q15119; -.
DR ProteomicsDB; 60445; -. [Q15119-1]
DR ProteomicsDB; 60446; -. [Q15119-2]
DR Antibodypedia; 1630; 548 antibodies from 35 providers.
DR DNASU; 5164; -.
DR Ensembl; ENST00000007708.7; ENSP00000007708.3; ENSG00000005882.12. [Q15119-2]
DR Ensembl; ENST00000503176.6; ENSP00000420927.1; ENSG00000005882.12. [Q15119-1]
DR Ensembl; ENST00000614357.4; ENSP00000481915.1; ENSG00000005882.12. [Q15119-2]
DR GeneID; 5164; -.
DR KEGG; hsa:5164; -.
DR MANE-Select; ENST00000503176.6; ENSP00000420927.1; NM_002611.5; NP_002602.2.
DR UCSC; uc002iqb.4; human. [Q15119-1]
DR CTD; 5164; -.
DR DisGeNET; 5164; -.
DR GeneCards; PDK2; -.
DR HGNC; HGNC:8810; PDK2.
DR HPA; ENSG00000005882; Tissue enhanced (skeletal muscle, tongue).
DR MIM; 602525; gene.
DR neXtProt; NX_Q15119; -.
DR OpenTargets; ENSG00000005882; -.
DR PharmGKB; PA33155; -.
DR VEuPathDB; HostDB:ENSG00000005882; -.
DR eggNOG; KOG0787; Eukaryota.
DR GeneTree; ENSGT01030000234646; -.
DR HOGENOM; CLU_023861_1_1_1; -.
DR InParanoid; Q15119; -.
DR OMA; APQIGDH; -.
DR OrthoDB; 1242599at2759; -.
DR PhylomeDB; Q15119; -.
DR TreeFam; TF314918; -.
DR BRENDA; 2.7.11.2; 2681.
DR PathwayCommons; Q15119; -.
DR Reactome; R-HSA-204174; Regulation of pyruvate dehydrogenase (PDH) complex.
DR Reactome; R-HSA-5362517; Signaling by Retinoic Acid.
DR SignaLink; Q15119; -.
DR SIGNOR; Q15119; -.
DR BioGRID-ORCS; 5164; 60 hits in 1107 CRISPR screens.
DR ChiTaRS; PDK2; human.
DR EvolutionaryTrace; Q15119; -.
DR GeneWiki; PDK2; -.
DR GenomeRNAi; 5164; -.
DR Pharos; Q15119; Tchem.
DR PRO; PR:Q15119; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q15119; protein.
DR Bgee; ENSG00000005882; Expressed in hindlimb stylopod muscle and 187 other tissues.
DR ExpressionAtlas; Q15119; baseline and differential.
DR Genevisible; Q15119; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005967; C:mitochondrial pyruvate dehydrogenase complex; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0004740; F:pyruvate dehydrogenase (acetyl-transferring) kinase activity; IDA:UniProtKB.
DR GO; GO:0031670; P:cellular response to nutrient; ISS:UniProtKB.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; TAS:ProtInc.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; 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; ISS:UniProtKB.
DR GO; GO:0050848; P:regulation of calcium-mediated signaling; IEA:Ensembl.
DR GO; GO:0010565; P:regulation of cellular ketone metabolic process; ISS:UniProtKB.
DR GO; GO:0006111; P:regulation of gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0010906; P:regulation of glucose metabolic process; ISS:UniProtKB.
DR GO; GO:0006885; P:regulation of pH; ISS: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..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..407
FT /note="[Pyruvate dehydrogenase (acetyl-transferring)]
FT kinase isozyme 2, mitochondrial"
FT /id="PRO_0000023440"
FT DOMAIN 135..364
FT /note="Histidine kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT BINDING 251..258
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:16401071"
FT BINDING 290
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:16401071"
FT BINDING 309..310
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 325..330
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:16401071"
FT MOD_RES 215
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q15118"
FT MOD_RES 216
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q15118"
FT MOD_RES 376
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BFP9"
FT VAR_SEQ 1..64
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042549"
FT VARIANT 342
FT /note="G -> R (in a glioblastoma multiforme sample; somatic
FT mutation; dbSNP:rs17855787)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_042296"
FT CONFLICT 80
FT /note="S -> T (in Ref. 1; AAC42010)"
FT /evidence="ECO:0000305"
FT CONFLICT 407
FT /note="S -> T (in Ref. 1; AAC42010)"
FT /evidence="ECO:0000305"
FT HELIX 6..12
FT /evidence="ECO:0007829|PDB:6LIN"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:5J6A"
FT HELIX 16..24
FT /evidence="ECO:0007829|PDB:5J71"
FT HELIX 33..37
FT /evidence="ECO:0007829|PDB:5J71"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:7EBH"
FT HELIX 46..68
FT /evidence="ECO:0007829|PDB:5J71"
FT HELIX 73..76
FT /evidence="ECO:0007829|PDB:5J71"
FT HELIX 79..96
FT /evidence="ECO:0007829|PDB:5J71"
FT TURN 97..100
FT /evidence="ECO:0007829|PDB:5J71"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:5M4K"
FT HELIX 106..122
FT /evidence="ECO:0007829|PDB:5J71"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:5J71"
FT HELIX 126..141
FT /evidence="ECO:0007829|PDB:5J71"
FT HELIX 145..175
FT /evidence="ECO:0007829|PDB:5J71"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:2BU8"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:6LIL"
FT STRAND 191..196
FT /evidence="ECO:0007829|PDB:5J71"
FT HELIX 197..216
FT /evidence="ECO:0007829|PDB:5J71"
FT STRAND 222..230
FT /evidence="ECO:0007829|PDB:5J71"
FT STRAND 237..240
FT /evidence="ECO:0007829|PDB:5J71"
FT HELIX 242..262
FT /evidence="ECO:0007829|PDB:5J71"
FT TURN 263..266
FT /evidence="ECO:0007829|PDB:5J71"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:6LIO"
FT STRAND 273..279
FT /evidence="ECO:0007829|PDB:5J71"
FT STRAND 281..290
FT /evidence="ECO:0007829|PDB:5J71"
FT HELIX 297..299
FT /evidence="ECO:0007829|PDB:5J71"
FT HELIX 301..304
FT /evidence="ECO:0007829|PDB:5J71"
FT TURN 306..309
FT /evidence="ECO:0007829|PDB:4MPC"
FT HELIX 323..325
FT /evidence="ECO:0007829|PDB:4V26"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:5M4P"
FT HELIX 329..339
FT /evidence="ECO:0007829|PDB:5J71"
FT STRAND 343..349
FT /evidence="ECO:0007829|PDB:5J71"
FT TURN 350..352
FT /evidence="ECO:0007829|PDB:5J71"
FT STRAND 353..363
FT /evidence="ECO:0007829|PDB:5J71"
FT TURN 364..366
FT /evidence="ECO:0007829|PDB:5J71"
FT HELIX 376..381
FT /evidence="ECO:0007829|PDB:5J71"
SQ SEQUENCE 407 AA; 46154 MW; 77DBA03EF922EF03 CRC64;
MRWVWALLKN ASLAGAPKYI EHFSKFSPSP LSMKQFLDFG SSNACEKTSF TFLRQELPVR
LANIMKEINL LPDRVLSTPS VQLVQSWYVQ SLLDIMEFLD KDPEDHRTLS QFTDALVTIR
NRHNDVVPTM AQGVLEYKDT YGDDPVSNQN IQYFLDRFYL SRISIRMLIN QHTLIFDGST
NPAHPKHIGS IDPNCNVSEV VKDAYDMAKL LCDKYYMASP DLEIQEINAA NSKQPIHMVY
VPSHLYHMLF ELFKNAMRAT VESHESSLIL PPIKVMVALG EEDLSIKMSD RGGGVPLRKI
ERLFSYMYST APTPQPGTGG TPLAGFGYGL PISRLYAKYF QGDLQLFSME GFGTDAVIYL
KALSTDSVER LPVYNKSAWR HYQTIQEAGD WCVPSTEPKN TSTYRVS
