Tmic
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Name[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial
Synonyms
  • 2.7.11.2
  • PDHK3
  • Pyruvate dehydrogenase kinase isoform 3
Gene NamePDK3
OrganismHuman
Amino acid sequence
>lcl|BSEQ0008229|[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial
MRLFRWLLKQPVPKQIERYSRFSPSPLSIKQFLDFGRDNACEKTSYMFLRKELPVRLANT
MREVNLLPDNLLNRPSVGLVQSWYMQSFLELLEYENKSPEDPQVLDNFLQVLIKVRNRHN
DVVPTMAQGVIEYKEKFGFDPFISTNIQYFLDRFYTNRISFRMLINQHTLLFGGDTNPVH
PKHIGSIDPTCNVADVVKDAYETAKMLCEQYYLVAPELEVEEFNAKAPDKPIQVVYVPSH
LFHMLFELFKNSMRATVELYEDRKEGYPAVKTLVTLGKEDLSIKISDLGGGVPLRKIDRL
FNYMYSTAPRPSLEPTRAAPLAGFGYGLPISRLYARYFQGDLKLYSMEGVGTDAVIYLKA
LSSESFERLPVFNKSAWRHYKTTPEADDWSNPSSEPRDASKYKAKQ
Number of residues406
Molecular Weight46938.485
Theoretical pI8.61
GO Classification
Functions
  • protein serine/threonine kinase activity
  • pyruvate dehydrogenase (acetyl-transferring) kinase activity
  • ATP binding
  • protein kinase activity
Processes
  • cellular response to fatty acid
  • small molecule metabolic process
  • hypoxia-inducible factor-1alpha signaling pathway
  • glucose metabolic process
  • regulation of reactive oxygen species metabolic process
  • cellular metabolic process
  • pyruvate metabolic process
  • regulation of acetyl-CoA biosynthetic process from pyruvate
  • peptidyl-serine phosphorylation
  • peroxisome proliferator activated receptor signaling pathway
  • regulation of glucose metabolic process
  • cellular response to glucose stimulus
Components
  • mitochondrial matrix
  • mitochondrion
General FunctionPyruvate dehydrogenase (acetyl-transferring) kinase activity
Specific FunctionInhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID1088285
UniProtKB IDQ15120
UniProtKB Entry NamePDK3_HUMAN
Cellular LocationMitochondrion matrix
Gene sequence
>lcl|BSEQ0017412|[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial (PDK3)
ATGCGGCTGTTCCGGTGGCTGCTGAAGCAGCCGGTGCCCAAGCAGATCGAGCGCTACTCG
CGCTTTTCGCCGTCGCCGCTCTCCATCAAACAATTCCTGGACTTCGGGAGAGATAATGCA
TGTGAGAAAACTTCATATATGTTTCTACGAAAGGAACTTCCTGTGCGGCTGGCTAACACA
ATGAGAGAAGTTAATCTTCTGCCGGATAATTTACTTAACCGCCCTTCAGTGGGATTGGTT
CAGAGTTGGTATATGCAGAGTTTTCTTGAACTTTTAGAATATGAAAATAAGAGCCCTGAG
GATCCACAGGTCTTGGATAACTTTCTACAAGTTCTGATTAAAGTCAGAAATAGACACAAT
GATGTGGTTCCTACAATGGCACAAGGAGTGATTGAATACAAGGAGAAGTTTGGGTTTGAT
CCTTTCATTAGCACTAACATCCAATATTTTCTGGATCGGTTTTATACCAACCGCATCTCT
TTCCGCATGCTTATTAATCAGCACACACTTCTGTTTGGGGGTGACACTAATCCTGTTCAT
CCTAAACACATAGGAAGTATCGATCCCACCTGTAACGTGGCGGATGTGGTGAAAGATGCA
TATGAAACAGCCAAGATGCTGTGTGAACAGTATTACCTGGTAGCTCCAGAGCTGGAAGTT
GAAGAATTCAATGCCAAAGCGCCAGACAAACCTATTCAGGTGGTTTATGTGCCCTCACAT
CTGTTTCATATGCTATTTGAGTTGTTCAAGAACTCAATGAGAGCGACAGTTGAACTCTAT
GAAGACAGAAAAGAGGGCTACCCTGCTGTTAAAACCCTCGTTACTTTGGGTAAAGAAGAC
TTATCCATTAAGATCAGTGACCTAGGTGGTGGTGTCCCACTTCGAAAAATAGATCGTCTT
TTTAACTACATGTATTCTACTGCTCCTAGACCCAGCCTGGAGCCTACCAGAGCTGCCCCT
TTGGCTGGATTTGGTTATGGTTTGCCAATTTCCCGTCTGTATGCTAGATATTTTCAAGGA
GATCTGAAACTGTATTCCATGGAAGGAGTGGGTACTGATGCTGTCATTTATTTGAAGGCT
CTTTCAAGTGAGTCATTTGAGAGACTTCCAGTTTTTAATAAGTCCGCATGGCGCCATTAC
AAGACCACGCCTGAAGCCGATGATTGGAGCAATCCCAGCAGTGAACCCAGGGATGCTTCA
AAATACAAAGCAAAACAAGACAAGATCAAGACTAATAGAACTTTCTAG
GenBank Gene IDL42452
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:8811
Chromosome LocationX
LocusNot Available
References
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  4. Baker JC, Yan X, Peng T, Kasten S, Roche TE: Marked differences between two isoforms of human pyruvate dehydrogenase kinase. J Biol Chem. 2000 May 26;275(21):15773-81. 10748134
  5. Korotchkina LG, Patel MS: Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase. J Biol Chem. 2001 Oct 5;276(40):37223-9. Epub 2001 Aug 2. 11486000
  6. Tuganova A, Boulatnikov I, Popov KM: Interaction between the individual isoenzymes of pyruvate dehydrogenase kinase and the inner lipoyl-bearing domain of transacetylase component of pyruvate dehydrogenase complex. Biochem J. 2002 Aug 15;366(Pt 1):129-36. 11978179
  7. Korotchkina LG, Sidhu S, Patel MS: Characterization of testis-specific isoenzyme of human pyruvate dehydrogenase. J Biol Chem. 2006 Apr 7;281(14):9688-96. Epub 2006 Jan 25. 16436377
  8. Degenhardt T, Saramaki A, Malinen M, Rieck M, Vaisanen S, Huotari A, Herzig KH, Muller R, Carlberg C: Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/delta. J Mol Biol. 2007 Sep 14;372(2):341-55. Epub 2007 Jul 19. 17669420
  9. Lu CW, Lin SC, Chen KF, Lai YY, Tsai SJ: Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance. J Biol Chem. 2008 Oct 17;283(42):28106-14. doi: 10.1074/jbc.M803508200. Epub 2008 Aug 21. 18718909
  10. Blouin JM, Penot G, Collinet M, Nacfer M, Forest C, Laurent-Puig P, Coumoul X, Barouki R, Benelli C, Bortoli S: Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complex. Int J Cancer. 2011 Jun 1;128(11):2591-601. doi: 10.1002/ijc.25599. Epub 2010 Oct 8. 20715114
  11. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
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  15. Devedjiev Y, Steussy CN, Vassylyev DG: Crystal structure of an asymmetric complex of pyruvate dehydrogenase kinase 3 with lipoyl domain 2 and its biological implications. J Mol Biol. 2007 Jul 13;370(3):407-16. Epub 2007 May 10. 17532006
  16. Kato M, Li J, Chuang JL, Chuang DT: Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol. Structure. 2007 Aug;15(8):992-1004. Epub 2007 Aug 2. 17683942
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