[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial
Details
- Name
- [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial
- Kind
- protein
- Synonyms
- 2.7.11.2
- PDH kinase 2
- PDHK2
- PDKII
- Pyruvate dehydrogenase kinase isoform 2
- Gene Name
- PDK2
- UniProtKB Entry
- Q15119Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0008259|[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial MRWVWALLKNASLAGAPKYIEHFSKFSPSPLSMKQFLDFGSSNACEKTSFTFLRQELPVR LANIMKEINLLPDRVLSTPSVQLVQSWYVQSLLDIMEFLDKDPEDHRTLSQFTDALVTIR NRHNDVVPTMAQGVLEYKDTYGDDPVSNQNIQYFLDRFYLSRISIRMLINQHTLIFDGST NPAHPKHIGSIDPNCNVSEVVKDAYDMAKLLCDKYYMASPDLEIQEINAANSKQPIHMVY VPSHLYHMLFELFKNAMRATVESHESSLILPPIKVMVALGEEDLSIKMSDRGGGVPLRKI ERLFSYMYSTAPTPQPGTGGTPLAGFGYGLPISRLYAKYFQGDLQLFSMEGFGTDAVIYL KALSTDSVERLPVYNKSAWRHYQTIQEAGDWCVPSTEPKNTSTYRVS
- Number of residues
- 407
- Molecular Weight
- 46153.39
- Theoretical pI
- 6.59
- GO Classification
- FunctionsATP binding / protein homodimerization activity / protein kinase activity / pyruvate dehydrogenase (acetyl-transferring) kinase activityProcessescellular response to nutrient / cellular response to reactive oxygen species / glucose homeostasis / glucose metabolic process / insulin receptor signaling pathway / intrinsic apoptotic signaling pathway by p53 class mediator / regulation of acetyl-CoA biosynthetic process from pyruvate / regulation of cellular ketone metabolic process / regulation of gluconeogenesis / regulation of glucose metabolic process / regulation of pHComponentsmitochondrial matrix / mitochondrion / nucleoplasm
- General Function
- Kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis
- Specific Function
- ATP binding
- Pfam Domain Function
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Mitochondrion matrix
- Gene sequence
>lcl|BSEQ0019562|[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (PDK2) ATGAAAGAGATCAACCTGCTTCCCGACCGAGTGCTGAGCACACCCTCCGTGCAGCTGGTG CAGAGCTGGTATGTCCAGAGCCTCCTGGACATCATGGAGTTCCTGGACAAGGATCCCGAG GACCATCGCACCCTGAGCCAGTTCACTGACGCCCTGGTCACCATCCGGAACCGGCACAAC GACGTGGTGCCCACCATGGCACAAGGCGTGCTTGAGTACAAGGACACCTACGGCGATGAC CCCGTCTCCAACCAGAACATCCAGTACTTCCTGGACCGCTTCTACCTCAGCCGCATCTCC ATCCGCATGCTCATCAACCAGCACACCCTCATCTTTGATGGCAGCACCAACCCAGCCCAT CCCAAACACATCGGCAGCATCGACCCCAACTGCAACGTCTCTGAGGTGGTCAAAGATGCC TACGACATGGCTAAGCTCCTGTGTGACAAGTATTACATGGCCTCACCTGACCTGGAGATC CAGGAGATCAATGCAGCCAACTCCAAACAGCCGATTCACATGGTCTACGTCCCCTCCCAC CTCTACCACATGCTCTTTGAGCTCTTCAAGAATGCCATGAGGGCGACTGTGGAAAGCCAT GAGTCCAGCCTCATTCTCCCACCCATCAAGGTCATGGTGGCCTTGGGTGAGGAAGATCTG TCCATCAAGATGAGTGACCGAGGTGGGGGTGTTCCCTTGAGGAAGATTGAGCGACTCTTC AGCTACATGTACTCCACAGCACCCACCCCCCAGCCTGGCACCGGGGGAACGCCGCTGGCT GGCTTTGGTTATGGGCTCCCCATTTCCCGCCTCTACGCCAAGTACTTCCAGGGAGACCTG CAGCTCTTCTCCATGGAAGGCTTTGGGACCGATGCTGTCATCTATCTCAAGGCCCTGTCC ACGGACTCGGTGGAGCGCCTGCCTGTCTACAACAAGTCAGCCTGGCGCCACTACCAGACC ATCCAGGAGGCCGGCGACTGGTGTGTGCCCAGCACGGAGCCCAAGAACACGTCCACGTAC CGCGTCAGCTAA
- Chromosome Location
- 17
- Locus
- 17q21.33
- External Identifiers
Resource Link UniProtKB ID Q15119 UniProtKB Entry Name PDK2_HUMAN GenBank Protein ID 1088283 GenBank Gene ID L42451 GeneCard ID PDK2 HGNC ID HGNC:8810 PDB ID(s) 2BTZ, 2BU2, 2BU5, 2BU6, 2BU7, 2BU8, 4MP2, 4MP7, 4MPC, 4MPE, 4MPN, 4V25, 4V26, 5J6A, 5J71, 5M4K, 5M4M, 5M4N, 5M4P, 6LIL, 6LIN, 6LIO, 6TMP, 6TMQ, 6TMZ, 6TN0, 6TN2, 7EA0, 7EAS, 7EBH, 7VBU, 7VBV, 7VBX KEGG ID hsa:5164 IUPHAR/Guide To Pharmacology ID 2142 NCBI Gene ID 5164 - General References
- Gudi R, Bowker-Kinley MM, Kedishvili NY, Zhao Y, Popov KM: Diversity of the pyruvate dehydrogenase kinase gene family in humans. J Biol Chem. 1995 Dec 1;270(48):28989-94. [Article]
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- Majer M, Popov KM, Harris RA, Bogardus C, Prochazka M: Insulin downregulates pyruvate dehydrogenase kinase (PDK) mRNA: potential mechanism contributing to increased lipid oxidation in insulin-resistant subjects. Mol Genet Metab. 1998 Oct;65(2):181-6. [Article]
- Hiromasa Y, Roche TE: Facilitated interaction between the pyruvate dehydrogenase kinase isoform 2 and the dihydrolipoyl acetyltransferase. J Biol Chem. 2003 Sep 5;278(36):33681-93. Epub 2003 Jun 18. [Article]
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- Li J, Kato M, Chuang DT: Pivotal role of the C-terminal DW-motif in mediating inhibition of pyruvate dehydrogenase kinase 2 by dichloroacetate. J Biol Chem. 2009 Dec 4;284(49):34458-67. doi: 10.1074/jbc.M109.065557. Epub 2009 Oct 15. [Article]
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Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details 4-({(2R,5S)-2,5-DIMETHYL-4-[(2R)-3,3,3-TRIFLUORO-2-HYDROXY-2-METHYLPROPANOYL]PIPERAZIN-1-YL}CARBONYL)BENZONITRILE experimental unknown target Details (2R)-N-{4-[Ethyl(phenyl)sulfamoyl]-2-methylphenyl}-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide experimental unknown target Details N-(2-AMINOETHYL)-2-{3-CHLORO-4-[(4-ISOPROPYLBENZYL)OXY]PHENYL} ACETAMIDE experimental unknown target Details