[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial

Name[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial
Synonyms2.7.11.2 PDHK4 Pyruvate dehydrogenase kinase isoform 4
Gene NamePDK4
OrganismHuman
Amino acid sequence
>lcl|BSEQ0017394|[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial
MKAARFVLRSAGSLNGAGLVPREVEHFSRYSPSPLSMKQLLDFGSENACERTSFAFLRQE
LPVRLANILKEIDILPTQLVNTSSVQLVKSWYIQSLMDLVEFHEKSPDDQKALSDFVDTL
IKVRNRHHNVVPTMAQGIIEYKDACTVDPVTNQNLQYFLDRFYMNRISTRMLMNQHILIF
SDSQTGNPSHIGSIDPNCDVVAVVQDAFECSRMLCDQYYLSSPELKLTQVNGKFPDQPIH
IVYVPSHLHHMLFELFKNAMRATVEHQENQPSLTPIEVIVVLGKEDLTIKISDRGGGVPL
RIIDRLFSYTYSTAPTPVMDNSRNAPLAGFGYGLPISRLYAKYFQGDLNLYSLSGYGTDA
IIYLKALSSESIEKLPVFNKSAFKHYQMSSEADDWCIPSREPKNLAKEVAM
Number of residues411
Molecular Weight46468.79
Theoretical pI6.65
GO Classification
Functions
    ATP binding
protein kinase activity
pyruvate dehydrogenase (acetyl-transferring) kinase activity
Processes
    glucose homeostasis
cellular response to starvation
glucose metabolic process
regulation of bone resorption
cellular metabolic process
cellular response to fatty acid
insulin receptor signaling pathway
regulation of fatty acid oxidation
protein phosphorylation
negative regulation of anoikis
pyruvate metabolic process
regulation of acetyl-CoA biosynthetic process from pyruvate
regulation of fatty acid biosynthetic process
response to starvation
regulation of cellular ketone metabolic process
regulation of pH
positive regulation of defense response to virus by host
reactive oxygen species metabolic process
xenophagy
small molecule metabolic process
regulation of glucose metabolic process
Components
    mitochondrion
mitochondrial inner membrane
mitochondrial matrix
General FunctionPyruvate dehydrogenase (acetyl-transferring) kinase activity
Specific FunctionKinase that plays a key role in 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 in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. 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. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism.
Transmembrane Regions
GenBank Protein ID1399197
UniProtKB IDQ16654
UniProtKB Entry NamePDK4_HUMAN
Cellular LocationMitochondrion matrix
Gene sequence
>lcl|BSEQ0017395|[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial (PDK4)
ATGAAGGCGGCCCGCTTCGTGCTGCGCAGCGCTGGCTCGCTCAACGGCGCCGGCCTGGTG
CCCCGAGAGGTGGAGCATTTCTCGCGCTACAGCCCGTCCCCGCTGTCCATGAAGCAGCTA
CTGGACTTTGGTTCAGAAAATGCATGTGAAAGAACTTCTTTTGCATTTTTGCGACAAGAA
TTGCCTGTGAGACTCGCCAACATTCTGAAGGAAATTGATATCCTCCCGACCCAATTAGTA
AATACCTCTTCAGTGCAATTGGTTAAAAGCTGGTATATACAGAGCCTGATGGATTTGGTG
GAATTCCATGAGAAAAGCCCAGATGACCAGAAAGCATTATCAGACTTTGTAGATACACTC
ATCAAAGTTCGAAATAGACACCATAATGTAGTCCCTACAATGGCACAAGGAATCATAGAG
TATAAAGATGCCTGTACAGTTGACCCAGTCACCAATCAAAATCTTCAATATTTCTTGGAT
CGATTTTACATGAACCGTATTTCTACTCGGATGCTGATGAACCAGCACATTCTTATATTT
AGTGACTCACAGACAGGAAACCCAAGCCACATTGGAAGCATTGATCCTAACTGTGATGTG
GTAGCAGTGGTCCAAGATGCCTTTGAGTGTTCAAGGATGCTCTGTGATCAGTATTATTTA
TCATCTCCAGAATTAAAGCTTACACAAGTGAATGGAAAATTTCCAGACCAACCAATTCAC
ATCGTGTATGTTCCTTCTCACCTCCATCATATGCTCTTTGAACTATTTAAGAATGCAATG
CGGGCAACAGTTGAACACCAGGAAAATCAGCCTTCCCTTACACCAATAGAGGTTATTGTT
GTCTTGGGAAAAGAAGACCTTACCATTAAGATTTCAGACAGAGGAGGTGGTGTTCCCCTG
AGAATTATTGACCGCCTCTTTAGTTATACATACTCCACTGCACCAACGCCTGTGATGGAT
AATTCCCGGAATGCTCCTTTGGCTGGTTTTGGTTACGGCTTGCCAATTTCTCGTCTGTAT
GCAAAGTACTTTCAAGGAGATCTGAATCTCTACTCTTTATCAGGATATGGAACAGATGCT
ATCATCTACTTAAAGGCTTTGTCTTCTGAGTCTATAGAAAAACTTCCAGTTTTTAACAAG
TCAGCCTTCAAACATTATCAGATGAGCTCTGAGGCTGATGACTGGTGTATCCCAAGCAGG
GAACCAAAGAACCTGGCAAAAGAAGTGGCCATGTGA
GenBank Gene IDU54617
GeneCard IDNone
GenAtlas ID
HGNC IDHGNC:8812
Chromosome Location7
Locus7q21.3
References
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  5. Abbot EL, McCormack JG, Reynet C, Hassall DG, Buchan KW, Yeaman SJ: Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells. FEBS J. 2005 Jun;272(12):3004-14.[15955060 ]
  6. 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 ]
  7. Grassian AR, Metallo CM, Coloff JL, Stephanopoulos G, Brugge JS: Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferation. Genes Dev. 2011 Aug 15;25(16):1716-33. doi: 10.1101/gad.16771811.[21852536 ]
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