Tmic
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Name[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial
Synonyms
  • 2.7.11.2
  • 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
  • pyruvate dehydrogenase (acetyl-transferring) kinase activity
  • ATP binding
  • protein kinase activity
Processes
  • 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
  • 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
Components
  • mitochondrial inner membrane
  • mitochondrial matrix
  • mitochondrion
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.
Pfam Domain Function
Transmembrane RegionsNot Available
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 IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:8812
Chromosome Location7
Locus7q21.3
References
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  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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