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Protein

[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial

Gene

Pdk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei290 – 2901ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi251 – 2588ATPBy similarity
Nucleotide bindingi309 – 3102ATPBy similarity
Nucleotide bindingi325 – 3306ATPBy similarity

GO - Molecular functioni

  • ATP binding Source: MGI
  • protein homodimerization activity Source: MGI
  • pyruvate dehydrogenase (acetyl-transferring) kinase activity Source: UniProtKB

GO - Biological processi

  • cellular response to nutrient Source: UniProtKB
  • cellular response to reactive oxygen species Source: MGI
  • glucose homeostasis Source: UniProtKB
  • glucose metabolic process Source: UniProtKB-KW
  • insulin receptor signaling pathway Source: UniProtKB
  • intrinsic apoptotic signaling pathway by p53 class mediator Source: MGI
  • protein phosphorylation Source: MGI
  • regulation of acetyl-CoA biosynthetic process from pyruvate Source: UniProtKB
  • regulation of cellular ketone metabolic process Source: UniProtKB
  • regulation of gluconeogenesis Source: UniProtKB
  • regulation of glucose metabolic process Source: UniProtKB
  • regulation of pH Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Carbohydrate metabolism, Glucose metabolism

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-204174. Regulation of pyruvate dehydrogenase (PDH) complex.
R-MMU-5362517. Signaling by Retinoic Acid.

Names & Taxonomyi

Protein namesi
Recommended name:
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (EC:2.7.11.2)
Alternative name(s):
Pyruvate dehydrogenase kinase isoform 2
Short name:
PDH kinase 2
Gene namesi
Name:Pdk2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1343087. Pdk2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • mitochondrial pyruvate dehydrogenase complex Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • nucleoplasm Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Disruption phenotypei

No visible phenotype, due to the fact that PDK2-deficient mice have increased PDK1 levels (PubMed:21411764). Mice have lower blood glucose levels in the fed state, but not after fasting. Likewise, they display increased pyruvate dehydrogenase activity in liver and skeletal muscle in the fed state, but not after fasting. Fasting mice lacking both PDK2 and PDK4 show strongly decreased blood glucose levels, increased circulating ketone body levels leading to ketoacidosis with dangerously low blood pH levels, hypothermia, and ultimately death (PubMed:22360721).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 407[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrialPRO_0000023441
Transit peptidei1 – ?MitochondrionSequence analysis

Proteomic databases

EPDiQ9JK42.
MaxQBiQ9JK42.
PaxDbiQ9JK42.
PRIDEiQ9JK42.

PTM databases

iPTMnetiQ9JK42.

Expressioni

Tissue specificityi

Detected in heart (at protein level).1 Publication

Inductioni

Up-regulated by glucose and palmitic acid. Up-regulated by PPARD.2 Publications

Gene expression databases

BgeeiQ9JK42.
CleanExiMM_PDK2.
GenevisibleiQ9JK42. MM.

Interactioni

Subunit structurei

Homodimer, and heterodimer with PDK1. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Pik3r2O089083EBI-643530,EBI-643570

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ9JK42. 4 interactions.
MINTiMINT-1606053.
STRINGi10090.ENSMUSP00000041447.

Structurei

3D structure databases

ProteinModelPortaliQ9JK42.
SMRiQ9JK42. Positions 12-404.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini135 – 364230Histidine kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the PDK/BCKDK protein kinase family.Curated
Contains 1 histidine kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0787. Eukaryota.
COG0642. LUCA.
GeneTreeiENSGT00550000074574.
HOGENOMiHOG000164315.
HOVERGENiHBG000511.
InParanoidiQ9JK42.
KOiK00898.
OMAiAPKHIEH.
OrthoDBiEOG71VSSV.
TreeFamiTF314918.

Family and domain databases

Gene3Di1.20.140.20. 1 hit.
3.30.565.10. 1 hit.
InterProiIPR018955. BCDHK/PDK_N.
IPR003594. HATPase_C.
IPR005467. His_kinase_dom.
[Graphical view]
PfamiPF10436. BCDHK_Adom3. 1 hit.
PF02518. HATPase_c. 1 hit.
[Graphical view]
SMARTiSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMiSSF55874. SSF55874. 1 hit.
SSF69012. SSF69012. 1 hit.
PROSITEiPS50109. HIS_KIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9JK42-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRWVRALLKN ASLAGAPKYI EHFSKFSPSP LSMKQFLDFG SSNACEKTSF
60 70 80 90 100
TFLRQELPVR LANIMKEINL LPDRVLGTPS VQLVQSWYVQ SLLDIMEFLD
110 120 130 140 150
KDPEDHRTLS QFTDALVTIR NRHNDVVPTM AQGVLEYKDT YGDDPVSNQN
160 170 180 190 200
IQYFLDRFYL SRISIRMLIN QHTLIFDGST NPAHPKHIGS IDPNCSVSDV
210 220 230 240 250
VKDAYDMAKL LCDKYYMASP DLEIQEVNAT NANQPIHMVY VPSHLYHMLF
260 270 280 290 300
ELFKNAMRAT VESHESSLTL PPIKIMVALG EEDLSIKMSD RGGGVPLRKI
310 320 330 340 350
ERLFSYMYST APTPQPGTGG TPLAGFGYGL PISRLYAKYF QGDLQLFSME
360 370 380 390 400
GFGTDAVIYL KALSTDSVER LPVYNKSAWR HYQTIQEAGD WCVPSTEPKN

TSTYRVS
Length:407
Mass (Da):46,041
Last modified:July 27, 2011 - v2
Checksum:iDBB9F3F967C6A5B1
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti299 – 2991K → R in AAF72038 (Ref. 1) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF267660 mRNA. Translation: AAF72038.1.
AL606480 Genomic DNA. Translation: CAI23968.1.
CH466556 Genomic DNA. Translation: EDL15963.1.
BC021764 mRNA. Translation: AAH21764.1.
CCDSiCCDS25270.1.
RefSeqiNP_598428.2. NM_133667.2.
UniGeneiMm.29768.

Genome annotation databases

EnsembliENSMUST00000038431; ENSMUSP00000041447; ENSMUSG00000038967.
GeneIDi18604.
KEGGimmu:18604.
UCSCiuc007kzu.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF267660 mRNA. Translation: AAF72038.1.
AL606480 Genomic DNA. Translation: CAI23968.1.
CH466556 Genomic DNA. Translation: EDL15963.1.
BC021764 mRNA. Translation: AAH21764.1.
CCDSiCCDS25270.1.
RefSeqiNP_598428.2. NM_133667.2.
UniGeneiMm.29768.

3D structure databases

ProteinModelPortaliQ9JK42.
SMRiQ9JK42. Positions 12-404.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9JK42. 4 interactions.
MINTiMINT-1606053.
STRINGi10090.ENSMUSP00000041447.

PTM databases

iPTMnetiQ9JK42.

Proteomic databases

EPDiQ9JK42.
MaxQBiQ9JK42.
PaxDbiQ9JK42.
PRIDEiQ9JK42.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000038431; ENSMUSP00000041447; ENSMUSG00000038967.
GeneIDi18604.
KEGGimmu:18604.
UCSCiuc007kzu.2. mouse.

Organism-specific databases

CTDi5164.
MGIiMGI:1343087. Pdk2.

Phylogenomic databases

eggNOGiKOG0787. Eukaryota.
COG0642. LUCA.
GeneTreeiENSGT00550000074574.
HOGENOMiHOG000164315.
HOVERGENiHBG000511.
InParanoidiQ9JK42.
KOiK00898.
OMAiAPKHIEH.
OrthoDBiEOG71VSSV.
TreeFamiTF314918.

Enzyme and pathway databases

ReactomeiR-MMU-204174. Regulation of pyruvate dehydrogenase (PDH) complex.
R-MMU-5362517. Signaling by Retinoic Acid.

Miscellaneous databases

NextBioi294514.
PROiQ9JK42.
SOURCEiSearch...

Gene expression databases

BgeeiQ9JK42.
CleanExiMM_PDK2.
GenevisibleiQ9JK42. MM.

Family and domain databases

Gene3Di1.20.140.20. 1 hit.
3.30.565.10. 1 hit.
InterProiIPR018955. BCDHK/PDK_N.
IPR003594. HATPase_C.
IPR005467. His_kinase_dom.
[Graphical view]
PfamiPF10436. BCDHK_Adom3. 1 hit.
PF02518. HATPase_c. 1 hit.
[Graphical view]
SMARTiSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMiSSF55874. SSF55874. 1 hit.
SSF69012. SSF69012. 1 hit.
PROSITEiPS50109. HIS_KIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mus musculus pyruvate dehydrogenase kinase 2 cDNA."
    Jeoung N.H., Harris R.A.
    Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Mammary tumor.
  5. "Regulation of PDK mRNA by high fatty acid and glucose in pancreatic islets."
    Xu J., Han J., Epstein P.N., Liu Y.Q.
    Biochem. Biophys. Res. Commun. 344:827-833(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY PALMITATE AND GLUCOSE.
  6. "Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/delta."
    Degenhardt T., Saramaki A., Malinen M., Rieck M., Vaisanen S., Huotari A., Herzig K.H., Muller R., Carlberg C.
    J. Mol. Biol. 372:341-355(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY PPARD.
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Lung and Pancreas.
  8. "PDH activation during in vitro muscle contractions in PDH kinase 2 knockout mice: effect of PDH kinase 1 compensation."
    Dunford E.C., Herbst E.A., Jeoung N.H., Gittings W., Inglis J.G., Vandenboom R., LeBlanc P.J., Harris R.A., Peters S.J.
    Am. J. Physiol. 300:R1487-R1493(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  9. "Induction of PDK4 in the heart muscle of JVS mice, an animal model of systemic carnitine deficiency, does not appear to reduce glucose utilization by the heart."
    Ushikai M., Horiuchi M., Kobayashi K., Matuda S., Inui A., Takeuchi T., Saheki T.
    Mol. Genet. Metab. 102:349-355(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  10. "Fasting induces ketoacidosis and hypothermia in PDHK2/PDHK4-double-knockout mice."
    Jeoung N.H., Rahimi Y., Wu P., Lee W.N., Harris R.A.
    Biochem. J. 443:829-839(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.

Entry informationi

Entry nameiPDK2_MOUSE
AccessioniPrimary (citable) accession number: Q9JK42
Secondary accession number(s): Q8VC63
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: July 27, 2011
Last modified: March 16, 2016
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.