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Protein

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

Gene

Pdk4

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

Functioni

Kinase 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.6 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei293ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi254 – 261ATPBy similarity8
Nucleotide bindingi312 – 313ATPBy similarity2
Nucleotide bindingi329 – 334ATPBy similarity6

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase
Biological processCarbohydrate metabolism, Glucose metabolism
LigandATP-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 4, mitochondrial (EC:2.7.11.2)
Alternative name(s):
Pyruvate dehydrogenase kinase isoform 4
Gene namesi
Name:Pdk4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1351481 Pdk4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Disruption phenotypei

No visible phenotype at birth. Mice have lower blood glucose and pyruvate levels after overnight fasting than normal, while the levels of ketone bodies are increased. After 48 h starving, their rate of glucose oxidation is increased, and glycolysis decreased, compared to wild type mice. Likewise, their rate of fatty acid oxidation is lower than normal in response to starvation. In contrast, there are no differences in blood glucose levels between fed mutant and wild type mice. In response to a high-fat diet, mutant mice have lower de novo fatty acid biosynthesis, and lower liver steatosis than wild-type. Mutant mice show normal bone formation and normal bone metabolism, excepting reduced bone loss when suspended to induce disuse osteoporosis.6 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000023446? – 412[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial
Transit peptidei1 – ?MitochondrionSequence analysis

Proteomic databases

PaxDbiO70571
PRIDEiO70571

PTM databases

iPTMnetiO70571
PhosphoSitePlusiO70571

Expressioni

Inductioni

Up-regulated by PPARD.1 Publication

Gene expression databases

BgeeiENSMUSG00000019577 Expressed in 243 organ(s), highest expression level in diaphragm
CleanExiMM_PDK4
ExpressionAtlasiO70571 baseline and differential
GenevisibleiO70571 MM

Interactioni

Subunit structurei

Homodimer. 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) (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei157Interaction with the other subunit in the homodimerBy similarity1
Sitei161Interaction with the other subunit in the homodimerBy similarity1
Sitei395Interaction with the other subunit in the homodimerBy similarity1

Protein-protein interaction databases

IntActiO70571, 2 interactors
STRINGi10090.ENSMUSP00000019721

Structurei

3D structure databases

ProteinModelPortaliO70571
SMRiO70571
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini138 – 368Histidine kinasePROSITE-ProRule annotationAdd BLAST231

Sequence similaritiesi

Belongs to the PDK/BCKDK protein kinase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0787 Eukaryota
COG0642 LUCA
GeneTreeiENSGT00550000074574
HOGENOMiHOG000164315
HOVERGENiHBG000511
InParanoidiO70571
KOiK00898
OMAiKFPGQPI
OrthoDBiEOG091G07DJ
PhylomeDBiO70571
TreeFamiTF314918

Family and domain databases

CDDicd00075 HATPase_c, 1 hit
Gene3Di1.20.140.20, 1 hit
3.30.565.10, 1 hit
InterProiView protein in InterPro
IPR036784 AK/P_DHK_N_sf
IPR018955 BCDHK/PDK_N
IPR039028 BCKD/PDK
IPR003594 HATPase_C
IPR036890 HATPase_C_sf
IPR005467 His_kinase_dom
PANTHERiPTHR11947 PTHR11947, 1 hit
PfamiView protein in Pfam
PF10436 BCDHK_Adom3, 1 hit
PF02518 HATPase_c, 1 hit
SMARTiView protein in SMART
SM00387 HATPase_c, 1 hit
SUPFAMiSSF55874 SSF55874, 1 hit
SSF69012 SSF69012, 1 hit
PROSITEiView protein in PROSITE
PS50109 HIS_KIN, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

O70571-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKAARFVMRS ASSLSSASLV PREVELFSRY SPSPLSMKQL LDFGSENACE
60 70 80 90 100
RTSFAFLRQE LPVRLANILK EIDILPDRLV NTPSVQLVKS WYIQSLMDLV
110 120 130 140 150
EFHEKSPEDQ KALSEFVDTL VKVRNRHHNV VPTMAQGILE YKDTCTVDPV
160 170 180 190 200
TNQNLQYFLD RFYMNRISTR MLMNQHILIF SDSKTGNPSH IGSIDPNCDV
210 220 230 240 250
VAVVQDAFEC AKMLCDQYYL TSPELNLTQV NGKFPGQPIH IVYVPSHLHH
260 270 280 290 300
MLFELFKNAM RATVEHQENR PSLTPVEATV VLGKEDLTIK ISDRGGGVPL
310 320 330 340 350
RITDRLFSYT YSTAPTPVMD NSRNAPLAGF GYGLPISRLY AKYFQGDLNL
360 370 380 390 400
YSMSGYGTDA IIYLKALSSE SVEKLPVFNK SAFKHYQMSS EADDWCIPSR
410
EPKNLAKEKL AV
Length:412
Mass (Da):46,596
Last modified:August 1, 1998 - v1
Checksum:i74815502E711054C
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0N4SW53A0A0N4SW53_MOUSE
[Pyruvate dehydrogenase (acetyl-tra...
Pdk4
109Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ001418 mRNA Translation: CAA04752.1
AF239176 Genomic DNA Translation: AAG44393.1
BC026134 mRNA Translation: AAH26134.1
CCDSiCCDS19902.1
RefSeqiNP_038771.1, NM_013743.2
UniGeneiMm.235547

Genome annotation databases

EnsembliENSMUST00000019721; ENSMUSP00000019721; ENSMUSG00000019577
GeneIDi27273
KEGGimmu:27273
UCSCiuc009awk.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ001418 mRNA Translation: CAA04752.1
AF239176 Genomic DNA Translation: AAG44393.1
BC026134 mRNA Translation: AAH26134.1
CCDSiCCDS19902.1
RefSeqiNP_038771.1, NM_013743.2
UniGeneiMm.235547

3D structure databases

ProteinModelPortaliO70571
SMRiO70571
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO70571, 2 interactors
STRINGi10090.ENSMUSP00000019721

PTM databases

iPTMnetiO70571
PhosphoSitePlusiO70571

Proteomic databases

PaxDbiO70571
PRIDEiO70571

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000019721; ENSMUSP00000019721; ENSMUSG00000019577
GeneIDi27273
KEGGimmu:27273
UCSCiuc009awk.1 mouse

Organism-specific databases

CTDi5166
MGIiMGI:1351481 Pdk4

Phylogenomic databases

eggNOGiKOG0787 Eukaryota
COG0642 LUCA
GeneTreeiENSGT00550000074574
HOGENOMiHOG000164315
HOVERGENiHBG000511
InParanoidiO70571
KOiK00898
OMAiKFPGQPI
OrthoDBiEOG091G07DJ
PhylomeDBiO70571
TreeFamiTF314918

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiPdk4 mouse
PROiPR:O70571
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000019577 Expressed in 243 organ(s), highest expression level in diaphragm
CleanExiMM_PDK4
ExpressionAtlasiO70571 baseline and differential
GenevisibleiO70571 MM

Family and domain databases

CDDicd00075 HATPase_c, 1 hit
Gene3Di1.20.140.20, 1 hit
3.30.565.10, 1 hit
InterProiView protein in InterPro
IPR036784 AK/P_DHK_N_sf
IPR018955 BCDHK/PDK_N
IPR039028 BCKD/PDK
IPR003594 HATPase_C
IPR036890 HATPase_C_sf
IPR005467 His_kinase_dom
PANTHERiPTHR11947 PTHR11947, 1 hit
PfamiView protein in Pfam
PF10436 BCDHK_Adom3, 1 hit
PF02518 HATPase_c, 1 hit
SMARTiView protein in SMART
SM00387 HATPase_c, 1 hit
SUPFAMiSSF55874 SSF55874, 1 hit
SSF69012 SSF69012, 1 hit
PROSITEiView protein in PROSITE
PS50109 HIS_KIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPDK4_MOUSE
AccessioniPrimary (citable) accession number: O70571
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: August 1, 1998
Last modified: November 7, 2018
This is version 149 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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