UniProtKB - O70571 (PDK4_MOUSE)
Protein
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial
Gene
Pdk4
Organism
Mus musculus (Mouse)
Status
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 + L-seryl-[pyruvate dehydrogenase E1 α subunit] = ADP + H+ + O-phospho-L-seryl-[pyruvate dehydrogenase E1 α subunit]EC:2.7.11.2
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 293 | ATPBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 254 – 261 | ATPBy similarity | 8 | |
Nucleotide bindingi | 312 – 313 | ATPBy similarity | 2 | |
Nucleotide bindingi | 329 – 334 | ATPBy similarity | 6 |
GO - Molecular functioni
- ATP binding Source: MGI
- protein kinase activity Source: MGI
- protein serine/threonine/tyrosine kinase activity Source: MGI
- protein serine/threonine kinase activity Source: GO_Central
- pyruvate dehydrogenase (acetyl-transferring) kinase activity Source: UniProtKB
GO - Biological processi
- cellular response to fatty acid Source: UniProtKB
- cellular response to starvation Source: UniProtKB
- glucose homeostasis Source: UniProtKB
- glucose metabolic process Source: UniProtKB-KW
- insulin receptor signaling pathway Source: UniProtKB
- negative regulation of anoikis Source: MGI
- negative regulation of pyruvate dehydrogenase activity Source: GO_Central
- protein phosphorylation Source: MGI
- reactive oxygen species metabolic process Source: UniProtKB
- regulation of acetyl-CoA biosynthetic process from pyruvate Source: UniProtKB
- regulation of bone resorption Source: UniProtKB
- regulation of cellular ketone metabolic process Source: UniProtKB
- regulation of fatty acid biosynthetic process Source: UniProtKB
- regulation of fatty acid oxidation Source: UniProtKB
- regulation of glucose metabolic process Source: UniProtKB
- regulation of pH Source: UniProtKB
- response to starvation Source: UniProtKB
Keywordsi
Molecular function | Kinase, Transferase |
Biological process | Carbohydrate metabolism, Glucose metabolism |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-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 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1351481, Pdk4 |
Subcellular locationi
Mitochondrion
- Mitochondrion matrix By similarity
Mitochondrion
- mitochondrial inner membrane Source: MGI
- mitochondrial matrix Source: UniProtKB-SubCell
- mitochondrion Source: MGI
Keywords - Cellular componenti
MitochondrionPathology & 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – ? | MitochondrionSequence analysis | ||
ChainiPRO_0000023446 | ? – 412 | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial |
Proteomic databases
PaxDbi | O70571 |
PRIDEi | O70571 |
PTM databases
iPTMneti | O70571 |
PhosphoSitePlusi | O70571 |
Expressioni
Inductioni
Up-regulated by PPARD.1 Publication
Gene expression databases
Bgeei | ENSMUSG00000019577, Expressed in diaphragm and 258 other tissues |
ExpressionAtlasi | O70571, baseline and differential |
Genevisiblei | O70571, 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 similaritySites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 157 | Interaction with the other subunit in the homodimerBy similarity | 1 | |
Sitei | 161 | Interaction with the other subunit in the homodimerBy similarity | 1 | |
Sitei | 395 | Interaction with the other subunit in the homodimerBy similarity | 1 |
Protein-protein interaction databases
BioGRIDi | 205153, 5 interactors |
IntActi | O70571, 2 interactors |
STRINGi | 10090.ENSMUSP00000019721 |
Miscellaneous databases
RNActi | O70571, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 138 – 368 | Histidine kinasePROSITE-ProRule annotationAdd BLAST | 231 |
Sequence similaritiesi
Belongs to the PDK/BCKDK protein kinase family.Curated
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG0787, Eukaryota |
GeneTreei | ENSGT01010000222389 |
HOGENOMi | CLU_023861_1_1_1 |
InParanoidi | O70571 |
OMAi | HPRHIGS |
OrthoDBi | 1242599at2759 |
PhylomeDBi | O70571 |
TreeFami | TF314918 |
Family and domain databases
Gene3Di | 1.20.140.20, 1 hit 3.30.565.10, 1 hit |
InterProi | View 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 |
PANTHERi | PTHR11947, PTHR11947, 1 hit |
Pfami | View protein in Pfam PF10436, BCDHK_Adom3, 1 hit PF02518, HATPase_c, 1 hit |
SMARTi | View protein in SMART SM00387, HATPase_c, 1 hit |
SUPFAMi | SSF55874, SSF55874, 1 hit SSF69012, SSF69012, 1 hit |
PROSITEi | View protein in PROSITE PS50109, HIS_KIN, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
O70571-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A0N4SW53 | A0A0N4SW53_MOUSE | Protein-serine/threonine kinase | Pdk4 | 109 | Annotation 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 |
CCDSi | CCDS19902.1 |
RefSeqi | NP_038771.1, NM_013743.2 |
Genome annotation databases
Ensembli | ENSMUST00000019721; ENSMUSP00000019721; ENSMUSG00000019577 |
GeneIDi | 27273 |
KEGGi | mmu:27273 |
UCSCi | uc009awk.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 |
CCDSi | CCDS19902.1 |
RefSeqi | NP_038771.1, NM_013743.2 |
3D structure databases
SMRi | O70571 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 205153, 5 interactors |
IntActi | O70571, 2 interactors |
STRINGi | 10090.ENSMUSP00000019721 |
PTM databases
iPTMneti | O70571 |
PhosphoSitePlusi | O70571 |
Proteomic databases
PaxDbi | O70571 |
PRIDEi | O70571 |
Protocols and materials databases
Antibodypediai | 15901, 614 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000019721; ENSMUSP00000019721; ENSMUSG00000019577 |
GeneIDi | 27273 |
KEGGi | mmu:27273 |
UCSCi | uc009awk.1, mouse |
Organism-specific databases
CTDi | 5166 |
MGIi | MGI:1351481, Pdk4 |
Phylogenomic databases
eggNOGi | KOG0787, Eukaryota |
GeneTreei | ENSGT01010000222389 |
HOGENOMi | CLU_023861_1_1_1 |
InParanoidi | O70571 |
OMAi | HPRHIGS |
OrthoDBi | 1242599at2759 |
PhylomeDBi | O70571 |
TreeFami | TF314918 |
Enzyme and pathway databases
Reactomei | R-MMU-204174, Regulation of pyruvate dehydrogenase (PDH) complex R-MMU-5362517, Signaling by Retinoic Acid |
Miscellaneous databases
BioGRID-ORCSi | 27273, 0 hits in 17 CRISPR screens |
ChiTaRSi | Pdk4, mouse |
PROi | PR:O70571 |
RNActi | O70571, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000019577, Expressed in diaphragm and 258 other tissues |
ExpressionAtlasi | O70571, baseline and differential |
Genevisiblei | O70571, MM |
Family and domain databases
Gene3Di | 1.20.140.20, 1 hit 3.30.565.10, 1 hit |
InterProi | View 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 |
PANTHERi | PTHR11947, PTHR11947, 1 hit |
Pfami | View protein in Pfam PF10436, BCDHK_Adom3, 1 hit PF02518, HATPase_c, 1 hit |
SMARTi | View protein in SMART SM00387, HATPase_c, 1 hit |
SUPFAMi | SSF55874, SSF55874, 1 hit SSF69012, SSF69012, 1 hit |
PROSITEi | View protein in PROSITE PS50109, HIS_KIN, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PDK4_MOUSE | |
Accessioni | O70571Primary (citable) accession number: O70571 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 24, 2001 |
Last sequence update: | August 1, 1998 | |
Last modified: | February 10, 2021 | |
This is version 165 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families