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Protein

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

Gene

PDK4

Organism
Ictidomys tridecemlineatus (Thirteen-lined ground squirrel) (Spermophilus tridecemlineatus)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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.

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

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Carbohydrate metabolism, Glucose metabolism, Hibernation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

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
OrganismiIctidomys tridecemlineatus (Thirteen-lined ground squirrel) (Spermophilus tridecemlineatus)
Taxonomic identifieri43179 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiSciuridaeXerinaeMarmotiniIctidomys
Proteomesi
  • UP000005215 Componenti: Unassembled WGS sequence

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000023448? – 412[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial
Transit peptidei1 – ?MitochondrionSequence analysis

Expressioni

Tissue specificityi

Detected in skeletal muscle and heart.1 Publication

Inductioni

Up-regulated during hibernation.1 Publication

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

STRINGi43179.ENSSTOP00000019435.

Structurei

3D structure databases

ProteinModelPortaliO88345.
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
Contains 1 histidine kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0787. Eukaryota.
COG0642. LUCA.
HOVERGENiHBG000511.
InParanoidiO88345.

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.

O88345-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKAARFAMHS ARSLSSVGLV PREVELFSRY SPSPLSMKQL LDFGSDNACE
60 70 80 90 100
RTSFSFLRQE LPVRLANILK EIDVLPDRLT NTSSVQLVKS WYIQSLMELV
110 120 130 140 150
EFHEKSPEDQ KNLSDFVDTL IKVRNRHHNV VPTMAQGILE YKDTCTVDPV
160 170 180 190 200
TNQSLQYFLD RFYMNRISTR MLMNQHILIF SDSQTGNPSH IGSIDPKCDV
210 220 230 240 250
VAVIQDAFES SKMLCDQYYL TSPELKLTQV NGKFPGQPIH IVYVPSHLHH
260 270 280 290 300
MLFELFKNAM RATVERQESW PSLTPVEVIV VLGKEDLTIK ISDRGGGVPL
310 320 330 340 350
RITDRLFSYM YSTAPTPVMD NSRNAPLAGF GYGLPISRLY AKYFQGDLNL
360 370 380 390 400
YSLSGYGTDA IIYLKALSSE SVEKLPVFNK SAFKHYQMSS EADDWCIPSR
410
EPRNLSKEKM AM
Length:412
Mass (Da):46,837
Last modified:November 1, 1998 - v1
Checksum:i4F51628DCBC84DBB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020845 mRNA. Translation: AAC40161.1.
RefSeqiNP_001269196.1. NM_001282267.1.

Genome annotation databases

GeneIDi101976272.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020845 mRNA. Translation: AAC40161.1.
RefSeqiNP_001269196.1. NM_001282267.1.

3D structure databases

ProteinModelPortaliO88345.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi43179.ENSSTOP00000019435.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi101976272.

Organism-specific databases

CTDi5166.

Phylogenomic databases

eggNOGiKOG0787. Eukaryota.
COG0642. LUCA.
HOVERGENiHBG000511.
InParanoidiO88345.

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...

Entry informationi

Entry nameiPDK4_ICTTR
AccessioniPrimary (citable) accession number: O88345
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: November 1, 1998
Last modified: October 5, 2016
This is version 99 of the entry and version 1 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. 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.