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Protein

[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial

Gene

PDK1

Organism
Homo sapiens (Human)
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. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress.4 Publications

Catalytic activityi

ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate.3 Publications

Enzyme regulationi

Activity is enhanced by binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity. Inhibited by dichloroacetate and radicicol.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei318ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi279 – 286ATPBy similarity8
Nucleotide bindingi337 – 338ATPBy similarity2
Nucleotide bindingi354 – 359ATPBy similarity6

GO - Molecular functioni

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

GO - Biological processi

  • cell proliferation Source: UniProtKB
  • glucose metabolic process Source: ProtInc
  • hypoxia-inducible factor-1alpha signaling pathway Source: UniProtKB
  • intrinsic apoptotic signaling pathway in response to oxidative stress Source: UniProtKB
  • regulation of acetyl-CoA biosynthetic process from pyruvate Source: Reactome
  • regulation of glucose metabolic process Source: UniProtKB

Keywordsi

Molecular functionKinase, Transferase
Biological processCarbohydrate metabolism, Glucose metabolism
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.2 2681
ReactomeiR-HSA-204174 Regulation of pyruvate dehydrogenase (PDH) complex
R-HSA-5362517 Signaling by Retinoic Acid
SignaLinkiQ15118
SIGNORiQ15118

Names & Taxonomyi

Protein namesi
Recommended name:
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (EC:2.7.11.2)
Alternative name(s):
Pyruvate dehydrogenase kinase isoform 1
Short name:
PDH kinase 1
Gene namesi
Name:PDK1
Synonyms:PDHK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000152256.13
HGNCiHGNC:8809 PDK1
MIMi602524 gene
neXtProtiNX_Q15118

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

Organism-specific databases

DisGeNETi5163
OpenTargetsiENSG00000152256
PharmGKBiPA33154

Chemistry databases

ChEMBLiCHEMBL4766
DrugBankiDB08809 Dichloroacetic Acid
GuidetoPHARMACOLOGYi2915

Polymorphism and mutation databases

DMDMi3183117

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 28MitochondrionSequence analysisCombined sourcesAdd BLAST28
ChainiPRO_000002343729 – 436[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrialAdd BLAST408

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei136Phosphotyrosine; by FGFR11 Publication1
Modified residuei243Phosphotyrosine; by FGFR1, ABL1, FLT3 and JAK21 Publication1
Modified residuei244Phosphotyrosine; by FGFR11 Publication1
Modified residuei405N6-succinyllysineBy similarity1

Post-translational modificationi

Phosphorylated by constitutively activated ABL1, FGFR1, FLT3 and JAK2 (in vitro), and this may also occur in cancer cells that express constitutively activated ABL1, FGFR1, FLT3 and JAK2. Phosphorylation at Tyr-243 and Tyr-244 strongly increases kinase activity, while phosphorylation at Tyr-136 has a lesser effect.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ15118
MaxQBiQ15118
PaxDbiQ15118
PeptideAtlasiQ15118
PRIDEiQ15118
ProteomicsDBi60444

PTM databases

iPTMnetiQ15118
PhosphoSitePlusiQ15118

Expressioni

Tissue specificityi

Expressed predominantly in the heart. Detected at lower levels in liver, skeletal muscle and pancreas.1 Publication

Inductioni

Up-regulated via the HIF1A signaling pathway in response to hypoxia.1 Publication

Gene expression databases

BgeeiENSG00000152256
CleanExiHS_PDK1
ExpressionAtlasiQ15118 baseline and differential
GenevisibleiQ15118 HS

Organism-specific databases

HPAiCAB017554
HPA027376
HPA059083

Interactioni

Subunit structurei

Homodimer, and heterodimer with PDK2. 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

Show more details

Protein-protein interaction databases

BioGridi111189, 67 interactors
DIPiDIP-29497N
IntActiQ15118, 262 interactors
MINTiQ15118
STRINGi9606.ENSP00000282077

Chemistry databases

BindingDBiQ15118

Structurei

Secondary structure

1436
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi42 – 50Combined sources9
Helixi59 – 67Combined sources9
Helixi72 – 94Combined sources23
Helixi99 – 102Combined sources4
Helixi105 – 122Combined sources18
Beta strandi125 – 127Combined sources3
Helixi132 – 148Combined sources17
Turni149 – 151Combined sources3
Helixi152 – 166Combined sources15
Helixi171 – 202Combined sources32
Beta strandi219 – 224Combined sources6
Helixi225 – 244Combined sources20
Beta strandi250 – 259Combined sources10
Beta strandi265 – 268Combined sources4
Helixi270 – 291Combined sources22
Turni293 – 295Combined sources3
Beta strandi301 – 307Combined sources7
Beta strandi309 – 318Combined sources10
Helixi325 – 328Combined sources4
Helixi329 – 332Combined sources4
Turni334 – 337Combined sources4
Beta strandi352 – 354Combined sources3
Helixi358 – 368Combined sources11
Beta strandi372 – 378Combined sources7
Turni379 – 381Combined sources3
Beta strandi382 – 392Combined sources11
Turni393 – 395Combined sources3
Helixi405 – 411Combined sources7

3D structure databases

ProteinModelPortaliQ15118
SMRiQ15118
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15118

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini163 – 393Histidine 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
InParanoidiQ15118
KOiK12077
OMAiQMVQFGE
OrthoDBiEOG091G07DJ
PhylomeDBiQ15118
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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15118-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRLARLLRGA ALAGPGPGLR AAGFSRSFSS DSGSSPASER GVPGQVDFYA
60 70 80 90 100
RFSPSPLSMK QFLDFGSVNA CEKTSFMFLR QELPVRLANI MKEISLLPDN
110 120 130 140 150
LLRTPSVQLV QSWYIQSLQE LLDFKDKSAE DAKAIYDFTD TVIRIRNRHN
160 170 180 190 200
DVIPTMAQGV IEYKESFGVD PVTSQNVQYF LDRFYMSRIS IRMLLNQHSL
210 220 230 240 250
LFGGKGKGSP SHRKHIGSIN PNCNVLEVIK DGYENARRLC DLYYINSPEL
260 270 280 290 300
ELEELNAKSP GQPIQVVYVP SHLYHMVFEL FKNAMRATME HHANRGVYPP
310 320 330 340 350
IQVHVTLGNE DLTVKMSDRG GGVPLRKIDR LFNYMYSTAP RPRVETSRAV
360 370 380 390 400
PLAGFGYGLP ISRLYAQYFQ GDLKLYSLEG YGTDAVIYIK ALSTDSIERL
410 420 430
PVYNKAAWKH YNTNHEADDW CVPSREPKDM TTFRSA
Length:436
Mass (Da):49,244
Last modified:November 1, 1996 - v1
Checksum:iD14CD594E0EA45A2
GO
Isoform 2 (identifier: Q15118-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     137-137: D → ERPRRTWLQVSSLCCMACKMI

Show »
Length:456
Mass (Da):51,623
Checksum:i067A55C29B224B48
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8R → L in ABB29979 (Ref. 2) Curated1
Sequence conflicti96L → R in BAH14173 (PubMed:14702039).Curated1
Sequence conflicti363R → C in ABB29979 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050477134A → T. Corresponds to variant dbSNP:rs35661499Ensembl.1
Natural variantiVAR_042295412N → T1 PublicationCorresponds to variant dbSNP:rs34250425Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_055172137D → ERPRRTWLQVSSLCCMACKM I in isoform 2. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L42450 mRNA Translation: AAC42009.1
DQ234350 mRNA Translation: ABB29979.1
AK304388 mRNA Translation: BAH14173.1
AK312700 mRNA Translation: BAG35578.1
AC018712 Genomic DNA No translation available.
AC093818 Genomic DNA No translation available.
CH471058 Genomic DNA Translation: EAX11173.1
CH471058 Genomic DNA Translation: EAX11174.1
BC039158 mRNA Translation: AAH39158.1
CCDSiCCDS2250.1 [Q15118-1]
CCDS63059.1 [Q15118-2]
PIRiI55465
RefSeqiNP_001265478.1, NM_001278549.1 [Q15118-2]
NP_002601.1, NM_002610.4 [Q15118-1]
UniGeneiHs.470633
Hs.733780

Genome annotation databases

EnsembliENST00000282077; ENSP00000282077; ENSG00000152256 [Q15118-1]
ENST00000392571; ENSP00000376352; ENSG00000152256 [Q15118-2]
ENST00000410055; ENSP00000386985; ENSG00000152256 [Q15118-1]
GeneIDi5163
KEGGihsa:5163
UCSCiuc002uhs.5 human [Q15118-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPDK1_HUMAN
AccessioniPrimary (citable) accession number: Q15118
Secondary accession number(s): B2R6T1
, B7Z937, D3DPD8, E9PD65, Q308M4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: July 18, 2018
This is version 169 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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