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Protein

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

Gene

Pdk1

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 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 (By similarity).By similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei316 – 3161ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi277 – 2848ATPBy similarity
Nucleotide bindingi335 – 3362ATPBy similarity
Nucleotide bindingi352 – 3576ATPBy similarity

GO - Molecular functioni

GO - Biological processi

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

ReactomeiREACT_278177. Regulation of pyruvate dehydrogenase (PDH) complex.
REACT_306383. Signaling by Retinoic Acid.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1926119. Pdk1.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial pyruvate dehydrogenase complex Source: UniProtKB
  • mitochondrion Source: MGI
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 2626MitochondrionSequence AnalysisAdd
BLAST
Chaini27 – 434408[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrialPRO_0000023438Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei136 – 1361Phosphotyrosine; by FGFR1By similarity
Modified residuei241 – 2411Phosphotyrosine; by FGFR1, ABL1, FLT3 and JAK2By similarity
Modified residuei242 – 2421Phosphotyrosine; by FGFR1By similarity
Modified residuei403 – 4031N6-succinyllysine1 Publication

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-241 and Tyr-242 strongly increases kinase activity, while phosphorylation at Tyr-136 has a lesser effect (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8BFP9.
PaxDbiQ8BFP9.
PRIDEiQ8BFP9.

PTM databases

PhosphoSiteiQ8BFP9.

Expressioni

Inductioni

Up-regulated by glucose and palmitate. Up- regulated via the HIF1A signaling pathway in response to hypoxia.2 Publications

Gene expression databases

BgeeiQ8BFP9.
CleanExiMM_PDK1.
ExpressionAtlasiQ8BFP9. baseline and differential.
GenevisibleiQ8BFP9. MM.

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) (By similarity).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000006669.

Structurei

3D structure databases

ProteinModelPortaliQ8BFP9.
SMRiQ8BFP9. Positions 41-421.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini161 – 391231Histidine 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

eggNOGiCOG0642.
GeneTreeiENSGT00550000074574.
HOGENOMiHOG000164315.
HOVERGENiHBG000511.
InParanoidiQ8BFP9.
KOiK12077.
OMAiEDAKTIY.
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. Sig_transdc_His_kinase_core.
[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.

Q8BFP9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRLARLLRGG TSVRPLCAVP CASRSLASAS ASGSGPASEL GVPGQVDFYA
60 70 80 90 100
RFSPSPLSMK QFLDFGSVNA CEKTSFMFLR QELPVRLANI MKEISLLPDN
110 120 130 140 150
LLRTPSVQLV QSWYIQSLQE LLDFKDKSAE DAKTIYEFTD TVIRIRNRHN
160 170 180 190 200
DVIPTMAQGV TEYKESFGVD PVTSQNVQYF LDRFYMSRIS IRMLLNQHSL
210 220 230 240 250
LFGGKGSPSH RKHIGSINPN CDVVEVIKDG YENARRLCDL YYVNSPELEL
260 270 280 290 300
EELNAKSPGQ TIQVVYVPSH LYHMVFELFK NAMRATMEHH ADKGVYPPIQ
310 320 330 340 350
VHVTLGEEDL TVKMSDRGGG VPLRKIDRLF NYMYSTAPRP RVETSRAVPL
360 370 380 390 400
AGFGYGLPIS RLYAQYFQGD LKLYSLEGYG TDAVIYIKAL STESVERLPV
410 420 430
YNKAAWKHYK ANHEADDWCV PSREPKDMTT FRSS
Length:434
Mass (Da):48,995
Last modified:July 27, 2011 - v2
Checksum:i8A514C863E751040
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti324 – 3241R → S in BAC32879 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK046805 mRNA. Translation: BAC32879.1.
AK153649 mRNA. Translation: BAE32134.1.
AL928963 Genomic DNA. Translation: CAM26372.1.
CH466519 Genomic DNA. Translation: EDL27100.1.
CH466519 Genomic DNA. Translation: EDL27102.1.
CH466519 Genomic DNA. Translation: EDL27104.1.
CCDSiCCDS16119.1.
RefSeqiNP_766253.2. NM_172665.5.
UniGeneiMm.34411.

Genome annotation databases

EnsembliENSMUST00000006669; ENSMUSP00000006669; ENSMUSG00000006494.
GeneIDi228026.
KEGGimmu:228026.
UCSCiuc008kbh.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK046805 mRNA. Translation: BAC32879.1.
AK153649 mRNA. Translation: BAE32134.1.
AL928963 Genomic DNA. Translation: CAM26372.1.
CH466519 Genomic DNA. Translation: EDL27100.1.
CH466519 Genomic DNA. Translation: EDL27102.1.
CH466519 Genomic DNA. Translation: EDL27104.1.
CCDSiCCDS16119.1.
RefSeqiNP_766253.2. NM_172665.5.
UniGeneiMm.34411.

3D structure databases

ProteinModelPortaliQ8BFP9.
SMRiQ8BFP9. Positions 41-421.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000006669.

PTM databases

PhosphoSiteiQ8BFP9.

Proteomic databases

MaxQBiQ8BFP9.
PaxDbiQ8BFP9.
PRIDEiQ8BFP9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000006669; ENSMUSP00000006669; ENSMUSG00000006494.
GeneIDi228026.
KEGGimmu:228026.
UCSCiuc008kbh.2. mouse.

Organism-specific databases

CTDi5163.
MGIiMGI:1926119. Pdk1.

Phylogenomic databases

eggNOGiCOG0642.
GeneTreeiENSGT00550000074574.
HOGENOMiHOG000164315.
HOVERGENiHBG000511.
InParanoidiQ8BFP9.
KOiK12077.
OMAiEDAKTIY.
OrthoDBiEOG71VSSV.
TreeFamiTF314918.

Enzyme and pathway databases

ReactomeiREACT_278177. Regulation of pyruvate dehydrogenase (PDH) complex.
REACT_306383. Signaling by Retinoic Acid.

Miscellaneous databases

ChiTaRSiPdk1. mouse.
NextBioi378903.
PROiQ8BFP9.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BFP9.
CleanExiMM_PDK1.
ExpressionAtlasiQ8BFP9. baseline and differential.
GenevisibleiQ8BFP9. 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. Sig_transdc_His_kinase_core.
[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. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Medulla oblongata and Thymus.
  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. "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.
  5. "HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption."
    Papandreou I., Cairns R.A., Fontana L., Lim A.L., Denko N.C.
    Cell Metab. 3:187-197(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY HYPOXIA, FUNCTION.
  6. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-403, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiPDK1_MOUSE
AccessioniPrimary (citable) accession number: Q8BFP9
Secondary accession number(s): Q3U5E5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: July 27, 2011
Last modified: July 22, 2015
This is version 101 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

External Data

Dasty 3

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 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.