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Q8BFP9 (PDK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Pdk1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length434 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine/threonine 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. Ref.5

Catalytic activity

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

Subunit structure

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.

Subcellular location

Mitochondrion matrix By similarity.

Induction

Up-regulated by glucose and palmitate. Up- regulated via the HIF1A signaling pathway in response to hypoxia. Ref.4 Ref.5

Post-translational modification

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.

Sequence similarities

Belongs to the PDK/BCKDK protein kinase family.

Contains 1 histidine kinase domain.

Ontologies

Keywords
   Biological processCarbohydrate metabolism
Glucose metabolism
   Cellular componentMitochondrion
   DomainTransit peptide
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

glucose metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

hypoxia-inducible factor-1alpha signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular signal transduction

Inferred from sequence alignment PubMed 14749367. Source: MGI

intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of acetyl-CoA biosynthetic process from pyruvate

Inferred from mutant phenotype PubMed 22195962. Source: UniProtKB

regulation of glucose metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentmitochondrial pyruvate dehydrogenase complex

Inferred from direct assay PubMed 22195962. Source: UniProtKB

mitochondrion

Inferred from direct assay PubMed 14651853PubMed 18614015. Source: MGI

plasma membrane

Inferred from sequence alignment PubMed 14749367. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

pyruvate dehydrogenase (acetyl-transferring) kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2626Mitochondrion Potential
Chain27 – 434408[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial
PRO_0000023438

Regions

Domain161 – 391231Histidine kinase
Nucleotide binding277 – 2848ATP By similarity
Nucleotide binding335 – 3362ATP By similarity
Nucleotide binding352 – 3576ATP By similarity

Sites

Binding site3161ATP By similarity

Amino acid modifications

Modified residue1361Phosphotyrosine; by FGFR1 By similarity
Modified residue2411Phosphotyrosine; by FGFR1, ABL1, FLT3 and JAK2 By similarity
Modified residue2421Phosphotyrosine; by FGFR1 By similarity
Modified residue4031N6-succinyllysine Ref.6

Experimental info

Sequence conflict3241R → S in BAC32879. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q8BFP9 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 8A514C863E751040

FASTA43448,995
        10         20         30         40         50         60 
MRLARLLRGG TSVRPLCAVP CASRSLASAS ASGSGPASEL GVPGQVDFYA RFSPSPLSMK 

        70         80         90        100        110        120 
QFLDFGSVNA CEKTSFMFLR QELPVRLANI MKEISLLPDN LLRTPSVQLV QSWYIQSLQE 

       130        140        150        160        170        180 
LLDFKDKSAE DAKTIYEFTD TVIRIRNRHN DVIPTMAQGV TEYKESFGVD PVTSQNVQYF 

       190        200        210        220        230        240 
LDRFYMSRIS IRMLLNQHSL LFGGKGSPSH RKHIGSINPN CDVVEVIKDG YENARRLCDL 

       250        260        270        280        290        300 
YYVNSPELEL EELNAKSPGQ TIQVVYVPSH LYHMVFELFK NAMRATMEHH ADKGVYPPIQ 

       310        320        330        340        350        360 
VHVTLGEEDL TVKMSDRGGG VPLRKIDRLF NYMYSTAPRP RVETSRAVPL AGFGYGLPIS 

       370        380        390        400        410        420 
RLYAQYFQGD LKLYSLEGYG TDAVIYIKAL STESVERLPV YNKAAWKHYK ANHEADDWCV 

       430 
PSREPKDMTT FRSS 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS16119.1.
RefSeqNP_766253.2. NM_172665.5.
UniGeneMm.34411.

3D structure databases

ProteinModelPortalQ8BFP9.
SMRQ8BFP9. Positions 41-421.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ8BFP9.

Proteomic databases

MaxQBQ8BFP9.
PaxDbQ8BFP9.
PRIDEQ8BFP9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000006669; ENSMUSP00000006669; ENSMUSG00000006494.
GeneID228026.
KEGGmmu:228026.
UCSCuc008kbh.1. mouse.

Organism-specific databases

CTD5163.
MGIMGI:1926119. Pdk1.

Phylogenomic databases

eggNOGCOG0642.
GeneTreeENSGT00550000074574.
HOGENOMHOG000164315.
HOVERGENHBG000511.
InParanoidQ3U5E5.
KOK12077.
OMAEDAKTIY.
OrthoDBEOG71VSSV.
TreeFamTF314918.

Gene expression databases

ArrayExpressQ8BFP9.
BgeeQ8BFP9.
CleanExMM_PDK1.
GenevestigatorQ8BFP9.

Family and domain databases

Gene3D1.20.140.20. 1 hit.
3.30.565.10. 1 hit.
InterProIPR018955. BCDHK/PDK_N.
IPR003594. HATPase_ATP-bd.
IPR005467. Sig_transdc_His_kinase_core.
[Graphical view]
PfamPF10436. BCDHK_Adom3. 1 hit.
PF02518. HATPase_c. 1 hit.
[Graphical view]
SMARTSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMSSF55874. SSF55874. 1 hit.
SSF69012. SSF69012. 1 hit.
PROSITEPS50109. HIS_KIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPdk1. mouse.
NextBio378903.
PROQ8BFP9.
SOURCESearch...

Entry information

Entry namePDK1_MOUSE
AccessionPrimary (citable) accession number: Q8BFP9
Secondary accession number(s): Q3U5E5
Entry history
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 92 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

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