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

Name[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial
Synonyms
  • 2.7.11.2
  • PDH kinase 1
  • PDHK1
  • Pyruvate dehydrogenase kinase isoform 1
Gene NamePDK1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0007401|[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial
MRLARLLRGAALAGPGPGLRAAGFSRSFSSDSGSSPASERGVPGQVDFYARFSPSPLSMK
QFLDFGSVNACEKTSFMFLRQELPVRLANIMKEISLLPDNLLRTPSVQLVQSWYIQSLQE
LLDFKDKSAEDAKAIYDFTDTVIRIRNRHNDVIPTMAQGVIEYKESFGVDPVTSQNVQYF
LDRFYMSRISIRMLLNQHSLLFGGKGKGSPSHRKHIGSINPNCNVLEVIKDGYENARRLC
DLYYINSPELELEELNAKSPGQPIQVVYVPSHLYHMVFELFKNAMRATMEHHANRGVYPP
IQVHVTLGNEDLTVKMSDRGGGVPLRKIDRLFNYMYSTAPRPRVETSRAVPLAGFGYGLP
ISRLYAQYFQGDLKLYSLEGYGTDAVIYIKALSTDSIERLPVYNKAAWKHYNTNHEADDW
CVPSREPKDMTTFRSA
Number of residues436
Molecular Weight49243.765
Theoretical pI9.05
GO Classification
Functions
  • pyruvate dehydrogenase (acetyl-transferring) kinase activity
  • ATP binding
  • protein kinase activity
Processes
  • pyruvate metabolic process
  • regulation of acetyl-CoA biosynthetic process from pyruvate
  • mitophagy in response to mitochondrial depolarization
  • regulation of glucose metabolic process
  • intrinsic apoptotic signaling pathway in response to oxidative stress
  • hypoxia-inducible factor-1alpha signaling pathway
  • cell proliferation
  • small molecule metabolic process
  • glucose metabolic process
  • cellular metabolic process
  • protein phosphorylation
Components
  • mitochondrion
  • mitochondrial matrix
  • mitochondrial pyruvate dehydrogenase complex
General FunctionPyruvate dehydrogenase (acetyl-transferring) kinase activity
Specific FunctionKinase 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID1088281
UniProtKB IDQ15118
UniProtKB Entry NamePDK1_HUMAN
Cellular LocationMitochondrion matrix
Gene sequence
>lcl|BSEQ0012693|[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (PDK1)
ATGAGGCTGGCGCGGCTGCTTCGCGGAGCCGCCTTGGCCGGCCCGGGCCCGGGGCTGCGC
GCCGCCGGCTTCAGCCGCAGCTTCAGCTCGGACTCGGGCTCCAGCCCGGCGTCCGAGCGC
GGCGTTCCGGGCCAGGTGGACTTCTACGCGCGCTTCTCGCCGTCCCCGCTCTCCATGAAG
CAGTTCCTGGACTTCGGATCAGTGAATGCTTGTGAAAAGACCTCATTTATGTTTCTGCGG
CAAGAGTTGCCTGTCAGACTGGCAAATATAATGAAAGAAATAAGTCTCCTTCCAGATAAT
CTTCTCAGGACACCATCCGTTCAATTGGTACAAAGCTGGTATATCCAGAGTCTTCAGGAG
CTTCTTGATTTTAAGGACAAAAGTGCTGAGGATGCTAAAGCTATTTATGAAAGGCCTAGA
AGAACATGGTTGCAGGTCTCTAGTTTATGCTGTATGGCCTGCAAGATGATCTTTACAGAT
ACTGTGATACGGATCAGAAACCGACACAATGATGTCATTCCCACAATGGCCCAGGGTGTG
ATTGAATACAAGGAGAGCTTTGGGGTGGATCCTGTCACCAGCCAGAATGTTCAGTACTTT
TTGGATCGATTCTACATGAGTCGCATTTCAATTAGAATGTTACTCAATCAGCACTCTTTA
TTGTTTGGTGGAAAAGGCAAAGGAAGTCCATCTCATCGAAAACACATTGGAAGCATAAAT
CCAAACTGCAATGTACTTGAAGTTATTAAAGATGGCTATGAAAATGCTAGGCGTCTGTGT
GATTTGTATTATATTAACTCTCCCGAACTAGAACTTGAAGAACTAAATGCAAAATCACCA
GGACAGCCAATACAAGTGGTTTATGTACCATCCCATCTCTATCACATGGTGTTTGAACTT
TTCAAGAATGCAATGAGAGCCACTATGGAACACCATGCCAACAGAGGTGTTTACCCCCCT
ATTCAAGTTCATGTCACGCTGGGTAATGAGGATTTGACTGTGAAGATGAGTGACCGAGGA
GGTGGCGTTCCTTTGAGGAAAATTGACAGACTTTTCAACTACATGTATTCAACTGCACCA
AGACCTCGTGTTGAGACCTCCCGCGCAGTGCCTCTGGCTGGTTTTGGTTATGGATTGCCC
ATATCACGTCTTTACGCACAATACTTCCAAGGAGACCTGAAGCTGTATTCCCTAGAGGGT
TACGGGACAGATGCAGTTATCTACATTAAGGCTCTGTCAACAGACTCAATAGAAAGACTC
CCAGTGTATAACAAAGCTGCCTGGAAGCATTACAACACCAACCACGAGGCTGATGACTGG
TGCGTCCCCAGCAGAGAACCCAAAGACATGACGACGTTCCGCAGTGCCTAG
GenBank Gene IDL42450
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:8809
Chromosome Location2
Locus2q31.1
References
  1. Gudi R, Bowker-Kinley MM, Kedishvili NY, Zhao Y, Popov KM: Diversity of the pyruvate dehydrogenase kinase gene family in humans. J Biol Chem. 1995 Dec 1;270(48):28989-94. 7499431
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  3. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. 15815621
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  5. McFate T, Mohyeldin A, Lu H, Thakar J, Henriques J, Halim ND, Wu H, Schell MJ, Tsang TM, Teahan O, Zhou S, Califano JA, Jeoung NH, Harris RA, Verma A: Pyruvate dehydrogenase complex activity controls metabolic and malignant phenotype in cancer cells. J Biol Chem. 2008 Aug 15;283(33):22700-8. doi: 10.1074/jbc.M801765200. Epub 2008 Jun 9. 18541534
  6. Lu CW, Lin SC, Chien CW, Lin SC, Lee CT, Lin BW, Lee JC, Tsai SJ: Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer. Am J Pathol. 2011 Sep;179(3):1405-14. doi: 10.1016/j.ajpath.2011.05.050. Epub 2011 Jul 18. 21763680
  7. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  8. Hitosugi T, Fan J, Chung TW, Lythgoe K, Wang X, Xie J, Ge Q, Gu TL, Polakiewicz RD, Roesel JL, Chen GZ, Boggon TJ, Lonial S, Fu H, Khuri FR, Kang S, Chen J: Tyrosine phosphorylation of mitochondrial pyruvate dehydrogenase kinase 1 is important for cancer metabolism. Mol Cell. 2011 Dec 23;44(6):864-77. doi: 10.1016/j.molcel.2011.10.015. 22195962
  9. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  10. Kato M, Li J, Chuang JL, Chuang DT: Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol. Structure. 2007 Aug;15(8):992-1004. Epub 2007 Aug 2. 17683942
  11. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. 17344846