[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial
Details
- Name
- [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial
- Synonyms
- 2.7.11.2
- PDH kinase 1
- PDHK1
- Pyruvate dehydrogenase kinase isoform 1
- Gene Name
- PDK1
- Organism
- Humans
- Amino acid sequence
>lcl|BSEQ0007401|[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial MRLARLLRGAALAGPGPGLRAAGFSRSFSSDSGSSPASERGVPGQVDFYARFSPSPLSMK QFLDFGSVNACEKTSFMFLRQELPVRLANIMKEISLLPDNLLRTPSVQLVQSWYIQSLQE LLDFKDKSAEDAKAIYDFTDTVIRIRNRHNDVIPTMAQGVIEYKESFGVDPVTSQNVQYF LDRFYMSRISIRMLLNQHSLLFGGKGKGSPSHRKHIGSINPNCNVLEVIKDGYENARRLC DLYYINSPELELEELNAKSPGQPIQVVYVPSHLYHMVFELFKNAMRATMEHHANRGVYPP IQVHVTLGNEDLTVKMSDRGGGVPLRKIDRLFNYMYSTAPRPRVETSRAVPLAGFGYGLP ISRLYAQYFQGDLKLYSLEGYGTDAVIYIKALSTDSIERLPVYNKAAWKHYNTNHEADDW CVPSREPKDMTTFRSA
- Number of residues
- 436
- Molecular Weight
- 49243.765
- Theoretical pI
- 9.05
- GO Classification
- FunctionsATP binding / protein kinase activity / pyruvate dehydrogenase (acetyl-transferring) kinase activityProcessescell proliferation / cellular metabolic process / glucose metabolic process / hypoxia-inducible factor-1alpha signaling pathway / intrinsic apoptotic signaling pathway in response to oxidative stress / mitophagy in response to mitochondrial depolarization / protein phosphorylation / pyruvate metabolic process / regulation of acetyl-CoA biosynthetic process from pyruvate / regulation of glucose metabolic process / small molecule metabolic processComponentsmitochondrial matrix / mitochondrial pyruvate dehydrogenase complex / mitochondrion
- General Function
- Pyruvate dehydrogenase (acetyl-transferring) kinase activity
- Specific Function
- 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.
- Pfam Domain Function
- Transmembrane Regions
- Not Available
- Cellular Location
- Mitochondrion 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
- Chromosome Location
- 2
- Locus
- 2q31.1
- External Identifiers
Resource Link UniProtKB ID Q15118 UniProtKB Entry Name PDK1_HUMAN GenBank Protein ID 1088281 GenBank Gene ID L42450 HGNC ID HGNC:8809 - General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]