5'-AMP-activated protein kinase subunit gamma-2

Details

Name

5'-AMP-activated protein kinase subunit gamma-2

Synonyms

• AMPK gamma2
• H91620p

Gene Name

PRKAG2

Organism

Humans

Amino acid sequence

>lcl|BSEQ0008688|5'-AMP-activated protein kinase subunit gamma-2
MGSAVMDTKKKKDVSSPGGSGGKKNASQKRRSLRVHIPDLSSFAMPLLDGDLEGSGKHSS
RKVDSPFGPGSPSKGFFSRGPQPRPSSPMSAPVRPKTSPGSPKTVFPFSYQESPPRSPRR
MSFSGIFRSSSKESSPNSNPATSPGGIRFFSRSRKTSGLSSSPSTPTQVTKQHTFPLESY
KHEPERLENRIYASSSPPDTGQRFCPSSFQSPTRPPLASPTHYAPSKAAALAAALGPAEA
GMLEKLEFEDEAVEDSESGVYMRFMRSHKCYDIVPTSSKLVVFDTTLQVKKAFFALVANG
VRAAPLWESKKQSFVGMLTITDFINILHRYYKSPMVQIYELEEHKIETWRELYLQETFKP
LVNISPDASLFDAVYSLIKNKIHRLPVIDPISGNALYILTHKRILKFLQLFMSDMPKPAF
MKQNLDELGIGTYHNIAFIHPDTPIIKALNIFVERRISALPVVDESGKVVDIYSKFDVIN
LAAEKTYNNLDITVTQALQHRSQYFEGVVKCNKLEILETIVDRIVRAEVHRLVVVNEADS
IVGIISLSDILQALILTPAGAKQKETETE

Number of residues

569

Molecular Weight

63065.57

Theoretical pI

Not Available

GO Classification

Functions

ADP binding / AMP binding / AMP-activated protein kinase activity / ATP binding / cAMP-dependent protein kinase inhibitor activity / cAMP-dependent protein kinase regulator activity / phosphorylase kinase regulator activity / protein kinase activator activity / protein kinase binding

Processes

activation of protein kinase activity / ATP biosynthetic process / carnitine shuttle / cell cycle arrest / cellular lipid metabolic process / energy reserve metabolic process / fatty acid biosynthetic process / gene expression / glycogen metabolic process / insulin receptor signaling pathway / intracellular signal transduction / macroautophagy / membrane organization / mitochondrion organization / negative regulation of protein kinase activity / negative regulation of protein serine/threonine kinase activity / organelle organization / positive regulation of peptidyl-threonine phosphorylation / positive regulation of protein kinase activity / regulation of fatty acid biosynthetic process / regulation of fatty acid metabolic process / regulation of fatty acid oxidation / regulation of glucose import / regulation of glycolytic process / small molecule metabolic process / sterol biosynthetic process / transcription initiation from RNA polymerase II promoter

Components

cytosol / extracellular space / nucleoplasm / nucleotide-activated protein kinase complex

General Function

Protein kinase binding

Specific Function

AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.

Pfam Domain Function

• CBS (PF00571)

Transmembrane Regions

Not Available

Cellular Location

Not Available

Gene sequence

>lcl|BSEQ0013355|5'-AMP-activated protein kinase subunit gamma-2 (PRKAG2)
ATGCCGCTCCTGGACGGAGACCTGGAGGGTTCCGGAAAGCATTCCTCTCGAAAGGTGGAC
AGCCCCTTCGGCCCGGGCAGCCCCTCCAAAGGGTTCTTCTCCAGAGGCCCCCAGCCCCGG
CCCTCCAGCCCCATGTCTGCACCTGTGAGGCCCAAGACCAGCCCCGGCTCTCCCAAAACC
GTGTTCCCGTTCTCCTACCAGGAGTCCCCGCCACGCTCCCCTCGACGCATGAGCTTCAGT
GGGATCTTCCGCTCCTCCTCCAAAGAGTCTTCCCCCAACTCCAACCCTGCTACCTCGCCC
GGGGGCATCAGGTTTTTCTCCCGCTCCAGAAAAACCTCCGGCCTCTCCTCCTCTCCGTCA
ACACCCACCCAAGTGACCAAGCAGCACACGTTTCCCCTGGAATCCTATAAGCACGAGCCT
GAACGGTTAGAGAATCGCATCTATGCCTCGTCTTCCCCCCCGGACACAGGGCAGAGGTTC
TGCCCGTCTTCCTTCCAGAGCCCGACCAGGCCTCCACTGGCATCACCGACACACTATGCT
CCCTCCAAAGCCGCGGCGCTGGCGGCGGCCCTGGGACCCGCGGAAGCCGGCATGCTGGAG
AAGCTGGAGTTCGAGGACGAAGCAGTAGAAGACTCAGAAAGTGGTGTTTACATGCGATTC
ATGAGGTCACACAAGTGTTATGACATCGTTCCAACCAGTTCAAAGCTTGTTGTCTTTGAT
ACTACATTACAAGTTAAAAAGGCCTTCTTTGCTTTGGTAGCCAACGGTGTCCGAGCAGCG
CCACTGTGGGAGAGTAAAAAACAAAGTTTTGTAGGAATGCTAACAATTACAGATTTCATA
AATATACTACATAGATACTATAAATCACCTATGGTACAGATTTATGAATTAGAGGAACAT
AAAATTGAAACATGGAGGGAGCTTTATTTACAAGAAACATTTAAGCCTTTAGTGAATATA
TCTCCAGATGCAAGCCTCTTCGATGCTGTATACTCCTTGATCAAAAATAAAATCCACAGA
TTGCCCGTTATTGACCCTATCAGTGGGAATGCACTTTATATACTTACCCACAAAAGAATC
CTCAAGTTCCTCCAGCTTTTTATGTCTGATATGCCAAAGCCTGCCTTCATGAAGCAGAAC
CTGGATGAGCTTGGAATAGGAACGTACCACAACATTGCCTTCATACATCCAGACACTCCC
ATCATCAAAGCCTTGAACATATTTGTGGAAAGACGAATATCAGCTCTGCCTGTTGTGGAT
GAGTCAGGAAAAGTTGTAGATATTTATTCCAAATTTGATGTAATTAATCTTGCTGCTGAG
AAAACATACAATAACCTAGATATCACGGTGACCCAGGCCCTTCAGCACCGTTCACAGTAT
TTTGAAGGTGTTGTGAAGTGCAATAAGCTGGAAATACTGGAGACCATCGTGGACAGAATA
GTAAGAGCTGAGGTCCATCGGCTGGTGGTGGTAAATGAAGCAGATAGTATTGTGGGTATT
ATTTCCCTGTCGGACATTCTGCAAGCCCTGATCCTCACACCAGCAGGTGCCAAACAAAAG
GAGACAGAAACGGAGTGA

Chromosome Location

7

Locus

Not Available

External Identifiers

Resource	Link
UniProtKB ID	Q9UGJ0
UniProtKB Entry Name	AAKG2_HUMAN
HGNC ID	HGNC:9386

General References

1. Cheung PC, Salt IP, Davies SP, Hardie DG, Carling D: Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding. Biochem J. 2000 Mar 15;346 Pt 3:659-69. [Article]
2. Lang T, Yu L, Tu Q, Jiang J, Chen Z, Xin Y, Liu G, Zhao S: Molecular cloning, genomic organization, and mapping of PRKAG2, a heart abundant gamma2 subunit of 5'-AMP-activated protein kinase, to human chromosome 7q36. Genomics. 2000 Dec 1;70(2):258-63. [Article]
3. 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]
4. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [Article]
5. 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]
6. Scott JW, Hawley SA, Green KA, Anis M, Stewart G, Scullion GA, Norman DG, Hardie DG: CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. J Clin Invest. 2004 Jan;113(2):274-84. [Article]
7. Scott JW, Ross FA, Liu JK, Hardie DG: Regulation of AMP-activated protein kinase by a pseudosubstrate sequence on the gamma subunit. EMBO J. 2007 Feb 7;26(3):806-15. Epub 2007 Jan 25. [Article]
8. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
9. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
10. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
11. Loffler AS, Alers S, Dieterle AM, Keppeler H, Franz-Wachtel M, Kundu M, Campbell DG, Wesselborg S, Alessi DR, Stork B: Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop. Autophagy. 2011 Jul;7(7):696-706. Epub 2011 Jul 1. [Article]
12. Towler MC, Hardie DG: AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007 Feb 16;100(3):328-41. [Article]
13. Hardie DG: AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol. 2007 Oct;8(10):774-85. [Article]
14. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
15. Gollob MH, Seger JJ, Gollob TN, Tapscott T, Gonzales O, Bachinski L, Roberts R: Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. Circulation. 2001 Dec 18;104(25):3030-3. [Article]
16. Blair E, Redwood C, Ashrafian H, Oliveira M, Broxholme J, Kerr B, Salmon A, Ostman-Smith I, Watkins H: Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis. Hum Mol Genet. 2001 May 15;10(11):1215-20. [Article]
17. Gollob MH, Green MS, Tang AS, Gollob T, Karibe A, Ali Hassan AS, Ahmad F, Lozado R, Shah G, Fananapazir L, Bachinski LL, Roberts R: Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. N Engl J Med. 2001 Jun 14;344(24):1823-31. [Article]
18. Arad M, Benson DW, Perez-Atayde AR, McKenna WJ, Sparks EA, Kanter RJ, McGarry K, Seidman JG, Seidman CE: Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J Clin Invest. 2002 Feb;109(3):357-62. [Article]
19. Burwinkel B, Scott JW, Buhrer C, van Landeghem FK, Cox GF, Wilson CJ, Grahame Hardie D, Kilimann MW: Fatal congenital heart glycogenosis caused by a recurrent activating R531Q mutation in the gamma 2-subunit of AMP-activated protein kinase (PRKAG2), not by phosphorylase kinase deficiency. Am J Hum Genet. 2005 Jun;76(6):1034-49. Epub 2005 May 2. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB00945	Acetylsalicylic acid	approved, vet_approved	unknown	activator	Details
DB12010	Fostamatinib	approved, investigational	unknown	inhibitor	Details
DB00273	Topiramate	approved	unknown	inducer	Details
DB00131	Adenosine phosphate	approved, investigational, nutraceutical, withdrawn	yes	activator	Details