5'-AMP-activated protein kinase subunit gamma-3

Details

Name
5'-AMP-activated protein kinase subunit gamma-3
Synonyms
  • AMPK gamma3
  • AMPKG3
Gene Name
PRKAG3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008689|5'-AMP-activated protein kinase subunit gamma-3
MEPGLEHALRRTPSWSSLGGSEHQEMSFLEQENSSSWPSPAVTSSSERIRGKRRAKALRW
TRQKSVEEGEPPGQGEGPRSRPAAESTGLEATFPKTTPLAQADPAGVGTPPTGWDCLPSD
CTASAAGSSTDDVELATEFPATEAWECELEGLLEERPALCLSPQAPFPKLGWDDELRKPG
AQIYMRFMQEHTCYDAMATSSKLVIFDTMLEIKKAFFALVANGVRAAPLWDSKKQSFVGM
LTITDFILVLHRYYRSPLVQIYEIEQHKIETWREIYLQGCFKPLVSISPNDSLFEAVYTL
IKNRIHRLPVLDPVSGNVLHILTHKRLLKFLHIFGSLLPRPSFLYRTIQDLGIGTFRDLA
VVLETAPILTALDIFVDRRVSALPVVNECGQVVGLYSRFDVIHLAAQQTYNHLDMSVGEA
LRQRTLCLEGVLSCQPHESLGEVIDRIAREQVHRLVLVDETQHLLGVVSLSDILQALVLS
PAGIDALGA
Number of residues
489
Molecular Weight
54257.56
Theoretical pI
Not Available
GO Classification
Functions
AMP-activated protein kinase activity / ATP binding / protein kinase binding
Processes
cell cycle arrest / fatty acid biosynthetic process / gene expression / glucose transport / glycogen biosynthetic process / insulin receptor signaling pathway / intracellular signal transduction / macroautophagy / membrane organization / mitochondrion organization / organelle organization / transcription initiation from RNA polymerase II promoter
Components
cytosol / extracellular space / 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
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0017559|5'-AMP-activated protein kinase subunit gamma-3 (PRKAG3)
ATGGAGCCCGGGCTGGAGCACGCACTGCGCAGGACCCCTTCCTGGAGCAGCCTTGGGGGT
TCTGAGCATCAAGAGATGAGCTTCCTAGAGCAAGAAAACAGCAGCTCATGGCCATCACCA
GCTGTGACCAGCAGCTCAGAAAGAATCCGTGGGAAACGGAGGGCCAAAGCCTTGAGATGG
ACAAGGCAGAAGTCGGTGGAGGAAGGGGAGCCACCAGGTCAGGGGGAAGGTCCCCGGTCC
AGGCCAGCTGCTGAGTCCACCGGGCTGGAGGCCACATTCCCCAAGACCACACCCTTGGCT
CAAGCTGATCCTGCCGGGGTGGGCACTCCACCAACAGGGTGGGACTGCCTCCCCTCTGAC
TGTACAGCCTCAGCTGCAGGCTCCAGCACAGATGATGTGGAGCTGGCCACGGAGTTCCCA
GCCACAGAGGCCTGGGAGTGTGAGCTAGAAGGCCTGCTGGAAGAGAGGCCTGCCCTGTGC
CTGTCCCCGCAGGCCCCATTTCCCAAGCTGGGCTGGGATGACGAACTGCGGAAACCCGGC
GCCCAGATCTACATGCGCTTCATGCAGGAGCACACCTGCTACGATGCCATGGCAACTAGC
TCCAAGCTAGTCATCTTCGACACCATGCTGGAGATCAAGAAGGCCTTCTTTGCTCTGGTG
GCCAACGGTGTGCGGGCAGCCCCTCTATGGGACAGCAAGAAGCAGAGCTTTGTGGGGATG
CTGACCATCACTGACTTCATCCTGGTGCTGCATCGCTACTACAGGTCCCCCCTGGTCCAG
ATCTATGAGATTGAACAACATAAGATTGAGACCTGGAGGGAGATCTACCTGCAAGGCTGC
TTCAAGCCTCTGGTCTCCATCTCTCCTAATGATAGCCTGTTTGAAGCTGTCTACACCCTC
ATCAAGAACCGGATCCATCGCCTGCCTGTTCTTGACCCGGTGTCAGGCAACGTACTCCAC
ATCCTCACACACAAACGCCTGCTCAAGTTCCTGCACATCTTTGGTTCCCTGCTGCCCCGG
CCCTCCTTCCTCTACCGCACTATCCAAGATTTGGGCATCGGCACATTCCGAGACTTGGCT
GTGGTGCTGGAGACAGCACCCATCCTGACTGCACTGGACATCTTTGTGGACCGGCGTGTG
TCTGCACTGCCTGTGGTCAACGAATGTGGTCAGGTCGTGGGCCTCTATTCCCGCTTTGAT
GTGATTCACCTGGCTGCCCAGCAAACCTACAACCACCTGGACATGAGTGTGGGAGAAGCC
CTGAGGCAGAGGACACTATGTCTGGAGGGAGTCCTTTCCTGCCAGCCCCACGAGAGCTTG
GGGGAAGTGATCGACAGGATTGCTCGGGAGCAGGTACACAGGCTGGTGCTAGTGGACGAG
ACCCAGCATCTCTTGGGCGTGGTCTCCCTCTCCGACATCCTTCAGGCACTGGTGCTCAGC
CCTGCTGGCATCGATGCCCTCGGGGCCTGA
Chromosome Location
2
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ9UGI9
UniProtKB Entry NameAAKG3_HUMAN
HGNC IDHGNC:9387
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. [PubMed:10698692]
  2. Milan D, Jeon JT, Looft C, Amarger V, Robic A, Thelander M, Rogel-Gaillard C, Paul S, Iannuccelli N, Rask L, Ronne H, Lundstrom K, Reinsch N, Gellin J, Kalm E, Roy PL, Chardon P, Andersson L: A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle. Science. 2000 May 19;288(5469):1248-51. [PubMed:10818001]
  3. 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. [PubMed:15489334]
  4. 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. [PubMed:14722619]
  5. 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. [PubMed:17255938]
  6. Towler MC, Hardie DG: AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007 Feb 16;100(3):328-41. [PubMed:17307971]
  7. Hardie DG: AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol. 2007 Oct;8(10):774-85. [PubMed:17712357]
  8. 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. [PubMed:21460634]
  9. Costford SR, Kavaslar N, Ahituv N, Chaudhry SN, Schackwitz WS, Dent R, Pennacchio LA, McPherson R, Harper ME: Gain-of-function R225W mutation in human AMPKgamma(3) causing increased glycogen and decreased triglyceride in skeletal muscle. PLoS One. 2007 Sep 19;2(9):e903. [PubMed:17878938]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00945Acetylsalicylic acidapproved, vet_approvedunknownactivatorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails