PRKAG2 explained

5'-AMP-activated protein kinase subunit gamma-2 is an enzyme that in humans is encoded by the PRKAG2 gene.^{[1] [2] [3]}

Function

AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha subunit, a noncatalytic beta subunit, and a noncatalytic regulatory gamma subunit. Various forms of each of these subunits exist, encoded by different genes. AMPK is an important energy-sensing enzyme that monitors cellular energy status and functions by inactivating key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This gene is a member of the AMPK gamma subunit family and encodes a protein with four CBS domains. Mutations in this gene have been associated with ventricular pre-excitation (Wolff–Parkinson–White syndrome), progressive conduction system disease and cardiac hypertrophy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.^[3]

Interactions

PRKAG2 has been shown to interact with PRKAB2^[4] and PRKAB1.^[4]

Further reading

• Gollob MH, Green MS, Tang AS, Roberts R . PRKAG2 cardiac syndrome: familial ventricular preexcitation, conduction system disease, and cardiac hypertrophy. . Curr. Opin. Cardiol. . 17 . 3 . 229–34 . 2002 . 12015471 . 10.1097/00001573-200205000-00004 . 33599152 .
• Gollob MH . Glycogen storage disease as a unifying mechanism of disease in the PRKAG2 cardiac syndrome. . Biochem. Soc. Trans. . 31 . Pt 1 . 228–31 . 2003 . 12546691 . 10.1042/BST0310228 .
• Ofir M, Hochhauser E, Vidne BA, etal . [AMP-activated protein kinase: how a mistake in energy gauge causes glycogen storage] . Harefuah . 146 . 10 . 770–5, 813–4 . 2007 . 17990392 .
• Hofmann B, Nishanian P, Baldwin RL, etal . HIV inhibits the early steps of lymphocyte activation, including initiation of inositol phospholipid metabolism. . J. Immunol. . 145 . 11 . 3699–705 . 1991 . 10.4049/jimmunol.145.11.3699 . 1978848 . free .
• MacRae CA, Ghaisas N, Kass S, etal . Familial Hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3. . J. Clin. Invest. . 96 . 3 . 1216–20 . 1995 . 7657794 . 10.1172/JCI118154 . 185741 .
• Hofmann B, Nishanian P, Nguyen T, etal . Human immunodeficiency virus proteins induce the inhibitory cAMP/protein kinase A pathway in normal lymphocytes. . Proc. Natl. Acad. Sci. U.S.A. . 90 . 14 . 6676–80 . 1993 . 7688126 . 10.1073/pnas.90.14.6676 . 46995 . 1993PNAS...90.6676H . free .
• Hofmann B, Nishanian P, Fan J, etal . HIV Gag p17 protein impairs proliferation of normal lymphocytes in vitro. . AIDS . 8 . 7 . 1016–7 . 1994 . 7946090 . 10.1097/00002030-199407000-00025 .
• Swingler S, Gallay P, Camaur D, etal . The Nef protein of human immunodeficiency virus type 1 enhances serine phosphorylation of the viral matrix. . J. Virol. . 71 . 6 . 4372–7 . 1997 . 9151826 . 10.1128/JVI.71.6.4372-4377.1997. 191654 .
• Stapleton D, Woollatt E, Mitchelhill KI, etal . AMP-activated protein kinase isoenzyme family: subunit structure and chromosomal location. . FEBS Lett. . 409 . 3 . 452–6 . 1997 . 9224708 . 10.1016/S0014-5793(97)00569-3 . 39329574 .
• Chen P, Mayne M, Power C, Nath A . The Tat protein of HIV-1 induces tumor necrosis factor-alpha production. Implications for HIV-1-associated neurological diseases. . J. Biol. Chem. . 272 . 36 . 22385–8 . 1997 . 9278385 . 10.1074/jbc.272.36.22385 . free .
• Zidovetzki R, Wang JL, Chen P, etal . Human immunodeficiency virus Tat protein induces interleukin 6 mRNA expression in human brain endothelial cells via protein kinase C- and cAMP-dependent protein kinase pathways. . AIDS Res. Hum. Retroviruses . 14 . 10 . 825–33 . 1998 . 9671211 . 10.1089/aid.1998.14.825 .
• Mayne M, Bratanich AC, Chen P, etal . HIV-1 tat molecular diversity and induction of TNF-alpha: implications for HIV-induced neurological disease. . Neuroimmunomodulation . 5 . 3–4 . 184–92 . 1998 . 9730685 . 10.1159/000026336 . 19529677 .
• Toward a complete human genome sequence. . Genome Res. . 8 . 11 . 1097–108 . 1999 . 9847074 . 10.1101/gr.8.11.1097. free . Sanger Centre . The . Washington University Genome Sequencing Cente . The .
• Cheung PC, Salt IP, Davies SP, etal . Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding. . Biochem. J. . 346 Pt 3 . 3. 659–69 . 2000 . 10698692 . 10.1042/0264-6021:3460659 . 1220898 .
• Lang T, Yu L, Tu Q, etal . Molecular cloning, genomic organization, and mapping of PRKAG2, a heart abundant gamma2 subunit of 5'-AMP-activated protein kinase, to human chromosome 7q36. . Genomics . 70 . 2 . 258–63 . 2001 . 11112354 . 10.1006/geno.2000.6376 .
• Blair E, Redwood C, Ashrafian H, etal . 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. . 10 . 11 . 1215–20 . 2001 . 11371514 . 10.1093/hmg/10.11.1215 . free .
• Gollob MH, Green MS, Tang AS, etal . Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. . N. Engl. J. Med. . 344 . 24 . 1823–31 . 2001 . 11407343 . 10.1056/NEJM200106143442403 . free .
• Hamilton SR, Stapleton D, O'Donnell JB, etal . An activating mutation in the gamma1 subunit of the AMP-activated protein kinase. . FEBS Lett. . 500 . 3 . 163–8 . 2001 . 11445078 . 10.1016/S0014-5793(01)02602-3 . 85248755 . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Familial Hypertrophic Cardiomyopathy Overview

Notes and References

1. Stapleton D, Mitchelhill KI, Gao G, Widmer J, Michell BJ, Teh T, House CM, Fernandez CS, Cox T, Witters LA, Kemp BE . Mammalian AMP-activated protein kinase subfamily . J Biol Chem . 271 . 2 . 611–4 . February 1996 . 8557660 . 10.1074/jbc.271.2.611 . free .
2. Gao G, Fernandez CS, Stapleton D, Auster AS, Widmer J, Dyck JR, Kemp BE, Witters LA . Non-catalytic beta- and gamma-subunit isoforms of the 5'-AMP-activated protein kinase . J Biol Chem . 271 . 15 . 8675–81 . June 1996 . 8621499 . 10.1074/jbc.271.15.8675 . free .
3. Web site: Entrez Gene: PRKAG2 protein kinase, AMP-activated, gamma 2 non-catalytic subunit.
4. Cheung . P C . Salt I P . Davies S P . Hardie D G . Carling D . March 2000 . Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding . Biochem. J. . 346 Pt 3 . 3 . 659–69 . ENGLAND. 0264-6021. 10698692 . 1220898 . 10.1042/0264-6021:3460659.