5'-AMP-activated protein kinase gamma-2 Protein
AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic subunit, alpha (yellow), and two regulatory subunits, beta and gamma (blue and green)[1]. The specific subunit coded for by PRKAG2 is known as 5'-AMP-activated protein kinase subunit gamma-2 (AMPK-gamma-2 or AAKG2) and is a 569 amino acid long polypeptide that contains four cystathionine-beta-synthase (CBS) domains (Uniprot Number: Q9UGJ0). These CBS domains (green) are evolutionarily conserved units that have shared structural and functional properties. CBS domains often function in metabolic enzymes, kinases, and channels [2]. The AAKG2 protein specifically uses it's CBS domains to regulate cellular energy metabolism, activate energy-producing pathways, inhibit energy-consuming pathways, and regulate cellular polarity. This protein is ubiquitously expressed everywhere except the liver and thymus. The highest levels of it's expression are found in the heart, placenta, and testis. Mutation of this protein may result in Wolff-Parkinson-White (WPW) syndrome, cardiomyopathy, familial hypertrophic type 6 (CMH6) [3], or glycogen storage disease of heart leathal congentital (GSDH) [4]. |
References
[1] http://www.ncbi.nlm.nih.gov/gene?db=gene&cmd=Retrieve&dopt=full_report&list_uids=51422
[2] Ignoul, S., and Eggermont, J. (2005). CBS domains: structure, function, and pathology in human proteins. American Physiological Society Cell Physiology, 289:C1369-78. DOI: doi:10.1152/ajpcell.00282.2005.
[3] Blair, E., Redwood, C., Ashraflan, H., et al. (2001). Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyoptahy: evidence for the central role of energy compromise in disease pathogenesis. Human Molecular Genetics, 10(11): 1215-20. doi: 10.1093/hmg/10.11.1215
[4] Burwinkel, B., Scott, J.W., Buhrer, C., et al. (2005). 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. The American Journal of Human Genetics, 76(6): 1034-49. doi: 10.1086/430840
[2] Ignoul, S., and Eggermont, J. (2005). CBS domains: structure, function, and pathology in human proteins. American Physiological Society Cell Physiology, 289:C1369-78. DOI: doi:10.1152/ajpcell.00282.2005.
[3] Blair, E., Redwood, C., Ashraflan, H., et al. (2001). Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyoptahy: evidence for the central role of energy compromise in disease pathogenesis. Human Molecular Genetics, 10(11): 1215-20. doi: 10.1093/hmg/10.11.1215
[4] Burwinkel, B., Scott, J.W., Buhrer, C., et al. (2005). 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. The American Journal of Human Genetics, 76(6): 1034-49. doi: 10.1086/430840
Margaret Beatka ([email protected])
Page Last Updated: 5/10/13
This web page was produced as an assignment for Genetics 677, as an undergraduate course at UW-Madison.
Page Last Updated: 5/10/13
This web page was produced as an assignment for Genetics 677, as an undergraduate course at UW-Madison.