1ll8

Structural highlights

Function

PASK_HUMAN Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate to respiratory regulation.^{[1] [2] [3] [4] [5] [6]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Wilson WA, Skurat AV, Probst B, de Paoli-Roach A, Roach PJ, Rutter J. Control of mammalian glycogen synthase by PAS kinase. Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16596-601. Epub 2005 Nov 7. PMID:16275910 doi:10.1073/pnas.0508481102
2. ↑ An R, da Silva Xavier G, Hao HX, Semplici F, Rutter J, Rutter GA. Regulation by Per-Arnt-Sim (PAS) kinase of pancreatic duodenal homeobox-1 nuclear import in pancreatic beta-cells. Biochem Soc Trans. 2006 Nov;34(Pt 5):791-3. PMID:17052199 doi:10.1042/BST0340791
3. ↑ Eckhardt K, Troger J, Reissmann J, Katschinski DM, Wagner KF, Stengel P, Paasch U, Hunziker P, Borter E, Barth S, Schlafli P, Spielmann P, Stiehl DP, Camenisch G, Wenger RH. Male germ cell expression of the PAS domain kinase PASKIN and its novel target eukaryotic translation elongation factor eEF1A1. Cell Physiol Biochem. 2007;20(1-4):227-40. PMID:17595531 doi:10.1159/000104169
4. ↑ da Silva Xavier G, Farhan H, Kim H, Caxaria S, Johnson P, Hughes S, Bugliani M, Marselli L, Marchetti P, Birzele F, Sun G, Scharfmann R, Rutter J, Siniakowicz K, Weir G, Parker H, Reimann F, Gribble FM, Rutter GA. Per-arnt-sim (PAS) domain-containing protein kinase is downregulated in human islets in type 2 diabetes and regulates glucagon secretion. Diabetologia. 2011 Apr;54(4):819-27. doi: 10.1007/s00125-010-2010-7. Epub 2010, Dec 23. PMID:21181396 doi:10.1007/s00125-010-2010-7
5. ↑ Schlafli P, Troger J, Eckhardt K, Borter E, Spielmann P, Wenger RH. Substrate preference and phosphatidylinositol monophosphate inhibition of the catalytic domain of the Per-Arnt-Sim domain kinase PASKIN. FEBS J. 2011 May;278(10):1757-68. doi: 10.1111/j.1742-4658.2011.08100.x. Epub, 2011 Apr 8. PMID:21418524 doi:10.1111/j.1742-4658.2011.08100.x
6. ↑ Kikani CK, Antonysamy SA, Bonanno JB, Romero R, Zhang FF, Russell M, Gheyi T, Iizuka M, Emtage S, Sauder JM, Turk BE, Burley SK, Rutter J. Structural bases of PAS domain-regulated kinase (PASK) activation in the absence of activation loop phosphorylation. J Biol Chem. 2010 Dec 24;285(52):41034-43. Epub 2010 Oct 13. PMID:20943661 doi:10.1074/jbc.M110.157594