Angiopoietin-related protein 4

Definition:

Mediates inactivation of the lipoprotein lipase LPL, and thereby plays a role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism. May also play a role in regulating glucose homeostasis and insulin sensitivity (Probable). Inhibits proliferation, migration, and tubule formation of endothelial cells and reduces vascular leakage. Upon heterologous expression, inhibits the adhesion of endothelial cell to the extracellular matrix (ECM), and inhibits the reorganization of the actin cytoskeleton, formation of actin stress fibers and focal adhesions in endothelial cells that have adhered to ANGPTL4-containing ECM (in vitro). Depending on context, may modulate tumor-related angiogenesis (By similarity).; [ANGPTL4 N-terminal chain]: Mediates inactivation of the lipoprotein lipase LPL, and thereby plays an important role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism. Has higher activity in LPL inactivation than the uncleaved protein.

References:

[1]. Wu Yin, et al. Genetic variation in ANGPTL4 provides insights into protein processing and function. J Biol Chem. 2009 May 8;284(19):13213-22. [Content Brief]

[2]. Yasuhiro Ito, et al. Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4. Cancer Res. 2003 Oct 15;63(20):6651-7. [Content Brief]

[3]. Viktoria Gusarova, et al. Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes. Nat Commun. 2018 Jun 13;9(1):2252. [Content Brief]

[4]. Kristian K Kristensen, et al. A disordered acidic domain in GPIHBP1 harboring a sulfated tyrosine regulates lipoprotein lipase. Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):E6020-E6029. [Content Brief]

[5]. Aurélie Cazes, et al. Extracellular matrix-bound angiopoietin-like 4 inhibits endothelial cell adhesion, migration, and sprouting and alters actin cytoskeleton. Circ Res. 2006 Nov 24;99(11):1207-15. [Content Brief]

[6]. Xia Lei, et al. Proteolytic processing of angiopoietin-like protein 4 by proprotein convertases modulates its inhibitory effects on lipoprotein lipase activity. J Biol Chem. 2011 May 6;286(18):15747-56. [Content Brief]

[7]. Simon Mysling, et al. The angiopoietin-like protein ANGPTL4 catalyzes unfolding of the hydrolase domain in lipoprotein lipase and the endothelial membrane protein GPIHBP1 counteracts this unfolding. Elife. 2016 Dec 8;5:e20958. [Content Brief]

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