ANGPTL3

This gene encodes a member of a family of secreted proteins that function in angiogenesis. The encoded protein, which is expressed predominantly in the liver, is further processed into an N-terminal coiled-coil domain-containing chain and a C-terminal fibrinogen chain. The N-terminal chain is important for lipid metabolism, while the C-terminal chain may be involved in angiogenesis. Mutations in this gene cause familial hypobetalipoproteinemia type 2. [provided by RefSeq, Aug 2015]

Angiopoietin Like 3

Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism (PubMed:11788823, PubMed:12909640, PubMed:23661675, PubMed:25495645). Proposed to play a role in the trafficking of energy substrates to either storage or oxidative tissues in response to food intake (By similarity). Has a stimulatory effect on plasma triglycerides (TG), which is achieved by suppressing plasma TG clearance via inhibition of LPL activity. The inhibition of LPL activity appears to be an indirect mechanism involving recruitment of proprotein convertases PCSK6 and FURIN to LPL leading to cleavage and dissociation of LPL from the cell surface; the function does not require ANGPTL3 proteolytic cleavage but seems to be mediated by the N-terminal domain, and is not inhibited by GPIHBP1 (PubMed:12097324, PubMed:19318355, PubMed:20581395). Can inhibit endothelial lipase, causing increased plasma levels of high density lipoprotein (HDL) cholesterol and phospholipids (PubMed:17110602, PubMed:19028676). Can bind to adipocytes to activate lipolysis, releasing free fatty acids and glycerol (PubMed:12565906). Suppresses LPL specifically in oxidative tissues which is required to route very low density lipoprotein (VLDL)-TG to white adipose tissue (WAT) for storage in response to food; the function may involve cooperation with circulating, liver-derived ANGPTL8 and ANGPTL4 expression in WAT (By similarity). Contributes to lower plasma levels of low density lipoprotein (LDL)-cholesterol by a mechanism that is independent of the canonical pathway implicating APOE and LDLR. May stimulate hypothalamic LPL activity (By similarity).
ANGPTL3(17-221):In vitro inhibits LPL activity; not effective on GPIHBP1-stabilized LPL.
Involved in angiogenesis. Binds to endothelial cells via integrin alpha-V/beta-3 (ITGAV:ITGB3), activates FAK, MAPK and Akt signaling pathways and induces cell adhesion and cell migration (PubMed:11877390). Secreted from podocytes, may modulate properties of glomerular endothelial cells involving integrin alpha-V/beta-3 and Akt signaling (PubMed:18535744). May increase the motility of podocytes. May induce actin filament rearrangements in podocytes implicating integrin alpha-V/beta-3 and Rac1 activation. Binds to hematopoietic stem cells (HSC) and is involved in the regulation of HSC activity probably implicating down-regulation of IKZF1/IKAROS (By similarity).

Acylglycerol homeostasis Source: BHF-UCL
Angiogenesis Source: UniProtKB-KW
Artery morphogenesis Source: BHF-UCL
Cell-matrix adhesion Source: UniProtKB
Cholesterol homeostasis Source: BHF-UCL
Cholesterol metabolic process Source: BHF-UCL
Fatty acid metabolic process Source: BHF-UCL
Glycerol metabolic process Source: BHF-UCL
Integrin-mediated signaling pathway Source: UniProtKB
Intracellular receptor signaling pathway Source: Reactome
Lipid homeostasis Source: BHF-UCL
Lipid storage Source: BHF-UCL
Negative regulation of lipoprotein lipase activity Source: BHF-UCL
Negative regulation of phospholipase activity Source: BHF-UCL
Phospholipid catabolic process Source: BHF-UCL
Phospholipid homeostasis Source: BHF-UCL
Phospholipid metabolic process Source: BHF-UCL
Positive regulation of angiogenesis Source: UniProtKB
Positive regulation of cell migration Source: UniProtKB
Positive regulation of lipid catabolic process Source: BHF-UCL
Regulation of lipoprotein lipase activity Source: Reactome
Response to hormone Source: Ensembl
Signal transduction Source: BHF-UCL
Triglyceride homeostasis Source: MGI

Secreted; Lamellipodium. Colocalized with HSPG2 and activated ITGB3 on podocytes.

Hypobetalipoproteinemia, familial, 2 (FHBL2): A disorder of lipid metabolism characterized by less than 5th percentile age- and sex-specific levels of low density lipoproteins, and dietary fat malabsorption. Affected individuals present with combined hypolipidemia, consisting of extremely low plasma levels of LDL cholesterol, HDL cholesterol, and triglycerides.

O-glycosylated at Thr-226 by GALNT2; blocks processing and activation by proprotein convertases.
In part proteolytically cleaved by proprotein convertases; proposed to be involved in activation.