ANGPTL4

This gene is a member of the angiopoietin/angiopoietin-like gene family and encodes a glycosylated, secreted protein with a fibrinogen C-terminal domain. This gene is induced under hypoxic conditions in endothelial cells and is the target of peroxisome proliferation activators. The encoded protein is a serum hormone directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity and also acts as an apoptosis survival factor for vascular endothelial cells. The encoded protein may play a role in several cancers and it also has been shown to prevent the metastatic process by inhibiting vascular activity as well as tumor cell motility and invasiveness. Decreased expression of this protein has been associated with type 2 diabetes. Alternatively spliced transcript variants encoding different isoforms have been described. This gene was previously referred to as ANGPTL2 but has been renamed ANGPTL4. [provided by RefSeq]

angiopoietin-like 4

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 (PubMed:19270337, PubMed:21398697, PubMed:27929370, PubMed:29899144). 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 (PubMed:14583458, PubMed:17068295). 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) (PubMed:17068295). 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 (PubMed:19270337, PubMed:21398697, PubMed:27929370, PubMed:29899144). Has higher activity in LPL inactivation than the uncleaved protein (PubMed:19270337, PubMed:21398697).

Angiogenesis Source: UniProtKB-KW
Lipid metabolic process Source: UniProtKB-KW
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of endothelial cell apoptotic process Source: Ensembl
Negative regulation of lipoprotein lipase activity Source: BHF-UCL
Positive regulation of angiogenesis Source: UniProtKB
Protein unfolding Source: ARUK-UCL
Regulation of metabolic process Source: Reactome
Response to hypoxia Source: UniProtKB
Triglyceride homeostasis Source: BHF-UCL

Secreted; Extracellular matrix. The unprocessed form interacts with the extracellular matrix (PubMed:17068295, PubMed:21398697). This may constitute a dynamic reservoir, a regulatory mechanism of the bioavailability of ANGPTL4 (Probable).

N-glycosylated.
ANGPTL4 N-terminal chain: Forms disulfide-linked dimers and tetramers.
Cleaved into a smaller N-terminal chain and a larger chain that contains the fibrinogen C-terminal domain; both cleaved and uncleaved forms are detected in the extracellular space. The cleaved form is not present within the cell.