APOC3

This gene encodes a protein component of triglyceride (TG)-rich lipoproteins (TRLs) including very low density lipoproteins (VLDL), high density lipoproteins (HDL) and chylomicrons. The encoded protein plays a role in role in the metabolism of these TRLs through multiple modes. This protein has been shown to promote the secretion of VLDL1, inhibit lipoprotein lipase enzyme activity, and delay catabolism of TRL remnants. Mutations in this gene are associated with low plasma triglyceride levels and reduced risk of ischemic cardiovascular disease, and hyperalphalipoproteinemia, which is characterized by elevated levels of high density lipoprotein (HDL) and HDL cholesterol in human patients. This gene and other related genes comprise an apolipoprotein gene cluster on chromosome 11. [provided by RefSeq, Sep 2017]

Full Name

Apolipoprotein C3

Function

Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma (PubMed:18201179, PubMed:22510806). Plays a multifaceted role in triglyceride homeostasis (PubMed:18201179, PubMed:22510806). Intracellularly, promotes hepatic very low density lipoprotein 1 (VLDL1) assembly and secretion; extracellularly, attenuates hydrolysis and clearance of triglyceride-rich lipoproteins (TRLs) (PubMed:18201179, PubMed:22510806). Impairs the lipolysis of TRLs by inhibiting lipoprotein lipase and the hepatic uptake of TRLs by remnant receptors (PubMed:18201179, PubMed:22510806). Formed of several curved helices connected via semiflexible hinges, so that it can wrap tightly around the curved micelle surface and easily adapt to the different diameters of its natural binding partners (PubMed:18408013).

Biological Process

Cholesterol efflux Source: BHF-UCL
Cholesterol homeostasis Source: BHF-UCL
Chylomicron assembly Source: Reactome
Chylomicron remnant clearance Source: BHF-UCL
Chylomicron remodeling Source: Reactome
G protein-coupled receptor signaling pathway Source: BHF-UCL
High-density lipoprotein particle remodeling Source: BHF-UCL
Lipoprotein metabolic process Source: InterPro
Negative regulation of cholesterol import Source: BHF-UCL
Negative regulation of fatty acid biosynthetic process Source: BHF-UCL
Negative regulation of high-density lipoprotein particle clearance Source: BHF-UCL
Negative regulation of lipid catabolic process Source: BHF-UCL
Negative regulation of lipid metabolic process Source: BHF-UCL
Negative regulation of lipoprotein lipase activity Source: BHF-UCL
Negative regulation of low-density lipoprotein particle clearance Source: BHF-UCL
Negative regulation of receptor-mediated endocytosis Source: BHF-UCL
Negative regulation of triglyceride catabolic process Source: BHF-UCL
Negative regulation of very-low-density lipoprotein particle clearance Source: BHF-UCL
Negative regulation of very-low-density lipoprotein particle remodeling Source: BHF-UCL
Phospholipid efflux Source: BHF-UCL
Regulation of Cdc42 protein signal transduction Source: BHF-UCL
Retinoid metabolic process Source: Reactome
Reverse cholesterol transport Source: BHF-UCL
Triglyceride catabolic process Source: BHF-UCL
Triglyceride homeostasis Source: BHF-UCL
Triglyceride metabolic process Source: HGNC-UCL
Very-low-density lipoprotein particle assembly Source: BHF-UCL

Cellular Location

Secreted

Involvement in disease

Hyperalphalipoproteinemia 2 (HALP2): A condition characterized by high levels of high density lipoprotein (HDL) and increased HDL cholesterol levels.

PTM

The most abundant glycoforms are characterized by an O-linked disaccharide galactose linked to N-acetylgalactosamine (Gal-GalNAc), further modified with up to 3 sialic acid residues. Less abundant glycoforms are characterized by more complex and fucosylated glycan moieties. O-glycosylated on Thr-94 with a core 1 or possibly core 8 glycan.