PNPLA2
Developmental stage
Induced during differentiation of primary preadipocytes to adipocytes. Expression increased from fetal to adult in retinal pigment epithelium.
Function
Catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets (PubMed:15364929, PubMed:15550674, PubMed:16150821, PubMed:16239926, PubMed:17603008, PubMed:34903883). Exhibits a strong preference for the hydrolysis of long-chain fatty acid esters at the sn-2 position of the glycerol backbone and acts coordinately with LIPE/HLS and DGAT2 within the lipolytic cascade (By similarity). Also possesses acylglycerol transacylase and phospholipase A2 activities (PubMed:15364929, PubMed:17032652, PubMed:17603008). Transfers fatty acid from triglyceride to retinol, hydrolyzes retinylesters, and generates 1,3-diacylglycerol from triglycerides (PubMed:17603008). Regulates adiposome size and may be involved in the degradation of adiposomes (PubMed:16239926). Catalyzes the formation of an ester bond between hydroxy fatty acids and fatty acids derived from triglycerides or diglycerides to generate fatty acid esters of hydroxy fatty acids (FAHFAs) in adipocytes (PubMed:35676490). Acts antagonistically with LDAH in regulation of cellular lipid stores (PubMed:28578400). Inhibits LDAH-stimulated lipid droplet fusion (PubMed:28578400). May play an important role in energy homeostasis (By similarity). May play a role in the response of the organism to starvation, enhancing hydrolysis of triglycerides and providing free fatty acids to other tissues to be oxidized in situations of energy depletion (By similarity).
Involvement in disease
Genetic variations in PNPLA2 may be associated with risk of diabetes mellitus type 2.
Neutral lipid storage disease with myopathy
NLSDM
Neutral lipid storage disorder (NLSD) with myopathy but without ichthyosis. NLSDs are characterized by the presence of triglyceride-containing cytoplasmic droplets in leukocytes and in other tissues, including bone marrow, skin, and muscle. Individuals with NLSDM did not show obesity, in spite of a defect in triglyceride degradation in fibroblasts and in marked triglyceride storage in liver, muscles, and other visceral cells.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Glycerolipid metabolism; triacylglycerol degradation.
Post-translational modifications
Phosphorylation at Ser-404 by PKA is increased during fasting and moderate intensity exercise, and moderately increases lipolytic activity (By similarity). Phosphorylation at Ser-404 is increased upon beta-adrenergic stimulation (PubMed:22733971).
Ubiquitinated by PEX2 in response to reactive oxygen species (ROS), leading to its degradation (PubMed:34903883). Ubiquitination is stimulated by LDAH (PubMed:28578400).
Tissue Specificity
Highest expression in adipose tissue. Also detected in heart, skeletal muscle, and portions of the gastrointestinal tract. Detected in normal retina and retinoblastoma cells. Detected in retinal pigment epithelium and, at lower intensity, in the inner segments of photoreceptors and in the ganglion cell layer of the neural retina (at protein level).
Cellular localization
- Lipid droplet
- Cell membrane
- Multi-pass membrane protein
- Cytoplasm
Alternative names
ATGL, FP17548, PNPLA2, Patatin-like phospholipase domain-containing protein 2, Adipose triglyceride lipase, Calcium-independent phospholipase A2-zeta, Desnutrin, Pigment epithelium-derived factor receptor, TTS2.2, Transport-secretion protein 2, iPLA2-zeta, PEDF-R, TTS2