Recombinant Human Patatin-like phospholipase domain-containing protein 2 (PNPLA2)

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)

Subcellular Location

Lipid droplet; Cell membrane (Multi-pass membrane protein); Cytoplasm

Disease Association

[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. [The disease is caused by variants affecting the gene represented in this entry]

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)

Subunit

Interacts with ABHD5; this association stimulates PNPLA2 triglyceride hydrolase activity (By similarity). Interacts with SERPINF1; this interaction stimulates the phospholipase A2 activity of PNPLA2 (PubMed:17032652). Despite a colocalization in lipid droplets, it probably does not interact with PLIN (By similarity). Interacts with PLIN5; prevents interaction with ABHD5 (By similarity). Interacts with FAF2 (PubMed:23297223)

Pathway

Glycerolipid metabolism; triacylglycerol degradation

• Zimmermann R. et al. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. — Science (2004)
• Strahl T. et al. TTS-2, a novel protein implicated in vesicular transport of the cell surface receptor ICAM-3. (JUN-)
• Wan D. et al. Large-scale cDNA transfection screening for genes related to cancer development and progression. — Proc. Natl. Acad. Sci. U.S.A. (2004)
• Taylor T.D. et al. Human chromosome 11 DNA sequence and analysis including novel gene identification. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Yu W. et al. PubMed: CI-60FCUVGGQO9DA (MAR-)
• Jenkins C.M. et al. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. — J. Biol. Chem. (2004)
• Langin D. et al. Adipocyte lipases and defect of lipolysis in human obesity. — Diabetes (2005)