patatin-like phospholipase domain-containing protein 2 (adipose triglyceride lipase, desnutrin, transport-secretion protein 2, TTS2, TTS2.2, Ca+2-independent phospholipase A2, IPLA2-zeta, pigment epithelium-derived factor, PNPLA2, ATGL, FP17548)

Function

• triglyceride lipolysis
• catalyzes initial step in triglyceride hydrolysis in adipocyte & non-adipocyte lipid droplets
• has acylglycerol transacylase activity
• may act coordinately with LIPE/HLS within the lipolytic cascade
• regulates adiposome size & may be involved in degradation of adiposomes
• role in energy homeostasis (putative)
• role in the response of organism to starvation, enhancing hydrolysis of triglycerides & providing free fatty acids to other tissues to be oxidized in situations of energy depletion
• activated by ABHD5 & SERPINF1
• ATP not essential
• interacts with ABHD5, association stimulates PNPLA2 triglyceride hydrolase activity (putative)
• interacts with SERPINF1
• despite a colocalization in lipid droplets, probably does not interact with PLIN (putative)
• may be phosphorylated (putative)

Triacylglycerol + H2O <--> diacylglycerol + a  carboxylate

Inhibition:

• inhibited by BEL ((E)-6-(bromomethylene)-3-(1-naphthalenyl)- 2H-tetrahydropyran-2-one), a suicide substrate inhibitor

Kinetic parameters:

• Optimum pH is 7.5 (1,2-dilinoleoyl)-phosphatidylcholine as substrate

Structure

contains 1 patatin domain

Compartment

lipid droplet membrane, cell membrane

Alternative splicing

named isoforms=2

Expression

• highest expression in adipose tissue
• detected in heart, skeletal muscle, & portions of the gastrointestinal tract
• detected in normal retina & retinoblastoma cells
• detected in retinal pigment epithelium > inner segments of photoreceptors & ganglion cell layer of the neural retina (at protein level)
• induced during differentiation of primary preadipocytes to adipocytes
• expression increased from fetal to adult in retinal pigment epithelium

Pathology

• genetic variations in PNPLA2 may be associated with risk of diabetes mellitus type 2
• defects in PNPLA2 are the cause of neutral lipid storage disease with myopathy

Polymorphism

• genetic variations in PNPLA2 may be associated with plasma free fatty acids, serum triglycerides levels, & fasting serum glucose concentrations

More general terms

• membrane protein
• glycoprotein
• patatin-like phospholipase domain-containing protein (PNPLA)

Additional terms

• pigment epithelium derived factor (PEDF, EPC-1, SERPINF1)

Database

• UniProt: http://www.uniprot.org/uniprot/Q96AD5.html