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FLASH GENE
Symbol PNPLA2 contributors: mct/npt/pgu - updated : 23-06-2017
HGNC name patatin-like phospholipase domain containing 2
HGNC id 30802
Corresponding disease
NLSDM neutral lipid storage disease without ichthyosis but with mild myopathy
Location 11p15.5      Physical location : 818.900 - 825.569
Synonym name
  • adipose triglyceride lipase
  • desnutrin
  • transport-secretion protein 2.2
  • pigment epithelium-derived factor receptor
  • triglyceride hydrolase
    • Synonym symbol(s) TTS-2.2, ATGL, iPLA2zeta, TTS2, PEDF-R, FP17548, DKFZp667M109
    EC.number 3.1.1.3
    DNA
    TYPE functioning gene
    STRUCTURE 6.67 kb     10 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 2443 55.2 504 - 2008 19029121
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Endocrineneuroendocrinepituitary  highly
    Hearing/Equilibriumear   highly
    Reproductivemale systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadiposebrown   Homo sapiens
    Connectiveadiposewhite   Homo sapiens
    Muscularstriatumskeletal   Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal patatin domain with a glycine-rich region, lipase domain that interacts with two C-terminal domains of GBF1, HDS (Homology downstream of Sec7) 1 and HDS2
  • a GXSXG serine hydrolase motif that is part of the catalytic dyad essential for lipase activit
  • an aspartate active site motif
  • a esterase of the alpha/beta hydrolase fold domain
  • four transmembrane domains interrupted by two extracellular loops and three intracellular regions along its polypeptide sequence
  • C-terminal region interacts with N-terminal domains of GBF1, including the catalytic Sec7 domain, but not with full-length GBF1 or its entire N-terminus , C-terminus domain whose hydrophobic portion is required for binding to lipid droplets (LDs)
    • HOMOLOGY
    interspecies homolog to murine Atgl
    Homologene
    FAMILY
  • patatin-like phospholipase family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    text associated with lipid droplets of adipocytes
    basic FUNCTION
  • having a catalytic activity and nutrient reservoir activity and responsible for the initial step in triglycerides catabolism and having a possible contribution to the pathophysiology of obesity
  • important component of the lipolytic process and the mobilization of lipid stores
  • adipocyte protein that may function as a lipase and play a role in the adaptive response to a low energy state, such as fasting, by providing fatty acids to other tissues for oxidation
  • participating in triacylglycerol hydrolysis and the acyl-CoA independent transacylation of acylglycerols, thereby facilitating energy mobilization and storage in adipocytes
  • playing an essential role in the metabolism of lipid droplets in the muscle
  • adipose triglyceride lipase involved in the degradation of intracellular triglycerides
  • lipid hydrolase with diverse substrate specificities such as triacylglycerol hydrolases, phospholipases, and a retinylester hydrolase
  • adipocyte-specific protein with lipid hydrolase activity
  • its activity is required for proper energy supply of the skeletal muscle during exercise
  • acts in retinal differentiation, survival and maintenance by interacting with high affinity receptors on the surface of target cells
  • crucial role for CIDEC-PNPLA2 interactions in regulating lipolysis, triglyceride accumulation, and insulin signaling in human adipocytes
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
    a component
  • component of the retina that is a phospholipase-linked membrane protein with high affinity for SERPINF1
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with FOXO1 (FOXO1 may play an important role in the regulation of lipolysis in adipocytes by controlling the expression of PNPLA2)
  • C-terminal 64 AAs of PLIN5 are critical for the differential binding of PNPLA2 to PLIN5 and PLIN1
  • interacting with SIRT1 (SIRT1 controls PNPLA2 transcription primarily by deacetylating FOXO1)
  • GBF1 and PNPLA2 interact directly and in cells, through multiple contact sites on each protein (interaction that may be involved in the membrane trafficking pathway mediated by GBF1, Arf1 and COPI, contributing to the localization of ATGL to lipid droplets)
  • regulates both basal and stimulated lipolysis by interacting with adipose triglyceride lipase PNPLA2
  • PDCD1 promotes fatty acid beta-oxidation (FAO) of endogenous lipids by increasing expression of CPT1A, and inducing lipolysis as indicated by elevation of the lipase PNPLA2, the lipolysis marker glycerol and release of fatty acids
  • COP1 binds to the consensus VP motif of PNPLA2 and targets it for proteasomal degradation by K-48 linked polyubiquitination
    • cell & other
    REGULATION
    induced by by fasting and glucocorticoids
    Phosphorylated by phosphorylated/activated by AMPK to increase lipolysis and brings fatty acid oxidation and UCP1 induction for thermogenesis
    ASSOCIATED DISORDERS
    corresponding disease(s) NLSDM
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    decreases intracellular triglyceride levels
    constitutional       gain of function
    by fasting in adipose tissue
    constitutional     --over  
    is sufficient to alter myocardial energy metabolism and improve cardiac function
    constitutional     --other  
    altered PNPLA2 and LIPE expression in skeletal muscle could promote diacylglycerol accumulation and disrupt insulin signaling and action
    constitutional     --over  
    LIPE or PNPLA2 overexpression resulted in increased triglyceride-specific hydrolase capacity, but only PNPLA2 overexpression increased whole cell lipolysis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    pharmacological inhibition of lipases LIPE and PNPLA2) may represent a powerful strategy to avoid the devastating condition of cachexia in response to cancer or other chronic diseases
    ANIMAL & CELL MODELS
  • Atgl-/- mice were protected from tumor-associated skeletal muscle loss
  • Mice deficient for adipose triglyceride lipase (ATGL-ko) exhibit defective lipolysis and accumulate TG in adipose tissue and muscle