PNPLA2
entrez
57104
canonical
uniprot
Q96AD5
canonical
ensembl
ENSG00000177666
resolver
ensp
ENSP00000337701
resolver
genesymbol
PNPLA2
resolver
genesymbol_syn
ATGL
resolver
hgnc
HGNC:30802
resolver
uniprot
O60643
resolver
uniprot
Q5EFF5
resolver
uniprot
Q6XYE5
resolver
uniprot
Q96ET6
resolver
uniprot
Q9NQ61
resolver
uniprot
Q9NQ62
resolver
uniprot_entry
PLPL2_HUMAN
resolver
uniprot_sec
O60643
resolver
uniprot_sec
Q5EFF5
resolver
uniprot_sec
Q6XYE5
resolver
uniprot_sec
Q96ET6
resolver
uniprot_sec
Q9NQ61
resolver
uniprot_sec
Q9NQ62
resolver
activity_regulation
ACTIVITY REGULATION: The triglyceride lipase activity is inhibited by BEL ((E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one), a suicide substrate inhibitor (PubMed:17032652). No differences in the acylglycerol transacylase was detected in the presence or absence of ATP (PubMed:15364929). {ECO:0000269|PubMed:15364929, ECO:0000269|PubMed:17032652}.
uniprot
proteins
amino_acid_sequence
MFPREKTWNISFAGCGFLGVYYVGVASCLREHAPFLVANATHIYGASAGALTATALVTGVCLGEAGAKFIEVSKEARKRFLGPLHPSFNLVKIIRSFLLKVLPADSHEHASGRLGISLTRVSDGENVIISHFNSKDELIQANVCSGFIPVYCGLIPPSLQGVRYVDGGISDNLPLYELKNTITVSPFSGESDICPQDSSTNIHELRVTNTSIQFNLRNLYRLSKALFPPEPLVLREMCKQGYRDGLRFLQRNGLLNRPNPLLALPPARPHGPEDKDQAVESAQAEDYSQLPGEDHILEHLPARLNEALLEACVEPTDLLTTLSNMLPVRLATAMMVPYTLPLESALSFTIRLLEWLPDVPEDIRWMKEQTGSICQYLVMRAKRKLGRHLPSRLPEQVELRRVQSLPSVPLSCAAYREALPGWMRNNLSLGDALAKWEECQRQLLLGLFCTNVAFPPEALRMRAPADPAPAPADPASPQHQLAGPAPLLSTPAPEARPVIGALGL
uniprot
proteins
disease_involvement
DISEASE: Note=Genetic variations in PNPLA2 may be associated with risk of diabetes mellitus type 2. {ECO:0000269|PubMed:16644682}.; DISEASE: Neutral lipid storage disease with myopathy (NLSDM) [MIM:610717]: 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. {ECO:0000269|PubMed:17187067}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.1.3
uniprot
proteins
ec_number
3.1.1.4
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q8BJ56, ECO:0000269|PubMed:15364929, ECO:0000269|PubMed:15550674, ECO:0000269|PubMed:16150821, ECO:0000269|PubMed:16239926, ECO:0000269|PubMed:17032652, ECO:0000269|PubMed:17603008, ECO:0000269|PubMed:28578400, ECO:0000269|PubMed:34903883, ECO:0000269|PubMed:35676490}.
uniprot
proteins
mass_dalton
55316
uniprot
proteins
mutagenesis
MUTAGEN 47; /note="S->A: Reduces rate of lipid hydrolysis; does not affect the localization around the rim of the adiposomes."; /evidence="ECO:0000269|PubMed:16150821, ECO:0000269|PubMed:16239926"; MUTAGEN 92; /note="K->R: Abolished ubiquitination by PEX2."; /evidence="ECO:0000269|PubMed:34903883
uniprot
proteins
pathway_participation
PATHWAY: Glycerolipid metabolism; triacylglycerol degradation.
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000250|UniProtKB:Q8BJ56, ECO:0000269|PubMed:22733971}.; PTM: Ubiquitinated by PEX2 in response to reactive oxygen species (ROS), leading to its degradation (PubMed:34903883). Ubiquitination is stimulated by LDAH (PubMed:28578400). {ECO:0000269|PubMed:28578400, ECO:0000269|PubMed:34903883}.
uniprot
proteins
pubmed
15364929
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15498874
uniprot
proteins
pubmed
15550674
uniprot
proteins
pubmed
16150821
uniprot
proteins
pubmed
16239926
uniprot
proteins
pubmed
16249444
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16644682
uniprot
proteins
pubmed
16705060
uniprot
proteins
pubmed
17032652
uniprot
proteins
pubmed
17187067
uniprot
proteins
pubmed
17603008
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22733971
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23297223
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
26091039
uniprot
proteins
pubmed
28578400
uniprot
proteins
pubmed
34903883
uniprot
proteins
pubmed
35676490
uniprot
proteins
sequence_length
504
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lipid droplet {ECO:0000269|PubMed:16239926, ECO:0000269|PubMed:28578400, ECO:0000269|PubMed:34903883}. Cell membrane {ECO:0000269|PubMed:17032652}; Multi-pass membrane protein {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q8BJ56}.
uniprot
proteins
transmembrane_region
TRANSMEM 9..29; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 43..63; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 138..158; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 330..350; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins