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Identification
HMDB Protein ID HMDBP07347
Secondary Accession Numbers
  • 12969
Name Patatin-like phospholipase domain-containing protein 2
Synonyms
  1. Adipose triglyceride lipase
  2. Calcium-independent phospholipase A2
  3. Desnutrin
  4. IPLA2-zeta
  5. Pigment epithelium-derived factor
  6. TTS2
  7. TTS2.2
  8. Transport-secretion protein 2
Gene Name PNPLA2
Protein Type Enzyme
Biological Properties
General Function Involved in metabolic process
Specific Function Catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets. Also has acylglycerol transacylase activity. May act coordinately with LIPE/HLS within the lipolytic cascade. Regulates adiposome size and may be involved in the degradation of adiposomes. May play an important role in energy homeostasis. 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.
Pathways
  • Glycerolipid metabolism
  • triacylglycerol degradation
Reactions
Triacylglycerol + Water → DG(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0) + a carboxylate details
Triacylglycerol + Water → 1,2-Diacyl-sn-glycerol + Fatty acid details
1,2-Diacyl-sn-glycerol + Water → 1-Acylglycerol + Fatty acid details
GO Classification
Biological Process
small molecule metabolic process
positive regulation of triglyceride catabolic process
negative regulation of sequestering of triglyceride
acylglycerol acyl-chain remodeling
triglyceride catabolic process
glycerophospholipid biosynthetic process
Cellular Component
endoplasmic reticulum membrane
cytosol
plasma membrane
lipid particle
integral to membrane
Molecular Function
retinyl-palmitate esterase activity
triglyceride lipase activity
Process
metabolic process
primary metabolic process
lipid metabolic process
Cellular Location
  1. Cell membrane
  2. Single-pass type II membrane protein
  3. Lipid droplet
Gene Properties
Chromosome Location 11
Locus 11p15.5
SNPs PNPLA2
Gene Sequence
>1515 bp
ATGTTTCCCCGCGAGAAGACGTGGAACATCTCGTTCGCGGGCTGCGGCTTCCTCGGCGTC
TACTACGTCGGCGTGGCCTCCTGCCTCCGCGAGCACGCGCCCTTCCTGGTGGCCAACGCC
ACGCACATCTACGGCGCCTCGGCCGGGGCGCTCACGGCCACGGCGCTGGTCACCGGGGTC
TGCCTGGGTGAGGCTGGTGCCAAGTTCATTGAGGTATCTAAAGAGGCCCGGAAGCGGTTC
CTGGGCCCCCTGCACCCCTCCTTCAACCTGGTAAAGATCATCCGCAGTTTCCTGCTGAAG
GTCCTGCCTGCTGATAGCCATGAGCATGCCAGTGGGCGCCTGGGCATCTCCCTGACCCGC
GTGTCAGACGGCGAGAATGTCATTATATCCCACTTCAACTCCAAGGACGAGCTCATCCAG
GCCAATGTCTGCAGCGGTTTCATCCCCGTGTACTGTGGGCTCATCCCTCCCTCCCTCCAG
GGGGTGCGCTACGTGGATGGTGGCATTTCAGACAACCTGCCACTCTATGAGCTTAAGAAC
ACCATCACAGTGTCCCCCTTCTCGGGCGAGAGTGACATCTGTCCGCAGGACAGCTCCACC
AACATCCACGAGCTGCGGGTCACCAACACCAGCATCCAGTTCAACCTGCGCAACCTCTAC
CGCCTCTCCAAGGCCCTCTTCCCGCCGGAGCCCCTGGTGCTGCGAGAGATGTGCAAGCAG
GGATACCGGGATGGCCTGCGCTTTCTGCAGCGGAACGGCCTCCTGAACCGGCCCAACCCC
TTGCTGGCGTTGCCCCCCGCCCGCCCCCACGGCCCAGAGGACAAGGACCAGGCAGTGGAG
AGCGCCCAAGCGGAGGATTACTCGCAGCTGCCCGGAGAAGATCACATCCTGGAGCACCTG
CCCGCCCGGCTCAATGAGGCCCTGCTGGAGGCCTGCGTGGAGCCCACGGACCTGCTGACC
ACCCTCTCCAACATGCTGCCTGTGCGTCTGGCCACGGCCATGATGGTGCCCTACACGCTG
CCGCTGGAGAGCGCTCTGTCCTTCACCATCCGCTTGCTGGAGTGGCTGCCCGACGTTCCC
GAGGACATCCGGTGGATGAAGGAGCAGACGGGCAGCATCTGCCAGTACCTGGTGATGCGC
GCCAAGAGGAAGCTGGGCAGGCACCTGCCCTCCAGGCTGCCGGAGCAGGTGGAGCTGCGC
CGCGTCCAGTCGCTGCCGTCCGTGCCGCTGTCCTGCGCCGCCTACAGAGAGGCACTGCCC
GGCTGGATGCGCAACAACCTCTCGCTGGGGGACGCGCTGGCCAAGTGGGAGGAGTGCCAG
CGCCAGCTGCTGCTCGGCCTCTTCTGCACCAACGTGGCCTTCCCGCCCGAAGCTCTGCGC
ATGCGCGCACCCGCCGACCCGGCTCCCGCCCCCGCGGACCCAGCATCCCCGCAGCACCAG
CTGGCCGGGCCTGCCCCCTTGCTGAGCACCCCTGCTCCCGAGGCCCGGCCCGTGATCGGG
GCCCTGGGGCTGTGA
Protein Properties
Number of Residues 504
Molecular Weight 55315.245
Theoretical pI 7.084
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Patatin-like phospholipase domain-containing protein 2
MFPREKTWNISFAGCGFLGVYYVGVASCLREHAPFLVANATHIYGASAGALTATALVTGV
CLGEAGAKFIEVSKEARKRFLGPLHPSFNLVKIIRSFLLKVLPADSHEHASGRLGISLTR
VSDGENVIISHFNSKDELIQANVCSGFIPVYCGLIPPSLQGVRYVDGGISDNLPLYELKN
TITVSPFSGESDICPQDSSTNIHELRVTNTSIQFNLRNLYRLSKALFPPEPLVLREMCKQ
GYRDGLRFLQRNGLLNRPNPLLALPPARPHGPEDKDQAVESAQAEDYSQLPGEDHILEHL
PARLNEALLEACVEPTDLLTTLSNMLPVRLATAMMVPYTLPLESALSFTIRLLEWLPDVP
EDIRWMKEQTGSICQYLVMRAKRKLGRHLPSRLPEQVELRRVQSLPSVPLSCAAYREALP
GWMRNNLSLGDALAKWEECQRQLLLGLFCTNVAFPPEALRMRAPADPAPAPADPASPQHQ
LAGPAPLLSTPAPEARPVIGALGL
GenBank ID Protein 32698724
UniProtKB/Swiss-Prot ID Q96AD5
UniProtKB/Swiss-Prot Entry Name PLPL2_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_020376.3
GeneCard ID PNPLA2
GenAtlas ID PNPLA2
HGNC ID HGNC:30802
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Jenkins CM, Mancuso DJ, Yan W, Sims HF, Gibson B, Gross RW: 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 Nov 19;279(47):48968-75. Epub 2004 Sep 10. [PubMed:15364929 ]
  4. Wan D, Gong Y, Qin W, Zhang P, Li J, Wei L, Zhou X, Li H, Qiu X, Zhong F, He L, Yu J, Yao G, Jiang H, Qian L, Yu Y, Shu H, Chen X, Xu H, Guo M, Pan Z, Chen Y, Ge C, Yang S, Gu J: Large-scale cDNA transfection screening for genes related to cancer development and progression. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15724-9. Epub 2004 Oct 21. [PubMed:15498874 ]
  5. Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M, Lass A, Neuberger G, Eisenhaber F, Hermetter A, Zechner R: Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science. 2004 Nov 19;306(5700):1383-6. [PubMed:15550674 ]
  6. Langin D, Dicker A, Tavernier G, Hoffstedt J, Mairal A, Ryden M, Arner E, Sicard A, Jenkins CM, Viguerie N, van Harmelen V, Gross RW, Holm C, Arner P: Adipocyte lipases and defect of lipolysis in human obesity. Diabetes. 2005 Nov;54(11):3190-7. [PubMed:16249444 ]
  7. Lake AC, Sun Y, Li JL, Kim JE, Johnson JW, Li D, Revett T, Shih HH, Liu W, Paulsen JE, Gimeno RE: Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members. J Lipid Res. 2005 Nov;46(11):2477-87. Epub 2005 Sep 8. [PubMed:16150821 ]
  8. Kim JY, Tillison K, Lee JH, Rearick DA, Smas CM: The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by insulin and TNF-alpha in 3T3-L1 adipocytes and is a target for transactivation by PPARgamma. Am J Physiol Endocrinol Metab. 2006 Jul;291(1):E115-27. Epub 2006 May 16. [PubMed:16705060 ]
  9. Smirnova E, Goldberg EB, Makarova KS, Lin L, Brown WJ, Jackson CL: ATGL has a key role in lipid droplet/adiposome degradation in mammalian cells. EMBO Rep. 2006 Jan;7(1):106-13. [PubMed:16239926 ]
  10. Notari L, Baladron V, Aroca-Aguilar JD, Balko N, Heredia R, Meyer C, Notario PM, Saravanamuthu S, Nueda ML, Sanchez-Sanchez F, Escribano J, Laborda J, Becerra SP: Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor. J Biol Chem. 2006 Dec 8;281(49):38022-37. Epub 2006 Oct 10. [PubMed:17032652 ]
  11. Schoenborn V, Heid IM, Vollmert C, Lingenhel A, Adams TD, Hopkins PN, Illig T, Zimmermann R, Zechner R, Hunt SC, Kronenberg F: The ATGL gene is associated with free fatty acids, triglycerides, and type 2 diabetes. Diabetes. 2006 May;55(5):1270-5. [PubMed:16644682 ]
  12. Fischer J, Lefevre C, Morava E, Mussini JM, Laforet P, Negre-Salvayre A, Lathrop M, Salvayre R: The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy. Nat Genet. 2007 Jan;39(1):28-30. Epub 2006 Dec 24. [PubMed:17187067 ]