PNPLA3: Difference between revisions

'''Patatin-like phospholipase domain-containing protein 3''' (PNPLA3), also knowsknown as '''adiponutrin''' (ADPN), '''acylglycerol O-acyltransferase''' or '''calcium-independent phospholipase A2-epsilon''' (iPLA2-epsilon) is an [[enzyme]] that in humans is encoded by the ''PNPLA3'' [[gene]].<ref name="pmid16799181">{{cite journal | authorvauthors = Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ | title = Characterization of the human patatin-like phospholipase family | journal = JJournal of Lipid ResResearch | volume = 47 | issue = 9 | pages = 1940–9 | yeardate = September 2006 | month = Aug | pmid = 16799181 | pmc = | doi = 10.1194/jlr.M600185-JLR200 | doi-access = free }}</ref><ref name="pmid19029121">{{cite journal | authorvauthors = Kienesberger PC, Oberer M, Lass A, Zechner R | title = Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions | journal = JJournal of Lipid ResResearch | volume = 50 Suppl | issuepages = S63-8 | pagesdate = S63–8 | year =April 2009 | monthissue = AprSuppl | pmid = 19029121 | pmc = 2674697 | doi = 10.1194/jlr.R800082-JLR200 |doi-access=free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PNPLA3 patatin-like phospholipase domain containing 3| url = httphttps://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=80339| accessdate = }}</ref>

Adiponutrin is a triacylglycerol [[lipase]] that mediates [[triacylglycerol]] hydrolysis in [[adipocyte]]s. The encoded protein, which appears to be membrane bound, may be involved in the balance of energy usage/storage in adipocytes.<ref name="entrez">{{cite web | title = Entrez Gene: PNPLA3 patatin-like phospholipase domain containing 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=80339| accessdate = }}</ref>

The gene is located on the long arm of [[chromosome 22]] at band 13.31 (22q13.31). It lies on the Watson (plus) strand and is 40,750 bases in lenghlength.

Upstream of the gene, putaiveputative binding sites for several transcription factors have been identified. These include [[PPAR-gamma]], [[POU2F1]], and [[Oct-2|POU2F2]]. IfIt is not known at present whether any of these transcriptions factors are actually involved in the regulation of this gene is not known at present.

The recommended name for the gene product is ''patatin-like phospholipase domain-containing protein 3''. It is a Singlesingle-pass type II membrane protein and is a multifunctional enzyme with both triacylglycerol lipase and acylglycerol O-acyltransferase activities. It is involved in the triacylglycerol hydrolysis in adipocytes and may play a role in energy metabolism.

The mature protein is 481 amino acids in length and the predicted molecular weight is 52.865 kiloDaltonskilodaltons (kDa). Two of the isoforms have been described, but the functional signifcance -significance (if any -) of these forms is not known.

==Clinical relevencerelevance==

An association between alcoholic liver disease in [[Caucasian race|caucasian]]s and variations in this gene has been reportedconfirmed.<ref name="pmid21140471pmid22110053">{{cite journal | authorvauthors = Stickel F, BuchHampe S,J Lau| K,title Zu= SchwabedissenGenetic HM,determinants Bergof T,alcoholic Ridingerliver M,disease Rietschel| M,journal Schafmayer= C,Gut Braun| F,volume Hinrichsen= H,61 Günther| R,issue Arlt= A,1 Seeger| M,pages Müller= S,150–9 Seitz| HK,date Soyka= M,January Lerch2012 M,| Lammertpmid F,= Sarrazin22110053 C,| Kubitzdoi R,= Häussinger10.1136/gutjnl-2011-301239 D,| Hellerbrands2cid C,= Bröring22559086 D,}}</ref> Schreiber S,A Kiefermutation F,of Spanagelisoleucine R,to Mannmethionine K,(I[ATC]>M[ATG]) DatzSNP C,rs738409 Krawczakhas M,been Wodarzconfirmed N,to Völzkeincrease H,susceptibility Hampeto Jnon-alcoholic |liver titledisease =and Geneticalso variationto have effects in thediabetes.<ref PNPLA3name="pmid29935383">{{cite genejournal is| associatedvauthors with= alcoholicPingitore liverP, injuryRomeo S | title = The role of PNPLA3 in caucasianshealth and disease | journal = HepatologyBiochimica |et volumeBiophysica =Acta (BBA) - Molecular and Cell Biology of Lipids | issuevolume = 1864 | pagesissue = 6 | yearpages = 2010900–906 | monthdate = SeptemberJune 2019 | pmid = 2114047129935383 | doi = 10.10021016/hepj.24017bbalip.2018.06.018 | urls2cid = | issn =49392249 }}</ref>

== References ==

== Further reading ==

* {{cite journal | authorvauthors = Dunham I, Shimizu N, Roe BA, ''etChissoe al.'S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP | title = The DNA sequence of human chromosome 22. | journal = Nature | volume = 402 | issue = 6761 | pages = 489–95 |year date = December 1999 | pmid = 10591208 | doi = 10.1038/990031 | bibcode = 1999Natur.402..489D | doi-access = free }}

* {{cite journal | authorvauthors =Strausberg RLCollins JE, FeingoldGoward EAME, GrouseCole LHCG, ''etSmink al.''LJ, |title=GenerationHuckle andEJ, initialKnowles analysisS, ofBye moreJM, thanBeare 15DM,000 full-lengthDunham I | title = Reevaluating human andgene mouseannotation: cDNAa sequences.second-generation analysis of chromosome 22 | journal =Proc. Natl.Genome Acad. Sci. U.S.A.Research | volume =99 13 | issue = 261 | pages = 16899–90327–36 |year date = January 2003 | pmid = 1247793212529303 | pmc = 430954 | doi = 10.10731101/pnasgr.242603899 | pmc=139241695703 }}

* {{cite journal | authorvauthors =Collins JELiu YM, GowardMoldes MEM, ColeBastard CGJP, ''etBruckert al.''E, Viguerie N, Hainque B, Basdevant A, Langin D, Pairault J, Clément K | title =Reevaluating humanAdiponutrin: A new gene annotation:regulated aby second-generationenergy analysisbalance ofin chromosomehuman 22.adipose tissue | journal =Genome Res.The Journal of Clinical Endocrinology and Metabolism | volume =13 89 | issue = 16 | pages = 27–362684–9 |year date = 2003June 2004 | pmid = 1252930315181042 | doi = 10.11011210/grjc.695703 2003-031978 | pmcdoi-access =430954 free }}

* {{cite journal | authorvauthors =Liu YMJenkins CM, MoldesMancuso MDJ, BastardYan JPW, ''etSims al.''HF, Gibson B, Gross RW | title =Adiponutrin: AIdentification, newcloning, geneexpression, regulatedand bypurification energyof balancethree innovel human adiposecalcium-independent tissue.phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities | journal =J. Clin.The Endocrinol.Journal Metab.of Biological Chemistry | volume =89 279 | issue = 647 | pages = 2684–948968–75 |year date = November 2004 | pmid = 1518104215364929 | doi = 10.12101074/jcjbc.2003M407841200 | doi-031978access = free }}

* {{cite journal | authorvauthors =Jenkins CMCollins JE, MancusoWright DJCL, YanEdwards WCA, ''etDavis al.''MP, |title=IdentificationGrinham JA, cloningCole CG, expressionGoward ME, andAguado purificationB, ofMallya threeM, novelMokrab humanY, calcium-independentHuckle phospholipaseEJ, A2Beare familyDM, membersDunham possessingI triacylglycerol| lipasetitle and= acylglycerolA transacylasegenome activities.annotation-driven approach to cloning the human ORFeome | journal =J. Biol.Genome Chem.Biology | volume =279 5 | issue = 4710 | pages = 48968–75R84 | year = 2005 | pmid = 1536492915461802 | pmc = 545604 | doi = 10.10741186/jbc.M407841200gb-2004-5-10-r84 | doi-access = free }}

* {{cite journal | authorvauthors =Collins Lake AC, Sun Y, Li JL, Kim JE, WrightJohnson CLJW, EdwardsLi CAD, ''etRevett al.''T, Shih HH, Liu W, Paulsen JE, Gimeno RE | title =A genomeExpression, annotation-drivenregulation, approachand totriglyceride cloninghydrolase theactivity humanof ORFeome.Adiponutrin family members | journal =Genome Biol.Journal of Lipid Research | volume =5 46 | issue = 1011 | pages = R842477–87 |year date = November 2005 | pmid = 1546180216150821 | doi = 10.11861194/gb-2004jlr.M500290-5-10-r84 JLR200 | pmcdoi-access =545604 free }}

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