PLPL3_MOUSE
ID PLPL3_MOUSE Reviewed; 413 AA.
AC Q91WW7;
DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 25-MAY-2022, entry version 127.
DE RecName: Full=1-acylglycerol-3-phosphate O-acyltransferase Pnpla3 {ECO:0000305|PubMed:22560221};
DE EC=2.3.1.51 {ECO:0000269|PubMed:22560221};
DE AltName: Full=Acylglycerol transacylase {ECO:0000250|UniProtKB:Q9NST1};
DE AltName: Full=Adiponutrin {ECO:0000303|PubMed:22560221};
DE Short=ADPN {ECO:0000303|PubMed:22560221};
DE AltName: Full=Calcium-independent phospholipase A2-epsilon {ECO:0000250|UniProtKB:Q9NST1};
DE Short=iPLA2-epsilon {ECO:0000250|UniProtKB:Q9NST1};
DE EC=3.1.1.4 {ECO:0000250|UniProtKB:Q9NST1};
DE AltName: Full=Lysophosphatidic acid acyltransferase {ECO:0000303|PubMed:22560221};
DE AltName: Full=Patatin-like phospholipase domain-containing protein 3 {ECO:0000250|UniProtKB:Q9NST1};
DE EC=3.1.1.3 {ECO:0000269|PubMed:22560221};
GN Name=Pnpla3 {ECO:0000312|MGI:MGI:2151796}; Synonyms=Adpn;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC STRAIN=SWR/J; TISSUE=Adipose tissue;
RX PubMed=11431482; DOI=10.1074/jbc.m105193200;
RA Baulande S., Lasnier F., Lucas M., Pairault J.;
RT "Adiponutrin, a transmembrane protein corresponding to a novel dietary- and
RT obesity-linked mRNA specifically expressed in the adipose lineage.";
RL J. Biol. Chem. 276:33336-33344(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP CATALYTIC ACTIVITY, FUNCTION, PATHWAY, INDUCTION BY HIGH-SUCROSE DIET,
RP SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF
RP ILE-148, AND TISSUE SPECIFICITY.
RX PubMed=22560221; DOI=10.1016/j.cmet.2012.04.008;
RA Kumari M., Schoiswohl G., Chitraju C., Paar M., Cornaciu I., Rangrez A.Y.,
RA Wongsiriroj N., Nagy H.M., Ivanova P.T., Scott S.A., Knittelfelder O.,
RA Rechberger G.N., Birner-Gruenberger R., Eder S., Brown H.A., Haemmerle G.,
RA Oberer M., Lass A., Kershaw E.E., Zimmermann R., Zechner R.;
RT "Adiponutrin functions as a nutritionally regulated lysophosphatidic acid
RT acyltransferase.";
RL Cell Metab. 15:691-702(2012).
CC -!- FUNCTION: Specifically catalyzes coenzyme A (CoA)-dependent acylation
CC of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to
CC generate phosphatidic acid (PA), an important metabolic intermediate
CC and precursor for both triglycerides and glycerophospholipids. Does not
CC esterify other lysophospholipids. Acyl donors are long chain (at least
CC C16) fatty acyl-CoAs: arachidonoyl-CoA, linoleoyl-CoA, oleoyl-CoA and
CC at a lesser extent palmitoyl-CoA (PubMed:22560221). Additionally
CC possesses low triacylglycerol lipase and CoA-independent acylglycerol
CC transacylase activities and thus may play a role in acyl-chain
CC remodeling of triglycerides (By similarity). Has hydrolytic activity
CC against glycerolipids triacylglycerol, diacylglycerol and
CC monoacylglycerol, with a strong preference for oleic acid as the acyl
CC moiety (By similarity). Possesses phospholipase A2 activity (By
CC similarity). {ECO:0000250|UniProtKB:Q9NST1,
CC ECO:0000269|PubMed:22560221}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-sn-glycero-3-phosphate + an acyl-CoA = a 1,2-diacyl-
CC sn-glycero-3-phosphate + CoA; Xref=Rhea:RHEA:19709,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57970, ChEBI:CHEBI:58342,
CC ChEBI:CHEBI:58608; EC=2.3.1.51;
CC Evidence={ECO:0000269|PubMed:22560221};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a triacylglycerol + H2O = a diacylglycerol + a fatty acid +
CC H(+); Xref=Rhea:RHEA:12044, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.3;
CC Evidence={ECO:0000269|PubMed:22560221};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,3-diacylglycerol + a 1-acylglycerol = a triacylglycerol +
CC glycerol; Xref=Rhea:RHEA:44440, ChEBI:CHEBI:17754, ChEBI:CHEBI:17855,
CC ChEBI:CHEBI:35759, ChEBI:CHEBI:47777;
CC Evidence={ECO:0000250|UniProtKB:Q9NST1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacylglycerol + a 1-acylglycerol = a triacylglycerol +
CC glycerol; Xref=Rhea:RHEA:44436, ChEBI:CHEBI:17754, ChEBI:CHEBI:17855,
CC ChEBI:CHEBI:35759, ChEBI:CHEBI:49172;
CC Evidence={ECO:0000250|UniProtKB:Q9NST1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 a 1-acylglycerol = a 1,2-diacylglycerol + glycerol;
CC Xref=Rhea:RHEA:44432, ChEBI:CHEBI:17754, ChEBI:CHEBI:35759,
CC ChEBI:CHEBI:49172; Evidence={ECO:0000250|UniProtKB:Q9NST1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + 1-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphate = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA;
CC Xref=Rhea:RHEA:37131, ChEBI:CHEBI:57287, ChEBI:CHEBI:57387,
CC ChEBI:CHEBI:74544, ChEBI:CHEBI:74546;
CC Evidence={ECO:0000269|PubMed:22560221};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37132;
CC Evidence={ECO:0000305|PubMed:22560221};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + hexadecanoyl-CoA
CC = 1-(9Z)-octadecenoyl-2-hexadecanoyl-sn-glycero-3-phosphate + CoA;
CC Xref=Rhea:RHEA:37143, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:74544, ChEBI:CHEBI:74551;
CC Evidence={ECO:0000269|PubMed:22560221};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37144;
CC Evidence={ECO:0000305|PubMed:22560221};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoyl-CoA + 1-(9Z-octadecenoyl)-sn-glycero-
CC 3-phosphate = 1-(9Z)-octadecenoyl-2-(9Z,12Z)-octadecadienoyl-sn-
CC glycero-3-phosphate + CoA; Xref=Rhea:RHEA:37159, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57383, ChEBI:CHEBI:74544, ChEBI:CHEBI:74563;
CC Evidence={ECO:0000269|PubMed:22560221};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37160;
CC Evidence={ECO:0000305|PubMed:22560221};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + 1-(9Z-octadecenoyl)-sn-
CC glycero-3-phosphate = 1-(9Z)-octadecenoyl-2-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoyl-sn-glycero-3-phosphate + CoA; Xref=Rhea:RHEA:37443,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57368, ChEBI:CHEBI:74544,
CC ChEBI:CHEBI:74928; Evidence={ECO:0000269|PubMed:22560221};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37444;
CC Evidence={ECO:0000305|PubMed:22560221};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 1-(9Z-octadecenoyl)-glycerol = 1,2-di-(9Z-octadecenoyl)-
CC glycerol + glycerol; Xref=Rhea:RHEA:38323, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:52323, ChEBI:CHEBI:75342;
CC Evidence={ECO:0000250|UniProtKB:Q9NST1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38324;
CC Evidence={ECO:0000250|UniProtKB:Q9NST1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-glycerol + 1-(9Z-octadecenoyl)-
CC glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + glycerol;
CC Xref=Rhea:RHEA:38327, ChEBI:CHEBI:17754, ChEBI:CHEBI:52323,
CC ChEBI:CHEBI:53753, ChEBI:CHEBI:75342;
CC Evidence={ECO:0000250|UniProtKB:Q9NST1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38328;
CC Evidence={ECO:0000250|UniProtKB:Q9NST1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,3-di-(9Z-octadecenoyl)-glycerol + 1-(9Z-octadecenoyl)-
CC glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + glycerol;
CC Xref=Rhea:RHEA:38331, ChEBI:CHEBI:17754, ChEBI:CHEBI:53753,
CC ChEBI:CHEBI:75342, ChEBI:CHEBI:75735;
CC Evidence={ECO:0000250|UniProtKB:Q9NST1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38332;
CC Evidence={ECO:0000250|UniProtKB:Q9NST1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-
CC octadecenoate + 1,3-di-(9Z-octadecenoyl)-glycerol + H(+);
CC Xref=Rhea:RHEA:38387, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75735;
CC Evidence={ECO:0000250|UniProtKB:Q9NST1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38388;
CC Evidence={ECO:0000250|UniProtKB:Q9NST1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-
CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:15801,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=3.1.1.4;
CC Evidence={ECO:0000250|UniProtKB:Q9NST1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802;
CC Evidence={ECO:0000250|UniProtKB:Q9NST1};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12.46 uM for oleoyl-CoA {ECO:0000269|PubMed:22560221};
CC Vmax=3.41 nmol/min/mg enzyme with oleoyl-CoA as acyl donor and 1-
CC oleoyl-sn-glycero-3-phosphate as acyl acceptor
CC {ECO:0000269|PubMed:22560221};
CC -!- PATHWAY: Phospholipid metabolism. {ECO:0000269|PubMed:22560221}.
CC -!- PATHWAY: Glycerolipid metabolism. {ECO:0000269|PubMed:22560221}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:11431482,
CC ECO:0000269|PubMed:22560221}; Single-pass membrane protein
CC {ECO:0000269|PubMed:11431482}. Lipid droplet
CC {ECO:0000269|PubMed:22560221}.
CC -!- TISSUE SPECIFICITY: Restricted to adipose tissue. Expressed in inguinal
CC and epididymal white adipose tissues and in interscapular brown adipose
CC tissue (PubMed:11431482). Also expressed in liver in response to high-
CC sucrose diet (PubMed:22560221). {ECO:0000269|PubMed:11431482,
CC ECO:0000269|PubMed:22560221}.
CC -!- INDUCTION: Up-regulated in response to high-sucrose diet.
CC {ECO:0000269|PubMed:22560221}.
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DR EMBL; AY037763; AAK68636.1; -; mRNA.
DR EMBL; BC028792; AAH28792.1; -; mRNA.
DR RefSeq; NP_473429.2; NM_054088.3.
DR AlphaFoldDB; Q91WW7; -.
DR SMR; Q91WW7; -.
DR STRING; 10090.ENSMUSP00000043826; -.
DR SwissLipids; SLP:000000281; -.
DR GlyGen; Q91WW7; 2 sites.
DR PhosphoSitePlus; Q91WW7; -.
DR PaxDb; Q91WW7; -.
DR PRIDE; Q91WW7; -.
DR ProteomicsDB; 289624; -.
DR DNASU; 116939; -.
DR GeneID; 116939; -.
DR KEGG; mmu:116939; -.
DR UCSC; uc007xbw.1; mouse.
DR CTD; 80339; -.
DR MGI; MGI:2151796; Pnpla3.
DR eggNOG; KOG3773; Eukaryota.
DR InParanoid; Q91WW7; -.
DR OrthoDB; 1204225at2759; -.
DR PhylomeDB; Q91WW7; -.
DR Reactome; R-MMU-1482883; Acyl chain remodeling of DAG and TAG.
DR BioGRID-ORCS; 116939; 2 hits in 76 CRISPR screens.
DR PRO; PR:Q91WW7; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q91WW7; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005811; C:lipid droplet; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; IDA:BHF-UCL.
DR GO; GO:0003841; F:1-acylglycerol-3-phosphate O-acyltransferase activity; IDA:UniProtKB.
DR GO; GO:0051265; F:diolein transacylation activity; ISO:MGI.
DR GO; GO:0036042; F:long-chain fatty acyl-CoA binding; IDA:BHF-UCL.
DR GO; GO:0042171; F:lysophosphatidic acid acyltransferase activity; IDA:BHF-UCL.
DR GO; GO:0035727; F:lysophosphatidic acid binding; IDA:BHF-UCL.
DR GO; GO:0051264; F:mono-olein transacylation activity; ISO:MGI.
DR GO; GO:0004623; F:phospholipase A2 activity; ISS:UniProtKB.
DR GO; GO:0004806; F:triglyceride lipase activity; IDA:BHF-UCL.
DR GO; GO:0006650; P:glycerophospholipid metabolic process; IDA:BHF-UCL.
DR GO; GO:0034389; P:lipid droplet organization; ISO:MGI.
DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IDA:BHF-UCL.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0002021; P:response to dietary excess; IMP:BHF-UCL.
DR GO; GO:0036153; P:triglyceride acyl-chain remodeling; ISO:MGI.
DR GO; GO:0019432; P:triglyceride biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0019433; P:triglyceride catabolic process; IDA:BHF-UCL.
DR CDD; cd07221; Pat_PNPLA3; 1.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR039185; Pat_PNPLA3.
DR InterPro; IPR033562; PLPL.
DR InterPro; IPR002641; PNPLA_dom.
DR PANTHER; PTHR12406; PTHR12406; 1.
DR Pfam; PF01734; Patatin; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR PROSITE; PS51635; PNPLA; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Glycoprotein; Hydrolase; Lipid biosynthesis;
KW Lipid droplet; Lipid metabolism; Membrane; Phospholipid biosynthesis;
KW Phospholipid metabolism; Reference proteome; Signal-anchor; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..413
FT /note="1-acylglycerol-3-phosphate O-acyltransferase Pnpla3"
FT /id="PRO_0000064459"
FT TOPO_DOM 1..42
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 43..63
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 64..413
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 10..179
FT /note="PNPLA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT REGION 389..413
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 14..19
FT /note="GXGXXG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOTIF 45..49
FT /note="GXSXG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOTIF 166..168
FT /note="DGA/G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT ACT_SITE 47
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT ACT_SITE 166
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 148
FT /note="I->M: Increases 1-acylglycerol-3-phosphate O-
FT acyltransferase activity 2-fold; promotes hepatic lipid
FT synthesis."
FT /evidence="ECO:0000269|PubMed:22560221"
SQ SEQUENCE 413 AA; 45772 MW; 7D697E81F66A83C4 CRC64;
MYDPERRWSL SFAGCGFLGF YHVGATLCLS ERAPHLLRDA RTFFGCSAGA LHAVTFVCSL
PLGRIMEILM DLVRKARSRN IGTLHPFFNI NKCIRDGLQE SLPDNVHQVI SGKVHISLTR
VSDGENVLVS EFHSKDEVVD ALVCSCFIPL FSGLIPPSFR GERYVDGGVS DNVPVLDAKT
TITVSPFYGE HDICPKVKST NFFHVNITNL SLRLCTGNLQ LLTRALFPSD VKVMGELCYQ
GYLDAFRFLE ENGICNGPQR SLSLSLVAPE ACLENGKLVG DKVPVSLCFT DENIWETLSP
ELSTALSEAI KDREGYLSKV CNLLPVRILS YIMLPCSLPV ESAIAAVHRL VTWLPDIQDD
IQWLQWATSQ VCARMTMCLL PSTRSRASKD DHRMLKHGHH PSPHKPQGNS AGL
