LIPL_RAT
ID LIPL_RAT Reviewed; 474 AA.
AC Q06000;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Lipoprotein lipase;
DE Short=LPL;
DE EC=3.1.1.34 {ECO:0000250|UniProtKB:P11151};
DE AltName: Full=Phospholipase A1;
DE EC=3.1.1.32 {ECO:0000250|UniProtKB:P06858};
DE Flags: Precursor;
GN Name=Lpl;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=1339374; DOI=10.1016/0378-1119(92)90127-b;
RA Brault D., Noe L., Etienne J., Hamelin J., Raisonnier A., Souli A.,
RA Chuat J.-C., Dugail I., Quignard-Boulange A., Lavau M., Galibert F.;
RT "Sequence of rat lipoprotein lipase-encoding cDNA.";
RL Gene 121:237-246(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 336-474, AND INDUCTION.
RC TISSUE=Heart;
RX PubMed=2233752; DOI=10.1210/mend-4-9-1416;
RA Raynolds M.V., Awald P.D., Gordon D.F., Gutierrez-Hartmann A., Rule D.C.,
RA Wood W.M., Eckel R.H.;
RT "Lipoprotein lipase gene expression in rat adipocytes is regulated by
RT isoproterenol and insulin through different mechanisms.";
RL Mol. Endocrinol. 4:1416-1422(1990).
RN [4]
RP NITRATION AT TYR-121; TYR-191 AND TYR-343, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=19715756; DOI=10.1016/j.freeradbiomed.2009.08.020;
RA Casanovas A., Carrascal M., Abian J., Lopez-Tejero M.D., Llobera M.;
RT "Lipoprotein lipase is nitrated in vivo after lipopolysaccharide
RT challenge.";
RL Free Radic. Biol. Med. 47:1553-1560(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND GLYCOSYLATION.
RX PubMed=19527804; DOI=10.1016/j.jprot.2009.06.002;
RA Casanovas A., Carrascal M., Abian J., Lopez-Tejero M.D., Llobera M.;
RT "Discovery of lipoprotein lipase pI isoforms and contributions to their
RT characterization.";
RL J. Proteomics 72:1031-1039(2009).
CC -!- FUNCTION: Key enzyme in triglyceride metabolism (By similarity).
CC Catalyzes the hydrolysis of triglycerides from circulating chylomicrons
CC and very low density lipoproteins (VLDL), and thereby plays an
CC important role in lipid clearance from the blood stream, lipid
CC utilization and storage (By similarity). Although it has both
CC phospholipase and triglyceride lipase activities it is primarily a
CC triglyceride lipase with low but detectable phospholipase activity (By
CC similarity). Mediates margination of triglyceride-rich lipoprotein
CC particles in capillaries (By similarity). Recruited to its site of
CC action on the luminal surface of vascular endothelium by binding to
CC GPIHBP1 and cell surface heparan sulfate proteoglycans (By similarity).
CC {ECO:0000250|UniProtKB:P06858}.
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=3.1.1.34;
CC Evidence={ECO:0000250|UniProtKB:P11151};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 2-acyl-sn-
CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:18689,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:57875; EC=3.1.1.32;
CC Evidence={ECO:0000250|UniProtKB:P06858};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-
CC octadecenoate + di-(9Z)-octadecenoylglycerol + H(+);
CC Xref=Rhea:RHEA:38575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75945;
CC Evidence={ECO:0000250|UniProtKB:P06858};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38576;
CC Evidence={ECO:0000250|UniProtKB:P06858};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O =
CC (9Z)-octadecenoate + (9Z-octadecenoyl)-sn-glycero-3-phosphocholine +
CC H(+); Xref=Rhea:RHEA:38699, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:74669, ChEBI:CHEBI:76083;
CC Evidence={ECO:0000250|UniProtKB:P06858};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38700;
CC Evidence={ECO:0000250|UniProtKB:P06858};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2,3-tributanoylglycerol + H2O = butanoate +
CC dibutanoylglycerol + H(+); Xref=Rhea:RHEA:40475, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17968, ChEBI:CHEBI:35020,
CC ChEBI:CHEBI:76478; Evidence={ECO:0000250|UniProtKB:P06858};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40476;
CC Evidence={ECO:0000250|UniProtKB:P06858};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) +
CC hexadecanoate + hexadecanoyl-sn-glycero-3-phosphocholine;
CC Xref=Rhea:RHEA:41384, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:64563, ChEBI:CHEBI:72999;
CC Evidence={ECO:0000250|UniProtKB:P06858};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41385;
CC Evidence={ECO:0000250|UniProtKB:P06858};
CC -!- ACTIVITY REGULATION: The apolipoprotein APOC2 acts as a coactivator of
CC LPL activity (By similarity). Ca(2+) binding promotes protein stability
CC and formation of the active homodimer. Interaction with GPIHBP1
CC protects LPL against inactivation by ANGPTL4 (By similarity).
CC {ECO:0000250|UniProtKB:P06858, ECO:0000250|UniProtKB:P11151}.
CC -!- SUBUNIT: Homodimer. Interacts with GPIHBP1 with 1:1 stoichiometry (By
CC similarity). Interacts with APOC2; the interaction activates LPL
CC activity in the presence of lipids (By similarity). Interaction with
CC heparan sulfate proteoglycans is required to protect LPL against loss
CC of activity. Associates with lipoprotein particles in blood plasma.
CC Interacts with LMF1 and SEL1L; interaction with SEL1L is required to
CC prevent aggregation of newly synthesized LPL in the endoplasmic
CC reticulum (ER), and for normal export of LPL from the ER to the
CC extracellular space (By similarity). Interacts with SORL1; SORL1 acts
CC as a sorting receptor, promoting LPL localization to endosomes and
CC later to lysosomes, leading to degradation of newly synthesized LPL (By
CC similarity). {ECO:0000250|UniProtKB:P06858,
CC ECO:0000250|UniProtKB:P11151}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P11151};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P11151};
CC Extracellular side {ECO:0000250|UniProtKB:P11151}. Secreted
CC {ECO:0000250|UniProtKB:P11151}. Secreted, extracellular space,
CC extracellular matrix {ECO:0000250|UniProtKB:P11151}. Note=Newly
CC synthesized LPL binds to cell surface heparan proteoglycans and is then
CC released by heparanase. Subsequently, it becomes attached to heparan
CC proteoglycan on endothelial cells. Locates to the plasma membrane of
CC microvilli of hepatocytes with triglyceride-rich lipoproteins (TRL).
CC Some of the bound LPL is then internalized and located inside non-
CC coated endocytic vesicles. {ECO:0000250|UniProtKB:P11151}.
CC -!- INDUCTION: Induced by insulin. Inhibited by isoproterenol.
CC {ECO:0000269|PubMed:2233752}.
CC -!- PTM: Tyrosine nitration after lipopolysaccharide (LPS) challenge down-
CC regulates the lipase activity. {ECO:0000269|PubMed:19715756}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
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DR EMBL; L03294; AAA41534.1; -; mRNA.
DR EMBL; BC081836; AAH81836.1; -; mRNA.
DR PIR; JH0790; JH0790.
DR RefSeq; NP_036730.1; NM_012598.2.
DR AlphaFoldDB; Q06000; -.
DR SMR; Q06000; -.
DR STRING; 10116.ENSRNOP00000016543; -.
DR BindingDB; Q06000; -.
DR ChEMBL; CHEMBL5906; -.
DR ESTHER; ratno-lipli; Lipoprotein_Lipase.
DR GlyGen; Q06000; 2 sites.
DR jPOST; Q06000; -.
DR PaxDb; Q06000; -.
DR PRIDE; Q06000; -.
DR ABCD; Q06000; 1 sequenced antibody.
DR GeneID; 24539; -.
DR KEGG; rno:24539; -.
DR UCSC; RGD:3017; rat.
DR CTD; 4023; -.
DR RGD; 3017; Lpl.
DR VEuPathDB; HostDB:ENSRNOG00000012181; -.
DR eggNOG; ENOG502QQ7P; Eukaryota.
DR HOGENOM; CLU_027171_1_0_1; -.
DR InParanoid; Q06000; -.
DR OMA; TIWITLG; -.
DR OrthoDB; 534956at2759; -.
DR PhylomeDB; Q06000; -.
DR TreeFam; TF324997; -.
DR BRENDA; 3.1.1.34; 5301.
DR Reactome; R-RNO-8963889; Assembly of active LPL and LIPC lipase complexes.
DR Reactome; R-RNO-8963901; Chylomicron remodeling.
DR Reactome; R-RNO-975634; Retinoid metabolism and transport.
DR PRO; PR:Q06000; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000012181; Expressed in heart and 20 other tissues.
DR Genevisible; Q06000; RN.
DR GO; GO:1902494; C:catalytic complex; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0042627; C:chylomicron; IEA:UniProtKB-KW.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; IEA:UniProtKB-KW.
DR GO; GO:0052740; F:1-acyl-2-lysophosphatidylserine acylhydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0034185; F:apolipoprotein binding; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; ISO:RGD.
DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; ISS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR GO; GO:0016298; F:lipase activity; IBA:GO_Central.
DR GO; GO:0004465; F:lipoprotein lipase activity; IDA:RGD.
DR GO; GO:0071813; F:lipoprotein particle binding; ISS:UniProtKB.
DR GO; GO:0052739; F:phosphatidylserine 1-acylhydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0008970; F:phospholipase A1 activity; ISS:UniProtKB.
DR GO; GO:0004620; F:phospholipase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0017129; F:triglyceride binding; IDA:RGD.
DR GO; GO:0004806; F:triglyceride lipase activity; ISO:RGD.
DR GO; GO:0071398; P:cellular response to fatty acid; ISO:RGD.
DR GO; GO:0031670; P:cellular response to nutrient; ISO:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; ISO:RGD.
DR GO; GO:0034371; P:chylomicron remodeling; ISS:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; ISO:RGD.
DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IDA:RGD.
DR GO; GO:0055096; P:low-density lipoprotein particle mediated signaling; ISO:RGD.
DR GO; GO:1900077; P:negative regulation of cellular response to insulin stimulus; IMP:RGD.
DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; ISO:RGD.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:RGD.
DR GO; GO:0010886; P:positive regulation of cholesterol storage; ISO:RGD.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:RGD.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; ISO:RGD.
DR GO; GO:0010890; P:positive regulation of sequestering of triglyceride; ISO:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR GO; GO:0009409; P:response to cold; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0019432; P:triglyceride biosynthetic process; IMP:RGD.
DR GO; GO:0019433; P:triglyceride catabolic process; ISS:UniProtKB.
DR GO; GO:0070328; P:triglyceride homeostasis; ISO:RGD.
DR GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; ISO:RGD.
DR CDD; cd00707; Pancreat_lipase_like; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR013818; Lipase.
DR InterPro; IPR016272; Lipase_LIPH.
DR InterPro; IPR033906; Lipase_N.
DR InterPro; IPR002330; Lipo_Lipase.
DR InterPro; IPR001024; PLAT/LH2_dom.
DR InterPro; IPR036392; PLAT/LH2_dom_sf.
DR InterPro; IPR000734; TAG_lipase.
DR PANTHER; PTHR11610; PTHR11610; 1.
DR PANTHER; PTHR11610:SF3; PTHR11610:SF3; 1.
DR Pfam; PF00151; Lipase; 1.
DR Pfam; PF01477; PLAT; 1.
DR PIRSF; PIRSF000865; Lipoprotein_lipase_LIPH; 1.
DR PRINTS; PR00822; LIPOLIPASE.
DR PRINTS; PR00821; TAGLIPASE.
DR SMART; SM00308; LH2; 1.
DR SUPFAM; SSF49723; SSF49723; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR TIGRFAMs; TIGR03230; lipo_lipase; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
DR PROSITE; PS50095; PLAT; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Chylomicron; Disulfide bond; Extracellular matrix;
KW Glycoprotein; Heparin-binding; Hydrolase; Lipid degradation;
KW Lipid metabolism; Membrane; Metal-binding; Nitration; Reference proteome;
KW Secreted; Signal; VLDL.
FT SIGNAL 1..27
FT /evidence="ECO:0000250"
FT CHAIN 28..474
FT /note="Lipoprotein lipase"
FT /id="PRO_0000017779"
FT DOMAIN 341..464
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT REGION 32..53
FT /note="Interaction with GPIHBP1"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT REGION 243..266
FT /note="Essential for determining substrate specificity"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT REGION 417..421
FT /note="Important for interaction with lipoprotein
FT particles"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT REGION 430..434
FT /note="Important for heparin binding"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT REGION 443..467
FT /note="Interaction with GPIHBP1"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT ACT_SITE 159
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT ACT_SITE 183
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT ACT_SITE 268
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT BINDING 194
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT BINDING 197
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT BINDING 199
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT BINDING 202
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT MOD_RES 121
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000269|PubMed:19715756"
FT MOD_RES 191
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000269|PubMed:19715756"
FT MOD_RES 343
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000269|PubMed:19715756"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 386
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..67
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DISULFID 243..266
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DISULFID 291..310
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DISULFID 302..305
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DISULFID 445..465
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT CONFLICT 336
FT /note="M -> V (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 474 AA; 53082 MW; F4F6F4BCCA4F1626 CRC64;
MESKALLLVA LGVWLQSLTA FRGGVAAADG GRDFSDIESK FALRTPEDTA EDTCHLIPGL
ADSVSNCHFN HSSKTFVVIH GWTVTGMYES WVPKLVAALY KREPDSNVIV VDWLYRAQQH
YPVSAGYTKL VGNDVARFIN WLEEEFNYPL DNVHLLGYSL GAHAAGVAGS LTNKKVNRIT
GLDPAGPNFE YAEAPSRLSP DDADFVDVLH TFTRGSPGRS IGIQKPVGHV DIYPNGGTFQ
PGCNIGEAIR VIAEKGLGDV DQLVKCSHER SIHLFIDSLL NEENPSKAYR CNSKEAFEKG
LCLSCRKNRC NNVGYEINKV RAKRSSKMYL KTRSQMPYKV FHYQVKIHFS GTENDKQNNQ
AFEISLYGTV AESENIPFTL PEVATNKTYS FLIYTEVDIG ELLMMKLKWK NDSYFRWSDW
WSSPSFVIEK IRVKAGETQK KVIFCAREKV SHLQKGKDAA VFVKCHDKSL KKSG
