ID LIPL_SHEEP Reviewed; 478 AA. AC Q29524; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 27-MAR-2024, entry version 143. 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 Ovis aries (Sheep). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Caprinae; Ovis. OX NCBI_TaxID=9940; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Welsh Mountain/Dorset; TISSUE=Adipose tissue; RX PubMed=8439555; DOI=10.1016/0167-4781(93)90286-m; RA Edwards W.D., Daniels S.W., Page R.A., Volpe C.P., Kille P., Sweeney G.E., RA Cryer A.; RT "Cloning and sequencing of a full length cDNA encoding ovine lipoprotein RT lipase."; RL Biochim. Biophys. Acta 1172:167-170(1993). 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 -!- PTM: Tyrosine nitration after lipopolysaccharide (LPS) challenge down- CC regulates the lipase activity. {ECO:0000250|UniProtKB:Q06000}. CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X68308; CAA48384.1; -; mRNA. DR PIR; S29846; S29846. DR RefSeq; NP_001009394.1; NM_001009394.1. DR AlphaFoldDB; Q29524; -. DR SMR; Q29524; -. DR STRING; 9940.ENSOARP00000011504; -. DR ESTHER; sheep-lipli; Lipoprotein_Lipase. DR GlyCosmos; Q29524; 2 sites, No reported glycans. DR PaxDb; 9940-ENSOARP00000011504; -. DR Ensembl; ENSOART00000011666.1; ENSOARP00000011504.1; ENSOARG00000010719.1. DR GeneID; 443408; -. DR KEGG; oas:443408; -. DR CTD; 4023; -. DR eggNOG; ENOG502QQ7P; Eukaryota. DR HOGENOM; CLU_027171_1_0_1; -. DR OMA; IRAQQHY; -. DR OrthoDB; 3428256at2759; -. DR Proteomes; UP000002356; Chromosome 2. DR Bgee; ENSOARG00000010719; Expressed in heart right ventricle and 55 other cell types or tissues. DR GO; GO:1902494; C:catalytic complex; IEA:Ensembl. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0042627; C:chylomicron; IEA:UniProtKB-KW. DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB. 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; IEA:Ensembl. DR GO; GO:0005509; F:calcium ion binding; IEA:Ensembl. DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; ISS:UniProtKB. DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB. DR GO; GO:0004465; F:lipoprotein lipase activity; ISS:UniProtKB. 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:0042803; F:protein homodimerization activity; IEA:Ensembl. DR GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl. DR GO; GO:0004806; F:triglyceride lipase activity; ISS:UniProtKB. DR GO; GO:0071398; P:cellular response to fatty acid; IEA:Ensembl. DR GO; GO:0031670; P:cellular response to nutrient; IEA:Ensembl. DR GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl. DR GO; GO:0034371; P:chylomicron remodeling; ISS:UniProtKB. DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:Ensembl. DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB. DR GO; GO:0055096; P:low-density lipoprotein particle mediated signaling; IEA:Ensembl. DR GO; GO:1904179; P:positive regulation of adipose tissue development; IEA:Ensembl. DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; IEA:Ensembl. DR GO; GO:0010886; P:positive regulation of cholesterol storage; IEA:Ensembl. DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IEA:Ensembl. DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IEA:Ensembl. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl. DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IEA:Ensembl. DR GO; GO:0010890; P:positive regulation of sequestering of triglyceride; IEA:Ensembl. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl. DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl. DR GO; GO:0009749; P:response to glucose; ISS:AgBase. DR GO; GO:0019433; P:triglyceride catabolic process; ISS:UniProtKB. DR GO; GO:0070328; P:triglyceride homeostasis; IEA:Ensembl. DR GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; IEA:Ensembl. DR CDD; cd00707; Pancreat_lipase_like; 1. DR CDD; cd01758; PLAT_LPL; 1. DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1. DR Gene3D; 2.60.60.20; PLAT/LH2 domain; 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 NCBIfam; TIGR03230; lipo_lipase; 1. DR PANTHER; PTHR11610; LIPASE; 1. DR PANTHER; PTHR11610:SF3; LIPOPROTEIN LIPASE; 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; SSF53474; alpha/beta-Hydrolases; 1. DR SUPFAM; SSF49723; Lipase/lipooxygenase domain (PLAT/LH2 domain); 1. DR PROSITE; PS00120; LIPASE_SER; 1. DR PROSITE; PS50095; PLAT; 1. PE 2: Evidence at transcript 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:0000255" FT CHAIN 28..478 FT /note="Lipoprotein lipase" FT /id="PRO_0000017781" FT DOMAIN 344..467 FT /note="PLAT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152" FT REGION 35..56 FT /note="Interaction with GPIHBP1" FT /evidence="ECO:0000250|UniProtKB:P06858" FT REGION 246..269 FT /note="Essential for determining substrate specificity" FT /evidence="ECO:0000250|UniProtKB:P06858" FT REGION 420..424 FT /note="Important for interaction with lipoprotein FT particles" FT /evidence="ECO:0000250|UniProtKB:P06858" FT REGION 433..437 FT /note="Important for heparin binding" FT /evidence="ECO:0000250|UniProtKB:P06858" FT REGION 446..470 FT /note="Interaction with GPIHBP1" FT /evidence="ECO:0000250|UniProtKB:P06858" FT ACT_SITE 162 FT /note="Nucleophile" FT ACT_SITE 186 FT /note="Charge relay system" FT ACT_SITE 271 FT /note="Charge relay system" FT BINDING 197 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P06858" FT BINDING 200 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 BINDING 205 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P06858" FT MOD_RES 124 FT /note="3'-nitrotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q06000" FT MOD_RES 194 FT /note="3'-nitrotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q06000" FT MOD_RES 346 FT /note="3'-nitrotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q06000" FT CARBOHYD 73 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 389 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 57..70 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152" FT DISULFID 246..269 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152" FT DISULFID 294..313 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152" FT DISULFID 305..308 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152" FT DISULFID 448..468 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152" SQ SEQUENCE 478 AA; 53588 MW; 10F41EE1FFB9C882 CRC64; MESKVLLLLA LSVWLQSLTV SRGGLVAADR ITRGKDFRDI ESKFALRTPE DTAEDTCHLI PGVTESVANC HFNHSSKTFV VIHGWTVTGM YESWVPKLVA ALYKREPDSN VIVVDWLSRA QQHYPVSAGY TKLVGQDVAK FMNWMADEFN YPLGNVHLLG YSLGAHAAGI AGSLTNKKVN RITGLDPAGP NFEYAEAPSR LSPDDADFVD VLHTFTRGSP GRSIGIQKPV GHVDIYPNGG TFQPGCNIGE ALRVIAERGL GDVDQLVKCS HERSVHLFID SLLNEENPSK AYRCNSKEAF EKGLCLSCRK NRCNNMGYEI NKVRAKRSSK MYLKTRSQMP YKVFHYQVKI HFSGTESNTY TNQAFEISLY GTVAESENIP FTLPEVSTNK TYSFLLYTEV DIGELLMLKL KWISDSYFSW SNWWSSPGFD IGKIRVKAGE TQKKVIFCSR EKMSYLQKGK SPVIFVKCHD KSLNRKSG //