LIPL_PAPAN
ID LIPL_PAPAN Reviewed; 475 AA.
AC P49060;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 125.
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 Papio anubis (Olive baboon).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Papio.
OX NCBI_TaxID=9555;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Heart muscle;
RX PubMed=7665091; DOI=10.1016/0378-1119(95)00301-l;
RA Cole S.A., Hixson J.E.;
RT "Baboon lipoprotein lipase: cDNA sequence and variable tissue-specific
RT expression of two transcripts.";
RL Gene 161:265-269(1995).
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 -!- TISSUE SPECIFICITY: Highest levels in the spinal cord.
CC {ECO:0000269|PubMed:7665091}.
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}.
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DR EMBL; U18091; AAC50199.1; -; mRNA.
DR RefSeq; NP_001106082.1; NM_001112612.1.
DR AlphaFoldDB; P49060; -.
DR SMR; P49060; -.
DR STRING; 9555.ENSPANP00000015005; -.
DR ESTHER; papan-lipli; Lipoprotein_Lipase.
DR Ensembl; ENSPANT00000075939; ENSPANP00000051087; ENSPANG00000006403.
DR GeneID; 100126663; -.
DR KEGG; panu:100126663; -.
DR CTD; 4023; -.
DR eggNOG; ENOG502QQ7P; Eukaryota.
DR GeneTree; ENSGT00940000157178; -.
DR OrthoDB; 534956at2759; -.
DR Proteomes; UP000028761; Chromosome 8.
DR Bgee; ENSPANG00000006403; Expressed in white adipose tissue and 65 other 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: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 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 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:0000250"
FT CHAIN 28..475
FT /note="Lipoprotein lipase"
FT /id="PRO_0000017778"
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 ACT_SITE 183
FT /note="Charge relay system"
FT ACT_SITE 268
FT /note="Charge relay system"
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:0000250|UniProtKB:Q06000"
FT MOD_RES 191
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q06000"
FT MOD_RES 343
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q06000"
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"
SQ SEQUENCE 475 AA; 53146 MW; 6E4602679C750C91 CRC64;
MESKALLLLA LAVWLQSLTA SRGGVAAADQ RRDFIDIESK FALRTPEDTA EDTCHLIPGV
AESVATCHFN HSSKTFMVIH GWTVTGMYES WVPKLVAALY KREPDSNVIV VDWLSRAQQH
YPVSAGYTKL VGQDVARFIN WMEEEFNYPL DNVHLLGYSL GAHAAGIAGS LTNKKVNRIT
GLDPAGPNFE YAEAPSRLSP DDADFVDVLH TFTRGSPGRS IGIQKPVGHV DIYPNGGTFQ
PGCNIGEAIR VIAERGLGDV DQLVKCSHER SIHLFIDSLL NEENPSKAYR CSSKEAFEKG
LCLSCRKNRC NNLGYEINKV RAKRSSKMYL KTRSQMPYKV FHYQVKIHFS GTESETHTNQ
AFEISLYGTV AESENIPFTL PEVSTNKTYS FLIYTEVDIG ELLMLKLKWK SDSYFSWSDW
WSSPGFAIQK IRVKAGETQK KVIFCSREKV SHLQKGKAPA VFVKCHDKSL NKKSG
