LIPL_CAVPO
ID LIPL_CAVPO Reviewed; 465 AA.
AC P11153;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 139.
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 Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=3692172; DOI=10.1016/0378-1119(87)90023-0;
RA Enerbaeck S., Semb H., Bengtsson-Olivecrona G., Carlsson P.,
RA Hermansson M.-L., Olivecrona T., Bjursell G.;
RT "Molecular cloning and sequence analysis of cDNA encoding lipoprotein
RT lipase of guinea pig.";
RL Gene 58:1-12(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2612912; DOI=10.1016/0378-1119(89)90513-1;
RA Enerbaeck S., Bjursell G.;
RT "Genomic organization of the region encoding guinea pig lipoprotein lipase;
RT evidence for exon fusion and unconventional splicing.";
RL Gene 84:391-397(1989).
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: High level of expression in expression in
CC adipocytes, heart muscle and mammary gland.
CC {ECO:0000269|PubMed:3692172}.
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; M15483; AAA37046.1; -; mRNA.
DR EMBL; M33381; AAA37039.1; -; Genomic_DNA.
DR EMBL; M33377; AAA37039.1; JOINED; Genomic_DNA.
DR EMBL; M33378; AAA37039.1; JOINED; Genomic_DNA.
DR EMBL; M33379; AAA37039.1; JOINED; Genomic_DNA.
DR EMBL; M33380; AAA37039.1; JOINED; Genomic_DNA.
DR PIR; JS0398; A27330.
DR RefSeq; NP_001166449.1; NM_001172978.1.
DR AlphaFoldDB; P11153; -.
DR SMR; P11153; -.
DR STRING; 10141.ENSCPOP00000003655; -.
DR ESTHER; cavpo-lipli; Lipoprotein_Lipase.
DR ABCD; P11153; 1 sequenced antibody.
DR GeneID; 100135570; -.
DR KEGG; cpoc:100135570; -.
DR CTD; 4023; -.
DR eggNOG; ENOG502QQ7P; Eukaryota.
DR HOGENOM; CLU_027171_1_0_1; -.
DR InParanoid; P11153; -.
DR OrthoDB; 534956at2759; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
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: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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0004806; F:triglyceride lipase activity; ISS:UniProtKB.
DR GO; GO:0034371; P:chylomicron remodeling; ISS:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0019433; P:triglyceride catabolic process; ISS:UniProtKB.
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..17
FT /evidence="ECO:0000255"
FT CHAIN 18..465
FT /note="Lipoprotein lipase"
FT /id="PRO_0000017773"
FT DOMAIN 331..454
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT REGION 233..256
FT /note="Essential for determining substrate specificity"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT REGION 407..411
FT /note="Important for interaction with lipoprotein
FT particles"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT REGION 420..424
FT /note="Important for heparin binding"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT REGION 433..457
FT /note="Interaction with GPIHBP1"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT ACT_SITE 149
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT ACT_SITE 173
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT ACT_SITE 258
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT BINDING 184
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT BINDING 189
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT BINDING 192
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P06858"
FT MOD_RES 111
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q06000"
FT MOD_RES 181
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q06000"
FT MOD_RES 333
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q06000"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 376
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 44..57
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DISULFID 233..256
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DISULFID 281..300
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DISULFID 292..295
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DISULFID 435..455
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
SQ SEQUENCE 465 AA; 52781 MW; E2515F36BEFD5F10 CRC64;
MNIDRKILNK ALAKEKVANC QKDYTDIESK FARRTPENTV EDTCHLIPGV TESVANCHFN
HSSKTFMVIH GWTVTGMYES WVPKLVAALY KREPDSNVIV VDWLRRAQHH YPESADYTKL
VGEDVARFIN WMEDEFKYSV DNVHLLGYSL GAHAAGVAGS RTNTKVSRIT GLDPAGPNFE
YAEATSRLSP DDAQFVDVLH TFTRGSPGRS IGIQKPVGHV DIYPNGGSFQ PGCNIQDALR
VISQKGFGDM DQLVKCSHER SIHLFIDSLL NEENPSKAYR CNSKEAFEKG LCLSCRKNRC
NNVGYEINKV RAKRSSKMYL KTRSQMPYKV FHYQVKIYFS GTETTTYTNQ AFEISLYGTV
AESENIPFTL PEVSANNTYS FLIYTEVDIG ELLMLKLKWI TESYFSWSSW WGRPTFTIEK
IRVKAGETQK KIVFCSREKV SKLQKGKEAP VFVKCHDKSL NKKSG
