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   24-JAN-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   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.ENSCPOP00000003656; -.
DR   ESTHER; cavpo-lipli; Lipoprotein_Lipase.
DR   GlyCosmos; P11153; 2 sites, No reported glycans.
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; 3428256at2759; -.
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   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..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
//