ID   LIPL_PIG                Reviewed;         478 AA.
AC   P49923;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   24-JAN-2024, entry version 137.
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   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Norwegian Landrace; TISSUE=Skeletal muscle;
RX   PubMed=1362860; DOI=10.1111/j.1365-2052.1992.tb00170.x;
RA   Harbitz I., Kristensen T., Kran S., Davies W.;
RT   "Isolation and sequencing of porcine lipoprotein lipase cDNA and its use in
RT   multiallelic restriction fragment length polymorphism detection.";
RL   Anim. Genet. 23:517-522(1992).
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}.
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DR   EMBL; X62984; CAA44725.1; -; mRNA.
DR   PIR; I47146; S18158.
DR   RefSeq; NP_999451.1; NM_214286.1.
DR   AlphaFoldDB; P49923; -.
DR   SMR; P49923; -.
DR   STRING; 9823.ENSSSCP00000057312; -.
DR   ESTHER; pig-lipli; Lipoprotein_Lipase.
DR   GlyCosmos; P49923; 2 sites, No reported glycans.
DR   PeptideAtlas; P49923; -.
DR   GeneID; 397537; -.
DR   KEGG; ssc:397537; -.
DR   CTD; 4023; -.
DR   InParanoid; P49923; -.
DR   OrthoDB; 3428256at2759; -.
DR   Proteomes; UP000008227; Unplaced.
DR   Proteomes; UP000314985; Unplaced.
DR   Proteomes; UP000694570; Unplaced.
DR   Proteomes; UP000694571; Unplaced.
DR   Proteomes; UP000694720; Unplaced.
DR   Proteomes; UP000694722; Unplaced.
DR   Proteomes; UP000694723; Unplaced.
DR   Proteomes; UP000694724; Unplaced.
DR   Proteomes; UP000694725; Unplaced.
DR   Proteomes; UP000694726; Unplaced.
DR   Proteomes; UP000694727; Unplaced.
DR   Proteomes; UP000694728; Unplaced.
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; IBA:GO_Central.
DR   GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR   GO; GO:0004465; F:lipoprotein lipase activity; 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:0004620; F:phospholipase activity; IBA:GO_Central.
DR   GO; GO:0004806; F:triglyceride lipase activity; ISS:UniProtKB.
DR   GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR   GO; GO:0009749; P:response to glucose; ISS:AgBase.
DR   GO; GO:0019433; P:triglyceride catabolic process; ISS:UniProtKB.
DR   GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; IBA:GO_Central.
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:0000250"
FT   CHAIN           28..478
FT                   /note="Lipoprotein lipase"
FT                   /id="PRO_0000017780"
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                   /evidence="ECO:0000250|UniProtKB:P06858"
FT   ACT_SITE        186
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT   ACT_SITE        271
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
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;  53455 MW;  D0500324117261E3 CRC64;
     MESKALLLVA LSVWLQSLIV SREGLATADR ISGGRDFTDI ESKFALRTPE DTVEDTCHLI
     PGVTESVANC HFNHSSKTFV VIHGWTVTGM YESWVPKLVA ALYKREPDSN VIVVDWLSRA
     QQHYPISAGY TKLVGQDVAT FIDWMAVEFS YPPNNVHLLG YSLGAHAAGI AGSLTKKKVN
     RITGLDPAGP NFEYAEAPSR LSPDDADFVD VLHTFTRGSP GRSIGIQKPV GHVDIYPNGG
     TFQPGCNIGE AIRVIAERGL GDVDQLVKCS HERSIHLFID SLLNEENPSK AYRCNSKEAF
     EKGLCLSCRK NRCNNLGYEI NKVRAKRSSK MYLKTRAQMP YKVFHYQVKM RFSGTESDTH
     TNQAFEISLY GTVAESENIP FTLPEVSTNK TYSFLIYTEV DIGELLMLKL KWVSDSYFSW
     SNWWSSPGFA IEKIRVKAGE TQKKVIFCSR EKKSHLQKGK SSVVFVKCHD KSLNRKSG
//