LIPL_FELCA
ID LIPL_FELCA Reviewed; 478 AA.
AC P55031;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 131.
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 Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT CHYLOMICRONEMIA SYNDROME GLY-435, AND
RP FUNCTION.
RX PubMed=8636438; DOI=10.1172/jci118541;
RA Ginzinger D.G., Lewis M.E.S., Ma Y., Jones B.R., Liu G., Jones S.D.;
RT "A mutation in the lipoprotein lipase gene is the molecular basis of
RT chylomicronemia in a colony of domestic cats.";
RL J. Clin. Invest. 97:1257-1266(1996).
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 (PubMed:8636438). 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, ECO:0000269|PubMed:8636438}.
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 -!- DISEASE: Note=Defects in LPL are a cause of chylomicronemia syndrome,
CC also known as type I hyperlipoproteinemia. Animals exhibit reduced body
CC mass, growth rates, and increased stillbirth rates.
CC {ECO:0000269|PubMed:8636438}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
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DR EMBL; U42725; AAB03848.1; -; mRNA.
DR RefSeq; NP_001036032.1; NM_001042567.1.
DR AlphaFoldDB; P55031; -.
DR SMR; P55031; -.
DR STRING; 9685.ENSFCAP00000011284; -.
DR ESTHER; felca-lipli; Lipoprotein_Lipase.
DR GeneID; 727696; -.
DR KEGG; fca:727696; -.
DR CTD; 4023; -.
DR eggNOG; ENOG502QQ7P; Eukaryota.
DR InParanoid; P55031; -.
DR OrthoDB; 534956at2759; -.
DR Proteomes; UP000011712; 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: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:0009749; P:response to glucose; ISS:AgBase.
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 1: Evidence at protein level;
KW Calcium; Cell membrane; Chylomicron; Disease variant; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Heparin-binding; Hydrolase;
KW Hyperlipidemia; Lipid degradation; Lipid metabolism; Membrane;
KW Metal-binding; Nitration; Reference proteome; Secreted; Signal; VLDL.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..478
FT /note="Lipoprotein lipase"
FT /id="PRO_0000017774"
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"
FT VARIANT 435
FT /note="R -> G (in chylomicronemia syndrome)"
FT /evidence="ECO:0000269|PubMed:8636438"
SQ SEQUENCE 478 AA; 53668 MW; F57014446127E8C9 CRC64;
MESKTLFLMA LGIWLQSLTT TRGWVAADDR ITGGRDFIDI ESKFALRTPE DIAEDTCHLI
PGVTESVANC HFNHTSKTFV VIHGWTVTGM YESWVPKLVA APYKREPDSN VIVVDWLSRA
QQHYPVSAGY TKLVGKDVAK FINWMAEEFH YPLDNVHLLG YSLGAHAAGI AGSLTNKKVN
RITGLDPAGP NFEYAEAPSR LSPDDADFVD VLHTFTRGSP GRSIGIQKPV GHVDIYPNGG
TFQPGCNIGE AIRVIAERGL GDVDQLVKCS HERSIHLFID SLLNEENPSK AYRCNSKEAF
EKGLCLSCRK NRCNNLGYEI NKVRAKRSSK MYLKTRSQMP YKVFHYQVKI HFSGTESDTQ
TNQVFEISLY GTVAESENIP FTLPEISANK TYSFLIYTEV DIGELLMLKL KWKSDSYFSW
SDWWSSPGFT IEKIRVKAGE TQKKVIFCSR EKVSHLQKGK ASVVFVKCHD KSLNKKSG
