LIPL_NEOVI
ID LIPL_NEOVI Reviewed; 475 AA.
AC O46647;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Lipoprotein lipase;
DE Short=LPL;
DE EC=3.1.1.34 {ECO:0000250|UniProtKB:P11151};
DE Flags: Precursor;
GN Name=LPL;
OS Neovison vison (American mink) (Mustela vison).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Mustelidae; Mustelinae;
OC Neogale.
OX NCBI_TaxID=452646;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND VARIANT CHYLOMICRONEMIA
RP SYNDROME LEU-241.
RC TISSUE=Heart;
RX PubMed=9852258; DOI=10.3892/ijmm.1.3.529;
RA Lindberg A., Nordstoga K., Christophersen B., Savonen R., van Tol A.,
RA Olivecrona G.;
RT "A mutation in the lipoprotein lipase gene associated with
RT hyperlipoproteinemia type I in mink: studies on lipid and lipase levels in
RT heterozygotes.";
RL Int. J. Mol. Med. 1:529-538(1998).
CC -!- FUNCTION: Key enzyme in triglyceride metabolism. Catalyzes the
CC hydrolysis of triglycerides from circulating chylomicrons and very low
CC density lipoproteins (VLDL), and thereby plays an important role in
CC lipid clearance from the blood stream, lipid utilization and storage
CC (PubMed:9852258). Mediates margination of triglyceride-rich lipoprotein
CC particles in capillaries. Recruited to its site of action on the
CC luminal surface of vascular endothelium by binding to GPIHBP1 and cell
CC surface heparan sulfate proteoglycans (By similarity).
CC {ECO:0000250|UniProtKB:P06858, ECO:0000269|PubMed:9852258}.
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 -!- 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.
CC {ECO:0000269|PubMed:9852258}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
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DR EMBL; AJ223493; CAA11411.1; -; Genomic_DNA.
DR AlphaFoldDB; O46647; -.
DR SMR; O46647; -.
DR ESTHER; musvi-lipli; Lipoprotein_Lipase.
DR Proteomes; UP000694425; 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: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: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..27
FT /evidence="ECO:0000250"
FT CHAIN 28..475
FT /note="Lipoprotein lipase"
FT /id="PRO_0000017777"
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 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 /evidence="ECO:0000250|UniProtKB:P06858"
FT ACT_SITE 183
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT ACT_SITE 268
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
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"
FT VARIANT 241
FT /note="P -> L (in chylomicronemia syndrome; no lipase
FT activity)"
FT /evidence="ECO:0000269|PubMed:9852258"
SQ SEQUENCE 475 AA; 52968 MW; 2F2DBF0090F0FB7C CRC64;
MESKALLLVA LGMWFQSLTA TRGGVAAADR GGDFIDIESK FALRTPEDTA EDTCHLIPGV
TESVANCHFN HSSKTFVVIH GWTVTGMYES WVPKLVAALY KREPDSNVIV VDWLSRAQQH
YPVSAGYTKL VGKDVAKFIN WMAEEFHYPL DNVHLLGYSL GAHAAGIAGS LTNKKVNRIT
GLDPAGPNFE YAEAPSRLSP DDADFVDVLH TFTRGSPGRS IGIQKPVGHV DIYPNGGTFQ
PGCNIGEAIR VIAERGLGDV DQLVKCSHER SIHLFIDSLL NEENPSKAYR CNSKEAFEKG
LCLSCRKNRC NNLGYEINKV RAKRSSKMYL KTRSQMPYKV FHYQVKIHFS GTESDTQTNQ
AFEISLYGTV AESENIPFTL PEVSANKTYS FLIYTEVDIG ELLMLKLKWK SDSYFSWSDW
WSSPGFAIEK IRVKAGETQK KVIFCSREKV SHLQKGKASV VFVKCHDKSL NKKSG
