ID G3SWM0_LOXAF Unreviewed; 472 AA.
AC G3SWM0;
DT 16-NOV-2011, integrated into UniProtKB/TrEMBL.
DT 16-NOV-2011, sequence version 1.
DT 24-JAN-2024, entry version 81.
DE RecName: Full=Lipoprotein lipase {ECO:0000256|ARBA:ARBA00018617, ECO:0000256|RuleBase:RU362020};
DE Short=LPL {ECO:0000256|RuleBase:RU362020};
DE EC=3.1.1.34 {ECO:0000256|ARBA:ARBA00013181, ECO:0000256|RuleBase:RU362020};
GN Name=LPL {ECO:0000313|Ensembl:ENSLAFP00000004733.3};
OS Loxodonta africana (African elephant).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Afrotheria; Proboscidea; Elephantidae; Loxodonta.
OX NCBI_TaxID=9785 {ECO:0000313|Ensembl:ENSLAFP00000004733.3, ECO:0000313|Proteomes:UP000007646};
RN [1] {ECO:0000313|Ensembl:ENSLAFP00000004733.3, ECO:0000313|Proteomes:UP000007646}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Isolate ISIS603380 {ECO:0000313|Ensembl:ENSLAFP00000004733.3,
RC ECO:0000313|Proteomes:UP000007646};
RA Di Palma F., Heiman D., Young S., Johnson J., Lander E.S., Lindblad-Toh K.;
RT "The Genome Sequence of Loxodonta africana (African elephant).";
RL Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSLAFP00000004733.3}
RP IDENTIFICATION.
RC STRAIN=Isolate ISIS603380 {ECO:0000313|Ensembl:ENSLAFP00000004733.3};
RG Ensembl;
RL Submitted (JUL-2023) to UniProtKB.
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 Mediates margination of triglyceride-rich lipoprotein particles in
CC capillaries. Recruited to its site of action on the luminal surface of
CC vascular endothelium by binding to GPIHBP1 and cell surface heparan
CC sulfate proteoglycans. {ECO:0000256|RuleBase:RU362020}.
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:0000256|ARBA:ARBA00000137,
CC ECO:0000256|RuleBase:RU362020};
CC -!- SUBUNIT: Homodimer. Interacts with APOC2; the interaction activates LPL
CC activity in the presence of lipids. {ECO:0000256|RuleBase:RU362020}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|RuleBase:RU362020};
CC Peripheral membrane protein {ECO:0000256|RuleBase:RU362020};
CC Extracellular side {ECO:0000256|RuleBase:RU362020}. Secreted
CC {ECO:0000256|RuleBase:RU362020}. Secreted, extracellular space,
CC extracellular matrix {ECO:0000256|ARBA:ARBA00004498,
CC ECO:0000256|RuleBase:RU362020}. Note=Newly synthesized LPL binds to
CC cell surface heparan proteoglycans and is then released by heparanase.
CC Subsequently, it becomes attached to heparan proteoglycan on
CC endothelial cells. Locates to the plasma membrane of microvilli of
CC hepatocytes with triglyceride-rich lipoproteins (TRL). Some of the
CC bound LPL is then internalized and located inside non-coated endocytic
CC vesicles. {ECO:0000256|RuleBase:RU362020}.
CC -!- PTM: Tyrosine nitration after lipopolysaccharide (LPS) challenge down-
CC regulates the lipase activity. {ECO:0000256|RuleBase:RU362020}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000256|ARBA:ARBA00010701, ECO:0000256|RuleBase:RU004262}.
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|PROSITE-ProRule:PRU00152}.
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DR AlphaFoldDB; G3SWM0; -.
DR STRING; 9785.ENSLAFP00000004733; -.
DR ESTHER; loxaf-g3swm0; Lipoprotein_Lipase.
DR Ensembl; ENSLAFT00000005641.3; ENSLAFP00000004733.3; ENSLAFG00000005641.3.
DR eggNOG; ENOG502QQ7P; Eukaryota.
DR GeneTree; ENSGT00940000157178; -.
DR HOGENOM; CLU_027171_1_0_1; -.
DR InParanoid; G3SWM0; -.
DR OMA; TIWITLG; -.
DR TreeFam; TF324997; -.
DR Proteomes; UP000007646; Unassembled WGS sequence.
DR GO; GO:1902494; C:catalytic complex; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0042627; C:chylomicron; IEA:UniProtKB-KW.
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:0034185; F:apolipoprotein binding; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IEA:Ensembl.
DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; IEA:Ensembl.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004465; F:lipoprotein lipase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0071813; F:lipoprotein particle binding; IEA:Ensembl.
DR GO; GO:0008970; F:phospholipase A1 activity; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl.
DR GO; GO:0071398; P:cellular response to fatty acid; IEA:Ensembl.
DR GO; GO:0031670; P:cellular response to nutrient; IEA:Ensembl.
DR GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl.
DR GO; GO:0034371; P:chylomicron remodeling; IEA:Ensembl.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:Ensembl.
DR GO; GO:0055096; P:low-density lipoprotein particle mediated signaling; IEA:Ensembl.
DR GO; GO:1904179; P:positive regulation of adipose tissue development; IEA:Ensembl.
DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; IEA:Ensembl.
DR GO; GO:0010886; P:positive regulation of cholesterol storage; IEA:Ensembl.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IEA:Ensembl.
DR GO; GO:0010890; P:positive regulation of sequestering of triglyceride; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR GO; GO:0019433; P:triglyceride catabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0070328; P:triglyceride homeostasis; IEA:Ensembl.
DR GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; IEA:Ensembl.
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; PS50095; PLAT; 1.
PE 3: Inferred from homology;
KW Calcium {ECO:0000256|PIRSR:PIRSR000865-2};
KW Cell membrane {ECO:0000256|ARBA:ARBA00022475,
KW ECO:0000256|RuleBase:RU362020};
KW Chylomicron {ECO:0000256|ARBA:ARBA00022513, ECO:0000256|RuleBase:RU362020};
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157,
KW ECO:0000256|RuleBase:RU362020};
KW Extracellular matrix {ECO:0000256|ARBA:ARBA00022530};
KW Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW Heparin-binding {ECO:0000256|ARBA:ARBA00022674,
KW ECO:0000256|RuleBase:RU362020};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|RuleBase:RU362020};
KW Lipid degradation {ECO:0000256|ARBA:ARBA00022963,
KW ECO:0000256|RuleBase:RU362020};
KW Lipid metabolism {ECO:0000256|RuleBase:RU362020};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|RuleBase:RU362020};
KW Metal-binding {ECO:0000256|PIRSR:PIRSR000865-2};
KW Nitration {ECO:0000256|ARBA:ARBA00023074, ECO:0000256|RuleBase:RU362020};
KW Reference proteome {ECO:0000313|Proteomes:UP000007646};
KW Secreted {ECO:0000256|ARBA:ARBA00022525, ECO:0000256|RuleBase:RU362020};
KW Signal {ECO:0000256|RuleBase:RU362020};
KW VLDL {ECO:0000256|ARBA:ARBA00023313, ECO:0000256|RuleBase:RU362020}.
FT SIGNAL 1..20
FT /evidence="ECO:0000256|RuleBase:RU362020"
FT CHAIN 21..472
FT /note="Lipoprotein lipase"
FT /evidence="ECO:0000256|RuleBase:RU362020"
FT /id="PRO_5005131917"
FT DOMAIN 341..464
FT /note="PLAT"
FT /evidence="ECO:0000259|PROSITE:PS50095"
FT ACT_SITE 159
FT /note="Nucleophile"
FT /evidence="ECO:0000256|PIRSR:PIRSR000865-1"
FT ACT_SITE 183
FT /note="Charge relay system"
FT /evidence="ECO:0000256|PIRSR:PIRSR000865-1"
FT ACT_SITE 268
FT /note="Charge relay system"
FT /evidence="ECO:0000256|PIRSR:PIRSR000865-1"
FT BINDING 197
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000256|PIRSR:PIRSR000865-2"
FT BINDING 202
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000256|PIRSR:PIRSR000865-2"
SQ SEQUENCE 472 AA; 52937 MW; F9E61B6458D82EFF CRC64;
MKSKAVLLVA LGVWLQSLPA SHRGVTAAQG GKDFRNIESK FALRTPEDTV EDTCHLIPGV
TESAANCHFN YSSKTFMVIH GWTVTGMYES WVPKLVAALY KREPDSNVIV VDWLSRAQHH
YPVSAGHTKL VGKDVAQFIN WMEDELNYPP NNVHLLGYSL GAHAAGIAGS LTNKKVNRIT
GLDPAGPNFE YAEAPSRLSP DDADFVDVLH TFTRGSPDRS IGIQKPIGHV DIYPNGGAFQ
PGCNIGEAIR VIAEKGLADV DQLVKCSHER SIHLFIDSLL NEANPSKAYR CNSKEAFDKG
LCLSCRKNRC NNLGYEINKV RTKRNSKMYL KTRSQMPYKV FHYQMKIHFS GTESTTKTNQ
VFEISLYGTL AESENIPVTL PEVSTNKTYS FLIYTEVDVG ELLMMKLKWN SDSYFSWSRW
WSSPTFAIDK IRVKAGETQK KVIFCSRNKV SYLEKGKAPA VFVKCYDRSL NR
//