LIPL_CHICK
ID LIPL_CHICK Reviewed; 490 AA.
AC P11602;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 165.
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 Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=White leghorn; TISSUE=Adipose tissue;
RX PubMed=2719965; DOI=10.1016/0167-4781(89)90174-7;
RA Cooper D.A., Stein J.C., Strieleman P.J., Bensadoun A.;
RT "Avian adipose lipoprotein lipase: cDNA sequence and reciprocal regulation
RT of mRNA levels in adipose and heart.";
RL Biochim. Biophys. Acta 1008:92-101(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=White leghorn;
RX PubMed=1730055; DOI=10.1016/0167-4781(92)90482-f;
RA Cooper D.A., Lu S.C., Viswanath R., Freiman R.N., Bensadoun A.;
RT "The structure and complete nucleotide sequence of the avian lipoprotein
RT lipase gene.";
RL Biochim. Biophys. Acta 1129:166-171(1992).
RN [3]
RP GLYCOSYLATION AT ASN-70; ASN-354 AND ASN-386, AND STRUCTURE OF
RP CARBOHYDRATES.
RX PubMed=1985932; DOI=10.1016/s0021-9258(17)35281-x;
RA Hoogewerf A.J., Bensadoun A.;
RT "Occurrence of sulfate in an asparagine-linked complex oligosaccharide of
RT chicken adipose lipoprotein lipase.";
RL J. Biol. Chem. 266:1048-1057(1991).
RN [4]
RP HEPARIN-BINDING DOMAIN, AND MUTAGENESIS OF ARG-306; LYS-307; ARG-309;
RP LYS-346; ARG-430; ARG-432; LYS-434; LYS-440 AND LYS-441.
RX PubMed=9643364;
RA Sendak R.A., Bensadoun A.;
RT "Identification of a heparin-binding domain in the distal carboxyl-terminal
RT region of lipoprotein lipase by site-directed mutagenesis.";
RL J. Lipid Res. 39:1310-1315(1998).
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: Ca(2+) binding promotes protein stability and
CC formation of the active homodimer. {ECO:0000250|UniProtKB:P06858}.
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). {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: N-glycan at Asn-70 is a triantennary complex oligosaccharide
CC containing sialic acid, galactose, mannose, and N-acetylglucosamine,
CC the reducing GlcNAc being sulfated at C6. {ECO:0000269|PubMed:1985932}.
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; X14670; CAA32800.1; -; mRNA.
DR EMBL; X60547; CAA43037.1; -; Genomic_DNA.
DR PIR; S04331; S04331.
DR RefSeq; NP_990613.1; NM_205282.1.
DR AlphaFoldDB; P11602; -.
DR SMR; P11602; -.
DR STRING; 9031.ENSGALP00000036979; -.
DR ESTHER; chick-lipli; Lipoprotein_Lipase.
DR iPTMnet; P11602; -.
DR PaxDb; P11602; -.
DR ABCD; P11602; 1 sequenced antibody.
DR Ensembl; ENSGALT00000037774; ENSGALP00000036979; ENSGALG00000015425.
DR GeneID; 396219; -.
DR KEGG; gga:396219; -.
DR CTD; 4023; -.
DR VEuPathDB; HostDB:geneid_396219; -.
DR eggNOG; ENOG502QQ7P; Eukaryota.
DR GeneTree; ENSGT00940000157178; -.
DR HOGENOM; CLU_027171_1_0_1; -.
DR InParanoid; P11602; -.
DR OMA; TIWITLG; -.
DR OrthoDB; 534956at2759; -.
DR PhylomeDB; P11602; -.
DR Reactome; R-GGA-8963889; Assembly of active LPL and LIPC lipase complexes.
DR PRO; PR:P11602; -.
DR Proteomes; UP000000539; Chromosome Z.
DR Bgee; ENSGALG00000015425; Expressed in heart and 12 other tissues.
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:0043395; F:heparan sulfate proteoglycan binding; ISS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR GO; GO:0016298; F:lipase activity; IBA:GO_Central.
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:0004620; F:phospholipase activity; IBA:GO_Central.
DR GO; GO:0004806; F:triglyceride lipase activity; ISS:UniProtKB.
DR GO; GO:0034371; P:chylomicron remodeling; ISS:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IBA:GO_Central.
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; 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..25
FT CHAIN 26..490
FT /note="Lipoprotein lipase"
FT /evidence="ECO:0000269|PubMed:2719965"
FT /id="PRO_0000017782"
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 243..266
FT /note="Essential for determining substrate specificity"
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 REGION 471..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 BINDING 430..441
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000269|PubMed:9643364"
FT MOD_RES 121
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 191
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 343
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:1985932"
FT CARBOHYD 354
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:1985932"
FT CARBOHYD 386
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:1985932"
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 MUTAGEN 306
FT /note="R->Q: Some loss of heparin-binding ability; when
FT associated with Q-307 and Q-309."
FT /evidence="ECO:0000269|PubMed:9643364"
FT MUTAGEN 307
FT /note="K->Q: Some loss of heparin-binding ability; when
FT associated with Q-306 and Q-309."
FT /evidence="ECO:0000269|PubMed:9643364"
FT MUTAGEN 309
FT /note="R->Q: Some loss of heparin-binding ability; when
FT associated with Q-306 and Q-307."
FT /evidence="ECO:0000269|PubMed:9643364"
FT MUTAGEN 346
FT /note="K->N: Reduced heparin-binding ability and some
FT decrease in specific enzymatic activity."
FT /evidence="ECO:0000269|PubMed:9643364"
FT MUTAGEN 430
FT /note="R->N: Reduced heparin-binding ability and some
FT reduction in specific enzymatic activity. Almost complete
FT loss of heparin binding and greatly reduced specific
FT enzymatic activity; when associated with N-432 and N-434."
FT /evidence="ECO:0000269|PubMed:9643364"
FT MUTAGEN 432
FT /note="R->N: Reduced heparin-binding ability. Almost
FT complete loss of heparin binding and greatly reduced
FT specific enzymatic activity; when associated with N-430 and
FT N-434."
FT /evidence="ECO:0000269|PubMed:9643364"
FT MUTAGEN 434
FT /note="K->N: Reduced heparin-binding ability. Almost
FT complete loss of heparin binding and greatly reduced
FT specific enzymatic activity; when associated with N-430 and
FT N-432."
FT /evidence="ECO:0000269|PubMed:9643364"
FT MUTAGEN 440
FT /note="K->N: No change in heparin-binding activity nor in
FT specific enzymatic activity. Reduced heparin-binding
FT activity and decreased specific enzymatic activity; when
FT associated with N-441."
FT /evidence="ECO:0000269|PubMed:9643364"
FT MUTAGEN 441
FT /note="K->N: Reduced heparin-binding activity and decreased
FT specific enzymatic activity. No further reduction of
FT heparin-binding nor of specific enzymatic activity; when
FT associated with N-440."
FT /evidence="ECO:0000269|PubMed:9643364"
FT CONFLICT 377
FT /note="P -> A (in Ref. 2; CAA43037)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 490 AA; 55132 MW; C014D23363E81FF3 CRC64;
MERGRGMGKT ALLAVLCLCL RGAAGSDPEA EMNFEGIESK FSLRTPAEPD EDVCYLVPGQ
MDSLAQCNFN HTSKTFVVIH GWTVTGMYES WVPKLVDALY KREPDSNVIV VDWLVRAQQH
YPVSAAYTKL VGKDVAMFID WMEEKFNYPL NNVHLLGYSL GAHAAGIAGS LTKKKVNRIT
GLDPAGPTFE YADAPIRLSP DDADFVDVLH TYTRGSPDRS IGIQKPVGHI DIYPNGGGFQ
PGCNLGEALR LIAEKGFSDV DQLVKCSHER SIHLFIDSLL YEEKPSMAYR CNTKEAFEKG
LCLSCRKNRC NNLGYKVNRV RTKRNTKMYL KTRAQMPYKV FHYQVKIHFF GKTNVTKVDQ
PFLISLYGTL DESENIPFTL PEVSSNKTFS FLIYTEVDIG DLLMLKLQWE KDTFFSWSDW
WTPFAFTIQR VRVKSGETQK KVVFCSRDGS SRLGKGEEAA IFVKCLEQPV SRKRGGAKKA
SKENSAHESA
