ID H0V2A3_CAVPO Unreviewed; 495 AA.
AC H0V2A3;
DT 22-FEB-2012, integrated into UniProtKB/TrEMBL.
DT 22-NOV-2017, sequence version 2.
DT 27-MAR-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|RuleBase:RU362020};
GN Name=LPL {ECO:0000313|Ensembl:ENSCPOP00000003656.3};
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141 {ECO:0000313|Ensembl:ENSCPOP00000003656.3, ECO:0000313|Proteomes:UP000005447};
RN [1] {ECO:0000313|Proteomes:UP000005447}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=2N {ECO:0000313|Proteomes:UP000005447};
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2] {ECO:0000313|Ensembl:ENSCPOP00000003656.3}
RP IDENTIFICATION.
RC STRAIN=2N {ECO:0000313|Ensembl:ENSCPOP00000003656.3};
RG Ensembl;
RL Submitted (NOV-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=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:0000256|ARBA:ARBA00000652};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38576;
CC Evidence={ECO:0000256|ARBA:ARBA00000652};
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:0000256|ARBA:ARBA00001601};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40476;
CC Evidence={ECO:0000256|ARBA:ARBA00001601};
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:0000256|ARBA:ARBA00001885};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38700;
CC Evidence={ECO:0000256|ARBA:ARBA00001885};
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:0000256|ARBA:ARBA00000879};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41385;
CC Evidence={ECO:0000256|ARBA:ARBA00000879};
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:0000256|ARBA:ARBA00000111};
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 EMBL; AAKN02003214; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; H0V2A3; -.
DR ESTHER; cavpo-lipli; Lipoprotein_Lipase.
DR Ensembl; ENSCPOT00000004099.3; ENSCPOP00000003656.3; ENSCPOG00000004054.4.
DR VEuPathDB; HostDB:ENSCPOG00000004054; -.
DR GeneTree; ENSGT00940000157178; -.
DR HOGENOM; CLU_027171_1_0_1; -.
DR InParanoid; H0V2A3; -.
DR OMA; IRAQQHY; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR Bgee; ENSCPOG00000004054; Expressed in heart and 13 other cell types or tissues.
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:0052740; F:1-acyl-2-lysophosphatidylserine acylhydrolase activity; IEA:UniProtKB-EC.
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:0052739; F:phosphatidylserine 1-acylhydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0008970; F:phospholipase A1 activity; IEA:UniProtKB-EC.
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:UP000005447};
KW Secreted {ECO:0000256|ARBA:ARBA00022525, ECO:0000256|RuleBase:RU362020};
KW Signal {ECO:0000256|ARBA:ARBA00022729};
KW Transmembrane {ECO:0000256|SAM:Phobius};
KW Transmembrane helix {ECO:0000256|SAM:Phobius};
KW VLDL {ECO:0000256|ARBA:ARBA00023313, ECO:0000256|RuleBase:RU362020}.
FT TRANSMEM 12..32
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT DOMAIN 360..483
FT /note="PLAT"
FT /evidence="ECO:0000259|PROSITE:PS50095"
FT ACT_SITE 178
FT /note="Nucleophile"
FT /evidence="ECO:0000256|PIRSR:PIRSR000865-1"
FT ACT_SITE 202
FT /note="Charge relay system"
FT /evidence="ECO:0000256|PIRSR:PIRSR000865-1"
FT ACT_SITE 287
FT /note="Charge relay system"
FT /evidence="ECO:0000256|PIRSR:PIRSR000865-1"
FT BINDING 216
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000256|PIRSR:PIRSR000865-2"
FT BINDING 221
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000256|PIRSR:PIRSR000865-2"
SQ SEQUENCE 495 AA; 56435 MW; 29B5A1C36444CCC2 CRC64;
MSILSLLLCH SYVFFLAYLV QCLFEIIIFQ IWGCDKRINL DKEIRVVFGG KDYTDIESKF
ARRTPENTVE DTCHLIPGVT ESVANCHFNH SSKTFMVIHG WTVTGMYESW VPKLVAALYK
REPDSNVIVV DWLRRAQHHY PESADYTKLV GEDVARFINW MEDEFKYSVD NVHLLGYSLG
AHAAGVAGSR TNTKVSRITG LDPAGPNFEY AEATSRLSPD DAQFVDVLHT FTRGSPGRSI
GIQKPVGHVD IYPNGGSFQP GCNIQDALRV ISQKGFGDMD QLVKCSHERS IHLFIDSLLN
EENPSKAYRC NSKEAFEKGL CLSCRKNRCN NVGYEINKVR AKRSSKMYLK TRSQMPYKVF
HYQVKIYFSG TETTTYTNQA FEISLYGTVA ESENIPFTLP EVSANNTYSF LIYTEVDIGE
LLMLKLKWIT ESYFSWSSWW GRPTFTIEKI RVKAGETQKK IVFCSREKVS KLQKGKEAPV
FVKCHDKSLN KKSGW
//
