Lipoprotein_Lipase

Relationship

Family: Lipoprotein_Lipase

Block: L

Parent Family: No family

Comment

Lipoprotein lipase (LPL) is a key enzyme of lipid metabolism that hydrolyses triglycerides, providing free fatty acids for cells and affecting the maturation of circulating lipoproteins. The enzyme is thought to play a role in the development of obesity and atherosclerosis. Defects in LPL are a cause of familial chylomicronemia syndrome (or type I hyperlipoproteinemia) and also of a form of deficiency characterised by hypertriglyceridemia. Familial chylomicronemia is a recessive disorder usually manifesting in childhood. On a normal diet, patients often present with abdominal pain, hepatosplenomegaly, lipemia retinalis, eruptive xanthomata, and massive hypertriglyceridemia, sometimes complicated with acute pancreatitis. Endothelial lipase (encoded by the LIPG gene) regulates the circulating level of high density lipoprotein cholesterol (HDL-C). It can also form a molecular bridge between endothelial cells and lipoproteins or circulating macrophages through interaction with heparan sulfate proteoglycans. This nonenzymatic action can increase cellular lipoprotein uptake and monocyte adhesion and contribute to atherosclerosis. LPL is a secreted glycoprotein that contains five disulfide bonds and requires an endoplasmic reticulum (ER) protein, lipase maturation factor 1 (LMF1), to successfully fold and traffic out of the ER to the Golgi. LPL is sorted into vesicles in an inactive state: helical LPL oligomer. LPL secretion is mediated by Syndecan-1 (SDC1), a heparan sulfate proteoglycan (HSPG). Stored LPL can be secreted into the interstitial space, where it interacts with HSPGs that bind to the multiple heparin binding sites on each LPL molecule . LPL is next bound by glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) and transported into the capillary, where it acts on chylomicrons and very-low-density lipoproteins (VLDLs) to hydrolyze packaged triglycerides and release FFAs. The angiopoietin-like (ANGPTL) family of proteins inhibit LPL in different tissues. Leth-Espensen et al. publish that the intrinsic instability of the hydrolase domain of lipoprotein lipase facilitates its inactivation by ANGPTL4-catalyzed unfolding. Inverse effects of APOC2 and ANGPTL4 on the conformational dynamics of lid-anchoring structures in lipoprotein lipase is published by Kumari et al.

Database

Interpro : IPR000734 Lipase , IPR002330 Lipoprotein lipase , IPR016272 Lipase, LIPH-type , IPR013818 Lipase

PIRSF : No PIRSF

Pdoc : PDOC00110

Pfam : PF00151 Lipase

Prints : PR00821 , PR00822

EC Number : 3.1.1.34

Sequences

Peptide in Fasta
Nucleotide in Fasta
Alignment with Multalin Text only
Seed alignment with MAFFT No colour
Alignment with MAFFT No colour
Dendrogram The dnd file

Structures (6)

Genes Proteins in Lipoprotein_Lipase family (318)

Fragments of genes in Lipoprotein_Lipase family (66)

Structures in Lipoprotein_Lipase family (6)

Substrates in Lipoprotein_Lipase family (3)

Inhibitors in Lipoprotein_Lipase family (7)

References (30)

Title : Angiopoietin-like protein 8: a multifaceted protein instrumental in regulating triglyceride metabolism - Wen_2023_Curr.Opin.Lipidol__
Author(s) : Wen Y , Chen YQ , Konrad RJ
Ref : Curr Opin Lipidol , : , 2023
PubMedID: 37962908

Title : The GPIHBP1-LPL complex and its role in plasma triglyceride metabolism: Insights into chylomicronemia - Jiang_2023_Biomed.Pharmacother_169_115874
Author(s) : Jiang S , Ren Z , Yang Y , Liu Q , Zhou S , Xiao Y
Ref : Biomed Pharmacother , 169 :115874 , 2023
PubMedID: 37951027

Title : The lipoprotein lipase that is shuttled into capillaries by GPIHBP1 enters the glycocalyx where it mediates lipoprotein processing - Song_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2313825120
Author(s) : Song W , Beigneux AP , Weston TA , Chen K , Yang Y , Nguyen LP , Guagliardo P , Jung H , Tran AP , Tu Y , Tran C , Birrane G , Miyashita K , Nakajima K , Murakami M , Tontonoz P , Jiang H , Ploug M , Fong LG , Young SG
Ref : Proc Natl Acad Sci U S A , 120 :e2313825120 , 2023
PubMedID: 37871217

Title : Inverse effects of APOC2 and ANGPTL4 on the conformational dynamics of lid-anchoring structures in lipoprotein lipase - Kumari_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2221888120
Author(s) : Kumari A , Gronnemose AL , Kristensen KK , Winther AL , Young SG , Jorgensen TJD , Ploug M
Ref : Proc Natl Acad Sci U S A , 120 :e2221888120 , 2023
PubMedID: 37094117
Gene_locus related to this paper: human-LPL

Title : Transcriptome-wide association study reveals cholesterol metabolism gene Lpl is a key regulator of cognitive dysfunction - Hu_2022_Front.Mol.Neurosci_15_1044022
Author(s) : Hu W , Liu J , Hu Y , Xu Q , Deng T , Wei M , Lu L , Mi J , Bergquist J , Xu F , Tian G
Ref : Front Mol Neurosci , 15 :1044022 , 2022
PubMedID: 36590920

Title : Lipoprotein Lipase and Its Regulators: An Unfolding Story - Wu_2021_Trends.Endocrinol.Metab_32_48
Author(s) : Wu SA , Kersten S , Qi L
Ref : Trends Endocrinol Metab , 32 :48 , 2021
PubMedID: 33277156
Gene_locus related to this paper: human-LPL

Title : The intrinsic instability of the hydrolase domain of lipoprotein lipase facilitates its inactivation by ANGPTL4-catalyzed unfolding - Leth-Espensen_2021_Proc.Natl.Acad.Sci.U.S.A_118_e2026650118
Author(s) : Leth-Espensen KZ , Kristensen KK , Kumari A , Winther AL , Young SG , Jorgensen TJD , Ploug M
Ref : Proc Natl Acad Sci U S A , 118 : , 2021
PubMedID: 33723082
Gene_locus related to this paper: human-LPL

Title : The structure of helical lipoprotein lipase reveals an unexpected twist in lipase storage - Gunn_2020_Proc.Natl.Acad.Sci.U.S.A_117_10254
Author(s) : Gunn KH , Roberts BS , Wang F , Strauss JD , Borgnia MJ , Egelman EH , Neher SB
Ref : Proc Natl Acad Sci U S A , 117 :10254 , 2020
PubMedID: 32332168
Gene_locus related to this paper: bovin-lipli , human-LPL

Title : GPIHBP1 and Lipoprotein Lipase, Partners in Plasma Triglyceride Metabolism - Young_2019_Cell.Metab_30_51
Author(s) : Young SG , Fong LG , Beigneux AP , Allan CM , He C , Jiang H , Nakajima K , Meiyappan M , Birrane G , Ploug M
Ref : Cell Metab , 30 :51 , 2019
PubMedID: 31269429
Gene_locus related to this paper: human-LPL

Title : GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients - Hu_2019_Elife_8_e47178
Author(s) : Hu X , Matsumoto K , Jung RS , Weston TA , Heizer PJ , He C , Sandoval NP , Allan CM , Tu Y , Vinters HV , Liau LM , Ellison RM , Morales JE , Baufeld LJ , Bayley NA , He L , Betsholtz C , Beigneux AP , Nathanson DA , Gerhardt H , Young SG , Fong LG , Jiang H
Ref : Elife , 8 : , 2019
PubMedID: 31169500

Title : Structure of lipoprotein lipase in complex with GPIHBP1 - Arora_2019_Proc.Natl.Acad.Sci.U.S.A_116_10360
Author(s) : Arora R , Nimonkar AV , Baird D , Wang C , Chiu CH , Horton PA , Hanrahan S , Cubbon R , Weldon S , Tschantz WR , Mueller S , Brunner R , Lehr P , Meier P , Ottl J , Voznesensky A , Pandey P , Smith TM , Stojanovic A , Flyer A , Benson TE , Romanowski MJ , Trauger JW
Ref : Proc Natl Acad Sci U S A , 116 :10360 , 2019
PubMedID: 31072929
Gene_locus related to this paper: human-LPL

Title : Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis - Birrane_2019_Proc.Natl.Acad.Sci.U.S.A_116_1723
Author(s) : Birrane G , Beigneux AP , Dwyer B , Strack-Logue B , Kristensen KK , Francone OL , Fong LG , Mertens HDT , Pan CQ , Ploug M , Young SG , Meiyappan M
Ref : Proc Natl Acad Sci U S A , 116 :1723 , 2019
PubMedID: 30559189
Gene_locus related to this paper: human-LPL

Title : A disordered acidic domain in GPIHBP1 harboring a sulfated tyrosine regulates lipoprotein lipase - Kristensen_2018_Proc.Natl.Acad.Sci.U.S.A_115_E6020
Author(s) : Kristensen KK , Midtgaard SR , Mysling S , Kovrov O , Hansen LB , Skar-Gislinge N , Beigneux AP , Kragelund BB , Olivecrona G , Young SG , Jorgensen TJD , Fong LG , Ploug M
Ref : Proc Natl Acad Sci U S A , 115 :E6020 , 2018
PubMedID: 29899144

Title : Mobility of HSPG-bound LPL explains how LPL is able to reach GPIHBP1 on capillaries - Allan_2017_J.Lipid.Res_58_216
Author(s) : Allan CM , Larsson M , Jung RS , Ploug M , Bensadoun A , Beigneux AP , Fong LG , Young SG
Ref : J Lipid Res , 58 :216 , 2017
PubMedID: 27811232

Title : The acidic domain of the endothelial membrane protein GPIHBP1 stabilizes lipoprotein lipase activity by preventing unfolding of its catalytic domain - Mysling_2016_Elife_5_e12095
Author(s) : Mysling S , Kristensen KK , Larsson M , Beigneux AP , Gardsvoll H , Loren FG , Bensadouen A , Jorgensen TJ , Young SG , Ploug M
Ref : Elife , 5 : , 2016
PubMedID: 26725083

Title : GPIHBP1 missense mutations often cause multimerization of GPIHBP1 and thereby prevent lipoprotein lipase binding - Beigneux_2015_Circ.Res_116_624
Author(s) : Beigneux AP , Fong LG , Bensadoun A , Davies BS , Oberer M , Gardsvoll H , Ploug M , Young SG
Ref : Circulation Research , 116 :624 , 2015
PubMedID: 25387803

Title : The GPIHBP1-LPL complex is responsible for the margination of triglyceride-rich lipoproteins in capillaries - Goulbourne_2014_Cell.Metab_19_849
Author(s) : Goulbourne CN , Gin P , Tatar A , Nobumori C , Hoenger A , Jiang H , Grovenor CR , Adeyo O , Esko JD , Goldberg IJ , Reue K , Tontonoz P , Bensadoun A , Beigneux AP , Young SG , Fong LG
Ref : Cell Metab , 19 :849 , 2014
PubMedID: 24726386

Title : Hippocampal lipoprotein lipase regulates energy balance in rodents - Picard_2014_Mol.Metab_3_167
Author(s) : Picard A , Rouch C , Kassis N , Moulle VS , Croizier S , Denis RG , Castel J , Coant N , Davis K , Clegg DJ , Benoit SC , Prevot V , Bouret S , Luquet S , Le Stunff H , Cruciani-Guglielmacci C , Magnan C
Ref : Mol Metab , 3 :167 , 2014
PubMedID: 24634821

Title : Angiopoietin-like protein 4 inhibition of lipoprotein lipase: evidence for reversible complex formation - Lafferty_2013_J.Biol.Chem_288_28524
Author(s) : Lafferty MJ , Bradford KC , Erie DA , Neher SB
Ref : Journal of Biological Chemistry , 288 :28524 , 2013
PubMedID: 23960078
Gene_locus related to this paper: human-LPL

Title : Assessing mechanisms of GPIHBP1 and lipoprotein lipase movement across endothelial cells - Davies_2012_J.Lipid.Res_53_2690
Author(s) : Davies BS , Goulbourne CN , Barnes RH, 2nd , Turlo KA , Gin P , Vaughan S , Vaux DJ , Bensadoun A , Beigneux AP , Fong LG , Young SG
Ref : J Lipid Res , 53 :2690 , 2012
PubMedID: 23008484
Gene_locus related to this paper: human-LPL

Title : Mutations in lipoprotein lipase that block binding to the endothelial cell transporter GPIHBP1 - Voss_2011_Proc.Natl.Acad.Sci.U.S.A_108_7980
Author(s) : Voss CV , Davies BS , Tat S , Gin P , Fong LG , Pelletier C , Mottler CD , Bensadoun A , Beigneux AP , Young SG
Ref : Proc Natl Acad Sci U S A , 108 :7980 , 2011
PubMedID: 21518912
Gene_locus related to this paper: human-LPL

Title : GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries - Davies_2010_Cell.Metab_12_42
Author(s) : Davies BS , Beigneux AP , Barnes RH, 2nd , Tu Y , Gin P , Weinstein MM , Nobumori C , Nyren R , Goldberg I , Olivecrona G , Bensadoun A , Young SG , Fong LG
Ref : Cell Metab , 12 :42 , 2010
PubMedID: 20620994

Title : Association of lipoprotein lipase D9N polymorphism with myocardial infarction in type 2 diabetes: the genetics, outcomes, and lipids in type 2 diabetes (GOLD) study - Izar_2009_Atherosclerosis_204_165
Author(s) : Izar MC , Helfenstein T , Ihara SS , Relvas WG , Santos AO , Fischer SC , Pinto LE , Lopes IE , Pomaro DR , Fonseca MI , Bodanese LC , Moriguchi EH , Saraiva JF , Introcaso L , Souza AD , Scartezini M , Torres KP , Zagury L , Jardim PC , Costa EA , Tacito LH , Forti A , Magalhaes ME , Chacra AR , Bertolami MC , Loures-Vale AA , Barros MA , Xavier HT , Lyra R , Argamanijan D , Guimaraes A , Novazzi JP , Kasinski N , Afiune A , Martinez TL , Santos RD , Nicolau JC , Cesar LA , Povoa RM , Carvalho AC , Han SW , Fonseca FA
Ref : Atherosclerosis , 204 :165 , 2009
PubMedID: 18823627
Gene_locus related to this paper: human-LPL

Title : Cloning of a unique lipase from endothelial cells extends the lipase gene family. -
Author(s) : Hirata K , Dichek HL , Cioffi JA , Choi SY , Leeper NJ , Quintana L , Kronmal GS , Cooper AD , Quertermous T
Ref : Journal of Biological Chemistry , 274 :14170 , 1999
PubMedID: 10318835
Gene_locus related to this paper: human-LIPG , mouse-Lipg

Title : A novel endothelial-derived lipase that modulates HDL metabolism - Jaye_1999_Nat.Genet_21_424
Author(s) : Jaye M , Lynch KJ , Krawiec J , Marchadier D , Maugeais C , Doan K , South V , Amin D , Perrone M , Rader DJ
Ref : Nat Genet , 21 :424 , 1999
PubMedID: 10192396
Gene_locus related to this paper: human-LIPG

Title : Lipoprotein lipase. Molecular model based on the pancreatic lipase x-ray structure: consequences for heparin binding and catalysis - van Tilbeurgh_1994_J.Biol.Chem_269_4626
Author(s) : van Tilbeurgh H , Roussel A , Lalouel JM , Cambillau C
Ref : Journal of Biological Chemistry , 269 :4626 , 1994
PubMedID: 8308035

Title : Lipoprotein lipase enhances the interaction of low density lipoproteins with artery-derived extracellular matrix proteoglycans - Edwards_1993_J.Lipid.Res_34_1155
Author(s) : Edwards IJ , Goldberg IJ , Parks JS , Xu H , Wagner WD
Ref : J Lipid Res , 34 :1155 , 1993
PubMedID: 8371063

Title : Lipoprotein lipase enhances binding of lipoproteins to heparan sulfate on cell surfaces and extracellular matrix - Eisenberg_1992_J.Clin.Invest_90_2013
Author(s) : Eisenberg S , Sehayek E , Olivecrona T , Vlodavsky I
Ref : J Clinical Investigation , 90 :2013 , 1992
PubMedID: 1430223

Title : A missense mutation at codon 188 of the human lipoprotein lipase gene is a frequent cause of lipoprotein lipase deficiency in persons of different ancestries - Monsalve_1990_J.Clin.Invest_86_728
Author(s) : Monsalve MV , Henderson H , Roederer G , Julien P , Deeb S , Kastelein JJ , Peritz L , Devlin R , Bruin T , Murthy MR , et al.
Ref : J Clinical Investigation , 86 :728 , 1990
PubMedID: 1975597
Gene_locus related to this paper: human-LPL

Title : Human lipoprotein lipase complementary DNA sequence - Wion_1987_Science_235_1638
Author(s) : Wion KL , Kirchgessner TG , Lusis AJ , Schotz MC , Lawn RM
Ref : Science , 235 :1638 , 1987
PubMedID: 3823907
Gene_locus related to this paper: human-LPL