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Gene_locus Report for: human-LPL

Homo sapiens (Human) Lipoprotein lipase LPL, LIPD

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. LPL hydrolyse triglycerides of circulating chylomicrons and very low density lipoproteins (VLDL). Binding to heparin sulfate proteogylcans at the cell surface is vital to the function. The apolipoprotein, APOC2, acts as a coactivator of LPL activity in the presence of lipids on the luminal surface of vascular endothelium. LPL interacts with accessory protein glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1). 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.


Relationship
Family|Lipoprotein_Lipase
Block| L
Position in NCBI Life Tree|Homo sapiens
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.)
> cellular organisms: N E > Eukaryota: N E > Opisthokonta: N E > Metazoa: N E > Eumetazoa: N E > Bilateria: N E > Deuterostomia: N E > Chordata: N E > Craniata: N E > Vertebrata: N E > Gnathostomata: N E > Teleostomi: N E > Euteleostomi: N E > Sarcopterygii: N E > Dipnotetrapodomorpha: N E > Tetrapoda: N E > Amniota: N E > Mammalia: N E > Theria: N E > Eutheria: N E > Boreoeutheria: N E > Euarchontoglires: N E > Primates: N E > Haplorrhini: N E > Simiiformes: N E > Catarrhini: N E > Hominoidea: N E > Hominidae: N E > Homininae: N E > Homo: N E > Homo sapiens: N E


Molecular evidence
Database
157 mutations: Table (e.g. : 2.1kbdel_human-LPL, 2kbdup_human-LPL, 3bpdelInt1_human-LPL ... more)
4 structures (e.g. : 6E7K, 6OAU, 6OAZ... more)
No kinetic

Disease: Hyperlipoproteinemia TypeI -



No Substrate
No inhibitor
>3 Genbank links 19 more: DQ083390, CR457054, M15856
>3 UniProt links 9 more: P06858, Q6IAV0, Q71UV2
1 Ncbi-nid : 187209
2 Ncbi-pid : 3293305, 307138
>3 Structure links 1 more: 6OAU, 6OB0, 6OAZ
>3 UniProt links 11 more: Q6IAV0, Q4JIZ7, P06858
>3 Interpro links 11 more: Q6IAV0, Q4JIZ7, P06858
>3 Prodom links 11 more: Q6IAV0, Q4JIZ7, P06858
>3 Pfam links 11 more: Q6IAV0, Q4JIZ7, P06858
>3 PIRSF links 11 more: Q6IAV0, Q4JIZ7, P06858
>3 SUPERFAM links 11 more: Q6IAV0, Q4JIZ7, P06858
1 EntrezGene : 4023
1 SNP : 4023
1 UniGene : 180878
1 HUGO HGNC : 6677
>3 OMIM links 1 more: 238600, 246650, 609708
1 Ensembl : ENSG00000175445
Sequence
Graphical view for this peptide sequence: human-LPL
Colored MSA for Lipoprotein_Lipase (raw)
MESKALLVLTLAVWLQSLTASRGGVAAADQRRDFIDIESKFALRTPEDTA
EDTCHLIPGVAESVATCHFNHSSKTFMVIHGWTVTGMYESWVPKLVAALY
KREPDSNVIVVDWLSRAQEHYPVSAGYTKLVGQDVARFINWMEEEFNYPL
DNVHLLGYSLGAHAAGIAGSLTNKKVNRITGLDPAGPNFEYAEAPSRLSP
DDADFVDVLHTFTRGSPGRSIGIQKPVGHVDIYPNGGTFQPGCNIGEAIR
VIAERGLGDVDQLVKCSHERSIHLFIDSLLNEENPSKAYRCSSKEAFEKG
LCLSCRKNRCNNLGYEINKVRAKRSSKMYLKTRSQMPYKVFHYQVKIHFS
GTESETHTNQAFEISLYGTVAESENIPFTLPEVSTNKTYSFLIYTEVDIG
ELLMLKLKWKSDSYFSWSDWWSSPGFAIQKIRVKAGETQKKVIFCSREKV
SHLQKGKAPAVFVKCHDKSLNKKSG
Legend This sequence has been compared to family alignement (MSA)
red => minority aminoacid
blue => majority aminoacid
color intensity => conservation rate
title => sequence position(MSA position)aminoacid rate
Catalytic site
Catalytic site in the MSA

MESKALLVLTLAVWLQSLTASRGGVAAADQRRDFIDIESKFALRTPEDTA
EDTCHLIPGVAESVATCHFNHSSKTFMVIHGWTVTGMYESWVPKLVAALY
KREPDSNVIVVDWLSRAQEHYPVSAGYTKLVGQDVARFINWMEEEFNYPL
DNVHLLGYSLGAHAAGIAGSLTNKKVNRITGLDPAGPNFEYAEAPSRLSP
DDADFVDVLHTFTRGSPGRSIGIQKPVGHVDIYPNGGTFQPGCNIGEAIR
VIAERGLGDVDQLVKCSHERSIHLFIDSLLNEENPSKAYRCSSKEAFEKG
LCLSCRKNRCNNLGYEINKVRAKRSSKMYLKTRSQMPYKVFHYQVKIHFS
GTESETHTNQAFEISLYGTVAESENIPFTLPEVSTNKTYSFLIYTEVDIG
ELLMLKLKWKSDSYFSWSDWWSSPGFAIQKIRVKAGETQKKVIFCSREKV
SHLQKGKAPAVFVKCHDKSLNKKSG


References
129 more
    Title: The intrinsic instability of the hydrolase domain of lipoprotein lipase facilitates its inactivation by ANGPTL4-catalyzed unfolding
    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 : PubMed

            

    Title: Lipoprotein Lipase and Its Regulators: An Unfolding Story
    Wu SA, Kersten S, Qi L
    Ref: Trends Endocrinol Metab, 32:48, 2021 : PubMed

            

    Title: The structure of helical lipoprotein lipase reveals an unexpected twist in lipase storage
    Gunn KH, Roberts BS, Wang F, Strauss JD, Borgnia MJ, Egelman EH, Neher SB
    Ref: Proc Natl Acad Sci U S A, :, 2020 : PubMed

            


Other Papers
Han 2022 Medicine.(Baltimore) 101 e29689

Send your questions or comments to :
Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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