Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol LPL contributors: mct - updated : 26-05-2020
HGNC name lipoprotein lipase
HGNC id 6677
Corresponding disease
LPL hyperlipoproteinemia, types I
SBPQ human blood pressure QTL
Location 8p21.3      Physical location : 19.796.581 - 19.824.769
Synonym symbol(s) LIPD, LIPL, HDLCQ11
EC.number 3.1.1.34
DNA
TYPE anonymous DNA segment
STRUCTURE 28.19 kb     10 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked Y status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
10 - 3747 - 475 - 2002 11893776
EXPRESSION
Rna function mRNA expression in normal human testis
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly Homo sapiens
 vessels    
Endocrinepancreas   highly Mus musculus
 placenta   highly Homo sapiens
Nervousbrain   highly Homo sapiens
Reproductivemale systemtestis    Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadiposewhite highly Homo sapiens
Connectiveadiposebrown   Homo sapiens
Muscularstriatumskeletal highly Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell
Endocrineislet cell (alpha,beta...) Mus musculus
Reproductivespermatid Homo sapiens
Reproductivespermatocyte Homo sapiens
cell lineage
cell lines
fluid/secretion milk
at STAGE
physiological period perinatal, pregnancy
Text increased in the mammary gland and decreased in the adipose tissue during lactation
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one PLAT domain
  • C-terminal LPL sequences, distinct from the heparin-binding domain, are crucial for GPIHBP1 binding , and C terminus of LPL, detached from the N terminus, is sufficient for specific binding to GPIHBP1
  • conjugated GlycoP
    mono polymer homomer , monomer , dimer
    HOMOLOGY
    interspecies homolog to murine Lpl
    intraspecies homolog to LIPC,highly
    Homologene
    FAMILY
  • AB hydrolase superfamily
  • lipase family
  • CATEGORY enzyme , transport
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text
  • located on the luminal surface of capillary
  • attached to the membrane by a GPI-anchor
  • basic FUNCTION
  • serine esterase
  • involved in plasma lipid transport
  • rate limiting for the hydrolysis and clearance of circulating triglyceride (TG), hydrolyzing triglycerides in chylomicrons and very low-density lipoproteins
  • catalysing the hydrolysis of the triacylglycerol component of circulating chylomicrons and very low density lipoproteins
  • AHR paradoxically regulates IGFBP1 and LPL expressions in the liver
  • both LIPG and LPL participate in the supply of nutrients and steroidogenesis in the testes, and especially LIPG may be important for the supply of cholesterol for testosterone production in the Leydig cells
  • plays a role in the binding of lipoprotein particles to cell-surface molecules, including sulfated glycosaminoglycans (GAGs)
  • Abeta-binding protein promoting cellular uptake and subsequent degradation of Abeta
  • its expression in placenta facilitates uptake of retinoids by this organ and their transfer to the embryo, mainly through its catalytic activity
  • is involved in regulation of fatty acid metabolism, and facilitates cellular uptake of lipoproteins, lipids and lipid-soluble vitamins
  • is a triglyceride-hydrolyzing enzyme that is synthesized within the cardiomyocyte and secreted towards the lumen under various conditions
  • neuronal LPL is an important regulator of lipid homeostasis in neurons and that alterations in LPL levels may have important effects on systemic metabolism and neuronal lipid biology
  • LPL expression is likely a novel feature of a microglial phenotype that supports remyelination and repair through the clearance of lipid debris
  • catalyzes the breakdown of circulating triglycerides in muscle and fat
  • is a secreted enzyme that hydrolyzes triglycerides from circulating lipoproteins
  • LPL is responsible for the intravascular processing of triglyceride-rich lipoproteins
  • catalytically active LPL can exist in a monomeric state, not only as a homodimer
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text lipid transport
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with apolipoprotein C2
  • bound avidly to GPIHBP1
  • GPIHBP1 is an endothelial cell protein that transports lipoprotein lipase (LPL) from the subendothelial spaces to the capillary lumen (
  • binding of LPL to GPIHBP1 requires only the C-terminal portion of LPL and does not depend on full-length LPL homodimers
  • is transported and attached to the capillary endothelium by the protein GPIHBP1
  • LPL inhibition is made possible by a free fatty acids, FA-induced activation of PPARB/PPARD, which augments angiopoietin-like 4 (ANGPTL4), an inhibitor of LPL activity
  • ANGPTL4 can both bind and inactivate LPL complexed to GPIHBP1 and that inactivation of LPL by ANGPTL4 greatly reduces the affinity of LPL for GPIHBP1
  • ANGPTL8 has a functional LPL inhibitory motif, but only inhibits LPL and increases plasma TG levels in the presence of ANGPTL3
  • ANGPTL4 promotes PCSK-mediated intracellular cleavage of LPL in adipocytes, likely contributing to regulation of LPL in adipose tissue
  • GPIHBP1's LU domain binds to LPL's C-terminal domain, largely by hydrophobic interactions
  • ANGPTL4 binds LPL near the active site at the lid domain and a nearby alpha-helix
  • ANGPTL3, much like ANGPTL4, is a physiologically relevant regulator of LPL activity, which causes irreversible inactivation of the enzyme
  • TCF21 is a novel regulator of preadipocyte differentiation, in part by directly promoting LPL expression
  • GPIHBP1 is LPL's essential partner: it binds LPL and transports it to the capillary lumen; it is essential for lipoprotein margination along capillaries, allowing lipolysis to proceed
  • ZHX2 protects hepatocytes from abnormal lipid deposition in Non-alcoholic fatty liver disease (NAFLD) through transcriptional repression of LPL, which subsequently retards cell growth and NAFLD-HCC progression
  • cell & other
    REGULATION
    activated by GIP thatbincreases adipocyte LPL expression through CREB1 and CRTC2-mediated trans-activation of the LPL gene)
    induced by cortisol
    inhibited by PRL and GH
    repressed by ANGPTL3, that inhibit LPL activity and plays important roles in modulating lipoprotein metabolism
    Other activated when heterodimerization occurred in a head-to-tail orientation
    regulated by by extracellular proteins divided into two main groups: the liver-derived apolipoproteins APOC1, APOC2, APOC3, APOA5, and APOE, and the angiopoietin-like proteins
    ASSOCIATED DISORDERS
    corresponding disease(s) LPL , SBPQ
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in prostate carcinoma
    constitutional germinal mutation      
    associated with the severity of Alzheimer disease pathophysiological features
    constitutional germinal mutation      
    in a Chinese infant with severe hypertriglyceridemia
    constitutional     --low  
    in the dentate gyrus of Alzheimer's disease brains
    Susceptibility
  • to overweight in post menopausal women
  • to familial combined hyperlipidemia, atherosclerosis,
  • chylomicronaemia, and dyslipidaemia associated with diabetes, insulin resistance, and infection
  • Alzheimer's disease
  • to preeclampsia
  • to coronary heart disease
  • to ischemic heart disease
  • Variant & Polymorphism SNP
    Candidate gene furin-resistant LPL is a useful reagent for both biochemical and biomedical studies
    Marker
  • LPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis
  • Therapy target
    ANIMAL & CELL MODELS