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FLASH GENE
Symbol ANGPTL3 contributors: mct/npt/pgu - updated : 06-06-2016
HGNC name angiopoietin-like 3
HGNC id 491
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver   moderately
Urinarykidneynephronrenal capsuleglomeruluslowly
cells
SystemCellPubmedSpeciesStageRna symbol
Urinarypodocyte
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a 19 AAs N terminal signal sequence, with a trimeric coiled-coil (CLD)
  • a short linker
  • a globular fibrinogen homology domain (FHD) with four cysteine residues implicated in intramolecular disulfide bonds
  • two potential N-glycosylation sites
  • a C-terminal fibrinogen (FBN)-like domain mediating binding to the TIE2 receptor and regulating blood vessel formation
    • secondary structure
  • an extended helical domain predicted to form dimeric or trimeric coiled-coils
    • conjugated GlycoP
    isoforms Precursor a mature protein of 441 aa for 51.5 kda
    HOMOLOGY
    interspecies homolog to murine Angptl3
    homolog to rattus Angptl3
    homolog to zebrafish angptl3
    intraspecies paralog to ANGPTL8
    Homologene
    FAMILY
  • angiopoietin-like family
    • CATEGORY adhesion , regulatory , signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    basic FUNCTION
  • regulating positively lipid metabolism (activating the lipolysis to stimulate the release of free fatty acid and glycerol from adipocytes)
  • playing a role in the positive regulation of angiogenesis
  • acting as an enzyme inhibitor (inhibiting the activity of lipoprotein lipase)
  • acting as an inhibitor of endothelial lipase and may be involved in the regulation of plasma HDL cholesterol and HDL-phospholipid levels
  • ANGPTL3, 4, and ANGPTL6/angiopoietin-related growth factor also appear to directly regulate lipid, glucose, and energy metabolism independently of angiogenic effects
  • play important roles in modulating lipoprotein metabolism in the body
  • ANGPTL3, ANGPTL4, and ANGPTL5, but not ANGPTL6, play nonredundant roles in triglyceride metabolism
  • involved in cell-matrix adhesion
  • secreted protein that regulate triglyceride (TG) metabolism in part by inhibiting lipoprotein lipase (LPL)
  • ANGPTL3, ANGPTL4, and possibly ANGPTL5 are regulators of lipoprotein metabolism
  • enhances LPL cleavage in the presence of either heparan sulfate proteoglycans or glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1)
  • ANGPTL3 inhibits lipoprotein lipase activity through enhancing its cleavage by PCSK5
  • capable of regulating the motility and permeability of podocytes and the mechanism of its regulation could be associated with the altered expression of nephrin
  • could be involved in proteinuria development and in podocyte injury
  • plays an important role in regulating the expression of nephrin in pathologic conditions
  • ANGPTL3, -4 and ANGPTL6/angiopoietin-related growth factor (AGF) directly regulate lipid, glucose and energy metabolism independent of angiogenic effects
  • act through its coiled-coil domains to enhance survival and replating capacity of human cord blood hematopoietic progenitors
  • possible role of ANGPTL3 at the crossroads of lipoproteins, fatty acids, and glucose metabolism
  • might play a crucial role in podocyte injury
  • inhibits two intravascular lipases, LPL and endothelial lipase, and the low plasma TG and HDL-cholesterol levels in ANGPTL3 deficiency reflect increased activity of these enzymes
  • plays a major role in promoting uptake of circulating very low density lipoprotein-triglycerides (VLDL-TGs) into white adipose tissue (WAT) rather than oxidative tissues (skeletal muscle, heart brown adipose tissue) in the fed state
  • regulates adipose tissue energy homeostasis
  • plays an important role in angiogenesis
  • secretory protein regulating plasma lipid levels via affecting lipoprotein lipase- and endothelial lipase-mediated hydrolysis of triglycerides and phospholipids
    • CELLULAR PROCESS cell migration & motility
    PHYSIOLOGICAL PROCESS development
    text
  • angiogenesis
  • positive regulation of cell migration
    • PATHWAY
    metabolism lipid/lipoprotein
    signaling signal transduction
  • integrin-mediated signaling pathway
  • lipid catabolism, triacylglycerol metabolism
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ITGAV
  • ITGB3
  • inhibit LPL activity through distinct mechanisms
  • potent inhibitor of LPL
  • FURIN is the primary convertase of ANGPTL3 and endothelial lipase in hepatocytes
  • ANGPTL8 also called betatrophin is a regulator of lipid metabolism through its interaction with ANGPTL3
  • ANGPTL8 has a functional LPL inhibitory motif, but only inhibits LPL and increases plasma TG levels in the presence of ANGPTL3
  • ANGPTL8 requires another member of the ANGPTL family, ANGPTL3, to act on LPL
  • ANGPTL3, much like ANGPTL4, is a physiologically relevant regulator of LPL activity, which causes irreversible inactivation of the enzyme
    • cell & other
    REGULATION
    activated by cleavage
    induced by LXR- or retinoid X receptor-selective agonists
    ASSOCIATED DISORDERS
    corresponding disease(s) FHBL2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    significantly increased podocyte motility, and dramatically increased the expression of nephrin
    tumoral     --over  
    in esophageal cancer tissues
    constitutional       loss of function
    does not affect the number of APOB-containing lipoproteins secreted by the liver but alters the particles that are made such that they are cleared more rapidly from the circulation via a noncanonical pathway(s)
    constitutional     --over  
    in glomerular podocytes of nephrotic syndrome
    constitutional       loss of function
    results in very low levels of LDL-cholesterol (C), HDL-C and triglyceride (TAG)
    Susceptibility atherosclerosis, coronary artery disease, diabetes mellitus
    Variant & Polymorphism
    Candidate gene
    Marker
  • association of ANGPTL3 expression with the prognosis of subgroups of patients with esophageal cancer
    • Therapy target
    SystemTypeDisorderPubmed
    metabolismlipidcholesterol
    therapeutic antibodies that neutralize ANGPTL4 and ANGPTL3 may be useful for treatment of some forms of hyperlipidemia
    metabolismlipid 
    potential therapeutic target to treat combined hyperlipidemia, a major risk factor for atherosclerotic coronary heart disease
    ANIMAL & CELL MODELS
    KK obese mouse