Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol ANGPTL3 contributors: mct/npt/pgu - updated : 06-06-2016
HGNC name angiopoietin-like 3
HGNC id 491
DNA
TYPE functioning gene
SPECIAL FEATURE gene in gene
text
  • located in an intron of DOCK7
  • STRUCTURE 8.82 kb     7 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - D1S203 - D1S822 - D1S2788 - D1S209 - D1S246 - ANGPTL3 - D1S2835 - cen
    Authors Gene Map (99)
    Physical map
    TACSTD2 1p32-p31 tumor-associated calcium signal transducer 2 AK2B 1p32.1 adenylate kinase 2 pseudogene KIAA1915 1p32.1 KIAA1915 protein JUN 1p32-p31 v-jun sarcoma virus 17 oncogene homolog (avian) LOC391044 1 similar to prohibitin FLJ10986 1p32.1 hypothetical protein FLJ10986 HOOK1 1p32.1 hook homolog 1 (Drosophila) CYP2J2 1p31.3-p31.2 cytochrome P450, family 2, subfamily J, polypeptide 2 MGC34837 1p32.1 hypothetical protein MGC34837 NFIA 1p31.3-p31.2 nuclear factor I/A BBP 1p32.1 beta-amyloid binding protein precursor INADL 1p32.1-p31.3 beta-amyloid binding protein precursor FLJ10884 1p32.1 hypothetical protein FLJ10884 LOC388637 1 similar to LOC163782 protein USP1 1p32.1-p31.3 ubiquitin specific protease 1 ANGPTL3 1p31 angiopoietin-like 3 AUTL1 1p31.3 AUT-like 1, cysteine endopeptidase (S. cerevisiae) LOC199897 1p32.1 hypothetical LOC199897 LOC388638 1 LOC388638 FOXD3 1p32-p31 forkhead box D3 ALG6 1p31.3 forkhead box D3 ITGB3BP 1p31.3 integrin beta 3 binding protein (beta3-endonexin) KIAA1799 1p31.3 KIAA1799 protein PGM1 1p22.3 phosphoglucomutase 1 ROR1 1p32-p31 receptor tyrosine kinase-like orphan receptor 1 MGC35130 1p31.3 hypothetical protein MGC35130 KIAA1573 1p31.3 KIAA1573 protein KIAA1579 1p31.3 hypothetical protein FLJ10770 JAK1 1p31.3 Janus kinase 1 (a protein tyrosine kinase) LOC391045 1 similar to Solute carrier family 2, facilitated glucose transporter, member 3 (Glucose transporter type 3, brain) MRPS21P1 1p31.3 mitochondrial ribosomal protein S21 pseudogene AK3 1p31 adenylate kinase 3 DNAJC6 1pter-q31.3 DnaJ (Hsp40) homolog, subfamily C, member 6 LEPR 1p31 leptin receptor PDE4B 1p31 phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila) DKFZp761D221 1p31.3 hypothetical protein DKFZp761D221
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - - 4500 - - - 1999 10644446
    - - 3000 - - - 1999 10644446
    - - 2800 - - - 1999 10644446
    - - 1700 - - liver and kidney 1999 10644446
    7 - 2126 53 460 - 2009 19028676
    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
  • 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