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FLASH GENE
Symbol ANGPT2 contributors: mct/ - updated : 07-12-2013
HGNC name angiopoietin 2
HGNC id 485
Location 8p23.2      Physical location : 6.357.176 - 6.420.784
Synonym name
  • Tie2-ligand
  • angiopoietin-2B
  • angiopoietin-2a
    • Synonym symbol(s) ANG2, AGP2, ANG-2
    DNA
    TYPE functioning gene
    STRUCTURE 63.61 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site   transcription factor
    text structure
  • ten Ets binding sites (EBSs)
    • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 5270 56.9 496 - 2009 19223473
    9 splicing 5267 - 495 - 2009 19223473
  • binding Tie 2 receptor but not inducing Tie 2 phosphorylation
  • lacking exon Bof ANGPT2 (encoding 53 AA)
  • secreted glycoprotein with 4 potential N-glycosylaiton sites
  • homeodimer of 61 kda (51 kda)
    • 8 - 5114 - 444 - 2009 19223473
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvesselscapillary   
    Endocrineneuroendocrine   highly
    Lymphoid/Immunethymus   moderately
    Reproductivefemale systemovary   
     female systemplacenta  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/liningendothelium highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    Reproductivegranulosa cell
    Reproductivelutein cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text placenta, umbilical cord
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a secretion 16 aa signal peptide
  • a N terminal region lacking homology to any known structure
  • a fibrogen-like domain at the C terminus
  • six potential N-glycosylation sites/calcium binding motif
    • secondary structure an alpha-helical rich coiled-coil segment
    conjugated GlycoP
    mono polymer homomer , dimer
    isoforms Precursor a 480 aa mature peptide
    HOMOLOGY
    interspecies homolog to rattus Angpt2 (86.49 pc)
    homolog to murine Angpt2 (85.28 pc)
    intraspecies paralog to ANGPT1
    Homologene
    FAMILY
  • vascular endothelial growth factor family
  • angiopoietin family
    • CATEGORY regulatory , signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,nucleus
    basic FUNCTION
  • secreted ligand for the vascular endothelial restricted receptor tyrosine kinase TEK
  • inducing phosphorylation of TEK
  • antagonizing ANGPT1 by blocking its ability to activate its ligand
  • involved in regulation of luteal angiogenesis
  • functioning as an autocrine protective factor in stressed endothelial cells, induced in stressed endothelial cells, where it acts as an autocrine TIE2 agonist and protective factor
  • stimulating migration of endothelial progenitors and their interaction with endothelium
  • with ANGPT1 may play an important role in the pathophysiology of septic shock in children
  • functions as an agonist when ANGPT1 is absent but as a dose-dependent antagonist when ANGPT1 is present
  • involved in endothelial-pericyte interactions
  • important mediator of inflammation, which is associated with risk of recurrent ischemic stroke
  • is a novel, endothelial-derived regulator of myeloid cell infiltration that modulates ITGB2-mediated adhesion in a paracrine manner
  • mediates angiogenic sprouting and vascular regression
  • balance between the pro-leakage effects of VEGFA and anti-leakage effects of the angiopoietins (ANGPT1, ANGPT2), in part, modulates vascular integrity and oxygen delivery
  • ANGPT2 promotes the pro-inflammatory activation of human macrophages
  • ANGPT1 and ANGPT2 are secreted factors that bind to the endothelial cell-specific receptor tyrosine kinase TEK (TEK) and regulate angiogenesis
  • protective role of ANGPT2 following cerebral ischemia, an action associated with a reduced blood-brain barrier (BBB) permeability
  • ANGPT1 and ANGPT2, ligands for TEK, play essential roles in balancing vessel stability and regression during both developmental and tumor-induced angiogenesis
    • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS development
    text angiogenesis
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
    • protein
  • TEK receptor
  • natural antagonist for TIE2(TEK) (can act as either a weak TEK agonist or a dose-dependent TEK antagonist)
  • as a direct target for FOXC2 is involved in vascular remodeling, patterning, and maturation in adipose tissues
  • TIE1-TEK interactions are dynamic, inhibitory, and differentially modulated by ANGPT1 and ANGPT2
  • antagonizes ANGPT1 function, leading to excessive vessel sprouting with impaired pericyte recruitment and vessel stabilization
  • acts as a TEK agonist during lymphangiogenesis
  • ANGPT2 plays a protective role in tumor endothelial cells by activating TEK, thereby limiting the antivascular effects of VEGF inhibition
  • expression level of TIE1 and its physical interaction with TEK defines whether ANGPT2 functions as a TEK2 agonist or antagonist, thereby determining the context-dependent differential endothelial sensitivity to ANGPT2
    • cell & other
    REGULATION
    induced by rapidly in endothelial cells by the transcription factor FOXO1 after inhibition of the phosphatidylinositol 3-kinase/AKT pathway
    Other regulated by shear stress
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in hepatocellular carcinoma
    constitutional     --over  
    associated with risk of stroke recurrence in the patients with lacunar infarction
    constitutional     --over  
    in proliferating hemangiomas
    Susceptibility to stroke recurrence in lacunar infarction
    Variant & Polymorphism SNP allele T of rs3739391 associated with the plasma levels of ANGPT2 and stroke recurrence in the same type of stroke patients
    Candidate gene
    Marker
  • a single measurement of serum ANGPT1 and ANGPT2 at 6-8 weeks of gestation designate the outcome of a pregnancy, as their levels are significantly decreased in failed than normal pregnancies
    • Therapy target
    SystemTypeDisorderPubmed
    obesity  
    . functional interference with FOXC2 or ANGPT2 might provide a therapeutic approach for prevention and treatment of obesity or its related disorders
    miscelleaneousvascularshock
    decrease or neutralize ANGPT2, such as RNA aptamers, blocking antibodies and eicosapentaenoic acid (EPA) may provide a clue to improve future therapy strategies for stroke
    miscelleaneousvascular 
    attractive target for improved antiangiogenic tumor therapy
    immunologyautoimmunearticular
    targeting ANGPT2 may be of therapeutic benefit in the treatment of RA
    ANIMAL & CELL MODELS
  • transgenic overexpression of ANGPT2 in mice
  • Ang2-knockout mice exhibited severe defects in the remodeling and function of both lymphatic and blood vasculature, but genetic rescue with Ang1 cDNA expression at the Ang2 locus only prevented the lymphatic vascular defects