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FLASH GENE
Symbol ANGPT1 contributors: mct/npt/pgu - updated : 22-12-2015
HGNC name angiopoietin 1
HGNC id 484
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a 15 aa signal peptide
  • a N terminal region lacking homology to any known structure
  • an alpha-helical rich coiled-coil segment
  • a fibrinogen-like domain at the C terminus
  • five consensus motifs for N-glycosylation calcium binding motif
    • conjugated GlycoP
    isoforms Precursor a 483 aa mature peptide
    HOMOLOGY
    interspecies homolog to C.elegans D1009.3
    ortholog to rattus Angpt1
    ortholog to murine Angpt1
    Homologene
    FAMILY
  • vascular endothelial growth factor family
  • angiopoietin family
    • CATEGORY regulatory , signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • secreted ligand for the vascular endothelial restricted receptor tyrosine kinase TEK, inducing phosphorylation of TEK producing activation of TEK
  • with ANGPT2 may play an important role in the pathophysiology of septic shock in children
  • involved in late stages of angiogenesis, in the regulation of luteal angiogenesis
  • promoting angiogenic remodeling as well as vessel maturation and stabilization
  • playing a role in the heart early development and in blood vessel formation
  • mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme
  • may be an important regulator of angiogenesis in inflammatory arthritis
  • modulating endothelial cell function and gene expression via the transcription factor FOXO1 and acting as a regulator of endothelial cell survival and blood vessel stability
  • inducing lymphatic vessels growth in adult tissues
  • shows anti-permeability activity through up-regulation of TJP2
  • may have a unique role in neurogenesis independent of its role in angiogenesis
  • endothelial growth factor with a critical role in division, survival, and adhesion of endothelial cells via TEK receptor activity
  • is a proneurogenic peptide on subventricular zone stem/progenitor cells
  • may play an important role in the pathogenesis of Behcet disease
  • antileakage action of ANGPT1 requires PDGF-dependent actions of pericytes in maintaining endothelial stability
  • plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor TEK
  • promotes endothelial differentiation from embryonic stem cells and induced pluripotent stem cells
  • decreases endothelial cell permeability and increases vascular stabilization via recruitment of pericytes and smooth muscle cells to growing blood vessels
  • 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
  • ANGPT1 signaling via the TEK receptor regulates vascular and hematopoietic systems
  • ANGPT1 and ANGPT2 are secreted factors that bind to the endothelial cell-specific receptor tyrosine kinase TEK (TEK) and regulate angiogenesis
  • can induce distinctive vascular remodeling through highly organized angiogenesis and tightening of endothelial cell (EC) junctions
  • VEGFA and ANGPT1 regulate endothelial cell (EC) junctions by determining the localization of the RHOA-specific guanine nucleotide exchange factor PLEKHG5
  • 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
    cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS development
    text
  • embryogenesis
  • morphogenesis
  • angiogenesis
    • PATHWAY
    metabolism
    signaling signal transduction
  • ANGPT1/TEK signaling has a pivotal role in embryonic stem cell- endothelial cell differentiation
  • ANGPT1-TEK signaling affects the differentiation capacity of hematopoietic lineages during development and increases the stem cell activity of hematopoietic stem and progenitor cell (HSPC) (
    • a component
  • ANGPT1/TEK axis modulates the expression and function of ABC transporters in glioma cells and brain tumor stem cells
  • ANGPT1/TEK signal potentiates basal Notch signal controlling vascular quiescence by up-regulating DLL4 through AKT-mediated activation of CTNNB1
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
    • protein
  • TIE2 (TEK) receptor tyrosine kinase (significant correlation between ANGPT1 gene expression and TEK gene expression in normal ovary with corpus luteum)
  • negatively regulating HNF1A in endothelial cells
  • activating intracellular PI.3' kinase
  • interacting with PLD1 (a new mediator of ANGPT1/TEK-induced signaling pathway, that participates in MAPK activation and endothelial cell migration)
  • interacting with ANGPT1 (ANGPT2 functions as an agonist when ANGPT1 is absent but as a dose-dependent antagonist when ANGPT1 is present)
  • TIE1-TEK interactions are dynamic, inhibitory, and differentially modulated by ANGPT1 and ANGPT2
  • regulates both vascular quiescence and angiogenesis through the receptor tyrosine kinase TEK
  • ANGPT2 antagonizes ANGPT1 function, leading to excessive vessel sprouting with impaired pericyte recruitment and vessel stabilization
  • requires IQGAP1 as an indispensable activator of RAC1
  • maintained PLEKHG5 at the junctions, inducing junction stabilization
  • under hypoxic conditions, TIE1 is critical for reducing ANGPT1-induced TEK activity and angiogenesis
  • KDM3B represses transcription of the angiogenesis regulatory gene, ANGPT1
  • ANGPT1 requires oxidant signaling through NCF1 to promote endothelial barrier defense
  • overexpression of CASP5 can promote the angiogenesis significantly, possibly by inhibiting the ANGPT1/Tie2 pathway and promoting VEGFA pathway
    • cell & other
    REGULATION
    induced by induced with ELF3 in synovial fibroblasts in response to inflammatory cytokines
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in hepatocellular carcinoma in progression and in synovial fibroblasts of rheumatoid arthritis (RA)
    constitutional     --low  
    in menorrhagia
    constitutional     --other  
    ectopic expression of Ang1 promotes neuronal differentiation and neurite outgrowth in neural progenitor cells
    constitutional     --over  
    in Behçet disease patients compared to controls
    Susceptibility to pregnancy complications
    Variant & Polymorphism other
  • ANGPT1 rs2507800 polymorphism may have a potential role in screening women to predict the risk of these pregnancy complications
    • 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
  • serum ANGPT1 showed potential to discriminate missed abortions (MA) from ectopic pregnancies (EP)
    • Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousvascular 
    candidate for therapeutic neovascularization and vascular protection
    ANIMAL & CELL MODELS
  • mice overexpressing Angpt1
  • in mice variant COMP-Angpt1 ameliorates leukocyte adhesion and reinforces endothelial tight junctions during endotoxemia