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FLASH GENE
Symbol ANGPT1 contributors: mct/npt/pgu - updated : 22-12-2013
HGNC name angiopoietin 1
HGNC id 484
Location 8q23.1      Physical location : 108.261.710 - 108.510.254
Synonym symbol(s) KIAA0003, AGPT, ANG1, AGP1
DNA
TYPE functioning gene
STRUCTURE 248.54 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site   transcription factor
text structure binding sites for ETS and AP-1 transcription factor family members (only the ETS factor ELF3 was capable of transactivating its promoter)
MAPPING cloned Y linked N status confirmed
Map cen - D8S1977 - D8S1610 - D8S1176 - D8S545 - D8S1844 - DPYS DPYS - D8S1496 - D8S556 - D8S207 - D8S1580 - D8S1780 - D8S1703 - D8S1768 - D8S1975 - D8S1588 - D8S200 - D8S85 - D8S1830 - ANGPT1 - TRHR - D8S1940 ,EBAG9 - D8S1594 - D8S1122 - D8S1960 - qter
Physical map
MFTC 8q22.3 mitochondrial folate transporter/carrier DKFZP564O0463 8q22.3 DKFZP564O0463 protein TARBP2P 8q22-q24 TAR (HIV) RNA binding protein 2 pseudogene RIMS2 8q22.3 regulating synaptic membrane exocytosis 2 DCSTAMP 8q23 DC-specific transmembrane protein DPYS 8q22 dihydropyrimidinase ST7 7q31.1-q31.3 suppression of tumorigenicity 7 LOC392258 8 similar to ribosomal protein L29 LOC392259 8 similar to KIAA0779 protein ZFPM2 8q22.3-q23 zinc finger protein, multitype 2 LOC346887 8q23.1 similar to hypothetical protein FLJ30794 OXR1 8q23 oxidation resistance 1 STARS 8q23.1 striated muscle activator of Rho-dependent signaling ANGPT1 8q22.3-q23 angiopoietin 1 MGC35555 8q23.1 hypothetical protein MGC35555 LOC389681 8 similar to nuclear receptor binding factor-2; comodulator of PPAR and RXR EIF3S6 8q22-q23 eukaryotic translation initiation factor 3, subunit 6 48kDa LOC392260 8 similar to dJ753D5.2 (novel protein similar to RPS17 (40S ribosomal protein S17)) KIAA0103 8q23.2 KIAA0103 FLJ30668 8q23.2 hypothetical protein FLJ30668 TRHR 8q23 thyrotropin-releasing hormone receptor CML66 8q23 chronic myelogenous leukemia tumor antigen 66 DC6 8q23.2 DC6 protein PKHD1L1 8q23.2 polycystic kidney and hepatic disease 1 (autosomal recessive)-like 1 MAPK6PS5 8q23 polycystic kidney and hepatic disease 1 (autosomal recessive)-like 1 EBAG9 8q23.3 estrogen receptor binding site associated, antigen, 9 FLJ20366 8q23.2 hypothetical protein FLJ20366 LOC392261 8 similar to hypothetical protein A930017M01 KCNV1 8q22.3-q24.1 potassium channel, subfamily V, member 1 LOC392262 8 similar to laminin-binding protein
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 4338 57.4 498 - 2009 19223473
EXPRESSION
Type widely
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessels    
Digestivesalivary gland   highly
Respiratoryrespiratory tracttrachea  highly
Urinarykidneynephronrenal capsuleglomerulus 
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow   
Connectivecartilage   
Muscular    
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell
not specificsynoviocyte
Urinarypodocyte
cell lineage
cell lines
fluid/secretion
at STAGE
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
  • 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