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FLASH GENE
Symbol AMOT contributors: mct/pgu - updated : 12-04-2016
HGNC name angiomotin
HGNC id 17810
Location Xq23      Physical location : 112.018.105 - 112.084.043
Synonym name
  • angiomotin p130 isoform
  • angiomotin p80 isoform
    • Synonym symbol(s) FLJ14282, KIAA1071, AMOT130
    DNA
    TYPE functioning gene
    STRUCTURE 65.94 kb     12 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    text
  • not completely determined alternatively spliced transcript variants encoding different isoforms have been described (PMID: 16043488)
    • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 6514 72 675 expressed during the migratory phase of retinal angiogenesis 2009 19565639
  • variant 1 - p80
  • promotes angiogenesis, in part, by conferring a hypermigratory phenotype to endothelial cells
  • AMOTL1 associates with this p80-angiomotin-containing complex via its coiled-coil domain
  • is a novel component of the CDH11 complex and Amot-p80 is critical for CDH11-mediated cell migration
    • 11 - 6945 130 1084 expressed during the period of blood vessel stabilization and maturation in retinal angiogenesis 2013 23564455
  • be coprecipitated with MAGI-1b
  • variant 2 - p130
  • N-terminal domain of p130 serves as a targeting domain responsible for localization of p130-AMOT to actin and tight junctions
  • ubiquitinated at lysine 481 by ITCH, resulting in increased AMOT130 stability
  • significant consequence of AMOT130 binding to ITCH is the induction of its ligase activity for self and substrate ubiquitination
  • recruits the E3 protein-ubiquitin ligase atrophin-1 interacting protein 4 (ITCH), that binds and ubiquitinates AMOT130, resulting in a reduction in AMOT130 residence at actin fibers and a significant enhancement of the stability of AMOT130 protein
  • phosphorylation by LATS1/2 is found to be a key feature that enables it to inhibit YAP1-dependent signaling and cell growth
    		•
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
     vesselcapillary  highly Homo sapiens
    Digestivemouthtongue  predominantly
    Endocrineneuroendocrinepituitary  moderately
    Lymphoid/Immunespleen   highly
    Nervousbrainbasal nuclei   
     spinal cord    
    Reproductivefemale systemplacenta  moderately
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/lining   
    Lymphoid    
    Muscular   moderately
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta (large vessels)
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a PPXY motif in the N terminus of AMOT necessary for its interactions , and N-terminal regions contain a conserved HXRXXS consensus site for LATS1/2-mediated phosphorylation
  • a coiled-coil domain
  • a lipid binding domain that bind with high affinity to membranes containing monophosphorylated phosphatidylinositols and cholesterol
  • a consensus motif for binding to PDZ domain at the C terminus, C-terminal PDZ-binding motifs, required for the interactions with AMOTL1, AMOTL2, MPDZ, and INADL
    • HOMOLOGY
    Homologene
    FAMILY
  • angiomotin family, Amot/JEAP family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
        intracellular
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton
    text
  • located to the leading edge of migrating endothelial cells
  • actin filament
  • lamellipodium
  • apparent at TJs as well as apical membranes, and mostly co-localized with MPDZ
  • targeted along with associated apical polarity proteins to the endocytic recycling compartment via its membrane binding domain
    • basic FUNCTION
  • mediating angiostatin inhibition of migration and tube formation of endothelial cells
  • stimulating cell motility
  • playing a role in the assembly of endothelial cell-cell junctions
  • maintaining tight junctions integrity by the coordinate regulation of Cdc42 and by linking specific components of the TJ to intracellular protein trafficking, when binding to ARHGAP17
  • important role in growth factor-induced migration of endothelial cells
  • AMOT appears to control the polarity of vascular tip cells whereas AMOTL1 mainly affects the stability of cell-cell junctions of the stalk cells
  • associates with cell junctions and binds apical polarity proteins, which underlie its ability to control cell shape and migration
  • may coordinate the dysregulation of cell polarity with the induction of neoplastic growth in mammary cells
  • functions downstream of Merlin and upstream of ARHGAP17, a small GTPase Activating Protein, as a positive regulator of RAC1
  • activate LATS2 through a novel conserved domain that binds and activates LATS2
  • membrane-associated protein that is expressed in ECs (endothelial cells) and controls migration, TJ (tight junction) formation, cell polarity and angiogenesis
  • AMOT, AMOTL1 and AMOTL2, play critical roles in the Hippo pathway by regulating the subcellular localization of the co-activators YAP1 and TAZ
  • is crucial for the maintenance of nuclear YAP1 to promote renal epithelial and Renal cell carcinoma (RCC) proliferation
  • multifunctional protein involved in endothelial cell migration and tube formation and angiogenesis
  • MAMDC4 and AMOT have a greater association in subconfluent cells compared with confluent cells, and this association is regulated at the endosomal membrane
  • EDIL3, AMOT and ECM1 are involved in the excessive angiogenesis and vasodilation observed in psoriasis
    • CELLULAR PROCESS cell organization/biogenesis
    cell communication
    PHYSIOLOGICAL PROCESS development
    text
  • actin cytoskeleton organization and biogenesis
  • positive regulation of angiogenesis
  • positive regulation of blood vessel endothelial cell migration
    • PATHWAY
    metabolism
    signaling
  • tankyrase-RNF146-AMOT axis is an upstream pathway regulating YAP1
  • Hippo pathway negatively regulates the actin-binding activity of AMOT family members through direct phosphorylation
    • a component
  • forms a ternary complex together with INADL (or its paralogue MPDZ) and PLEKHG5, involved in directional migration of capillaries in the embryo
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • angiostatin
  • ARHGAP17 via its coiled-coil domain
  • interacting with MPDZ and INADL (interaction not necessarily responsible for their proper subcellular distribution
  • directly binds the scaffolding proteins INADL and MPDZ and redistributes them and their binding partners from the plasma membrane to endosomes
  • AMOT, AMOTL1 and AMOTL2, are YAP1-associated proteins
  • AMOT and AMOTL1 interact with YAP1 via the first WW domain of YAP1
  • interacting with YAP1 and TAZ (YAP1 and TAZ inhibition by AMOT-mediated tight junction localization)
  • functions downstream of NF2 and upstream of ARHGAP17, a small GTPase Activating Protein, as a positive regulator of RAC1
  • MCAM binds to angiomotin to stimulate a proangiogenic response
  • ITCH bind and ubiquitinate AMOT at residue Lys-481
  • promotes the ubiquitination of YAP1 by ITCH and prevents ITCH from binding to large tumor suppressor 1
  • acts as a YAP1 cofactor, preventing YAP1 phosphorylation and augmenting its activity toward a specific set of genes that facilitate tumorigenesis
  • AMOT is a direct substrate of LATS1/LATS2 mediating functions of the Hippo pathway in endothelial cell migration and angiogenesis
  • LATS1, LATS2 can synergize with F-actin perturbations by phosphorylating free AMOT130 to keep it from associating with F-actin
  • MAMDC4 interacts with both AMOT and occludin and preferentially associates with occludin in confluent cells but with AMOT family members in subconfluent cells
  • MAMDC4 competes with YAP1 for binding to AMOT proteins in subconfluent cells
  • AMOT can interact with YAP1 to either stimulate or inhibit YAP1 activity, playing a potential role in cell proliferation
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancer tissues and was important in the promotion of breast cancer cell proliferation and invasion
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousvascular 
    using angiomotin antibodies for specifically targeting endothelial migration in angiogenesis-dependent diseases
    ANIMAL & CELL MODELS