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FLASH GENE
Symbol FAT1 contributors: mct/ - updated : 16-03-2017
HGNC name FAT tumor suppressor homolog 1 (Drosophila)
HGNC id 3595
Corresponding disease
Location 4q35.2      Physical location : 187.508.937 - 187.644.987
Synonym name
  • FAT tumor suppressor (Drosophila) homolog
  • cadherin ME5
  • cadherin family member 7
  • cadherin-related tumor suppressor
  • cadherin-related family member 8
  • protocadherin Fat 1
  • Synonym symbol(s) FAT, ME5, CDHF7, hFat1, CDHR8
    DNA
    TYPE functioning gene
    STRUCTURE 136.05 kb     27 Exon(s)
    MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    27 - 14773 - 4588 - 2008 17500054
  • localized along the cellular leading edge
  • up-regulated in migration, induces cellular process formation when overexpressed, and is necessary for efficient wound healing
  • - - - - - - PMID: 17500054
    confined to intercellular junctions
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     intestinelarge intestinecolon highly
    Nervousnervecranial nerve  highly
    Reproductivefemale systembreastmammary gland highly
    Respiratoryrespiratory tractlarynx  moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connective   moderately
    Epithelialbarrier/lining   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text epithelium, embryonic tissue
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one laminin A/neurexin/sex hormone-binding globulin domains (LNS)
  • five EGF-like domains
  • intracellular EVH1 domain, a domain that interacts with Ena/VASP proteins, as well as putative beta-catenin binding sites
  • 34 cadherin repeats
  • HOMOLOGY
    interspecies homolog to rattus Fath (88.16 pc)
    homolog to murine Fat1 (88.19 pc)
    ortholog to Drosophila tumor suppressor Fat
    Homologene
    FAMILY
  • cadherin superfamily
  • CATEGORY adhesion
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane,junction
        intracellular
    intracellular,nucleus
    text
  • type I transmembrane protein
  • localized at lamellipodial edges or cell-cell boundaries in normal cells
  • FAT1 and RERE colocalized at cell-cell junctions, in the perinuclear area, and in the nucleus
  • basic FUNCTION
  • putative adhesion molecule
  • essential for maintenance of the complex cytoarchitecture of the glomerular filtration barrier within the kidney
  • playing a necessary role for polarization and directed migration
  • regulates actin cytoskeletal organization at cell peripheries, thereby modulating cell contacts and polarity
  • atypical cadherin induced robustly after arterial injury, has significant effects on mammalian vascular smooth muscle cell (VSMC) growth and migration
  • FAT1 and ATRS (ATN1 and RERE), act in concert after vascular injury but show further that distinct Atr isoforms have disparate effects on vascular smooth muscle cells directional migration
  • may be involved in the migration and invasion mechanisms of oral squamous cell carcinoma and, therefore, it could be an important target for the development of new therapeutic strategies
  • uncleaved FAT1 could promote altered signaling, and the novel products of alternate processing provide a dominant negative function in melanoma
  • regulate diverse biological functions as cell proliferation and planar cell polarity, and also to affect wound healing
  • novel signaling mechanism mediated by FAT1 in regulating the activity of PDCD4 and thereby the key transcription factor AP1, which then affects known mediators of neoplasia and inflammation
  • FAT1 and FAT4 suppress tumor growth via activation of Hippo signaling, whereas FAT1 promotes tumor migration via induction of actin polymerization
  • FAT1 is tumor suppressive or oncogenic in a context&
  • 8209;dependent manner
  • is a critical determinant of muscle form, misregulation of which associates with FSHD
  • acts to control neurite outgrowth, also driving cells towards terminal differentiation via inhibitory effects on proliferation
  • is a new upstream Hippo element regulating early stages of differentiation in neuronal cells
  • FAT1 and FAT4 binding coordinates likely distinct pathways at apical junctions to regulate neural progenitor proliferation, neural tube closure and apical constriction
  • atypical FAT1 cadherin acts as a molecular 'brake' on mitochondrial respiration that regulates vascular smooth muscle cell (SMC) proliferation after arterial injury
  • FAT1 controls likely mitochondrial activity to restrain cell growth during the reparative, proliferative state induced by vascular injury
  • CELLULAR PROCESS cell cycle
    cell communication
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacted with both ATN1 and ATN2 (these interactions required FAT1 AAs 4300-4400 and an intact Atro-box in the ATNs)
  • interactions between FAT1 and Atrophins (ATN1, RERE) might contribute to FAT1 effects on vascular smooth muscle cells
  • negative correlation between the expression of FAT1 and PDCD4
  • evidence for a mechanism to control CASP8-dependent cell death by the atypical cadherin FAT1
  • SH3RF1 acts as a negative post-translational regulator of FAT1 levels
  • cell & other
    REGULATION
    Other cleaved into a non-covalent heterodimer before achieving cell surface expression
    ASSOCIATED DISORDERS
    corresponding disease(s) GNTP
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    activated in clear cell renal carcinoma with good outcome
    constitutional     --over  
    resulted in formation of cellular protrusions or increased wound healing
    tumoral     --low  
    repressed in oral cancer owing to homozygous deletion or epigenetic silencing and is preferentially downregulated in invasive breast cancer (
    constitutional       loss of function
    is associated with an FSHD-like phenotype
    Susceptibility to bipolar disorder
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    digestiveliver 
    new therapeutic target for the prevention and treatment of hepatic fibrosis in chronic liver disease
    ANIMAL & CELL MODELS
  • mutation of Fat1 in mouse embryos causes defects in cranial neural tube closure, accompanied by an increase in the proliferation of cortical precursors and altered apical junctions, with perturbations in apical constriction and actin accumulation