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FLASH GENE
Symbol SAV1 contributors: mct/npt/pgu - updated : 14-10-2020
HGNC name salvador homolog 1 (Drosophila)
HGNC id 17795
Location 14q22.1      Physical location : 51.100.359 - 51.135.023
Synonym name
  • WW45 protein
  • WW domain containing gene
  • 45 kDa WW domain protein
  • Synonym symbol(s) WW45, SAV, WWP4, salvador, 1700040G09Rik
    DNA
    TYPE functioning gene
    STRUCTURE 34.66 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 3031 - 383 - 2006 16930133
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two WW domain (2 conserved trp residues)
  • a coiled-coil region
  • HOMOLOGY
    interspecies homolog to murine Ww45
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text present in both the cytoplasm and nucleus
    basic FUNCTION
  • playing an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing
  • restricts cell numbers by functioning as a dual regulator of cell proliferation and apoptosis
  • required to enhance STK4-mediated apoptosis and thus is a critical player in an STK4-driven cell death signaling pathway
  • playing a crucial role in cell-cycle exit and epithelial terminal differentiation
  • key mediator of STK4 signalling in the coordinate coupling of proliferation arrest with terminal differentiation for proper epithelial tissue development in mammals
  • allows RASSF1 to modulate TP73 independently of the hippo pathway
  • essential component of the ability of RASSF1 to promote apoptosis and to stimulate TP73
  • potential human tumor suppressor and a proapoptotic effector of RASSF1
  • potential positive feedback loop, where Hippo stabilises its own positive regulator by antagonising HERC4-mediated degradation of SAV1
  • SAV1 worked as a cancer suppressor in pancreatic ductal adenocarcinoma
  • scaffold protein SAV1 promotes the activation of the MST-LATS kinase cascade
  • Hippo signaling component, that inhibits AKT1, a function independent of its role in Hippo signaling
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    RASSF1/Salvador pathway is acting independently of RAS
    a component
  • SAV1 and STK3 heterodimerize through their SARAH domains
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds STK4 (phosphorylated by STK4, and the stabilizing effect of STK4 on SAV1 requires its interaction with SAV1 but is probably not due to phosphorylation of SAV1 by STK4)
  • binds to LATS1 protein kinase
  • STK3 and the scaffold protein Salvador (SAV1), directly interact with NEK2 and regulate its ability to localize to centrosomes, and phosphorylate CEP250 and rootletin
  • can also bind RASSF1 (RASSF1 requires the presence of Salvador for full apoptotic activity and to activate TP73)
  • HAX1 is a binding partner of SAV1, and attenuates its protective role against apoptosis in MCF-7 breast cancer cells
  • STK3/STK4 timulated the binding of SAV1 to PPARG, a transcription factor that plays a key role in adipogenesis
  • enhances the effects of Hippo kinase activity at multiple points in the Hippo pathway
  • SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK
  • SAV1 suppresses AKT1 activation by blocking Akt's movement to plasma membrane
  • STK25 as the kinase component of STRIPAK can inhibit the function of the STRIPAK inhibitor SAV1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    induces apoptosis in human tumor cells and inhibits their growth and survival
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivepancreas
    considered as a target for pancreatic cancer therapy
    ANIMAL & CELL MODELS