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FLASH GENE
Symbol RASSF5 contributors: mct/ - updated : 29-04-2016
HGNC name Ras association (RalGDS/AF-6) domain family member 5
HGNC id 17609
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • sequence motifs that evidence SH3 domain binding and diacylglycerol/phorbol ester binding in the N-terminal region
  • an effector domain (the minimal region of the protein responsible for its growth-suppressive effects)
  • an RA (Ras association) and SARAH (Sav/Rassf/Hpo) domain in the C-terminal region, with a hydrophobic-rich nuclear export signal (NES) towards the C-terminus and two nuclear localization signals-one each at the N-terminus and the C-terminus
  • mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to murine Rassf5
    ortholog to rattus rassf5
    Homologene
    FAMILY
  • Ser/Thr protein kinase family, RASSF family
  • STE20 subfamily
  • CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • cytoskeletal localization is required for growth-suppressive effects
  • shuttles between the nucleus and the cytoplasm, and its export from the nucleus is sensitive to leptomycin B, suggesting that RASSF5 is exported from the nucleus by a XPO1-dependent export pathway (
  • basic FUNCTION
  • involved in neuropeptide signaling pathway, intracellular signaling cascade
  • regulating lymphocyte adhesion through the spatial distribution of ITGAL
  • cytoskeletal protein that suppresses growth by inhibition of the ERK pathway
  • nucleocytoplasmic shuttling protein, translocated into the nucleus and nucleolus via arginine-rich nuclear targeting signals
  • may function as tumour suppressors by regulating the cell cycle and apoptosis
  • induces apoptosis in a manner dependent on its nuclear export
  • mediates a negative effect of activated RAS on microtubule nucleation
  • plays an important role in mediating apoptosis in response to death receptor ligands, TNF and TNF-related apoptosis-inducing ligand
  • direct role for RASSF5 in death receptor ligand-mediated apoptosis
  • required for TNF-mediated apoptosis and for full activation of MST1
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    intracellular signaling cascade
    a component part of a novel regulatory network composed of RASSF5, the mitotic kinase Aurora A, the small GTPase KRAS, and the microtubule cytoskeleton
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Mg2+
  • protein
  • bind to the active Ras oncogene product
  • interacts with the tyrosine kinase LCK through its C-terminal Src homology 2 binding motif and LCK-mediated phosphorylation is critical for the efficient translocation of RASSF5 into the nuclear compartment
  • interacts strongly with MST1 but only weakly with other components of the mammalian Hippo signaling pathway
  • binds directly to the ITGB2 alpha chain cytoplasmic tail
  • interacting with SKAP1 (needed for RASSF5 binding to membranes in a manner dependent on the PH domain of SKAP1 and the PI3K pathway)
  • connection between SKAP1-RASSF5-TERF2IP and the PI3K pathway
  • can act as an inhibitor or a potential positive regulator of STK3, depending on whether it binds to STK3 before or after activation-loop phosphorylation
  • specific activation of RAP1B contributes to neuronal polarization via interaction with RALA and RASSF5 in addition to PI3-kinase
  • two effectors of RAP1A regulate integrins, RASSF5 and APBB1IP
  • UBE2I acts as a functional binding partner of FYB1 and plays a selective role in integrin-mediated T cell adhesion via modulation of RAP1A-RASSF5 membrane recruitment and RAC1 activation
  • RASSF5, is the key downstream target of TET1, and TET1 promotes RASSF5 expression by demethylating a CpG site within RASSF5 promoter
  • cell & other
  • directly interacts with tubulin and is capable of nucleating microtubules
  • REGULATION
    Other phosphorylated by ATM on Ser131 and is involved in the activation of both STK3 and LATS1, leading to the stabilization of TP73 )
    LCK-mediated phosphorylation regulates the nucleocytoplasmic shuttling and cell growth control activities of RASSF5
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in several cancer cell lines, especially in hepatocellular carcinoma
    tumoral        
    strongly suppressed in neuroblastic tumors and reconstitution of its expression diminishes the tumorigenic phenotype
    tumoral       loss of function
    epigenetic inactivation of NORE1 due to aberrant promoter hypermethylation is a frequent event in colorectal tumorigenesis and might be implicated in the malignant progression of colorectal tumors
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    NORE1A mRNA down-regulation is one of the common gene abnormalities in non-small cell lung carcinoma (NSLC), both of which imply a key preventive role of NORE1A against the carcinogenesis of NSCLC
    ANIMAL & CELL MODELS
  • Rassf5-null mice were significantly more resistant to TNF-induced apoptosis and failed to activate Mst1 (