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FLASH GENE
Symbol RASSF5 contributors: mct/ - updated : 29-04-2013
HGNC name Ras association (RalGDS/AF-6) domain family member 5
HGNC id 17609
Location 1q32.1      Physical location : 206.680.878 - 206.762.615
Synonym name
  • RAP1 binding molecule
  • tumor suppressor RASSF3
  • Ras effector-like protein
  • new ras effector 1
  • regulator for cell adhesion and polarization enriched in lymphoid tissue
  • Synonym symbol(s) RAPL, Maxp1, NORE1, RASSF3, NORE1A, NORE1B, MGC17344, MGC10823
    DNA
    TYPE functioning gene
    STRUCTURE 81.74 kb     6 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC388731 1 hypothetical gene supported by AK097788 FLJ32569 1q32.1 hypothetical protein FLJ32569 SLC26A9 1q31-q32 solute carrier family 26, member 9 LOC391156 1 LOC391156 FNBP2 1q31.3 formin binding protein 2 IKBKE 1q32.1 inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon RASSF5 1q32.1 Ras association (RalGDS/AF-6) domain family 5 LGTN 1q31-q32 ligatin DYRK3 1q32 dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 3 MAPKAPK2 1q32 mitogen-activated protein kinase-activated protein kinase 2 IL10 1q31.3-q32.1 interleukin 10 IL19 1q32.2 interleukin 19 IL20 1q32 interleukin 20 IL24 1q32 interleukin 24 TOSO 1q32.1 regulator of Fas-induced apoptosis PIGR 1q32 polymeric immunoglobulin receptor FKSG87 1q32.1 FKSG87 protein LOC387623 1 hypothetical gene supported by NM_024115 SARG 1q32.1 specifically androgen-regulated protein DKFZp451J1719 1q32.1 hypothetical DKFZp451J1719 PFKFB2 1q31 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 C4BPB 1q32 complement component 4 binding protein, beta C4BPA 1q32 complement component 4 binding protein, alpha LOC343024 1q32.1 similar to C4BP alpha chain precursor - rabbit
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 3637 47 418 a fraction of the NORE1A in cells is localized to their centrosomes 2008 18211824
  • also called NORE1A or variant 1
  • harbors an arginine-rich NLS within the N-terminal region spanning the 51th to 100th amino acid residues, and the NLS is required for the entry of NORE1 into the nucleus and nucleolus
  • induces apoptosis in a cytoplasmic localization-dependent manner
  • both NORE1A and NORE1B decrease cellular growth and colony forming ability of tumor cells and enhance tumor cell response to apoptotic stress (PMID: 20969767)
  • 5 - 3521 - 336 - 2003 12845325
    also called RASSF5B or variant 2
    5 splicing 3531 30.5 265 localized in the cytoplasm and translocated into the nucleus upon leptomycin B treatment despite the absence of N-terminal nuclear localization signal (PMID: 20064523) 2008 18211824
  • also called NORE1B or variant 3
  • N-terminal truncated form of NORE1A and having no NLS located within the N-terminus of NORE1A
  • both NORE1A and NORE1B decrease cellular growth and colony forming ability of tumor cells and enhance tumor cell response to apoptotic stress (PMID: 20969767)
  • - - 3498 - 390 - 2003 12845325
    also called RASSF5D or variant 4
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon   Homo sapiens
    Lymphoid/Immunespleen   highly
     thymus   highly
    Reproductivemale systemprostate   
    Respiratoryrespiratory tracttrachea  highly
    Visualeyeanterior segmentiris  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    Endocrineislet cell (alpha,beta...)
    Respiratoryalveolar macrophage
    cell lineage
    cell lines
    fluid/secretion lymph
    at STAGE
    physiological period fetal
    Text spleen
    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
  • 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 (