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FLASH GENE
Symbol RND3 contributors: npt/mct - updated : 23-10-2012
HGNC name Rho family GTPase 3
HGNC id 671
Location 2q23.3      Physical location : 151.324.711 - 151.344.180
Synonym name
  • ras homolog gene family, member E
  • protein MemB
  • Rho-related GTP-binding protein Rho8
    • Synonym symbol(s) RHOE, ARHE, Rho8, memB
    DNA
    TYPE functioning gene
    STRUCTURE 19.47 kb     6 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 2683 - 244 - 1996 8649376
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
    Cardiovascularheart   highly
    Digestiveliver   highly
    Nervousbrain    
    Reproductivemale systemprostate   
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text placenta, brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a KERRA (Lys-Glu-Arg-Arg-Ala) sequence of AAs in the N-terminus, which functions as the lipid raft-targeting determinant
    • conjugated LipoP , Other
    HOMOLOGY
    interspecies homolog to Drosophila Rho-1
    homolog to C.elegans rho1
    ortholog to murine Rnd3
    ortholog to rattus arhe
    Homologene
    FAMILY
  • small GTPase superfamily
  • Rho family
    • CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    text associated with the plasma membrane after farnesylation
    basic FUNCTION
  • regulating the organization of the actin cytoskeleton in response to extracellular growth factors
  • acting as negative regulator of actin assembly and of cell adhesion
  • role for in the regulation of the TP53-mediated stress response
  • function by regulating ROCK1 signaling to control the balance between cell survival and cell death in response to genotoxic stress
  • with ROCK1 are important during keratinocyte differentiation
  • integrates two processes essential for keratinocyte differentiation and stratification: regulation of proliferative status and integrin adhesion
  • inhibits RHOA/ROCK1 signaling to promote actin stress fiber and focal adhesion disassembly
  • regulating the actin cytoskeleton and cell proliferation
  • could act as a tumour suppressor to limit proliferation, but when mutations bypass this activity of RND3, it can promote cancer invasion through its effects in the actin cytoskeleton
  • RND1, RND2, and RND3 are well known as key regulators of the actin cytoskeleton in various cell types, but they comprise a distinct subgroup of the RHO family in that they are GTP bound and constitutively active (pMID: 22357615)
  • induces a very transient decrease in stress fibres but subsequently stimulates a strong increase in stress fibres, in contrast to the reduction observed in other cell types
    • CELLULAR PROCESS cell organization/biogenesis
    cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • GTP
    • protein
  • binding to socius (UBXD5)
  • bind and inhibit rho kinase-1 (ROCK1) (induces neurite-like formation through inhibition of the RHOA/ROCK1 signalling)
  • inhibits the phosphorylation of the translational repressor EIF4EBP1 in response to extracellular stimuli
  • also inhibits the expression and the transcriptional activity of the EIF4E target MYC
  • negatively regulates PLEKHG5, and that as a RhoA-GEF it plays a key role in early embryonic cell shape changes
  • with RND1 both antagonise RhoA/ROCK-mediated actomyosin contractility, thereby regulating cell migration, smooth muscle contractility and neurite extension
  • RND1, RND2, RND3 bind directly to ARHGAP35 and equally induce activation of ARHGAP35 (pMID: 22357615)
  • PLEKHG5 is a RND3 effector that interacts with RNDs via a RAF1-like Ras-binding domain
  • acts by increasing RHOB expression, which is then required for RND3-induced stress fibre assembly
  • PLXNB1 binds in a GTP-dependent manner to RAC1, RAC2, RAC3, RND1, RND2, RND3, and RHOD
  • PLXNB2 competes with ARHGAP35 for binding to RND3, thus blocking the RND3-mediated inhibition of RHOA and also recruits RhoGEFs to directly stimulate RHOA activity
    • cell & other
    REGULATION
    repressed by oestradiol
    FXD3 (its expression downregulates migration and invasion in melanoma cells and RND3, a target known to be involved in these properties)
    Other resistant to Rho-specific GTPase activating proteins
    regulated not by GTP/GDP cycling, but at the level of expression and by post-translational modifications such as prenylation and phosphorylation
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS