Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol RASGRF2 contributors: mct - updated : 24-06-2019
HGNC name Ras protein-specific guanine nucleotide-releasing factor 2
HGNC id 9876
Location 5q14.1      Physical location : 80.256.557 - 80.521.953
Synonym name guanine nucleotide-releasing factor 2
Synonym symbol(s) RGRF2, GRF2, RAS-GRF2, DKFZp781H1715
DNA
TYPE functioning gene
STRUCTURE 269.80 kb     27 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
27 - 8482 140.6 1237 - 2017 27856453
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrineneuroendocrinepituitary  highly
 parathyroid   moderately
Nervousbrain   moderately
Visualeye   predominantly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connective   moderately
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two pleckstrin (PH) homology domains
  • an ilimaquinone (IQ) domain mediating the calcium-dependent interaction with calmodulin but being dispensable for the Ras-GEF activity
  • the DH (DBL-homology) domain mediating interaction with RASGRF1 and EPB49 and being required for RAC1 activation
  • a Ras-GEF domain and an N-terminal Ras-GEF domain forming a Ras-binding site and mediate Ras activation
  • a Ras exchanger motif (REM),
  • a PEST region containing a destruction box (DB),
  • a CDC25 domain
  • mono polymer homomer , heteromer , oligo
    HOMOLOGY
    interspecies homolog to rattus Rasgrf2 (95.9 pc)
    homolog to murine Rasgrf2 (95.5 pc)
    homolog to zebrafish rasgfr2 (86.1 pc)
    Homologene
    FAMILY
    CATEGORY signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • functioning as a calcium-regulated nucleotide exchange factor activating both Ras and RAC1 through the exchange of bound GDP for GTP
  • preferentially activating HRAS in vivo compared to RRAS based on their different types of prenylation
  • functioning in synaptic plasticity by contributing to the induction of long term potentiation
  • involved in T-cell receptor- and NF-AT-mediated immune responses
  • RASGRF1 and -GRF2 may act as adaptors that bind PLCG1 and restrict Ca2+ signalling to the vicinity of focal adhesions, indicating a new role for these GRFs that is required for IL1 induction of the RAS&
  • 8594;ERK pathway and MMP3 expression
  • mediates Ca(2+)-dependent activation of the ERK pathway
  • role for RASGRF2 in the regulation of mesolimbic dopamine neuron activity, reward response, and alcohol use and abuse
  • RASGRF2 regulates both the basal level and environmentally induced increase of newborn neuron survival, as well as in the induction of a distinct form of synaptic plasticity of newborn neurons that contributes to distinct features of hippocampus-derived learning and memory
  • is a calcium sensor and MAPK/ERK activating protein, which has been linked to neurotransmitter release and monoaminergic receptor adaptations
  • controls likely dopaminergic signalling and adaptations to alcohol also in other brain regions, beyond the nucleus accumbens
  • functional role uncovered for RASGRF2 in control of nuclear migration in cone photoreceptors during postnatal retinal development
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling signal transduction
  • regulation of Rho protein signal transduction
  • regulation of small GTPase mediated signal transduction
  • a component
  • heterooligomer with RASGRF1
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • interacting with Ras and RAC1
  • interacting in a calcium-dependent manner with calmodulin
  • interacting with CDK5R1 and EPB49
  • interacting with the AMPA receptor through GRIA1
  • interacting with microtubules
  • binding to RAS is necessary for ubiquitination of RASGRF2
  • CDC42-GDP can inhibit RRAS2 activation by RASGRF1, RASGRF2
  • RASGRF1/2 associates with PLCG1
  • ANXA6 acts as a scaffold for RASGRF2 and RAS proteins and its interaction with RASGRF2 is modulated by GTP and/or activation of Ras proteins
  • cell & other
    REGULATION
    Other phosphorylated by CDK5
    ubiquitinated upon interaction with Ras
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral imprinting      
    frequent methylation and silencing in the carcinogenesis of non-small cell lung cancer (NSCLC)
    Susceptibility to alcoholic cirrhosis
    Variant & Polymorphism SNP
  • A allele of the RASGRF2 polymorphism (rs26907) was significantly more prevalent among alcoholic patients with cirrhosis compared to alcoholic patients without alcoholic liver disease (ALD)
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • ethanol intake and preference were decreased in Rasgrf2(-/-) mice relative to WT controls