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FLASH GENE
Symbol RASGRF1 contributors: mct/pgu - updated : 25-10-2014
HGNC name Ras protein-specific guanine nucleotide-releasing factor 1
HGNC id 9875
Location 15q25.1      Physical location : 79.252.290 - 79.383.215
Synonym name
  • guanine nucleotide exchange factor(S. cerevisiae CDC25-related, son of sevenless-related)
  • Ras-specific guanine nucleotide-releasing factor, CDC25 homolog
  • guanine nucleotide-releasing factor, 55 kD
  • guanine nucleotide-releasing factor 1
  • Ras-specific nucleotide exchange factor CDC25
  • Synonym symbol(s) GRF1, CDC25, CDC25L, GNRP, GRF55, P90A, H-GRF55, PP13187, ras-GRF1
    DNA
    TYPE functioning gene
    STRUCTURE 130.93 kb     28 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure major transcription start site of Rasgrf1 is 1324 bp upstream of the ATG translation start codon
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC146013 15q24.1 similar to SH2 domain protein 2A (T cell-specific adapter protein) (TSAd) (VEGF receptor-associated protein) (SH2 domain containing adapter protein) KIP2 15q24.3 similar to SH2 domain protein 2A (T cell-specific adapter protein) (TSAd) (VEGF receptor-associated protein) (SH2 domain containing adapter protein) IDH3A 15q25.1-q25.2 isocitrate dehydrogenase 3 (NAD+) alpha BG1 15q24-q25 isocitrate dehydrogenase 3 (NAD+) alpha DNAJA4 15q24.1 DnaJ (Hsp40) homolog, subfamily A, member 4 REC14 15q24.1 recombination protein REC14 CRABP1 15q24 cellular retinoic acid binding protein 1 IREB2 15q24 iron-responsive element binding protein 2 LOC123688 15q24.1 similar to RIKEN cDNA C630028N24 gene PSMA4 15q24.1 proteasome (prosome, macropain) subunit, alpha type, 4 CHRNA5 15q24 cholinergic receptor, nicotinic, alpha polypeptide 5 CHRNA3 15q24 cholinergic receptor, nicotinic, alpha polypeptide 3 CHRNB4 15q24 cholinergic receptor, nicotinic, beta polypeptide 4 LOC390612 15 similar to ribosomal protein L18; 60S ribosomal protein L18 LOC388142 15 LOC388142 LOC390613 15 similar to Dynamin-1 (D100) (Dynamin, brain) (B-dynamin) ADAMTS7 15pter-qter a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 7 LOC390614 15 similar to cDNA sequence BC053073; G-protein coupled receptor SALPR; somatostatin and angiotensin-like peptide receptor LOC388143 15 similar to 60S ribosomal protein L21 MORF4L1 15q24 mortality factor 4 like 1 CTSH 15q24-q25 cathepsin H RASGRF1 15q24 Ras protein-specific guanine nucleotide-releasing factor 1 LOC390615 15 similar to HNRPC protein LOC390616 15 similar to RIKEN cDNA 6430502M16 gene P24B 15q24-q25 integral type I protein KIAA1024 15q24.2 KIAA1024 protein LOC390617 15 similar to Transcription factor DP-1 (E2F dimerization partner 1) (DRTF1-polypeptide-1) (DRTF1) LOC390618 15 similar to ribosomal protein L7-like 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    28 - 6414 190 1273 - 2006 17030618
    14 - 4860 - 489 - 2006 17030618
    27 - 6366 - 1257 - 2006 17030618
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
    Nervousbrain   highly Mus musculusAdult
     brain   highly Mus musculusFetal
    Reproductivefemale systemuterus   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervousperipherous   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    IMPRINTING maternally
    text maternally imprinted in neonatal brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one N-terminal RAS-GEF domain
  • two pleckstrin (PH) homology domains
  • one DBL-homology (DBH) domain
  • one IQ domain
  • HOMOLOGY
    Homologene
    FAMILY Rho family GTPase-activating protein
    CATEGORY regulatory , signaling neurotransmitter
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    text
  • synaptosomal membrane
  • present mainly at synaptosome and its expression after birth increases in parallel with the development of neuronal circuitry
  • basic FUNCTION
  • guanine nucleotide releasing factor, specific for Ras proteins
  • regulating postnatal growth through synthesis or release of growth hormone
  • with ARHGAP5, control pivotal aspects of neural development, including neuronal differentiation and process outgrowth
  • neuron-specific guanine nucleotide exchange factor for the small GTPases RAS and RAC1
  • RASGRF1 and ARHGAP5 function to modulate Rho signaling in response to integrin engagement
  • proper neonatal RASGRF1 expression levels are critical for development
  • central role in governing striatal adaptations to dopamine replacement therapy, validating a viable treatment for L-dopa-induced dyskinesia (LID) based on intracellular signaling modulation
  • RASGRF1 and ARHGAP5 are essential genes that have distinct, but overlapping roles in the developing nervous system
  • its function in both the epithelium and stroma is required for mammary gland development
  • is potentially required in both the epithelial and stromal compartments for ductal outgrowth and may play a role in mammary epithelial cell differentiation
  • plays an important role in alveolar rhabdomyosarcomas pathogenesis
  • 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
  • could mediate forms of synaptic plasticity and might participate in the regulation of neuronal excitability and neurite outgrowth though various signal transduction pathway
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with ARHGAP5, regulates actin stress fiber dynamics via hydrolysis of Rho-GTP
  • microtubule-destabilizing factor STMN3 is a novel RASGRF1-interacting protein (STMN3 influences the signaling properties of RASGRF)
  • binds nerve growth factor (NGF)-activated TrkA (NTRK1)
  • can activate both RAS and RAC1, via intrinsic CDC25 and DH domains, respectively
  • RASGRF1/2 associates with PLCG1
  • RASGRF1 is an important upstream component of signal transduction pathways regulating PTTG1 expression and controlling beta cell development and physiological responses
  • cell & other
    REGULATION
    Other imprinting is regulated by a CTCF-dependent methylation-sensitive enhancer blocker
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in temporal lobe epilepsy (TLE)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    new potential therapeutic target to inhibit alveolar rhabdomyosarcomas growth
    ANIMAL & CELL MODELS
  • Rasgrf1 expression from the wild-type paternal allele contributes to learning and memory in neonatal mice
  • Rasgrf1-deficient mice were significantly resistant to the development of dyskinesia during chronic L-dopa treatment