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FLASH GENE
Symbol RAPGEF4 contributors: shn - updated : 12/05/2012
HGNC name Rap guanine nucleotide exchange factor (GEF) 4
HGNC id 16626
Location 2q31.1      Physical location : 173.600.524 - 173.917.618
Synonym name
  • RAP guanine-nucleotide-exchange factor (GEF) 4
  • cAMP-regulated guanine nucleotide exchange factor II
  • exchange protein directly activated by cAMP 2
  • exchange factor directly activated by cAMP 2
  • putative protein product of Nbla00496
  • Synonym symbol(s) cAMP-GEF2, EPAC2, CGEF2, Nbla00496, CAMP-GEFII
    DNA
    TYPE functioning gene
    STRUCTURE 317.09 kb     31 Exon(s)
    MAPPING cloned Y linked N status provisional
    Map cen - D2S2381 - D2S326 - RAPGEF4 - D2S2307 - D2S2188 - qter
    RNA
    TRANSCRIPTS type messenger
    text three transcripts (PMID: 11707077)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    28 splicing 4120 110 867 highly enriched in the brain and adrenal glands 1998 9856955
    transcript variant 2
    31 splicing 4361 110 1011 highly enriched in the brain and adrenal glands 1998 9856955
    transcript variant 1
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
     pancreas exocrine   moderately
    Endocrineadrenal gland   highly
     neuroendocrine   moderately
     thyroid   moderately
    Nervousbrainforebrain  predominantly
    Visualeyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Visualcone photoreceptor Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N-terminal Ras-GEF domain
  • two cAMP-binding domains
  • a Dishevelled, Egl-10, Pleckstrin (DEP) domain
  • catalytic region harbors a CDC25-homology domain for GEF activity,
  • a REM (Ras exchange motif), and a putative RA (Ras association) domain
  • two cyclic nucleotide binding domain
  • HOMOLOGY
    interspecies ortholog to Rapgef4, Rattus norvegicus
    ortholog to Rapgef4, Mus musculus
    ortholog to RAPGEF4, Pan troglodytes
    Homologene
    FAMILY
  • cyclic adenosine monophosphate binding proteins family
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    text
  • cytoplasmic
  • membrane-associated
  • basic FUNCTION
  • acting as a guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases
  • involved in cAMP-dependent, PKA-independent exocytosis through interaction with RIMS2
  • involved in the regulation of cell adhesion and insulin secretion
  • with RAPGEF4, are differentially expressed within the retina
  • a GEF for Rap, a Ras-like small GTPase that promotes formation of thin spines and AMPAR endocytosis and is required for long-term depression, depotentiation, long-term potentiation and spatial memory storage
  • Epac2 activation causes spine shrinkage, enhances spine motility, promotes AMPAR removal from spines and depresses excitatory transmission
  • promotes mediates dopamine-dependent synaptic remodeling
  • mediates neuromodulation by DAR-D1/D5 and link dopamine signaling with synapse structural remodeling
  • involved in normal and pathological brain plasticity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS exocytosis transport
    PATHWAY
    metabolism
    signaling
    a component
  • probably part of a complex with RIMS2 and GTP-activated RAB3A
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • cAMP
  • protein
  • activates RAP1A, member of RAS oncogene family
  • regulating synaptic membrane exocytosis 2, RIMS2
  • light chain 2 of microtubule-associated protein 1A, MAP1A
  • Sulfonylurea receptor 1, SUR1
  • discs large homolog 4, DLG4
  • glutamate receptor 2, GLUR2; glutamate receptor 3, GLUR3
  • neuroligin 1, NLGN1 and neuroligin 3, NLGN1
  • syntabulin could be a novel effector of RAPGEF4 and play a critical role in cAMP-enhanced insulin secretion (
  • in the absence of F11R, the exchange factors RAPGEF3 and RAPGEF4 are down-regulated, which prevents the activation of the small GTPase RABGEF1
  • cell & other
    REGULATION
    activated by
  • cAMP analog 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (8-CPT)
  • ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • to autism with four rare nonsynonymous variants identified
  • Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS