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FLASH GENE
Symbol KALRN contributors: mct/npt/pgu - updated : 20-12-2014
HGNC name kalirin, RhoGEF kinase
HGNC id 4814
Location 3q21.2      Physical location : 123.813.557 - 124.440.035
Synonym name
  • kalirin-7
  • huntingtin-associated protein interacting protein (duo)
  • serine/threonine kinase with Dbl- and pleckstrin homology domains
  • Synonym symbol(s) DUO, P-CIP10, DUET, FLJ16443, HAPIP, TRAD, Hs.8004, Kalirin, KALRN-7
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 626.48 kb     60 Exon(s)
    regulatory sequence Promoter
    text structure
  • alternate first exons lie >100 kb upstream of exon 2
  • numerous potential regulatory elements
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    text multiple transcriptional start sites result in full-length transcripts possessing different 5' ends encoding proteins with differing amino termini
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    34 - 6524 192.2 1663 brain specific 2008 18199770
    also known as Trad and Duet
    - - 5780 - 1289 brain specific 2008 18199770
  • only second GEF domain
  • DUO
  • 60 - 10835 - 2986 - 2008 18199770
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Nervousbrainforebraincerebral cortex  
    nervousbrainbasal nucleiputamen  
    Nervousbraindiencephalonamygdala highly
     braindiencephalonhypothalamus  
     brainbasal nucleicaudate nucleus highly
     nerve   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervouspyramidal cell
    Skeletonosteoblast Homo sapiens
    Skeletonosteoclast Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text brain
    PROTEIN
    PHYSICAL PROPERTIES acid
    STRUCTURE
    motifs/domains
  • N-terminal Sec14 domain, that bound phosphoinositides and ABL1 contributing to spine morphogenesis
  • nine spectrin-like repeat, which separate its essential N-terminal Sec14 domain from its catalytic domain, play an essential role in its contribution to the formation and function of dendritic spines
  • 2 guanine nucleotide exchange factor domains for the GTPases RAC1 and RHOA
  • a Thr1590, following the first GEF domain, is the only CDK5 phosphorylation site
  • a pleckstrin homology (PH) domain
  • HOMOLOGY
    interspecies homolog to C.elegans f55c7.7b
    homolog to rattus Duo (p-cip10)
    intraspecies homolog to human protein Trio,highly
    Homologene
    FAMILY
  • protein kinase superfamily
  • CAMK Ser/Thr protein kinase family
  • CATEGORY transport
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    basic FUNCTION
  • multidomain guanine nucleotide exchange factor (promoting the exchange of GDP by GTP)
  • may be functioning in vesicle trafficking
  • may be playing a role in axonal development and mature brain
  • playing a necessary role for maintenance of hippocampal pyramidal neuron dendrites and dendritic spines
  • playing a critical role in nerve growth factor signaling through NTRK1
  • controls activity-dependent structural and functional plasticity of dendritic spines
  • plays a critical role in axon extension and maintenance of dendritic spines
  • multifunctional Rho GDP/GTP exchange factor, playing a vital role in cytoskeletal organization, affecting process initiation and outgrowth in neurons
  • key regulator of spine morphogenesis
  • may represent a common risk factor for vascular diseases
  • Rho guanine nucleotide exchange factor localized to the postsynaptic density (PSD), and modulating dendritic spine morphology
  • is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus
  • role in secretory granule function and having an expression outside of the nervous system
  • functions as a guanine nucleotide exchange factor for RAC1 in smooth muscle cells (SMCs), and promotes SMC migration and proliferation
  • GTP-exchange factor protein playing a role in cytoskeletal remodeling and dendritic spine formation in neurons
  • may play a role in paracrine and/or endocrine signaling events that control skeletal bone remodeling and the maintenance of bone mass
  • is critical for spine morphogenesis on cortical pyramidal neurons
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text vesicle transport
    PATHWAY
    metabolism
    signaling signal transduction
    Rho GTPase-signaling pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • HAP1
  • RAC1
  • interaction with NTRK1 by the pleckstrin homology domain
  • interacts with AMPA receptors and controls their synaptic expression
  • SNX1 and SNX2 interact with the RAC1 and RHOG guanine nucleotide exchange factor KALRN
  • stable interaction between the PH domain of KALRN and the juxtamembrane region of GRIN2B preceding its cytosolic C-terminal domain
  • NRG1 signaling promotes dendritic spine growth through kalirin
  • cell & other
    REGULATION
    Other regulated by CDK5 that regulate Kalirin function throughout development
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in Alzheimer disease hippocampus
    Susceptibility
  • to coronary heart disease
  • adult ADHD vulnerability
  • to ischemic stroke
  • to schizophrenia
  • Variant & Polymorphism SNP
  • intronic SNP, rs9289231, associated with early-onset coronary heart disease in all white
  • rs11712039 associated with ischemic stroke
  • D1338N substitution significantly diminished the protein ability to catalyse the activation of RAC1, increasing the risk of schizophrenia
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • KALRN-knockout mice have specific reductions in cortical, but not hippocampal, Rac1 signaling and spine density, and exhibit reduced cortical glutamatergic transmission
  • mice with reduced kalirin expression showed reduced neuropil volume in the rodent homologue of the superior temporal sulcus (STS)