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FLASH GENE
Symbol KCNA3 contributors: mct - updated : 09-02-2013
HGNC name potassium voltage-gated channel, shaker-related subfamily, member 3
HGNC id 6221
Location 1p13.3      Physical location : 111.214.309 - 111.217.655
Synonym name
  • potassium channel 3
  • voltage-gated potassium channel protein Kv1.3
  • Synonym symbol(s) HLK3, KV1.3, MK3, HGK5, HPCN3, HUKIII, MK3, PCN3
    DNA
    TYPE functioning gene
    STRUCTURE 3.35 kb     1 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    GSTM2 1p13.3 glutathione S-transferase M2 (muscle) GSTM1 1p13.3 glutathione S-transferase M1 GSTM5 1p13.3 glutathione S-transferase M5 GSTM3 1p13.3 glutathione S-transferase M3 (brain) EPS8L3 1p13.2-p11 EPS8-like 3 CSF1 1p21-p13.3 colony stimulating factor 1 (macrophage) AHCYL1 1p12 S-adenosylhomocysteine hydrolase-like 1 PRO0233 1p13.2 PRO0233 protein ALX3 1p23-p21 aristaless-like homeobox 3 LOC164153 1p13.2 similar to RIKEN cDNA 4930522D07 LOC388661 1 LOC388661 LOC388662 1 similar to Orphan sodium- and chloride-dependent neurotransmitter transporter NTT4 KCNC4 1p21 potassium voltage-gated channel, Shaw-related subfamily, member 4 LOC388663 1 LOC388663 RBM15 1p13 RNA binding motif protein 15 SLC16A4 1p13.1 solute carrier family 16 (monocarboxylic acid transporters), member 4 HBXIP 1p13.1 hepatitis B virus x interacting protein PROK1 1p21 prokineticin 1 LOC388664 1 similar to prochymosin KCNA10 1p13.1 potassium voltage-gated channel, shaker-related subfamily, member 10 KCNA2 1p13 potassium voltage-gated channel, shaker-related subfamily, member 2 KCNA3 1p13.3 potassium voltage-gated channel, shaker-related subfamily, member 3 LOC137829 1p13.2 similar to Nuclear receptor binding factor-2 CD53 1p13 CD53 antigen RIF1 1p13.2 receptor-interacting factor 1 MGC54289 1p13.2 hypothetical protein MGC54289 CEPT1 1p12 choline/ethanolaminephosphotransferase FLJ22457 1p13.2 hypothetical protein FLJ22457 CHI3L2 1p13.3 chitinase 3-like 2 LOC149620 1p13.2 similar to CHIA protein CHIA 1p21.3-p13.1 similar to CHIA protein LOC128344 1p13.2 hypothetical protein LOC128344 LOC388665 1 similar to DKFZP564K247 protein LOC391066 1 similar to pepsinogen B OVGP1 1p13 oviductal glycoprotein 1, 120kDa (mucin 9, oviductin) MEP50 1p13.2 MEP50 protein ATP5F1 1p12 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit b, isoform 1 MGC24133 1p13.2 hypothetical protein MGC24133 AD026 1p13.1 AD026 protein ADORA3 1p13.3 adenosine A3 receptor RAP1A 1p13.3 RAP1A, member of RAS oncogene family
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 3346 - 575 - 2012 22378744
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly Homo sapiensFetal
    Endocrinepancreasislet of Langerhans   
    Hearing/Equilibriumear     Homo sapiensAdult
    Lymphoid/Immunelymph node    
     thymus    
    Nervousbraindiencephalonamygdala  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    Muscularstriatumskeletal  
    Nervouscentral    Homo sapiensFetal
    Nervousperipherous    Homo sapiensFetal
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet Homo sapiensAdult
    Blood/Hematopoieticprogenitor cell Homo sapiensFetal
    Lymphoid/ImmuneT cell Homo sapiensAdult
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • six putative membrane-spanning domains and
  • an hydrophobic pore including the P domain with the K+ channel signature, flanked by TM domains 5 and 6, sensitive to changes in membrane potential
  • a C-terminal PDZ binding domain, and PDZ-dependent interactions affect both KCNA3 localization and function
  • mono polymer tetramer , complex
    HOMOLOGY
    interspecies homolog to murine Kv1.3
    homolog to Drosophila shaker-related subfamily
    Homologene
    FAMILY potassium channel family A (shaker) subfamily
    CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,membrane
    text
  • hypoxia disrupts AP1/clathrin-mediated forward trafficking of KCNA3 from the trans-Golgi to the plasma membrane thus contributing to decreased KCNA3 surface expression in T lymphocytes
  • N-glycosylation promotes its cell surface expression
  • basic FUNCTION
  • mediating the voltage-dependent potassium ion permeability of excitable membranes
  • assuming opened or closed conformations in response to the voltage difference across the membrane
  • involved in the pathway regulating body weight and energy homeostasis and in the pathway regulating glucose homeostasis (regulation of insulin sensitivity)
  • regulating membrane potential and calcium signaling in T cells
  • having a molecular role in apoptosis
  • required for induction of apoptosis by BAX, at least in lymphocytes
  • slower activation kinetics of KCNA3 in immunological synapse is likely to be the consequence of the redistribution of the channels into distinct membrane domains
  • might play a role in the apoptotic signalling not only in lymphocytes but also in other cells
  • forms the Kv channel of the platelet and megakaryocyte, which sets the resting membrane potential, regulates agonist-evoked Ca(2+) increases and influences circulating platelet numbers
  • may regulate neurotransmitter release differentially in neurons that respond to different frequencies of sound
  • KCNA3 potassium channels are functional in vascular smooth muscle cells and have positive effects on cell migration
  • regulates the duration of the action potential in the presynaptic terminal of C fibers, limiting transmitter release to the postsynaptic cell
  • plays an important role in regulating membrane excitability in diverse cell types ranging from T-lymphocytes to neurons
  • KCNA3 channels play an important role in T-cell activation, and their inhibition suppresses T-cell function
  • signaling cascade linking its functional expression to cell proliferation is activated by the voltage-dependent conformational change of the channels without needing ion conduction
  • heavily glycosylated membrane protein, playing an essential role in modulating membrane excitability in many cell types
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • tetramer forming a complex through its cytoplasmic segment T1 facing the membrane pore with four beta subunits forming the associated cytoplasmic auxiliary subunits
  • traffic and localization of KCNA3/KCNA5 heteromers implicated in the complex regulation of immune system cells
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associating with the N terminus region of alpha subunit
  • KCNE2 influences blood-cerebrospinal fluid anion flux by regulating KCNQ1 and KCNA3 in the choroid plexus epithelium
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in autoimmune diseases (type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularatheroma 
    selective targeting of KCNA3 in CD4(+)CD28null T cells may hold potential therapeutic promise for acute coronary syndrome
    immunologyautoimmune 
    therapeutic target for T cell-mediated autoimmune diseases, by KCNA3 blockers
    ANIMAL & CELL MODELS