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    KCNJ3 potassium inwardly-rectifying channel, subfamily J, member 3 [ Homo sapiens ]

    Gene ID: 3760, updated on 20-May-2012
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    Summary

    Official Symbol
    KCNJ3provided by HGNC
    Official Full Name
    potassium inwardly-rectifying channel, subfamily J, member 3provided by HGNC
    Primary source
    HGNC:6264
    See related
    Ensembl:ENSG00000162989; HPRD:03323; MIM:601534; Vega:OTTHUMG00000131937
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    KGA; GIRK1; KIR3.1; FLJ22731
    Summary
    Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and plays an important role in regulating heartbeat. It associates with three other G-protein-activated potassium channels to form a heteromultimeric pore-forming complex that also couples to neurotransmitter receptors in the brain and whereby channel activation can inhibit action potential firing by hyperpolarizing the plasma membrane. These multimeric G-protein-gated inwardly-rectifying potassium (GIRK) channels may play a role in the pathophysiology of epilepsy, addiction, Down's syndrome, ataxia, and Parkinson's disease. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, May 2012]
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    Genomic context

    Location :
    2q24.1
    Sequence :
    Chromosome: 2; NC_000002.11 (155555093..155713014)
    See KCNJ3 in Epigenomics, MapViewer

    Chromosome 2 - NC_000002.11Genomic Context describing neighboring genes Neighboring gene DnaJ (Hsp40) homolog, subfamily A, member 1 pseudogene 2 Neighboring gene UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 13 (GalNAc-T13) Neighboring gene prohibitin pseudogene 4 Neighboring gene chromobox homolog 3 pseudogene 6 Neighboring gene ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1 pseudogene 2

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Association study of the KCNJ3 gene as a susceptibility candidate for schizophrenia in the Chinese population. Yamada K, et al. Hum Genet, 2012 Mar. PMID 21927946.
    2. Kir3.1 channel is functionally involved in TLR4-mediated signaling. Jo HY, et al. Biochem Biophys Res Commun, 2011 Apr 22. PMID 21420934.
    3. G protein {beta}{gamma} gating confers volatile anesthetic inhibition to Kir3 channels. Styer AM, et al. J Biol Chem, 2010 Dec 31. PMID 21044958.
    4. Cloning and characterisation of GIRK1 variants resulting from alternative RNA editing of the KCNJ3 gene transcript in a human breast cancer cell line. Wagner V, et al. J Cell Biochem, 2010 Jun 1. PMID 20512921.
    5. Association study of 182 candidate genes in anorexia nervosa. Pinheiro AP, et al. Am J Med Genet B Neuropsychiatr Genet, 2010 Jul. PMID 20468064.

    See all (33) citations in PubMed

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. These data suggest that the KCNJ3 gene is genetically associated with schizophrenia in Asian populations and add further evidence to the "channelopathy theory of psychiatric illnesses".
      Title: Association study of the KCNJ3 gene as a susceptibility candidate for schizophrenia in the Chinese population.
    2. Kir3.1 channel is involved in the TLR4-mediated signal at an early event by facilitating the recruitment of TLR4 into lipid raft.
      Title: Kir3.1 channel is functionally involved in TLR4-mediated signaling.
    3. halothane predominantly interferes with Gbetagamma-mediated Kir3 currents, such as those functioning during inhibitory synaptic activity
      Title: G protein {beta}{gamma} gating confers volatile anesthetic inhibition to Kir3 channels.
    4. The very high abundance of mRNA's encoding GIRK1 together with the presence of GIRK1 protein suggests a pathophysiological role in breast cancer
      Title: Cloning and characterisation of GIRK1 variants resulting from alternative RNA editing of the KCNJ3 gene transcript in a human breast cancer cell line.
    5. We identified several known single nucleotide polymorphisms in KCNJ3 and KCNJ5, but no mutations in either of the genes.
      Title: Genetic variation in the inwardly rectifying K channel subunits KCNJ3 (GIRK1) and KCNJ5 (GIRK4) in patients with sinus node dysfunction.
    6. S385 identified as in vitro phosphorylation site. Mutation of this residue to alanine resulted in reduced sensitivity of Kir3.1* currents to H89 & Forskolin, confirming in vivo role for this novel site of the Kir3.1 channel subunit in regulation by PKA.
      Title: Mass spectrometric analysis reveals a functionally important PKA phosphorylation site in a Kir3 channel subunit.
    7. Sar 1 H79G and Rab 1 S25N mutants efficiently blocked the plasma membrane trafficking of the Kir3.1/Kir3.4 complex however they did not block the Gbeta1gamma2/Kir3.1 interaction. Gbeta1-4 can interact with Kir3.1 in the absence of Kir3.4.
      Title: Intracellular trafficking and assembly of specific Kir3 channel/G protein complexes.
    8. GIRK1 was overexpressed in breast carcinoma suggesting its involvement in proliferation and oncogenesis and its possible use as a putative pharmaceutical target.
      Title: Expression of K+ channels in normal and cancerous human breast.
    9. Observational study of gene-disease association. (HuGE Navigator)
      Title: Association study of 182 candidate genes in anorexia nervosa.
    10. GIRK1 and GIRK2 channels, but not GIRK3 or GIRK4, may may activate signaling pathways in development of lung cancer
      Title: Expression of G-protein inwardly rectifying potassium channels (GIRKs) in lung cancer cell lines.
    Submit: New GeneRIF Correction See all (12)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    P48549 P62873 GNB1    HPRD  PubMed  
    P48549 P48544 KCNJ5    HPRD  PubMed  
    P48549 P48051 KCNJ6    HPRD  PubMed  
    P48549 Q92806 KCNJ9    HPRD  PubMed  
    BioGRID:109962 BioGRID:106663 ADRB2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109962 BioGRID:108147 DRD2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109962 BioGRID:108149 DRD4    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109962 BioGRID:109044 GNB1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109962 BioGRID:109964 KCNJ5    BioGRID  PubMed Phenotypic Enhancement; Reconstituted Complex 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Activation of G protein gated Potassium channels, organism-specific biosystem (from REACTOME)
      Activation of G protein gated Potassium channels, organism-specific biosystemActivation of Kir 3 channels occurs after binding of G beta gamma subunits of GPCR. Activation of Kir3/GIRK leads to K+ efflux. The dissociation of GPCR into G alpha and G beta gamma subunits is acti...
    • Activation of GABAB receptors, organism-specific biosystem (from REACTOME)
      Activation of GABAB receptors, organism-specific biosystemGABA B receptors are metabotropic receptors that are functionally linked to C type G protein coupled receptors.? GABA B receptors are activated upon ligand binding. The GABA B1 subunit binds ligand a...
    • Calcium Regulation in the Cardiac Cell, organism-specific biosystem (from WikiPathways)
      Calcium Regulation in the Cardiac Cell, organism-specific biosystemCalcium is a common signaling mechanism, as once it enters the cytoplasm it exerts allosteric regulatory affects on many enzymes and proteins. Calcium can act in signal transduction after influx resu...
    • Cholinergic synapse, organism-specific biosystem (from KEGG)
      Cholinergic synapse, organism-specific biosystemAcetylcholine (ACh) is a neurotransmitter widely distributed in the central (and also peripheral, autonomic and enteric) nervous system (CNS). In the CNS, ACh facilitates many functions, such as lear...
    • Dopaminergic synapse, organism-specific biosystem (from KEGG)
      Dopaminergic synapse, organism-specific biosystemDopamine (DA) is an important and prototypical slow neurotransmitter in the mammalian brain, where it controls a variety of functions including locomotor activity, motivation and reward, learning an...
    • Dopaminergic synapse, conserved biosystem (from KEGG)
      Dopaminergic synapse, conserved biosystemDopamine (DA) is an important and prototypical slow neurotransmitter in the mammalian brain, where it controls a variety of functions including locomotor activity, motivation and reward, learning an...
    • G Protein Signaling Pathways, organism-specific biosystem (from WikiPathways)
      G Protein Signaling Pathways, organism-specific biosystemG proteins, short for guanine nucleotide-binding proteins, are a family of proteins involved in second messenger cascades. G proteins are so called because they function as "molecular switches". They...
    • G protein gated Potassium channels, organism-specific biosystem (from REACTOME)
      G protein gated Potassium channels, organism-specific biosystemInwardly rectifying G protein activated K+ channels (GIRK) are tetrameric assemblies of Ki3 3 family subunits (Kir 3.1, 3.2 3.3 and 3.4). The activation of G protein coupled receptor by ligand result...
    • GABA B receptor activation, organism-specific biosystem (from REACTOME)
      GABA B receptor activation, organism-specific biosystemFunctional GABA B receptors are heteromers of GABA B1 and B2 subunits, complexed with G protein alpha-i, 0, beta, and gamma subunits. They function as metabotropic receptors. When GABA is bound to th...
    • GABA receptor activation, organism-specific biosystem (from REACTOME)
      GABA receptor activation, organism-specific biosystemGamma aminobutyric acid (GABA) receptors are the major inhibitory receptors in human synapses. They are of two types. GABA A receptors are fast-acting ligand gated chloride ion channels that mediate ...
    • Glutamatergic synapse, organism-specific biosystem (from KEGG)
      Glutamatergic synapse, organism-specific biosystemGlutamate is the major excitatory neurotransmitter in the mammalian central nervous system(CNS). Glutamate is packaged into synaptic vesicles in the presynaptic terminal. Once released into the synap...
    • Glutamatergic synapse, conserved biosystem (from KEGG)
      Glutamatergic synapse, conserved biosystemGlutamate is the major excitatory neurotransmitter in the mammalian central nervous system(CNS). Glutamate is packaged into synaptic vesicles in the presynaptic terminal. Once released into the synap...
    • Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits, organism-specific biosystem (from REACTOME)
      Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits, organism-specific biosystemGABA B receptors are coupled to Gproteins and function by increasing the K+ and decreasing the Ca2+ inside the cell. The increase in K+ increases the negative membrane potential of the cell thereby h...
    • Inwardly rectifying K+ channels, organism-specific biosystem (from REACTOME)
      Inwardly rectifying K+ channels, organism-specific biosystemInwardly rectifying K+ channels (Kir channels) show an inward rather than outward (like the voltage gated K+ channels) flow of K+ thereby contributing to maintenance of resting membrane potential an...
    • Morphine addiction, organism-specific biosystem (from KEGG)
      Morphine addiction, organism-specific biosystemMorphine is an alkaloid from the plant extracts of opium poppy. Although morphine is highly effective for the treatment of pain, it is also known to be intensely addictive. We now know that the most ...
    • Morphine addiction, conserved biosystem (from KEGG)
      Morphine addiction, conserved biosystemMorphine is an alkaloid from the plant extracts of opium poppy. Although morphine is highly effective for the treatment of pain, it is also known to be intensely addictive. We now know that the most ...
    • Neuronal System, organism-specific biosystem (from REACTOME)
      Neuronal System, organism-specific biosystemThe human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication a...
    • Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell, organism-specific biosystem (from REACTOME)
      Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell, organism-specific biosystemThe neurotransmitter in the synaptic cleft released by the pre-synaptic neuron binds specific receptors located on the post-synaptic terminal. These receptors are either ion channels or G protein cou...
    • Potassium Channels, organism-specific biosystem (from REACTOME)
      Potassium Channels, organism-specific biosystemPotassium channels are tetrameric ion channels that are widely distributed and are found in all cell types. Potassium channels control resting membrane potential in neurons, contribute to regulation ...
    • Retrograde endocannabinoid signaling, organism-specific biosystem (from KEGG)
      Retrograde endocannabinoid signaling, organism-specific biosystemEndogenous cannabinoids (endocannabinoids) serve as retrograde messengers at synapses in various regions of the brain. The family of endocannabinoids includes at least five derivatives of arachidonic...
    • Retrograde endocannabinoid signaling, conserved biosystem (from KEGG)
      Retrograde endocannabinoid signaling, conserved biosystemEndogenous cannabinoids (endocannabinoids) serve as retrograde messengers at synapses in various regions of the brain. The family of endocannabinoids includes at least five derivatives of arachidonic...
    • Serotonergic synapse, organism-specific biosystem (from KEGG)
      Serotonergic synapse, organism-specific biosystemSerotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter that plays important roles in physiological functions such as learning and memory, emotion, sleep, pain, motor function and endoc...
    • Transmission across Chemical Synapses, organism-specific biosystem (from REACTOME)
      Transmission across Chemical Synapses, organism-specific biosystemChemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron,...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    G-protein activated inward rectifier potassium channel activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    contributes_to inward rectifier potassium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    voltage-gated ion channel activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    ion transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    potassium ion transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to electrical stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    synaptic transmission TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    T-tubule IEA
    Inferred from Electronic Annotation
    more info
    		  
    external side of plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    integral to membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    voltage-gated potassium channel complex TAS
    Traceable Author Statement
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    G protein-activated inward rectifier potassium channel 1
    Names
    G protein-activated inward rectifier potassium channel 1
    GIRK-1
    inward rectifier K+ channel KIR3.1
    inward rectifier K(+) channel Kir3.1
    potassium channel, inwardly rectifying subfamily J member 3
    potassium inwardly-rectifying channel subfamily J member 3 splice variant 1e
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001260508.1 → NP_001247437.1  G protein-activated inward rectifier potassium channel 1 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an exon in the coding region, compared to variant 1. This difference results in a frameshift and a protein (isoform 2; also known as GIRK1d) with a truncated C-terminus, compared to isoform 1.
      Source sequence(s)
      AC093633, AK293824, U50964

    2. NM_001260509.1 → NP_001247438.1  G protein-activated inward rectifier potassium channel 1 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks the 3' terminal exon and uses an alternate splice site in the upstream coding region, compared to variant 1. These differences result in a protein (isoform 3; also known as GIRK1c) with a truncated and novel C-terminus, compared to isoform 1.
      Source sequence(s)
      GU068048, U50964

    3. NM_001260510.1 → NP_001247439.1  G protein-activated inward rectifier potassium channel 1 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks multiple 3' terminal exons and contains an additional coding segment, compared to variant 1. These differences result in a protein (isoform 4; also known as GIRK1e) with a truncated and novel C-terminus, compared to isoform 1.
      Source sequence(s)
      GU074516, U50964

    4. NM_002239.3 → NP_002230.1  G protein-activated inward rectifier potassium channel 1 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1; also known as GIRK1a).
      Source sequence(s)
      AC093633, U50964
      Consensus CDS
      CCDS2200.1
      UniProtKB/Swiss-Prot
      P48549
      Related
      ENSP00000295101, OTTHUMP00000162768, ENST00000295101, OTTHUMT00000254890
      Conserved Domains (1) summary
      cl11596
      Location:47 – 385
      Blast Score: 1561
      Ion_trans_2; Ion channel

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000002.11 Reference GRCh37.p5 Primary Assembly

      Range
      155555093..155713014
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000134.1 Alternate HuRef

      Range
      147441981..147599821
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC061961.6 (2000..35618) None
    genomic AC093633.3 AAX93197.1
    genomic AC107060.5 None
    genomic CH471058.2 EAX11461.1
    mRNA AK026384.1 None
    mRNA AK293824.1 BAG57228.1
    mRNA AK293924.1 BAG57305.1
    mRNA AW949825.1 None
    mRNA BC022495.1 AAH22495.1
    mRNA GU068048.1 ADB11083.1
    mRNA GU074515.1 ADB11081.1
    mRNA GU074516.1 ADB11082.1
    mRNA U50964.1 AAB42176.1
    other-genetic DQ892363.2 ABM83289.1
    other-genetic DQ895572.2 ABM86498.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P48549.1 GenPept UniProtKB/Swiss-Prot:P48549
    Q53R59 GenPept UniProtKB/TrEMBL:Q53R59
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
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