Kir2.1

KCNJ2
Identifiers
Aliases	KCNJ2 , ATFB9, HHBIRK1, HHIRK1, IRK1, KIR2.1, LQT7, SQT3, potassium voltage-gated channel subfamily J member 2, potassium inwardly rectifying channel subfamily J member 2
External IDs	OMIM: 600681; MGI: 104744; HomoloGene: 20249; GeneCards: KCNJ2; OMA:KCNJ2 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17q24.3 Start 70,168,673 bp [1] End 70,180,044 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11 E2|11 75.23 cM Start 110,956,990 bp [2] End 110,967,647 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in inferior ganglion of vagus nerve Skeletal muscle tissue of rectus abdominis dorsal motor nucleus of vagus nerve Skeletal muscle tissue of biceps brachii pons myocardium of left ventricle subthalamic nucleus corpus callosum superior vestibular nucleus inferior olivary nucleus Top expressed in muscle of thigh granulocyte genital tubercle superior frontal gyrus lip primary visual cortex temporal muscle dentate gyrus of hippocampal formation granule cell esophagus upper arm More reference expression data BioGPS More reference expression data
Gene ontology Molecular function voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization voltage-gated ion channel activity identical protein binding phosphatidylinositol-4,5-bisphosphate binding inward rectifier potassium channel activity G-protein activated inward rectifier potassium channel activity Cellular component integral component of membrane rough endoplasmic reticulum Golgi apparatus membrane intercalated disc T-tubule voltage-gated potassium channel complex plasma membrane dendritic spine integral component of plasma membrane smooth endoplasmic reticulum soma dendrite intrinsic component of membrane Biological process cardiac muscle cell action potential regulation of ion transmembrane transport magnesium ion transport cardiac muscle cell action potential involved in contraction ion transport cellular potassium ion homeostasis potassium ion transport regulation of cardiac muscle cell contraction cellular response to mechanical stimulus membrane repolarization during action potential potassium ion transmembrane transport positive regulation of potassium ion transmembrane transport regulation of skeletal muscle contraction via regulation of action potential regulation of resting membrane potential regulation of membrane repolarization relaxation of skeletal muscle regulation of heart rate by cardiac conduction membrane repolarization during cardiac muscle cell action potential protein homotetramerization relaxation of cardiac muscle membrane depolarization during cardiac muscle cell action potential potassium ion import across plasma membrane cardiac conduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3759 16518 Ensembl ENSG00000123700 ENSMUSG00000041695 UniProt P63252 P35561 RefSeq (mRNA) NM_000891 NM_008425 RefSeq (protein) NP_000882 NP_032451 Location (UCSC) Chr 17: 70.17 – 70.18 Mb Chr 11: 110.96 – 110.97 Mb PubMed search [3] [4]
Wikidata
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The K_ir2.1 inward-rectifier potassium channel is a lipid-gated ion channel encoded by the KCNJ2 gene. ^{[5] [6] [7] [8]}

Clinical significance

A defect in this gene is associated with Andersen-Tawil syndrome. ^[9]

A mutation in the KCNJ2 gene has also been shown to cause short QT syndrome. ^[10]

In research

In neurogenetics, Kir2.1 is used in Drosophila research to inhibit neurons, as overexpression of this channel will hyperpolarize cells.

In optogenetics, a trafficking sequence from Kir2.1 has been added to halorhodopsin to improve its membrane localization. The resulting protein eNpHR3.0 is used in optogenetic research to inhibit neurons with light. ^[11]

Expression of Kir2.1 gene in human HEK293 cells induce a transient outward current, creating a steady membrane potential close to the reversal potential of potassium. ^[12]

Interactions

Kir2.1 has been shown to interact with:

• DLG4, ^[13]
• Interleukin 16, ^[14] and
• TRAK2 ^[15]

References

1. GRCh38: Ensembl release 89: ENSG00000123700 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000041695 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Hansen SB (May 2015). "Lipid agonism: The PIP2 paradigm of ligand-gated ion channels". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1851 (5): 620–628. doi:10.1016/j.bbalip.2015.01.011. PMC   4540326 . PMID   25633344.
6. Raab-Graham KF, Radeke CM, Vandenberg CA (December 1994). "Molecular cloning and expression of a human heart inward rectifier potassium channel". NeuroReport. 5 (18): 2501–2505. doi:10.1097/00001756-199412000-00024. PMID   7696590.
7. Derst C, Karschin C, Wischmeyer E, Hirsch JR, Preisig-Müller R, Rajan S, et al. (March 2001). "Genetic and functional linkage of Kir5.1 and Kir2.1 channel subunits". FEBS Letters. 491 (3): 305–311. Bibcode:2001FEBSL.491..305D. doi:10.1016/S0014-5793(01)02202-5. PMID   11240146. S2CID   14452157.
8. Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, et al. (December 2005). "International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews. 57 (4): 509–526. doi:10.1124/pr.57.4.11. PMID   16382105. S2CID   11588492.
9. Donaldson MR, Yoon G, Fu YH, Ptacek LJ (2004). "Andersen-Tawil syndrome: a model of clinical variability, pleiotropy, and genetic heterogeneity". Annals of Medicine. 36 (Suppl 1): 92–97. doi:10.1080/17431380410032490. PMID   15176430. S2CID   7362563.
10. Priori SG, Pandit SV, Rivolta I, Berenfeld O, Ronchetti E, Dhamoon A, et al. (April 2005). "A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene". Circulation Research. 96 (7): 800–807. doi: 10.1161/01.RES.0000162101.76263.8c . PMID   15761194.
11. Gradinaru V, Zhang F, Ramakrishnan C, Mattis J, Prakash R, Diester I, et al. (April 2010). "Molecular and cellular approaches for diversifying and extending optogenetics". Cell. 141 (1): 154–165. doi:10.1016/j.cell.2010.02.037. PMC   4160532 . PMID   20303157.
12. Zhang DY, Lau CP, Li GR (April 2009). "Human Kir2.1 channel carries a transient outward potassium current with inward rectification". Pflugers Archiv. 457 (6): 1275–1285. doi:10.1007/s00424-008-0608-0. PMID   19002489. S2CID   3120804.
13. Nehring RB, Wischmeyer E, Döring F, Veh RW, Sheng M, Karschin A (January 2000). "Neuronal inwardly rectifying K(+) channels differentially couple to PDZ proteins of the PSD-95/SAP90 family". The Journal of Neuroscience. 20 (1): 156–162. doi:10.1523/JNEUROSCI.20-01-00156.2000. PMC   6774109 . PMID   10627592.
14. Kurschner C, Yuzaki M (September 1999). "Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein". The Journal of Neuroscience. 19 (18): 7770–7780. doi:10.1523/JNEUROSCI.19-18-07770.1999. PMC   6782450 . PMID   10479680.
15. Grishin A, Li H, Levitan ES, Zaks-Makhina E (October 2006). "Identification of gamma-aminobutyric acid receptor-interacting factor 1 (TRAK2) as a trafficking factor for the K+ channel Kir2.1". The Journal of Biological Chemistry. 281 (40): 30104–30111. doi: 10.1074/jbc.M602439200 . PMID   16895905.

Further reading

• Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, et al. (December 2005). "International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews. 57 (4): 509–526. doi:10.1124/pr.57.4.11. PMID   16382105. S2CID   11588492.
• Wood LS, Tsai TD, Lee KS, Vogeli G (October 1995). "Cloning and functional expression of a human gene, hIRK1, encoding the heart inward rectifier K+-channel". Gene. 163 (2): 313–317. doi:10.1016/0378-1119(95)00244-Z. PMID   7590287.
• Kubo Y, Baldwin TJ, Jan YN, Jan LY (March 1993). "Primary structure and functional expression of a mouse inward rectifier potassium channel". Nature. 362 (6416): 127–133. Bibcode:1993Natur.362..127K. doi:10.1038/362127a0. PMID   7680768. S2CID   4243856.
• Raab-Graham KF, Radeke CM, Vandenberg CA (December 1994). "Molecular cloning and expression of a human heart inward rectifier potassium channel". NeuroReport. 5 (18): 2501–2505. doi:10.1097/00001756-199412000-00024. PMID   7696590.
• Ashen MD, O'Rourke B, Kluge KA, Johns DC, Tomaselli GF (January 1995). "Inward rectifier K+ channel from human heart and brain: cloning and stable expression in a human cell line". The American Journal of Physiology. 268 (1 Pt 2): H506 –H511. doi:10.1152/ajpheart.1995.268.1.H506. PMID   7840300.
• Tang W, Qin CL, Yang XC (1996). "Cloning, localization, and functional expression of a human brain inward rectifier potassium channel (hIRK1)". Receptors & Channels. 3 (3): 175–183. PMID   8821791.
• Tare M, Prestwich SA, Gordienko DV, Parveen S, Carver JE, Robinson C, et al. (January 1998). "Inwardly rectifying whole cell potassium current in human blood eosinophils". The Journal of Physiology. 506 (Pt 2): 303–318. doi:10.1111/j.1469-7793.1998.303bw.x. PMC   2230727 . PMID   9490857.
• Rae JL, Shepard AR (March 1998). "Inwardly rectifying potassium channels in lens epithelium are from the IRK1 (Kir 2.1) family". Experimental Eye Research. 66 (3): 347–359. doi:10.1006/exer.1997.0432. PMID   9533862.
• Kurschner C, Yuzaki M (September 1999). "Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein". The Journal of Neuroscience. 19 (18): 7770–7780. doi: 10.1523/JNEUROSCI.19-18-07770.1999 . PMC   6782450 . PMID   10479680.
• Tucker SJ, Ashcroft FM (November 1999). "Mapping of the physical interaction between the intracellular domains of an inwardly rectifying potassium channel, Kir6.2". The Journal of Biological Chemistry. 274 (47): 33393–33397. doi: 10.1074/jbc.274.47.33393 . PMID   10559219.
• Nehring RB, Wischmeyer E, Döring F, Veh RW, Sheng M, Karschin A (January 2000). "Neuronal inwardly rectifying K(+) channels differentially couple to PDZ proteins of the PSD-95/SAP90 family". The Journal of Neuroscience. 20 (1): 156–162. doi: 10.1523/JNEUROSCI.20-01-00156.2000 . PMC   6774109 . PMID   10627592.
• Leonoudakis D, Mailliard W, Wingerd K, Clegg D, Vandenberg C (March 2001). "Inward rectifier potassium channel Kir2.2 is associated with synapse-associated protein SAP97". Journal of Cell Science. 114 (Pt 5): 987–998. doi: 10.1242/jcs.114.5.987 . PMID   11181181.
• Derst C, Karschin C, Wischmeyer E, Hirsch JR, Preisig-Müller R, Rajan S, et al. (March 2001). "Genetic and functional linkage of Kir5.1 and Kir2.1 channel subunits". FEBS Letters. 491 (3): 305–311. Bibcode:2001FEBSL.491..305D. doi:10.1016/S0014-5793(01)02202-5. PMID   11240146. S2CID   14452157.
• Stockklausner C, Ludwig J, Ruppersberg JP, Klöcker N (March 2001). "A sequence motif responsible for ER export and surface expression of Kir2.0 inward rectifier K(+) channels". FEBS Letters. 493 (2–3): 129–133. Bibcode:2001FEBSL.493..129S. doi: 10.1016/S0014-5793(01)02286-4 . PMID   11287009. S2CID   19230587.
• Dart C, Leyland ML (June 2001). "Targeting of an A kinase-anchoring protein, AKAP79, to an inwardly rectifying potassium channel, Kir2.1". The Journal of Biological Chemistry. 276 (23): 20499–20505. doi: 10.1074/jbc.M101425200 . PMID   11287423.
• Plaster NM, Tawil R, Tristani-Firouzi M, Canún S, Bendahhou S, Tsunoda A, et al. (May 2001). "Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome". Cell. 105 (4): 511–519. doi: 10.1016/S0092-8674(01)00342-7 . PMID   11371347. S2CID   17015195.
• Jeong JS, Lee HJ, Jung JS, Shin SH, Son YJ, Yoon JH, et al. (November 2001). "Characterization of inwardly rectifying K(+) conductance across the basolateral membrane of rat tracheal epithelia". Biochemical and Biophysical Research Communications. 288 (4): 914–920. doi:10.1006/bbrc.2001.5831. PMID   11688996.
• Giovannardi S, Forlani G, Balestrini M, Bossi E, Tonini R, Sturani E, et al. (April 2002). "Modulation of the inward rectifier potassium channel IRK1 by the Ras signaling pathway". The Journal of Biological Chemistry. 277 (14): 12158–12163. doi: 10.1074/jbc.M110466200 . PMID   11809752.
• Preisig-Müller R, Schlichthörl G, Goerge T, Heinen S, Brüggemann A, Rajan S, et al. (May 2002). "Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen's syndrome". Proceedings of the National Academy of Sciences of the United States of America. 99 (11): 7774–7779. Bibcode:2002PNAS...99.7774P. doi: 10.1073/pnas.102609499 . PMC   124349 . PMID   12032359.
• Ai T, Fujiwara Y, Tsuji K, Otani H, Nakano S, Kubo Y, et al. (June 2002). "Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia". Circulation. 105 (22): 2592–2594. doi: 10.1161/01.CIR.0000019906.35135.A3 . PMID   12045162.

External links

• GeneReviews/NCBI/NIH/UW entry on Andersen-Tawil syndrome
• OMIM entries on Anderson-Tawil syndrome
• KCNJ2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Kir2.1+channel at the U.S. National Library of Medicine Medical Subject Headings (MeSH)