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Gene and Protein Information ![]() |
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Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 2 | 1 | 393 | 1q23.2 | KCNJ9 | potassium inwardly rectifying channel subfamily J member 9 | 20 |
Mouse | 2 | 1 | 393 | 1 79.66 cM | Kcnj9 | potassium inwardly-rectifying channel, subfamily J, member 9 | 13,19,29 |
Rat | 2 | 1 | 393 | 13q24 | Kcnj9 | potassium inwardly-rectifying channel, subfamily J, member 9 | 6,28 |
Database Links ![]() |
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Alphafold | Q92806 (Hs), P48543 (Mm), Q63511 (Rn) |
CATH/Gene3D | 2.60.40.1400 |
ChEMBL Target | CHEMBL3038490 (Hs) |
Ensembl Gene | ENSG00000162728 (Hs), ENSMUSG00000038026 (Mm), ENSRNOG00000007645 (Rn) |
Entrez Gene | 3765 (Hs), 16524 (Mm), 116560 (Rn) |
Human Protein Atlas | ENSG00000162728 (Hs) |
KEGG Gene | hsa:3765 (Hs), mmu:16524 (Mm), rno:116560 (Rn) |
OMIM | 600932 (Hs) |
Pharos | Q92806 (Hs) |
RefSeq Nucleotide | NM_004983 (Hs), NM_008429 (Mm), NM_053834 (Rn) |
RefSeq Protein | NP_004974 (Hs), NP_032455 (Mm), NP_446286 (Rn) |
UniProtKB | Q92806 (Hs), P48543 (Mm), Q63511 (Rn) |
Wikipedia | KCNJ9 (Hs) |
Associated Proteins ![]() |
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Associated Protein Comments | ||||||||||||||||||||||||
Trafficking and expression:
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Functional Characteristics ![]() |
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G protein-activated inward-rectifier current |
Ion Selectivity and Conductance ![]() |
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Ion Selectivity and Conductance Comments | ||||||
Kir3.3 forms functional heteromers with Kir3.2 (31pS, [10]) and Kir3.1 (39pS, [11,14]). |
Download all structure-activity data for this target as a CSV file
Activators | ||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||
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Activator Comments | ||||||||||||||||
Kir3.3 in complex with Kir3.1 is activated by Gβγ subunits (pEC50 = 11 [11]). |
Tissue Distribution ![]() |
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Physiological Functions ![]() |
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Physiological Functions Comments | ||||||||
For review see [22]. |
Phenotypes, Alleles and Disease Models ![]() |
Mouse data from MGI | ||||||||||||||||||||||||||||||
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Clinically-Relevant Mutations and Pathophysiology ![]() |
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1. Aguado C, Colón J, Ciruela F, Schlaudraff F, Cabañero MJ, Perry C, Watanabe M, Liss B, Wickman K, Luján R. (2008) Cell type-specific subunit composition of G protein-gated potassium channels in the cerebellum. J Neurochem, 105 (2): 497-511. [PMID:18088366]
2. Balana B, Bahima L, Bodhinathan K, Taura JJ, Taylor NM, Nettleton MY, Ciruela F, Slesinger PA. (2013) Ras-association domain of sorting Nexin 27 is critical for regulating expression of GIRK potassium channels. PLoS ONE, 8 (3): e59800. [PMID:23536889]
3. Balana B, Maslennikov I, Kwiatkowski W, Stern KM, Bahima L, Choe S, Slesinger PA. (2011) Mechanism underlying selective regulation of G protein-gated inwardly rectifying potassium channels by the psychostimulant-sensitive sorting nexin 27. Proc Natl Acad Sci USA, 108 (14): 5831-6. [PMID:21422294]
4. Ciruela F, Fernández-Dueñas V, Sahlholm K, Fernández-Alacid L, Nicolau JC, Watanabe M, Luján R. (2010) Evidence for oligomerization between GABAB receptors and GIRK channels containing the GIRK1 and GIRK3 subunits. Eur J Neurosci, 32 (8): 1265-77. [PMID:20846323]
5. Cruz HG, Ivanova T, Lunn ML, Stoffel M, Slesinger PA, Lüscher C. (2004) Bi-directional effects of GABA(B) receptor agonists on the mesolimbic dopamine system. Nat Neurosci, 7 (2): 153-9. [PMID:14745451]
6. Dissmann E, Wischmeyer E, Spauschus A, Pfeil DV, Karschin C, Karschin A. (1996) Functional expression and cellular mRNA localization of a G protein-activated K+ inward rectifier isolated from rat brain. Biochem Biophys Res Commun, 223 (2): 474-9. [PMID:8670306]
7. Fernández-Alacid L, Aguado C, Ciruela F, Martín R, Colón J, Cabañero MJ, Gassmann M, Watanabe M, Shigemoto R, Wickman K et al.. (2009) Subcellular compartment-specific molecular diversity of pre- and post-synaptic GABA-activated GIRK channels in Purkinje cells. J Neurochem, 110 (4): 1363-76. [PMID:19558451]
8. Fowler CE, Aryal P, Suen KF, Slesinger PA. (2007) Evidence for association of GABA(B) receptors with Kir3 channels and regulators of G protein signalling (RGS4) proteins. J Physiol (Lond.), 580 (Pt 1): 51-65. [PMID:17185339]
9. Hilgemann DW, Ball R. (1996) Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2. Science, 273 (5277): 956-9. [PMID:8688080]
10. Jelacic TM, Kennedy ME, Wickman K, Clapham DE. (2000) Functional and biochemical evidence for G-protein-gated inwardly rectifying K+ (GIRK) channels composed of GIRK2 and GIRK3. J Biol Chem, 275 (46): 36211-6. [PMID:10956667]
11. Jelacic TM, Sims SM, Clapham DE. (1999) Functional expression and characterization of G-protein-gated inwardly rectifying K+ channels containing GIRK3. J Membr Biol, 169 (2): 123-9. [PMID:10341034]
12. Karschin C, Karschin A. (1997) Ontogeny of gene expression of Kir channel subunits in the rat. Mol Cell Neurosci, 10 (3-4): 131-48. [PMID:9532576]
13. Kobayashi T, Ikeda K, Ichikawa T, Abe S, Togashi S, Kumanishi T. (1995) Molecular cloning of a mouse G-protein-activated K+ channel (mGIRK1) and distinct distributions of three GIRK (GIRK1, 2 and 3) mRNAs in mouse brain. Biochem Biophys Res Commun, 208 (3): 1166-73. [PMID:7702616]
14. Kofuji P, Davidson N, Lester HA. (1995) Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by G beta gamma subunits and function as heteromultimers. Proc Natl Acad Sci USA, 92 (14): 6542-6. [PMID:7604029]
15. Koyrakh L, Luján R, Colón J, Karschin C, Kurachi Y, Karschin A, Wickman K. (2005) Molecular and cellular diversity of neuronal G-protein-gated potassium channels. J Neurosci, 25 (49): 11468-78. [PMID:16339040]
16. Kozell LB, Walter NA, Milner LC, Wickman K, Buck KJ. (2009) Mapping a barbiturate withdrawal locus to a 0.44 Mb interval and analysis of a novel null mutant identify a role for Kcnj9 (GIRK3) in withdrawal from pentobarbital, zolpidem, and ethanol. J Neurosci, 29 (37): 11662-73. [PMID:19759313]
17. Labouèbe G, Lomazzi M, Cruz HG, Creton C, Luján R, Li M, Yanagawa Y, Obata K, Watanabe M, Wickman K et al.. (2007) RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Nat Neurosci, 10 (12): 1559-68. [PMID:17965710]
18. Lalive AL, Munoz MB, Bellone C, Slesinger PA, Lüscher C, Tan KR. (2014) Firing modes of dopamine neurons drive bidirectional GIRK channel plasticity. J Neurosci, 34 (15): 5107-14. [PMID:24719090]
19. Lesage F, Duprat F, Fink M, Guillemare E, Coppola T, Lazdunski M, Hugnot JP. (1994) Cloning provides evidence for a family of inward rectifier and G-protein coupled K+ channels in the brain. FEBS Lett, 353 (1): 37-42. [PMID:7926018]
20. Lesage F, Fink M, Barhanin J, Lazdunski M, Mattéi MG. (1995) Assignment of human G-protein-coupled inward rectifier K+ channel homolog GIRK3 gene to chromosome 1q21-q23. Genomics, 29 (3): 808-9. [PMID:8575783]
21. Lunn ML, Nassirpour R, Arrabit C, Tan J, McLeod I, Arias CM, Sawchenko PE, Yates 3rd JR, Slesinger PA. (2007) A unique sorting nexin regulates trafficking of potassium channels via a PDZ domain interaction. Nat Neurosci, 10 (10): 1249-59. [PMID:17828261]
22. Lüscher C, Slesinger PA. (2010) Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease. Nat Rev Neurosci, 11 (5): 301-15. [PMID:20389305]
23. Ma D, Zerangue N, Raab-Graham K, Fried SR, Jan YN, Jan LY. (2002) Diverse trafficking patterns due to multiple traffic motifs in G protein-activated inwardly rectifying potassium channels from brain and heart. Neuron, 33 (5): 715-29. [PMID:11879649]
24. Morgan AD, Carroll ME, Loth AK, Stoffel M, Wickman K. (2003) Decreased cocaine self-administration in Kir3 potassium channel subunit knockout mice. Neuropsychopharmacology, 28 (5): 932-8. [PMID:12637950]
25. Munoz MB, Slesinger PA. (2014) Sorting nexin 27 regulation of G protein-gated inwardly rectifying K⁺ channels attenuates in vivo cocaine response. Neuron, 82 (3): 659-69. [PMID:24811384]
26. Pravetoni M, Wickman K. (2008) Behavioral characterization of mice lacking GIRK/Kir3 channel subunits. Genes Brain Behav, 7 (5): 523-31. [PMID:18194467]
27. Torrecilla M, Marker CL, Cintora SC, Stoffel M, Williams JT, Wickman K. (2002) G-protein-gated potassium channels containing Kir3.2 and Kir3.3 subunits mediate the acute inhibitory effects of opioids on locus ceruleus neurons. J Neurosci, 22 (11): 4328-34. [PMID:12040038]
28. Vaughn J, Wolford JK, Prochazka M, Permana PA. (2000) Genomic structure and expression of human KCNJ9 (Kir3.3/GIRK3). Biochem Biophys Res Commun, 274 (2): 302-9. [PMID:10913335]
29. Wickman K, Pu WT, Clapham DE. (2002) Structural characterization of the mouse Girk genes. Gene, 284 (1-2): 241-50. [PMID:11891065]
Adelman JP, Clapham DE, Hibino H, Inanobe A, Jan LY, Karschin A, Kubo Y, Kurachi Y, Lazdunski M, Miki T, Nichols CG, Palmer LG, Pearson WL, Sackin H, Seino S, Slesinger PA, Tucker S, Vandenberg CA. Inwardly rectifying potassium channels (KIR) in GtoPdb v.2023.1. IUPHAR/BPS Guide to Pharmacology CITE. 2023; 2023(1). Available from: https://doi.org/10.2218/gtopdb/F74/2023.1.