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Not curated in GtoImmuPdb
Target id: 435
Nomenclature: Kir3.2
Family: Inwardly rectifying potassium channels (KIR)
Annotation status:
Annotated and reviewed, awaiting update
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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 | 423 | 21q22.13 | KCNJ6 | potassium inwardly rectifying channel subfamily J member 6 | 10,50 |
Mouse | 2 | 1 | 425 | 16 55.44 cM | Kcnj6 | potassium inwardly-rectifying channel, subfamily J, member 6 | 33,60 |
Rat | 2 | 1 | 425 | 11q11 | Kcnj6 | potassium inwardly-rectifying channel, subfamily J, member 6 | 54 |
Database Links ![]() |
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Alphafold | P48051 (Hs), P48542 (Mm), P48550 (Rn) |
CATH/Gene3D | 2.60.40.1400 |
ChEMBL Target | CHEMBL2406895 (Hs), CHEMBL4680029 (Mm) |
Ensembl Gene | ENSG00000157542 (Hs), ENSMUSG00000043301 (Mm), ENSRNOG00000001658 (Rn) |
Entrez Gene | 3763 (Hs), 16522 (Mm), 25743 (Rn) |
Human Protein Atlas | ENSG00000157542 (Hs) |
KEGG Gene | hsa:3763 (Hs), mmu:16522 (Mm), rno:25743 (Rn) |
OMIM | 600877 (Hs) |
Pharos | P48051 (Hs) |
RefSeq Nucleotide | NM_002240 (Hs), NM_001025585 (Mm), NM_010606 (Mm), NM_001025584 (Mm), NM_001025590 (Mm), NM_013192 (Rn) |
RefSeq Protein | NP_002231 (Hs), NP_001020755 (Mm), NP_034736 (Mm), NP_001020756 (Mm), NP_001020761 (Mm), NP_037324 (Rn) |
UniProtKB | P48051 (Hs), P48542 (Mm), P48550 (Rn) |
Wikipedia | KCNJ6 (Hs) |
Selected 3D Structures ![]() |
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Associated Proteins ![]() |
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Associated Protein Comments | ||||||||||||||||||||||||||||||||||||
The main functional assemblies in the brain are Kir3.1/3.2, Kir3.1/3.3 and Kir3.2/3.3 [2,9,12,26,28,32,34,36,42,55]. Kir3.2c contains PDZ binding motif that binds PDZ domain of SNX27 [37]. |
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 | ||||||
Kir3.2 forms functional heteromers with Kir3.3 (31pS, [18]). |
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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View species-specific activator tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Activator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Kir3.2 is also activated by Gβγ subunits [26]. The studies of the action of phosphatidylinositol 4,5-bisphosphate, Na+ and ethanol were performed using Kir3.1/3.2 heteromers or Kir3.2 heterotetramers. |
Gating inhibitors ![]() |
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Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific gating inhibitor tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Gating Inhibitor Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The following references encompass data regarding the Kir3.1/3.2 heteromer: [23-24,29,57,61,63]. Kir3.2 is also inhibited by Gαi subunits[47]. RGS (regulators of G-protein signalling) proteins accelerate GTP hydrolysis of Gαsubunits, so that they increase the amount of GDP-bound Gα subunits, thus reducing the numbers of Gα-free Gβγ subunits [8,49]. Gα subunits bind to Kir3.2 [5,47]. ER forward export motif identified in Kir3.2 [39]. SNX27 regulates trafficking of Kir3.2c and Kir3.3 channels [37]. Data for verapamil and dizocilpine is derived from experiments using weaver mouse Kir3.2. |
Channel Blockers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Channel Blocker Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The following references encompass data regarding the Kir3.1/3.2 heteromer: [25] |
Tissue Distribution ![]() |
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Physiological Functions ![]() |
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Physiological Functions Comments | ||||||||
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Phenotypes, Alleles and Disease Models ![]() |
Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Clinically-Relevant Mutations and Pathophysiology Comments |
In the weaver mouse the natural missense mutation at molecular location G156S in Kir3.2 permits Na+, as well as K+, ions to pass through the channel and reduces its sensitivity to Gβγ [27,44,52]. The weaver mouse experiences spontaneous tonic-clonic seizures [1,46,51]. |
Gene Expression and Pathophysiology ![]() |
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Biologically Significant Variants ![]() |
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Biologically Significant Variant Comments | ||||||||||||||
Distribution of Kir3.2 is related to isoform expression. At least seven exons contribute to producing at least four splice variants [15,56,60]. In the brain some Kir3.2 isoforms exist as complexes, not only with Kir3.1, but also with Kir3.3 [18,55] and Kir 3.4 [34]. |
1. Adelbrecht C, Murer MG, Lauritzen I, Lesage F, Ladzunski M, Agid Y, Raisman-Vozari R. (1997) An immunocytochemical study of a G-protein-gated inward rectifier K+ channel (GIRK2) in the weaver mouse mesencephalon. Neuroreport, 8 (4): 969-74. [PMID:9141074]
2. 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]
3. Arora D, Hearing M, Haluk DM, Mirkovic K, Fajardo-Serrano A, Wessendorf MW, Watanabe M, Luján R, Wickman K. (2011) Acute cocaine exposure weakens GABA(B) receptor-dependent G-protein-gated inwardly rectifying K+ signaling in dopamine neurons of the ventral tegmental area. J Neurosci, 31 (34): 12251-7. [PMID:21865468]
4. Aryal P, Dvir H, Choe S, Slesinger PA. (2009) A discrete alcohol pocket involved in GIRK channel activation. Nat Neurosci, 12 (8): 988-95. [PMID:19561601]
5. Clancy SM, Fowler CE, Finley M, Suen KF, Arrabit C, Berton F, Kosaza T, Casey PJ, Slesinger PA. (2005) Pertussis-toxin-sensitive Galpha subunits selectively bind to C-terminal domain of neuronal GIRK channels: evidence for a heterotrimeric G-protein-channel complex. Mol Cell Neurosci, 28 (2): 375-89. [PMID:15691717]
6. Cruz HG, Berton F, Sollini M, Blanchet C, Pravetoni M, Wickman K, Lüscher C. (2008) Absence and rescue of morphine withdrawal in GIRK/Kir3 knock-out mice. J Neurosci, 28 (15): 4069-77. [PMID:18400906]
7. 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]
8. Doupnik CA, Davidson N, Lester HA, Kofuji P. (1997) RGS proteins reconstitute the rapid gating kinetics of gbetagamma-activated inwardly rectifying K+ channels. Proc Natl Acad Sci USA, 94 (19): 10461-6. [PMID:9294233]
9. 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]
10. Ferrer J, Nichols CG, Makhina EN, Salkoff L, Bernstein J, Gerhard D, Wasson J, Ramanadham S, Permutt A. (1995) Pancreatic islet cells express a family of inwardly rectifying K+ channel subunits which interact to form G-protein-activated channels. J Biol Chem, 270 (44): 26086-91. [PMID:7592809]
11. 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]
12. Hearing M, Kotecki L, Marron Fernandez de Velasco E, Fajardo-Serrano A, Chung HJ, Luján R, Wickman K. (2013) Repeated cocaine weakens GABA(B)-Girk signaling in layer 5/6 pyramidal neurons in the prelimbic cortex. Neuron, 80 (1): 159-70. [PMID:24094109]
13. Ho IH, Murrell-Lagnado RD. (1999) Molecular determinants for sodium-dependent activation of G protein-gated K+ channels. J Biol Chem, 274 (13): 8639-48. [PMID:10085101]
14. Huang CL, Feng S, Hilgemann DW. (1998) Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma. Nature, 391 (6669): 803-6. [PMID:9486652]
15. Inanobe A, Horio Y, Fujita A, Tanemoto M, Hibino H, Inageda K, Kurachi Y. (1999) Molecular cloning and characterization of a novel splicing variant of the Kir3.2 subunit predominantly expressed in mouse testis. J Physiol (Lond.), 521 Pt 1: 19-30. [PMID:10562331]
16. Inanobe A, Yoshimoto Y, Horio Y, Morishige KI, Hibino H, Matsumoto S, Tokunaga Y, Maeda T, Hata Y, Takai Y et al.. (1999) Characterization of G-protein-gated K+ channels composed of Kir3.2 subunits in dopaminergic neurons of the substantia nigra. J Neurosci, 19 (3): 1006-17. [PMID:9920664]
17. Isomoto S, Kondo C, Takahashi N, Matsumoto S, Yamada M, Takumi T, Horio Y, Kurachi Y. (1996) A novel ubiquitously distributed isoform of GIRK2 (GIRK2B) enhances GIRK1 expression of the G-protein-gated K+ current in Xenopus oocytes. Biochem Biophys Res Commun, 218 (1): 286-91. [PMID:8573147]
18. 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]
19. Karschin C, Dissmann E, Stühmer W, Karschin A. (1996) IRK(1-3) and GIRK(1-4) inwardly rectifying K+ channel mRNAs are differentially expressed in the adult rat brain. J Neurosci, 16 (11): 3559-70. [PMID:8642402]
20. 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]
21. 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]
22. Kobayashi T, Ikeda K, Kojima H, Niki H, Yano R, Yoshioka T, Kumanishi T. (1999) Ethanol opens G-protein-activated inwardly rectifying K+ channels. Nat Neurosci, 2 (12): 1091-7. [PMID:10570486]
23. Kobayashi T, Ikeda K, Kumanishi T. (2000) Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes. Br J Pharmacol, 129 (8): 1716-22. [PMID:10780978]
24. Kobayashi T, Washiyama K, Ikeda K. (2003) Inhibition of G protein-activated inwardly rectifying K+ channels by fluoxetine (Prozac). Br J Pharmacol, 138 (6): 1119-28. [PMID:12684268]
25. Kobayashi T, Washiyama K, Ikeda K. (2004) Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs. Neuropsychopharmacology, 29 (10): 1841-51. [PMID:15150531]
26. 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]
27. Kofuji P, Hofer M, Millen KJ, Millonig JH, Davidson N, Lester HA, Hatten ME. (1996) Functional analysis of the weaver mutant GIRK2 K+ channel and rescue of weaver granule cells. Neuron, 16 (5): 941-52. [PMID:8630252]
28. 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]
29. Kuzhikandathil EV, Oxford GS. (2002) Classic D1 dopamine receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) directly inhibits G protein-coupled inwardly rectifying potassium channels. Mol Pharmacol, 62 (1): 119-26. [PMID:12065762]
30. 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]
31. 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]
32. Leaney JL. (2003) Contribution of Kir3.1, Kir3.2A and Kir3.2C subunits to native G protein-gated inwardly rectifying potassium currents in cultured hippocampal neurons. Eur J Neurosci, 18 (8): 2110-8. [PMID:14622172]
33. 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]
34. Lesage F, Guillemare E, Fink M, Duprat F, Heurteaux C, Fosset M, Romey G, Barhanin J, Lazdunski M. (1995) Molecular properties of neuronal G-protein-activated inwardly rectifying K+ channels. J Biol Chem, 270 (48): 28660-7. [PMID:7499385]
35. Lewohl JM, Wilson WR, Mayfield RD, Brozowski SJ, Morrisett RA, Harris RA. (1999) G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action. Nat Neurosci, 2 (12): 1084-90. [PMID:10570485]
36. Liao YJ, Jan YN, Jan LY. (1996) Heteromultimerization of G-protein-gated inwardly rectifying K+ channel proteins GIRK1 and GIRK2 and their altered expression in weaver brain. J Neurosci, 16 (22): 7137-50. [PMID:8929423]
37. 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]
38. Lüscher C, Jan LY, Stoffel M, Malenka RC, Nicoll RA. (1997) G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. Neuron, 19 (3): 687-95. [PMID:9331358]
39. 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]
40. 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]
41. Morishige K, Inanobe A, Yoshimoto Y, Kurachi H, Murata Y, Tokunaga Y, Maeda T, Maruyama Y, Kurachi Y. (1999) Secretagogue-induced exocytosis recruits G protein-gated K+ channels to plasma membrane in endocrine cells. J Biol Chem, 274 (12): 7969-74. [PMID:10075694]
42. 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]
43. Murer G, Adelbrecht C, Lauritzen I, Lesage F, Lazdunski M, Agid Y, Raisman-Vozari R. (1997) An immunocytochemical study on the distribution of two G-protein-gated inward rectifier potassium channels (GIRK2 and GIRK4) in the adult rat brain. Neuroscience, 80 (2): 345-57. [PMID:9284339]
44. Navarro B, Kennedy ME, Velimirovíc B, Bhat D, Peterson AS, Clapham DE. (1996) Nonselective and G betagamma-insensitive weaver K+ channels. Science, 272 (5270): 1950-3. [PMID:8658170]
45. Padgett CL, Lalive AL, Tan KR, Terunuma M, Munoz MB, Pangalos MN, Martínez-Hernández J, Watanabe M, Moss SJ, Luján R et al.. (2012) Methamphetamine-evoked depression of GABA(B) receptor signaling in GABA neurons of the VTA. Neuron, 73 (5): 978-89. [PMID:22405207]
46. Patil N, Cox DR, Bhat D, Faham M, Myers RM, Peterson AS. (1995) A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiation. Nat Genet, 11 (2): 126-9. [PMID:7550338]
47. Peleg S, Varon D, Ivanina T, Dessauer CW, Dascal N. (2002) G(alpha)(i) controls the gating of the G protein-activated K(+) channel, GIRK. Neuron, 33 (1): 87-99. [PMID:11779482]
48. Pravetoni M, Wickman K. (2008) Behavioral characterization of mice lacking GIRK/Kir3 channel subunits. Genes Brain Behav, 7 (5): 523-31. [PMID:18194467]
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John P. Adelman, David E. Clapham, Hiroshi Hibino, Atsushi Inanobe, Lily Y. Jan, Andreas Karschin, Yoshihiro Kubo, Yoshihisa Kurachi, Michel Lazdunski, Takashi Miki, Colin G. Nichols, Lawrence G. Palmer, Wade L. Pearson, Henry Sackin, Susumu Seino, Paul A. Slesinger, Stephen Tucker, Carol A. Vandenberg.
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