K<sub>ir</sub>2.2 | Inwardly rectifying potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

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Target not currently curated in GtoImmuPdb

Target id: 431

Nomenclature: Kir2.2

Family: Inwardly rectifying potassium channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 1 433 17p11.1 KCNJ12 potassium inwardly rectifying channel subfamily J member 12 4,14
Mouse 2 1 427 11 B2 Kcnj12 potassium inwardly-rectifying channel, subfamily J, member 12 11-12
Rat 2 1 427 10q22 Kcnj12 potassium inwardly-rectifying channel, subfamily J, member 12 6
Previous and Unofficial Names
IRK2 | MB-IRK2 | KCNJN1 | ATP-sensitive inward rectifier potassium channel 12 | RB-IRK2 | potassium channel, inwardly rectifying subfamily J, member 12 | potassium inwardly-rectifying channel | potassium inwardly rectifying channel subfamily J member 12
Database Links
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kir2.1 9,16
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
chapsyn-110 7
veli-1 7-8
veli-3 7-8
α1-, β1-, β2-syntrophin 7
α-dystrobrevin-2 7
α-dystrobrevin-1 7
Dp71 7
dystrophin 7
actin-binding LIM protein 7
Dlg3 7
Dlg2 7
SAP-97 7-8
PSD-95 7
SAP102 7
CASK 7-8
Functional Characteristics
IK1 in heart, ‘strong’ inward–rectifier current
Ion Selectivity and Conductance
Species:  Mouse
Rank order:  K+ [34.2 pS]
References:  11

Download all structure-activity data for this target as a CSV file

Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
Intracellular Mg2+ Hs - 5.0 pIC50 - 40.0 15
pIC50 5.0 (IC50 1.1x10-5 M) [15]
Holding voltage: 40.0 mV
Gating inhibitors
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
Ba2+ Mm Antagonist - - 5x10-5 -150.0 – -50.0 11
Conc range: 5x10-5 M [11]
Holding voltage: -150.0 – -50.0 mV
Cs+ Mm Antagonist - - 5x10-6 - 5x10-5 -150.0 – -50.0 11
Conc range: 5x10-6 - 5x10-5 M [11]
Holding voltage: -150.0 – -50.0 mV
Ba2+ Rn Antagonist 5.2 pKi - -80.0 13
pKi 5.2 [13]
Holding voltage: -80.0 mV
View species-specific gating inhibitor tables
Gating Inhibitor Comments
Endogenous inhibitors are intracellular Mg2+ and polyamines (spermine4+, spermidine3+, putrescine2+).
Tissue Distribution
Aortic endothelial cells.
Species:  Human
Technique:  Western Blot
References:  2
Heart, forebrain, cerebellum, skeletal muscle.
Species:  Mouse
Technique:  Northern Blot
References:  11
Cerebellum > motor trigeminal nucleus > olfactory bulb, piriform cortex, cerebral cortex, hippocampus, dentate gyrus, pontine nucleus.
Species:  Mouse
Technique:  In situ hybridisation
References:  3
Medial habenula, spinal medulla > cortex, hippocampus, basal ganglia (caudate putamen, nucleus accumbens, globus pallidus), thalamus, substantia nigra, cerebellum > hypothalamus.
Species:  Rat
Technique:  Immunohistochemistry
References:  10
Thalamus > cerebellum (granule cell layer), brainstem (inf. olivary, motor trigeminal, facial, cochlear and hypoglossal nuclei) > basal ganglia (habenula, vertical limb of the diagonal band) > superior colliculus.
Species:  Rat
Technique:  In situ hybridisation
References:  5
Functional Assays
Patch clamp measurement of the K+ current in cardiac myocytes of Kir2.2 knockout mice using patch clamp.
Species:  Mouse
Tissue:  Heart.
Response measured:  Reduction of IK1 current.
References:  16
Physiological Functions
Maintenance of the resting membrane potential and regulation of the excitability in neurons.
Species:  Mouse
Tissue:  Brain.
References:  1
Formation of the heart IK1 current, with Kir2.1.
Species:  Mouse
Tissue:  Heart.
References:  16


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1. Day M, Carr DB, Ulrich S, Ilijic E, Tkatch T, Surmeier DJ. (2005) Dendritic excitability of mouse frontal cortex pyramidal neurons is shaped by the interaction among HCN, Kir2, and Kleak channels. J. Neurosci., 25 (38): 8776-87. [PMID:16177047]

2. Fang Y, Schram G, Romanenko VG, Shi C, Conti L, Vandenberg CA, Davies PF, Nattel S, Levitan I. (2005) Functional expression of Kir2.x in human aortic endothelial cells: the dominant role of Kir2.2. Am. J. Physiol., Cell Physiol., 289 (5): C1134-44. [PMID:15958527]

3. Horio Y, Morishige K, Takahashi N, Kurachi Y. (1996) Differential distribution of classical inwardly rectifying potassium channel mRNAs in the brain: comparison of IRK2 with IRK1 and IRK3. FEBS Lett., 379 (3): 239-43. [PMID:8603697]

4. Hugnot JP, Pedeutour F, Le Calvez C, Grosgeorge J, Passage E, Fontes M, Lazdunski M. (1997) The human inward rectifying K+ channel Kir 2.2 (KCNJ12) gene: gene structure, assignment to chromosome 17p11.1, and identification of a simple tandem repeat polymorphism. Genomics, 39 (1): 113-6. [PMID:9027495]

5. 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]

6. Koyama H, Morishige K, Takahashi N, Zanelli JS, Fass DN, Kurachi Y. (1994) Molecular cloning, functional expression and localization of a novel inward rectifier potassium channel in the rat brain. FEBS Lett., 341 (2-3): 303-7. [PMID:8137958]

7. Leonoudakis D, Conti LR, Anderson S, Radeke CM, McGuire LM, Adams ME, Froehner SC, Yates 3rd JR, Vandenberg CA. (2004) Protein trafficking and anchoring complexes revealed by proteomic analysis of inward rectifier potassium channel (Kir2.x)-associated proteins. J. Biol. Chem., 279 (21): 22331-46. [PMID:15024025]

8. Leonoudakis D, Conti LR, Radeke CM, McGuire LM, Vandenberg CA. (2004) A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels. J. Biol. Chem., 279 (18): 19051-63. [PMID:14960569]

9. Preisig-Müller R, Schlichthörl G, Goerge T, Heinen S, Brüggemann A, Rajan S, Derst C, Veh RW, Daut J. (2002) Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen's syndrome. Proc. Natl. Acad. Sci. U.S.A., 99 (11): 7774-9. [PMID:12032359]

10. Prüss H, Derst C, Lommel R, Veh RW. (2005) Differential distribution of individual subunits of strongly inwardly rectifying potassium channels (Kir2 family) in rat brain. Brain Res. Mol. Brain Res., 139 (1): 63-79. [PMID:15936845]

11. Takahashi N, Morishige K, Jahangir A, Yamada M, Findlay I, Koyama H, Kurachi Y. (1994) Molecular cloning and functional expression of cDNA encoding a second class of inward rectifier potassium channels in the mouse brain. J. Biol. Chem., 269 (37): 23274-9. [PMID:8083233]

12. Takumi T, Tsuji L, Kondo C, Takahashi N, Morishige K, Copeland NG, Gilbert DJ, Jenkins NA, Kurachi Y. (1996) Assignment of the murine inward rectifier potassium channel Irk2 (Kir2.2) gene to the central region of mouse chromosome 11. Genomics, 37 (2): 270-2. [PMID:8921409]

13. Töpert C, Döring F, Wischmeyer E, Karschin C, Brockhaus J, Ballanyi K, Derst C, Karschin A. (1998) Kir2.4: a novel K+ inward rectifier channel associated with motoneurons of cranial nerve nuclei. J. Neurosci., 18 (11): 4096-105. [PMID:9592090]

14. Wible BA, De Biasi M, Majumder K, Taglialatela M, Brown AM. (1995) Cloning and functional expression of an inwardly rectifying K+ channel from human atrium. Circ. Res., 76 (3): 343-50. [PMID:7859381]

15. Yamashita T, Horio Y, Yamada M, Takahashi N, Kondo C, Kurachi Y. (1996) Competition between Mg2+ and spermine for a cloned IRK2 channel expressed in a human cell line. J. Physiol. (Lond.), 493 ( Pt 1): 143-56. [PMID:8735700]

16. Zaritsky JJ, Redell JB, Tempel BL, Schwarz TL. (2001) The consequences of disrupting cardiac inwardly rectifying K(+) current (I(K1)) as revealed by the targeted deletion of the murine Kir2.1 and Kir2.2 genes. J. Physiol. (Lond.), 533 (Pt 3): 697-710. [PMID:11410627]


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