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Kir2.1

Family: Inwardly rectifying potassium channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Ion Selectivity and Conductance
Activators
Gating Inhibitors
Pore Blockers
Tissue Distribution
Physiological Functions
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
References
Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 1 427 17q23.1-24.2 KCNJ2 potassium inwardly-rectifying channel, subfamily J, member 2 20
Mouse 2 1 428 11 E2 Kcnj2 potassium inwardly-rectifying channel, subfamily J, member 2 9
Rat 2 1 427 10q32.1 Kcnj2 potassium inwardly-rectifying channel, subfamily J, member 2 28
Previous and Unofficial Names
IRK1
Kir2.1
LQT7
IRK-1
RBL-IRK1
inward rectifier K(+) channel Kir2.1
inward rectifier potassium channel 2
potassium channel, inwardly rectifying subfamily J member 2
potassium inwardly-rectifying channel, subfamily J, member 2
Kcnf1
Database Links
Ensembl ENSG00000123700 (Hs), ENSMUSG00000041695 (Mm), ENSRNOG00000004720 (Rn)
Entrez Gene 3759 (Hs), 16518 (Mm), 29712 (Rn)
GeneCards KCNJ2 (Hs)
GenitoUrinary Development Molecular Anatomy Project Kcnj2 (Mm)
HomoloGene 20249 (Hs)
Human Protein Reference Database 02815 (Hs)
InterPro P63252 (Hs), P35561 (Mm), Q64273 (Rn)
KEGG Gene hsa:3759 (Hs), mmu:16518 (Mm), rno:29712 (Rn)
OMIM 600681 (Hs)
Orphanet Gene ORPHA122791 (Hs)
PharmGKB Gene PA214 (Hs)
PhosphoSitePlus P63252 (Hs), P35561 (Mm)
Protein Ontology (PRO) PRO:000002056 (Hs)
RefSeq Nucleotide NM_000891 (Hs), NM_008425 (Mm), NM_017296 (Rn)
RefSeq Protein NP_000882 (Hs), NP_032451 (Mm), NP_058992 (Rn)
TreeFam ENSG00000123700 (Hs), ENSMUSG00000041695 (Mm), ENSRNOG00000004720 (Rn)
UniGene Hs. 1547 (Hs)
UniProt P63252 (Hs), P35561 (Mm), Q64273 (Rn)
Wikipedia Kir2.1
Potassium channels
Search for 3D structures on the PDB
Search by keyword: Inwardly rectifying potassium channels Kir2.1 Search by accession number: Q64273, P35561, P63252
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kir4.1 4
Kir2.x 18,23
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
PSD-93/Chapsyn 110 13
Filamin-A 22
AKAP79 3
Veli-1 or Veli-3 10-11
CASK 10-11
SAP97 10-12
PSD95 16
Ion Selectivity and Conductance
Species:  Mouse
Rank order:  K+ [21.0 pS]
References:  9
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
PIP2 Mm - - 1x10-5 - 5x10-5 -30.0 6,21,25
Gating inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
oleoyl-CoA Mm - - 1.8x10-8 - 1x10-5 -135.0 – -100.0 21,24
Gating Inhibitor Comments
Gating is also inhibited by PKA and tyrosine kinase phosphorylation [26-27]
Pore Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
Rb+ Mm - - 1x10-3 - 1x10-2 -130.0 – -50.0 1
spermine Mm 9.05 pKd - 40.0 7,29
spermidine Mm 8.1 pKd - 40.0 29
putrescine Mm 5.12 pKd - 40.0 7,29
Mg2+ Mm 4.8 pKd - 40.0 29
Ba2+ Mm 3.88 – 5.6 pKd 1x10-6 - 1x10-4 0.0 – -80.0 2
Cs+ Mm 1.3 – 4.0 pKd 3x10-5 - 3x10-4 0.0 – -102.0 1
Pore Blocker Comments
The action of the majority of these molecules is voltage dependant [1-2,29].
Tissue Distribution
Aortic endothelial cells.
Species:  Human
Technique:  Western blotting
References:  5
Forebrain, skeletal muscle, heart, macrophage cells.
Species:  Mouse
Technique:  Northern Blot
References:  9
Olfactory bulb, neocortex, hippocampus (dentate gyrus), basal ganglia (caudate putamen, nucleus accumbens, lateral olfactory tract nucleus), midbrain (superior colliculus, anterior pretectal nucleus, deep mesencephalic nucleus). motorneurons.
Species:  Rat
Technique:  In situ hybridisation
References:  8,19
Schwann cell microvilli
Species:  Rat
Technique:  Immunocytochemistry
References:  15
Tissue Distribution Comments
Expression in the thalamus has been reported by [19], but not by [8].
Physiological Functions
Maintenance of a resting membrane potential.
Species:  None
Tissue: 
References: 
Repolarisation of cardiac action potential.
Species:  None
Tissue:  Heart.
References: 
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB		 MGI:104744  MP:0000455 abnormal maxilla morphology PMID: 10904001 
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB		 MGI:104744  MP:0001613 abnormal vasodilation PMID: 10904001 
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB		 MGI:104744  MP:0009890 cleft secondary palate PMID: 10904001 
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB		 MGI:104744  MP:0001575 cyanosis PMID: 10904001 
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB		 MGI:104744  MP:0002058 neonatal lethality PMID: 10904001 
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB		 MGI:104744  MP:0009888 palatal shelves fail to meet at midline PMID: 10904001 
Kcnj2tm1Swz Kcnj2tm1Swz/Kcnj2tm1Swz
involves: 129S1/Sv * 129X1/SvJ * FVB		 MGI:104744  MP:0001954 respiratory distress PMID: 10904001 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Atrial fibrillation, familial, 9; ATFB9
OMIM:  613980
Orphanet:  334
References: 
Mutations not determined
Disease:  Andersen-Tawil syndrome.
OMIM:  170390
Orphanet:  37553
Role:  Disruption of the flow of potassium ions in skeletal and cardiac muscle.
Comments:  Characteristics of Andersen-Tawil syndrome are periodic paralysis, cardiac arrhythmia and developmental adnormalities.
References:  14,17
Click column headers to sort
Type Species Molecular location Description Reference
Deletion Human 314-15 17
Deletion Human 95-98 17
Missense Human E303K 17
Missense Human V302M 14
Missense Human G300V 17
Missense Human R218W/Q 17
Missense Human G144S 17
Missense Human S136F 17
Missense Human D71V 17
Disease:  Short QT syndrome-3
OMIM:  609622
Orphanet:  51083
References: 
Mutations not determined

REFERENCES

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1. Abrams, CJ; Davies, NW; Shelton, PA; Stanfield, PR. (1996) The role of a single aspartate residue in ionic selectivity and block of a murine inward rectifier K+ channel Kir2.1. J. Physiol. (Lond.), 493 ( Pt 3): 643-9. [PMID:8799888]

2. Alagem, N; Dvir, M; Reuveny, E. (2001) Mechanism of Ba(2+) block of a mouse inwardly rectifying K+ channel: differential contribution by two discrete residues. J. Physiol. (Lond.), 534 (Pt. 2): 381-93. [PMID:11454958]

3. Dart, C; Leyland, ML. (2001) Targeting of an A kinase-anchoring protein, AKAP79, to an inwardly rectifying potassium channel, Kir2.1. J. Biol. Chem., 276 (23): 20499-505. [PMID:11287423]

4. Fakler, B; Bond, CT; Adelman, JP; Ruppersberg, JP. (1996) Heterooligomeric assembly of inward-rectifier K+ channels from subunits of different subfamilies: Kir2.1 (IRK1) and Kir4.1 (BIR10). Pflugers Arch., 433 (1-2): 77-83. [PMID:9019734]

5. 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]

6. 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]

7. Ishihara, K; Hiraoka, M; Ochi, R. (1996) The tetravalent organic cation spermine causes the gating of the IRK1 channel expressed in murine fibroblast cells. J. Physiol. (Lond.), 491 ( Pt 2): 367-81. [PMID:8866861]

8. 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]

9. Kubo, Y; Baldwin, TJ; Jan, YN; Jan, LY. (1993) Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature, 362 (6416): 127-33. [PMID:7680768]

10. Leonoudakis, D; Conti, LR; Anderson, S; Radeke, CM; McGuire, LM; Adams, ME; Froehner, SC; Yates, 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]

11. 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]

12. Leonoudakis, D; Mailliard, W; Wingerd, K; Clegg, D; Vandenberg, C. (2001) Inward rectifier potassium channel Kir2.2 is associated with synapse-associated protein SAP97. J. Cell. Sci., 114 (Pt 5): 987-98. [PMID:11181181]

13. Leyland, ML; Dart, C. (2004) An alternatively spliced isoform of PSD-93/chapsyn 110 binds to the inwardly rectifying potassium channel, Kir2.1. J. Biol. Chem., 279 (42): 43427-36. [PMID:15304517]

14. Ma, D; Tang, XD; Rogers, TB; Welling, PA. (2007) An andersen-Tawil syndrome mutation in Kir2.1 (V302M) alters the G-loop cytoplasmic K+ conduction pathway. J. Biol. Chem., 282 (8): 5781-9. [PMID:17166852]

15. Mi, H; Deerinck, TJ; Jones, M; Ellisman, MH; Schwarz, TL. (1996) Inwardly rectifying K+ channels that may participate in K+ buffering are localized in microvilli of Schwann cells. J. Neurosci., 16 (8): 2421-9. [PMID:8786419]

16. Nehring, RB; Wischmeyer, E; Döring, F; Veh, RW; Sheng, M; Karschin, A. (2000) Neuronal inwardly rectifying K(+) channels differentially couple to PDZ proteins of the PSD-95/SAP90 family. J. Neurosci., 20 (1): 156-62. [PMID:10627592]

17. Plaster, NM; Tawil, R; Tristani-Firouzi, M; Canún, S; Bendahhou, S; Tsunoda, A; Donaldson, MR; Iannaccone, ST; Brunt, E; Barohn, R; Clark, J; Deymeer, F; George, AL; Fish, FA; Hahn, A; Nitu, A; Ozdemir, C; Serdaroglu, P; Subramony, SH; Wolfe, G; Fu, YH; Ptácek, LJ. (2001) Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell, 105 (4): 511-9. [PMID:11371347]

18. 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]

19. 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]

20. Raab-Graham, KF; Radeke, CM; Vandenberg, CA. (1994) Molecular cloning and expression of a human heart inward rectifier potassium channel. Neuroreport, 5 (18): 2501-5. [PMID:7696590]

21. Rapedius, M; Soom, M; Shumilina, E; Schulze, D; Schönherr, R; Kirsch, C; Lang, F; Tucker, SJ; Baukrowitz, T. (2005) Long chain CoA esters as competitive antagonists of phosphatidylinositol 4,5-bisphosphate activation in Kir channels. J. Biol. Chem., 280 (35): 30760-7. [PMID:15980413]

22. Sampson, LJ; Leyland, ML; Dart, C. (2003) Direct interaction between the actin-binding protein filamin-A and the inwardly rectifying potassium channel, Kir2.1. J. Biol. Chem., 278 (43): 41988-97. [PMID:12923176]

23. Schram, G; Melnyk, P; Pourrier, M; Wang, Z; Nattel, S. (2002) Kir2.4 and Kir2.1 K(+) channel subunits co-assemble: a potential new contributor to inward rectifier current heterogeneity. J. Physiol. (Lond.), 544 (Pt 2): 337-49. [PMID:12381809]

24. Shumilina, E; Klöcker, N; Korniychuk, G; Rapedius, M; Lang, F; Baukrowitz, T. (2006) Cytoplasmic accumulation of long-chain coenzyme A esters activates KATP and inhibits Kir2.1 channels. J. Physiol. (Lond.), 575 (Pt 2): 433-42. [PMID:16777940]

25. Soom, M; Schönherr, R; Kubo, Y; Kirsch, C; Klinger, R; Heinemann, SH. (2001) Multiple PIP2 binding sites in Kir2.1 inwardly rectifying potassium channels. FEBS Lett., 490 (1-2): 49-53. [PMID:11172809]

26. Wischmeyer, E; Döring, F; Karschin, A. (1998) Acute suppression of inwardly rectifying Kir2.1 channels by direct tyrosine kinase phosphorylation. J. Biol. Chem., 273 (51): 34063-8. [PMID:9852063]

27. Wischmeyer, E; Karschin, A. (1996) Receptor stimulation causes slow inhibition of IRK1 inwardly rectifying K+ channels by direct protein kinase A-mediated phosphorylation. Proc. Natl. Acad. Sci. U.S.A., 93 (12): 5819-23. [PMID:8650176]

28. Wischmeyer, E; Lentes, KU; Karschin, A. (1995) Physiological and molecular characterization of an IRK-type inward rectifier K+ channel in a tumour mast cell line. Pflugers Arch., 429 (6): 809-19. [PMID:7603835]

29. Yang, J; Jan, YN; Jan, LY. (1995) Control of rectification and permeation by residues in two distinct domains in an inward rectifier K+ channel. Neuron, 14 (5): 1047-54. [PMID:7748552]

To cite this database page, please use the following:

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, Wade L. Pearson, Susumu Seino, Carol A. Vandenberg.
Inwardly rectifying potassium channels: Kir2.1. Last modified on 20/01/2012. Accessed on 23/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=430.


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