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Kir4.2

Family: Inwardly rectifying potassium channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Ion Selectivity and Conductance
Voltage Dependence
Activators
Gating Inhibitors
Pore Blockers
Tissue Distribution
Functional Assays
Biologically Significant Variants
General Comments
References
Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 1 375 21q22.2 KCNJ15 potassium inwardly-rectifying channel, subfamily J, member 15 8
Mouse 2 1 402 16 C4 Kcnj15 potassium inwardly-rectifying channel, subfamily J, member 15 6
Rat 2 1 405 11q11 Kcnj15 potassium inwardly-rectifying channel, subfamily J, member 15 2
Previous and Unofficial Names
Kir1.3
mLV1
IRKK
Kir4.2
Kir1.3
ATP-sensitive inward rectifier potassium channel 15
inward rectifier K(+) channel Kir4.2
potassium channel, inwardly rectifying subfamily J member 15
potassium inwardly-rectifying channel, subfamily J, member 15
4930414N08Rik
AI182284
AI267127
Database Links
Ensembl ENSG00000157551 (Hs), ENSMUSG00000062609 (Mm), ENSRNOG00000001656 (Rn)
Entrez Gene 3772 (Hs), 16516 (Mm), 170847 (Rn)
GeneCards KCNJ15 (Hs)
GenitoUrinary Development Molecular Anatomy Project Kcnj15 (Mm)
HomoloGene 1690 (Hs)
Human Protein Reference Database 03659 (Hs)
InterPro Q99712 (Hs), O88932 (Mm), Q91ZF1 (Rn)
KEGG Gene hsa:3772 (Hs), mmu:16516 (Mm), rno:170847 (Rn)
OMIM 602106 (Hs)
PharmGKB Gene PA30046 (Hs)
PhosphoSitePlus Q99712 (Hs), Q3TNE6 (Mm)
Protein Ontology (PRO) PRO:000001983 (Hs)
RefSeq Nucleotide NM_170736 (Hs), NM_001039056 (Mm), NM_001039057 (Mm), NM_133321 (Rn)
RefSeq Protein NP_733932 (Hs), NP_001034145 (Mm), NP_001034146 (Mm), NP_579855 (Rn)
TreeFam ENSG00000157551 (Hs), ENSMUSG00000062609 (Mm), ENSRNOG00000001656 (Rn)
UniGene Hs. 411299 (Hs)
UniProt Q99712 (Hs), O88932 (Mm), Q91ZF1 (Rn)
Wikipedia Kir4.2
Potassium channels
Search for 3D structures on the PDB
Search by keyword: Inwardly rectifying potassium channels Kir4.2 Search by accession number: Q99712, Q91ZF1, O88932
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kir5.1 6-7
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
CaR 3
CIPP 4
Ion Selectivity and Conductance
Species:  Rat
Rank order:  K+ [25.2 pS]
References:  7
Ion Selectivity and Conductance Comments
A functional channel is also formed by a Kir4.2/5.1 heteromer (K+, 54.2pS, [7]).
Voltage Dependence Comments
Kir4.2 forms channels that display moderate rectification: in low (2 mM) K+, currents are essentially ohmic below 0 mV, while in isomolar K+ rectification is strong, with little outward current above 0 mV [6].
Activators
Key to terms and symbols Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
Ko+ Mm - - 1x10-1 -140.0 – 80.0 6
Activator Comments
In excised patches channels are constitutively active [7]. In Xenopus oocytes prolonged exposure to elevated extracellular K+ causes slow activation of whole cell current by an unknown mechanism [6].
Gating inhibitors
Key to terms and symbols Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
H+ (intracellular) Rn 6.7 – 7.07 pEC50 - -100.0 7
Gating Inhibitor Comments
Kir4.2/5.1 heteromers also form functional channels that are pH sensitive (pEC50=7.64, [7]).
Pore Blockers
Key to terms and symbols Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
Ba2+ Mm - - 1x10-5 - 1x10-4 -120.0 – 100.0 6
Cs+ Mm - - 1x10-5 - 1x10-4 -120.0 – 100.0 6
Tissue Distribution
Kidney, pancreas > lung > prostate, testes, leukocytes.
Species:  Human
Technique:  Northern Blot
References:  5,8
E12.5: Thymus and thyroid gland.
E14.5: Heart valves, thymus medulla, thyroid gland, perichondrium, epidermis.
E17.5: Head (maxillar and mandibular regions, olfactory epithelium, tongue, oropharynx and nasopharynx epithelium, submandibular and lacrimal glands, submandibular and sublingual ducts, teeth primordia, vibrissae, hair follicles), kidney (developing tubules), stomach, thymus, heart valves, lung, bladder, limbs (perichondrium, ligaments, tendons).
Species:  Mouse
Technique:  In situ hybridisation
References:  9
Hepatocyte basolateral membrane.
Species:  Rat
Technique:  Immunohistochemistry
References:  2
Functional Assays
Voltage clamp recording of the cloned channel in heterologous expression systems.
Species:  Mouse
Tissue:  Xenopus oocytes.
Response measured:  Current.
References:  6-7
Voltage clamp recording of cloned channel in heterologous expression systems.
Species:  Rat
Tissue:  HEK 293T cells.
Response measured:  Current.
References:  2
Biologically Significant Variants
Nucleotide accession:  NM_001039056 
Protein accession:  NP_001034145 
Amino acids:  375
Type:  Splice variant
Species:  Mouse
References:  6
Nucleotide accession:  NM_001039057 
Protein accession:  NP_001034146 
Amino acids:  402
Type:  Splice variant
Species:  Mouse
References: 
General Comments
Mouse and rat Kir4.2 channel activity has been successfully studied in heterologous expression systems, while human Kir4.2 has not. Channels that may be comprised of human Kir4.2 have been recorded in Calu-3 cells, a model for human airway gland serous cells [1]. Proteins CIPP and CaR, reported as auxiliary subunits, were identified in yeast 2 hybrid screens [3-4]. No evidence of their interactions in native tissue has been reported to date. Likewise, interactions between Kir5.1 and Kir4.2 have been demonstrated electrophysiologically in heterologous expression systems [6-7], but interaction of these proteins in native tissue has not been demonstrated.

REFERENCES

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1. Aguilar-Bryan, L; Nichols, CG; Wechsler, SW; Clement, JP; Boyd, AE; González, G; Herrera-Sosa, H; Nguy, K; Bryan, J; Nelson, DA. (1995) Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science, 268 (5209): 423-6. [PMID:7716547]

2. Hill, CE; Briggs, MM; Liu, J; Magtanong, L. (2002) Cloning, expression, and localization of a rat hepatocyte inwardly rectifying potassium channel. Am. J. Physiol. Gastrointest. Liver Physiol., 282 (2): G233-40. [PMID:11804844]

3. Huang, C; Sindic, A; Hill, CE; Hujer, KM; Chan, KW; Sassen, M; Wu, Z; Kurachi, Y; Nielsen, S; Romero, MF; Miller, RT. (2007) Interaction of the Ca2+-sensing receptor with the inwardly rectifying potassium channels Kir4.1 and Kir4.2 results in inhibition of channel function. Am. J. Physiol. Renal Physiol., 292 (3): F1073-81. [PMID:17122384]

4. Kurschner, C; Mermelstein, PG; Holden, WT; Surmeier, DJ. (1998) CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0 family members, NMDA receptor subunits, neurexins, and neuroligins. Mol. Cell. Neurosci., 11 (3): 161-72. [PMID:9647694]

5. Ohira, M; Seki, N; Nagase, T; Suzuki, E; Nomura, N; Ohara, O; Hattori, M; Sakaki, Y; Eki, T; Murakami, Y; Saito, T; Ichikawa, H; Ohki, M. (1997) Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21. Genome Res., 7 (1): 47-58. [PMID:9037601]

6. Pearson, WL; Dourado, M; Schreiber, M; Salkoff, L; Nichols, CG. (1999) Expression of a functional Kir4 family inward rectifier K+ channel from a gene cloned from mouse liver. J. Physiol. (Lond.), 514 ( Pt 3): 639-53. [PMID:9882736]

7. Pessia, M; Imbrici, P; D'Adamo, MC; Salvatore, L; Tucker, SJ. (2001) Differential pH sensitivity of Kir4.1 and Kir4.2 potassium channels and their modulation by heteropolymerisation with Kir5.1. J. Physiol. (Lond.), 532 (Pt 2): 359-67. [PMID:11306656]

8. Shuck, ME; Piser, TM; Bock, JH; Slightom, JL; Lee, KS; Bienkowski, MJ. (1997) Cloning and characterization of two K+ inward rectifier (Kir) 1.1 potassium channel homologs from human kidney (Kir1.2 and Kir1.3). J. Biol. Chem., 272 (1): 586-93. [PMID:8995301]

9. Thiery, E; Gosset, P; Damotte, D; Delezoide, AL; de Saint-Sauveur, N; Vayssettes, C; Créau, N. (2000) Developmentally regulated expression of the murine ortholog of the potassium channel KIR4.2 (KCNJ15). Mech. Dev., 95 (1-2): 313-6. [PMID:10906485]

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: Kir4.2. Last modified on 01/07/2010. Accessed on 20/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=439.


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