Description: potassium inwardly-rectifying channel, subfamily J, member 3
Gene: Kcnj3     Synonyms: Kir3.1, GIRK1, Kcnf3, Kcnj3



KCNJ3 (also known as KGA; GIRK1; KIR3.1) encodes the integral membrane protein Kir3.1, a potassium inwardly-rectifying channel, subfamily J, member 3. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and plays an important role in regulating heartbeat. It associates with three other G-protein-activated potassium channels to form a heteromultimeric pore-forming complex.



The Kir3.1 gene contains three exons separated by two introns, and its total length exceeds 45 kb. The two transmembrane domains, pore region, and part of the putative carboxyl terminus are encoded by exon 1, whereas the remainder of the tail is encoded by exons 2 and 3. The mRNA transcription initiation site was established, and the first 1520 bp upstream were sequenced; this region lacked a traditional TATA or CAAT box, but contained a GC-rich region as well as various putative transcription factor-binding elements. The 1520 bp upstream and 84 bp downstream of the transcription initiation site were tested for promoter activity in GH4-C1 cells. This sequence of 1604 bp contains a number of fragments that either stimulate or repress transcription, as tested by transient expression of various Kir3.1 promoter/luciferase fusion gene constructs in GH4-C1 cells. Schoots 1997 [966]

RGD ID Chromosome Position Species
2958 3 37068672-37256990 Rat
736667 2 55289567-55447936 Mouse
733789 2 155555093-155713014 Human

Kcnj3 : potassium inwardly-rectifying channel, subfamily J, member 3



Acc No Sequence Length Source
NM_031610 n/A n/A NCBI
NM_008426 n/A n/A NCBI
NM_002239 n/A n/A NCBI



Accession Name Definition Evidence
GO:0016020 membrane Double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins. IEA
GO:0016021 integral to membrane Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane. IEA
GO:0009986 cell surface The external part of the cell wall and/or plasma membrane. IDA
GO:0009897 external side of plasma membrane The side of the plasma membrane that is opposite to the side that faces the cytoplasm. IDA
GO:0030315 T-tubule Invagination of the plasma membrane of a muscle cell that extends inward from the cell surface around each myofibril. The ends of T-tubules make contact with the sarcoplasmic reticulum membrane. IDA
GO:0005945 6-phosphofructokinase complex A protein complex that possesses 6-phosphofructokinase activity; homodimeric, homooctameric, and allosteric homotetrameric forms are known. IEA

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G-protein Interaction

Kir3 channels are activated following stimulation of G protein-coupled receptors (GPCRs) that use the Gi/o family of G proteins. Stimulation of the GPCR promotes exchange of GDP for GTP on the Gα subunit which, in turn, leads to activation of the Gα subunit and the Gβγ dimer. Gβγ dimers bind to and activate Kir3 channels (Reuveny et al. 1994 [968]; Wickman et al. 1994 [969]; Huang et al. 1995 [970]). Gα subunits are required for terminating Kir3 activation. The intrinsic GTPase activity of the Gα subunit hydrolyses GTP, leading to inactivation of the Gβγ dimer. Regulator of G protein signalling (RGS) proteins accelerate the GTPase activity of Gα subunits (GAP), leading to faster activation and deactivation of Kir3 channels (Doupnik et al. 1997 [971]). (From Fowler [965])

Heterotetramers with other kir3

The Kir3 family consists of the Kir3.1, Kir3.2, Kir3.3, and Kir3.4 subunits, and the majority of functional Kir3 channels are believed to exist as heterotetram- ers containing the Kir3.1 subunit, although some studies report on functional Kir3.2 homomers and Kir3.2/3.3 combinations (Wischmeyer et al., 1997; Inanobe et al., 1999; Jelacic et al., 2000).

Constitutive and agonist-induced interactions between Kir3 channels and various Gβγ combinations in living cells are reported by Riven [967].

Gβ1-4 can interact with Kir3.1 in the absence of Kir3.4. Gβ5 does not directly interact with the channel but can still be co-immunoprecipated as part of a larger complex.[963]

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Kir3.1 is expressed in cells of different lineage, i.e., cardiac atrial myocytes as well as various neuronal cell types. Currently no human cell line is known to express the Kir3.1 channel. Schoots 1997 [966]

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G protein-gated inwardly rectifying potassium (GIRK or Kir3) channel activity is important for regulating excitability in the heart and brain (Stanfield et al. 2002 [957]).

Kir3.1 channel is involved in the TLR4-mediated (Toll-like receptor in immune system) signal at an early event by facilitating the recruitment of TLR4 into lipid raft. [961]

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Single Channel Recording of GIRK1 in CHO cells

Kv.11.1 Coexpression of GIRKI and GIRK2 in oocytes and CHO cells produce channels that have macro- scopic and single channel characteristics similar to those de- scribed in central neurons. In contrast, the single channel properties of either GIRK2 or CIR expressed alone are clearly different than any of the native inward rectifiers so far de- scribed. Additionally, GIRK1 does not appear to form func- tional homomeric channels in oocytes or mammalian cell lines, and probably does not form homomeric channels in vivo [999]



Jo HY et al. Kir3.1 channel is functionally involved in TLR4-mediated signaling.
Biochem. Biophys. Res. Commun., 2011 Apr 22 , 407 (687-91).


Styer AM et al. G protein {beta}{gamma} gating confers volatile anesthetic inhibition to Kir3 channels.
J. Biol. Chem., 2010 Dec 31 , 285 (41290-9).


Robitaille M et al. Intracellular trafficking and assembly of specific Kir3 channel/G protein complexes.
Cell. Signal., 2009 Apr , 21 (488-501).


Brevet M et al. Expression of K+ channels in normal and cancerous human breast.
Histol. Histopathol., 2008 Aug , 23 (965-72).


Stanfield PR et al. Constitutively active and G-protein coupled inward rectifier K+ channels: Kir2.0 and Kir3.0.
Rev. Physiol. Biochem. Pharmacol., 2002 , 145 (47-179).


Doupnik CA et al. RGS proteins reconstitute the rapid gating kinetics of gbetagamma-activated inwardly rectifying K+ channels.
Proc. Natl. Acad. Sci. U.S.A., 1997 Sep 16 , 94 (10461-6).



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