Kir3.3

Description: potassium inwardly-rectifying channel, subfamily J, member 9
Gene: Kcnj9
Alias: Kir3.3, Girk3, Kcnj9

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Introduction

KCNJ9 (also known as GIRK3; KIR3.3) encodes the integral membrane protein Kir3.3. This is a potassium inwardly-rectifying channel, subfamily J, member 9, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins. It associates with another G-protein-activated potassium channel to form a heteromultimeric pore-forming complex.

http://www.ncbi.nlm.nih.gov/gene/3765

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]).

Experimental data

Rat Kir3.3 gene in CHO host cells
	Click for details 25 °C show 37 cells	Click for details 35 °C show 45 cells

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Gene

Species	NCBI gene ID	Chromosome	Position
Human	3765	1	9025
Mouse	16524	1	8814
Rat	116560	13	7102

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Transcript

Species	NCBI accession	Length (nt)
Human	NM_004983.3	4202
Mouse	NM_001360808.1	3914
Rat	NM_053834.2	2308

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Protein Isoforms

Species	Uniprot ID	Length (aa)
Human	Q92806	393
Mouse	P48543	393
Rat	Q63511	393

Isoforms

Transcript

Length (nt)

Protein

Length (aa)

Variant

Isoform

Known

NM_004983.3

4202

NP_004974.2

393

Predicted

XM_047419850.1

5740

XP_047275806.1

393

transcript variant X4

isoform X2

XM_047419844.1

6189

XP_047275800.1

450

transcript variant X1

isoform X1

XM_047419848.1

5088

XP_047275804.1

450

transcript variant X3

isoform X1

XM_047419846.1

4991

XP_047275802.1

450

transcript variant X2

isoform X1

XM_054336480.1

5862

XP_054192455.1

393

transcript variant X4

isoform X2

XM_054336479.1

5088

XP_054192454.1

450

transcript variant X3

isoform X1

XM_054336478.1

4991

XP_054192453.1

450

transcript variant X2

isoform X1

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Post-Translational Modifications

PTM

Position

Type

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Structure

Kir3.3 predicted AlphaFold size

Species	Area (Å²)	Reference
Human	6340.00	source
Mouse	6885.59	source
Rat	6404.58	source

Methodology for AlphaFold size prediction and disclaimer are available here

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Kinetics

Single channel Conductance of Kir3.3/Kir3.1 in CHO

Kir3.1/3.3 basal activity at different voltages applied to the patch membrane. No channel activity was observed at +60 mV

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Expression and Distribution

Kir3.3 is expressed in mouse brain. Kofuji [195]

5-HT autoreceptors and G protein-gated inwardly rectifying potassium channels (Kir3/GIRK family), as well as their functional connectivity, has been demonstrated in raphe neurons (Penington [994]).

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CNS Sub-cellular Distribution

Kir3.3 subunit protein is expressed in raphe-derived axons at the light and electron microscopic level, but none of the other Kir3 subfamily members or the KATP channel subunits Kir6.1 and Kir6.2. (Pruess [993])

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Function

The GluR7 receptor gene GRIK3 is located on chromosome 1p34–33, where a significant linkage with schizo- phrenia has been reported (DeLisi et al., 2002 [991]. Significant changes of GluR7 expression in schizophrenia have been reported in multiple brain regions (Sokolov, 1998 [992]). (From [989])

The serotonergic system of the brainstem raphe is involved in mood control, the sleep-wake cycle, auto- nomic function, and stress response. The axons of certain dorsal raphe neurons form a dense serotonergic supraependymal plexus lining the brain ventricles, likely regulating ependymal metabolism and activity including ciliary movements and glucose homeostasis. In raphe neurons, serotonin exerts its function partly via 5-HT autoreceptors and G protein-gated inwardly rectifying potassium channels (Kir3/GIRK). Kir3.3 containing potassium channels may be of functional importance in autoregulation and excitability of supraependymal fibres and the complex serotonergic regulation along the parenchyma/CSF border. (Pruess [993])

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Interaction

Recombinantly expressed NCAM180 specifically reduces inward currents of neuron-specific Kir3.1/ 3.2 and Kir3.1/3.3 but not Kir3.1/3.4 channels in Xenopus oocytes and CHO cells (Delling [990]).

NCAM, TrkB and Kir3.3 interact directly with each other via their intracellular domains. Overexpression of the developmentally late appearing Kir3.3 subunit leads to a decrease in NCAM-mediated neurite outgrowth. Kir3.3 chan- nel expression at the cell surface; thus activity is regulated by NCAM and TrkB independently of BDNF ligand binding. These observations indicate that the interplay of recognition molecules, neurotrophin receptors, and ion channels regulate neurite outgrowth. Kleene [988]

G-Protein

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])