Kir3.1

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

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Introduction

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.

http://www.ncbi.nlm.nih.gov/gene/3760

Experimental data

Rat Kir3.1 gene in CHO host cells
	Click for details 25 °C show 48 cells	Click for details 35 °C show 23 cells

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Gene

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]

Species	NCBI gene ID	Chromosome	Position
Human	3760	2	159659
Mouse	16519	2	186343
Rat	50599	3	161750

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Transcript

Species	NCBI accession	Length (nt)
Human	NM_002239.4	4628
Mouse	NM_008426.2	5232
Rat	NM_031610.3	1827

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Protein Isoforms

Species	Uniprot ID	Length (aa)
Human	P48549	501
Mouse	P63250	501
Rat	P63251	501

Isoforms

Transcript

Length (nt)

Protein

Length (aa)

Variant

Isoform

Known

NM_002239.4

4628

NP_002230.1

501

transcript variant 1

isoform 1

NM_001260508.2

4411

NP_001247437.1

235

transcript variant 2

isoform 2

NM_001260509.2

1031

NP_001247438.1

308

transcript variant 3

isoform 3

NM_001260510.2

897

NP_001247439.1

253

transcript variant 4

isoform 4

Known

NM_008426.2

5232

NP_032452.1

501

transcript variant 1

isoform 1

NM_001304810.1

5015

NP_001291739.1

235

transcript variant 2

isoform 2

NM_001355118.1

4902

NP_001342047.1

501

transcript variant 3

isoform 1

Predicted

XM_030247723.2

10776

XP_030103583.1

501

transcript variant X2

isoform X1

XM_036158746.1

10423

XP_036014639.1

501

transcript variant X9

isoform X1

XM_030247737.2

10859

XP_030103597.1

501

transcript variant X7

isoform X1

XM_030247725.2

11018

XP_030103585.1

501

transcript variant X3

isoform X1

XM_030247736.2

10698

XP_030103596.1

501

transcript variant X6

isoform X1

XM_030247738.2

10821

XP_030103598.1

501

transcript variant X8

isoform X1

XM_030247730.2

10555

XP_030103590.1

501

transcript variant X5

isoform X1

XM_030247739.2

10358

XP_030103599.1

501

transcript variant X10

isoform X1

XM_030247729.2

10837

XP_030103589.1

501

transcript variant X4

isoform X1

XM_030247740.2

10164

XP_030103600.1

501

transcript variant X11

isoform X1

XM_036158749.1

9514

XP_036014642.1

501

transcript variant X12

isoform X1

XM_030247752.2

3720

XP_030103612.1

269

transcript variant X16

isoform X3

XM_030247722.2

10077

XP_030103582.1

501

transcript variant X1

isoform X1

XM_030247751.2

9173

XP_030103611.1

501

transcript variant X14

isoform X1

XM_030247749.2

9485

XP_030103609.1

501

transcript variant X13

isoform X1

XM_006497731.5

9628

XP_006497794.1

270

transcript variant X15

isoform X2

Known

NM_031610.3

1827

NP_113798.1

501

Predicted

XM_039105733.1

1460

XP_038961661.1

280

transcript variant X3

isoform X3

XM_039105734.1

1443

XP_038961662.1

235

transcript variant X4

isoform X4

XM_039105731.1

1556

XP_038961659.1

322

transcript variant X1

isoform X1

XM_039105732.1

1396

XP_038961660.1

308

transcript variant X2

isoform X2

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Post-Translational Modifications

PTM

Position

Type

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Structure

Kir3.1 predicted AlphaFold size

Species	Area (Å²)	Reference
Human	4844.39	source
Mouse	3634.91	source
Rat	4677.75	source

Methodology for AlphaFold size prediction and disclaimer are available here

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Kinetics

Single Channel Recording of GIRK1 in CHO cells

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]

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Expression and Distribution

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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Function

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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Interaction

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]