Kir6.1

Description: potassium inwardly-rectifying channel, subfamily J, member 8
Gene: Kcnj8
Alias: Kir6.1, kcnj8, sltr, gnite, slmbr

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Introduction

KATP channels are present in most, if not all, excitable tissues, and share the property of being inhibited by intracellular nucleotide triphosphates (Ashcroft 1988 [1048]). Structurally unique amongst K channels, these KATP channels are formed by coexpression of an ABC protein (SUR1, or SUR2; Aguilar-Bryan et al., 1995 [1049]; Inagaki et al., 1996 [1050]) and an inward rectifier K channel subunit (Kir6.1 or Kir6.2; Inagaki et al., 1995a [1051], b [1052]; Inagaki et al., 1996 [1050]). Expression of Kir6.2 alone does not result in functional ion channels, suggesting an intimate and requisite interaction between these two subunits. (Shyng [207])

The gene KCNJ8 (also known as KIR6.1; uKATP-1) encodes Kir6.1, an integral membrane protein, inward-rectifier type potassium channel, subfamily J, member 8. 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.

http://www.ncbi.nlm.nih.gov/gene/3764

Experimental data

Rat Kir6.1 gene in CHO host cells
	Click for details 25 °C show 39 cells	Click for details 35 °C show 11 cells

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Gene

Species	NCBI gene ID	Chromosome	Position
Human	3764	12	9751
Mouse	16523	6	6777
Rat	25472	4	6921

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Transcript

Species	NCBI accession	Length (nt)
Human	NM_004982.4	2274
Mouse	NM_008428.5	2564
Rat	NM_017099.4	1577

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Protein Isoforms

Species	Uniprot ID	Length (aa)
Human	Q15842	424
Mouse	P97794	424
Rat	Q63664	424

Isoforms

Transcript

Length (nt)

Protein

Length (aa)

Variant

Isoform

Known

NM_001330363.1

2559

NP_001317292.1

424

transcript variant 2

isoform 1

NM_001330366.1

2530

NP_001317295.1

127

transcript variant 3

isoform 2

NM_008428.5

2564

NP_032454.1

424

transcript variant 1

isoform 1

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Post-Translational Modifications

PTM

Position

Type

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Structure

The KATP channel is an octameric complex comprised of four Kir6.0 subunits from the inward rectifier family of potassium channels and four sulfonylurea receptors (SURs), a member of the ATP- binding cassette family of proteins. The pore-forming sub- unit Kir6.0 has two different members, Kir6.1 and Kir6.2, which share 70% amino acid identity. The regulatory sub- unit SUR is encoded by two distinct genes, SUR1 and SUR2, and is the site of action for antidiabetic drugs such as glibenclamide used in the treatment of type 2 diabetes mellitus (Babenko et al. 1998 [1059]; Seino 1999 [1060]; Rodrigo and Standen 2005 [1041]; Ashcroft and Gribble 1998 [1062]).

Kir6.1 predicted AlphaFold size

Species	Area (Å²)	Reference
Human	4905.45	source
Mouse	5262.84	source
Rat	5238.31	source

Methodology for AlphaFold size prediction and disclaimer are available here

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CNS Sub-cellular Distribution

KATP channels - of which kKr6.1 is a key unit - are present on endomembranes, in particular in mitochondria (‘‘mitoKATP’’) (Inoue et al. 1991 [1057]; Paucek et al. 1992 [1058]).

Cell imaging showed that a major proportion of heterologously expressed Kir6.1-GFP and endogenously expressed Kir6.1 was distributed in the endoplasmic reticulum with little in the mitochondria or plasma membrane. (Ng [1056])

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Function

ATP-sensitive potassium (KATP) channels - of which Kir6.1 is a central unit - are involved in a number of physiological and pathophysiological processes and form a link between cellular metabolism and membrane excitability. (Ng [1056])

Kir6.1 plays a role in modifying Ca2+ release from intracellular stores. (Ng [1056])

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Interaction

KATP channels -of which Kir6.1 is a key unit - are inhibited by increasing intracellular [ATP] and activated by increasing [ADP]. (Ng [1056])

The KATP channel opener diazoxide increased reactive oxygen species production, and glibenclamide abolished this effect. However, in cells lacking Kir6.1 or expressing siRNA or dominant negative constructs of Kir6.1, the same effect was seen. (Ng [1056])