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FLASH GENE

Symbol

KCNJ11

contributors: mct/shn - updated : 24-08-2016

HGNC name	potassium inwardly-rectifying channel, subfamily J, member 11
HGNC id	6257

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	HHF1 hyperinsulinemic hypoglycemia, familial, 1 HHF2 hyperinsulinemic hypoglycemia, familial, 2 MODY13 maturity-onset diabetes of the young, type 13 NIDDM15 diabetes mellitus, non insulin-dependent, 15 PNDM3 permanent neonatal diabetes mellitus 3
Location	11p15.1      Physical location : 17.406.797 - 17.410.878
Synonym name	ATP-sensitive inward rectifier potassium channel 11
	beta-cell inward rectifier subunit
	inward rectifier K(+) channel Kir6.2
	inwardly rectifying potassium channel KIR6.2
	potassium channel inwardly rectifing subfamily J member 11
	potassium channel, inwardly rectifying subfamily J member 11
Synonym symbol(s)	BIR, JRKK, KIR6.2, PHHI, IKATP, HHF2, MGC133230, TNDM3

DNA

TYPE	functioning gene
STRUCTURE	4.08 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	upstream region contains an Alu repeat (over 900 bp of KCNJ11 5' sequence are required for similar high level expression, and deletion of the Alu repeat results in an increase in promoter activity) (Ashfield 1998)

MAPPING

cloned

Y

linked

N

status

provisional

Map	pter - D11S1981 - D11S921 - KCNJ11 - D11S902 - D11S4138 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000525 1 - 3418 NP_000516 43.39 390 - 1998 9703328 NM_001166290 2 - 2763 NP_001159762 - 303 - -

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine       Endocrine pancreas           thyroid         Visual eye

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Muscular striatum cardiac     Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two membrane-spanning domains
	an amphipatic region pore, including the P domain with the K+ channel signature
	an ATP-binding regulatory domain

mono polymer

homomer , tetramer

HOMOLOGY

interspecies	ortholog to KCNJ11, Pan troglodytes
	ortholog to Kcnj11, Rattus norvegicus
	ortholog to Kcnj11, Mus musculus
	ortholog to kcnj11, Danio rerio

Homologene

FAMILY

potassium channel subfamily J

CATEGORY

transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,cytosolic

basic FUNCTION	having inward rectifier potassium channel activity
	inhibiting, by the binding to adenine nucleotides, which closes the channel, the ATP sensitive Katp channel
	ATP-sensitive K(+) (K(ATP)) channels, comprised of pore-forming KCNJ11 and regulatory ABCC8 subunits, play a critical role in regulating insulin secretion
	might play a significant role in beta cell survival in addition to its role in the regulation of insulin secretion
	plays a role in the pathogenesis of decreased insulin sensitivity in essential hypertension patients

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	constituent with SUR1 of an ATP dependent potassium channel(Katp)
	stoichiometric association in a complex of 4 (KCNJ11) (ABCC8)
	component of ATP sensitive K+ channels

INTERACTION

DNA

RNA

small molecule

protein	sulfonylurea receptor 2A, SUR2A
	he two intracellular domains of Kir6.2 physically interact with each other
	Kir 6.1 to produce functional channels
	interacting with ANK2 (ANK2 has multiple roles in the active trafficking of KCNJ11 to the plasma membrane, as well as key roles in the retention and stabilization of KCNJ11 in relation to the plasma membrane and cytoskeleton)
	ABCC8 controls KCNJ11 gating by modulating KCNJ11 interactions with INPP5J
	slide helix elements that are required for functional channel expression and control of KCNJ11 gating by intracellular ATP
	SPTBN4–targeted CAMK2A directly phosphorylates the inwardly-rectifying potassium channel, KCNJ11
	SPTBN4 is required for CAMK2D, ANK2, KCNJ11, and ABCC8 expression in beta cells
	KCNJ11 acts as an oncogene in hepatocellular carcinoma (HCC) though forming a complex with LDHA

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

HHF2 , NIDDM15 , PNDM3 , HHF1 , MODY13

Susceptibility

to type 2 diabetes with weight gain and obesity

Variant & Polymorphism other	E23K polymorphism enhancing susceptibility to type 2 diabetes, and to gestational diabetes mellitus

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	mice expressing a dominant-negative form of the KATP channel subunit Kir6. 2 develop hypoglycemia with hyperinsulinemia in neonates and hyperglycemia with hypoinsulinemia and decreased beta cell population in adults
	transgenic mice expressing beta cell K(ATP) channels with reduced ATP sensitivity develop severe hyperglycemia, hypoinsulinemia, and ketoacidosis and die within 5 days
	mice lacking the Kir6.2 subunit of K(ATP) channels are susceptible to generalized seizures after brief hypoxia
	mouse expressing a Kir6.2 mutation (V59M) specifically in pancreatic beta cells develop severe diabetes soon after birth and display a reduced percentage of beta cells with abnormal morphology and lower insulin content
	mice carrying a human Kir6.2 mutation (Val59-->Met59) targeted to either muscle or nerve display motor impairments originate in the central nervous system rather than in muscle or peripheral nerves