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FLASH GENE

Symbol

ABCC8

contributors: mct - updated : 30-06-2015

HGNC name	ATP-binding cassette, sub-family C (CFTR/MRP), member 8
HGNC id	59

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	HHF1 hyperinsulinemic hypoglycemia, familial, 1 PHHIF persistent neonatal hyperinsulinemic hypoglycemia of infancy PNDM2 permanent neonatal diabetes mellitus 2
Location	11p15.1      Physical location : 17.414.432 - 17.498.449
Synonym name	sulfonylurea receptor 1
	sulfonylurea receptor (hyperinsulinemia)
Synonym symbol(s)	SUR1, ABC36, MRP8, HRINS, PHHI, SUR, HI, TNDM2

DNA

TYPE	functioning gene
STRUCTURE	83.95 kb     39 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000352 39 - 4935 NP_000343 177 1581 - 2001 11306805 NM_001287174 39 - 4938 NP_001274103 - 1582 - -

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 Endocrine pancreas       highly Nervous brain         Respiratory lung

tissue

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

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	N-terminal transmembrane domain of ABCC8 (TMD0) interacts with KCNJ11
	two nucleotide binding folds
	an endoplasmic retention signal
	in addition at C terminal an anterograde signal composed in part of a dileucine motif and downstream phenylalanine
	an extracellular N terminal
	three asymetric membrane spanning domains (five, six and six helices)
	two nucleotide binding sites between TM2 and TM3
	C terminal to TM3 and in addition required for KATP channels to exit the ER/cis-Golgi compartments and transit to the cell surface

conjugated

GlycoP , HemoP

HOMOLOGY

interspecies

homolog to murine Abcc8

Homologene

FAMILY

ABC transporter family

CATEGORY

receptor , transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,cytosolic,vesicle

basic FUNCTION	ABC transporter, traffic ATPase, regulator of AFFP-sensitive K+ channels(Katp) and insulin release
	activating Katp by nucleotide binding or hydrolysis on ABCC8, which opens the channel
	following stroke, brain, or spinal cord injury, ABCC8 is increased in neurovascular cells at the site of injury
	ABCC8 and TRPM4 have an intrinsic capacity for stable co-association
	exposure of ABCC8-TRPM4 channels to Mg2+ greatly amplified the effect of a subsequent decrease in the intracellular ATP concentration

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	constituent with KIR6.2 (KCNJ11) of the ATP dependent potassium channel
	stoichiometric association in a complex of 4 (KCNJ11) (ABCC8)
	component of ATP sensitive K+ channels
	following stroke, brain, or spinal cord injury, ABCC8 is increased in neurovascular cells at the site of injury
	ABCC8 and TRPM4 co-assemble to form the unique ABCC8-TRPM4 channel

INTERACTION

DNA

RNA

small molecule

protein	KIR6.2 (KCNJ11)
	ABCC8 controls KCNJ11 gating by modulating KCNJ11 interactions with INPP5J
	ABCC8 controls K(ATP) channel activity but not TRPM4 channels
	SPTBN4 is required for CAMK2D, ANK2, KCNJ11, and ABCC8 expression in pancreatic beta cells

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

HHF1 , PHHIF , PNDM2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation     gain of function F132L, constitute a new genetic aetiology for neonatal diabetes and they act by reducing the K(ATP) channel's ATP sensitivity constitutional       gain of function cause beta-cell dysfunction with non-autoimmune diabetes mellitus in neonates or infants

Susceptibility

may be a minor contributor of NIDDM and obesity in French Caucasians, and hyperinsulinemia in non diabetic Mexican Americans

Variant & Polymorphism SNP	R1273R
	S1369A increasing the risk of type 2 diabetes

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology acquired   suppression of ABCC8 with antisense oligodeoxynucleotide after spinal cord injury presents an opportunity for reducing the devastating sequelae of spinal cord injury

ANIMAL & CELL MODELS

Abcc8(-/-) mice given antisense oligodeoxynucleotide against Abcc8 prevented progressive hemorrhagic necrosis, yielded significantly better neurological function, and resulted in lesions that were one-fourth to one-third the size of those in control animals