ABCC8 Membrane Protein Introduction

Introduction of ABCC8

ABCC8, also known as HRINS, SUR1, SUR, SUR1delta2, ABC36, TNDM2, MRP8, HHF1, PHHI, HI, sulfonylurea receptor (Hyperinsulinemia), or ATP-binding cassette, subfamily C (CFTR/MRP), member 8, is a transmembrane protein of around 177 kDa and consists of 1581 amino acids. In humans, it resides on the chromosome 11p15.1, encoded by the ABCC8 gene. This protein is a subunit of the ATP-sensitive potassium channel that is observed across the cell membrane in pancreatic beta cells. Beta cells release a hormone called insulin and the K-ATP channel is responsible for the control of the secretion of insulin out of beta cells and into the bloodstream. There are some diseases related to ABCC8 mutations including hypoglycemia and leucine-induced hyperinsulinemic. Among its associated pathways are type 2 diabetes mellitus and inwardly rectifying K+ channels.

Basic Information of ABCC8
Protein Name ATP-binding cassette sub-family C member 8
Gene Name ABCC8
Aliases Sulfonylurea receptor 1
Organism Homo sapiens (Human)
UniProt ID Q09428
Transmembrane Times 17
Length (aa) 1581

Function of ABCC8 Membrane Protein

The protein product of the ABCC8 gene belongs to the ATP-binding cassette (ABC) transporter superfamily. ABC transporters are classified into seven distinct subfamilies, including ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White. And ABC proteins can transport varieties of molecules across extracellular and intracellular membranes. ABCC8 is also a member of multidrug resistance-associated protein (MRP) subfamily. This protein plays a role in multi-drug resistance and acts as a modulator of insulin secretion and ATP-sensitive potassium channels. It has been reported that deficiencies in ABCC8 are observed in patients with hyperinsulinemic and hypoglycemia of infancy, which is an autosomal recessive disease of unregulated and high insulin release. Furthermore, mutations also have been correlated with non-insulin-dependent diabetes mellitus type 2, an autosomal dominant disorder of defective insulin secretion. Additionally, orthologs of ABCC8 now have been detected in all mammals for which complete genome information is available. There are some alternatively spliced transcript variants are found for this gene.

ABCC8 Membrane Protein Introduction Fig.1 Spatial relationships between ABCC8 gene regions and Sur1 protein structure. (Jha, 2018)

Application of ABCC8 Membrane Protein in Literature

  1. Işık E., et al. Congenital hyperinsulinism and evolution to sulfonylurea-responsive diabetes later in life due to a novel homozygous p.L171F ABCC8 mutation. J Clin Res Pediatr Endocrinol. 2018. PubMed ID: 29739729

    Patients with homozygous ABCC8 mutations will present with congenital hyperinsulinism (CHI) during newborn periods, the hyperinsulinism shows variability in terms of clinical severity and age at presentation and causes diabetes later in life. ABCC8 mutations patients managed medically should be followed as they may suffer from an increased risk of developing diabetes.

  2. Engwa G.A., et al. Possible association between ABCC8 C49620T polymorphism and type 2 diabetes in a Nigerian population. BMC Med Genet. 2018, 19(1): 78. PubMed ID: 29751826

    ABCC8 C49620T polymorphism exhibits possible connection with T2D marked by the dominance of the mutant TT genotype in T2D patients. Nevertheless, the relationship among TT genotype and lipid abnormalities for possible beneficial influence on people with T2D is unclear.

  3. Piccini B., et al. Transient Neonatal Diabetes Mellitus in a Very Preterm Infant due to ABCC8 Mutation. AJP Rep. 2018, 8(1): e39-e42. PubMed ID: 29527407

    Neonatal diabetes mellitus (NDM) is a kind of monogenic diabetes occurring within 6 months from baby birth, which can be permanent or transient (TNDM). The paper reports a case of a preterm infant with TNDM because of an ABCC8 mutation confirmed by next-generation sequencing (NGS).

  4. Jha R.M., et al. Regionally clustered ABCC8 polymorphisms in a prospective cohort predict cerebral oedema and outcome in severe traumatic brain injury. J Neurol Neurosurg Psychiatry. 2018, 89(11): 1152-1162. PubMed ID: 29674479

    ABCC8 codes for sulfonylurea receptor 1, a central regulatory protein of cerebral oedema in numerous neurological disorders such as traumatic brain injury (TBI). This review identifies four ABCC8 tag SNPs related to cerebral oedema and outcome in TBI, tagging a region involving 33 polymorphisms.

  5. Song J., et al. KCNJ11, ABCC8 and TCF7L2 polymorphisms and the response to sulfonylurea treatment in patients with type 2 diabetes: a bioinformatics assessment. BMC Med Genet. 2017, 18(1): 64. PubMed ID: 28587604

    Type 2 diabetes (T2D) is a worldwide epidemic and sulfonylurea is one of the widely used drugs for the treatment of patients with T2D. This study indicates that a personalized medicine means by tailoring sulfonylurea therapy of T2D patients based on their genotypes of KCNJ11, ABCC8, and TCF7L2 that could obtain an optimal treatment efficacy.

ABCC8 Preparation Options

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  1. Jha R M, et al. (2018). Regionally clustered ABCC8 polymorphisms in a prospective cohort predict cerebral oedema and outcome in severe traumatic brain injury. J Neurol Neurosurg Psychiatry. 89(11): 1152-1162.

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