ATP-binding cassette sub-family C member 8

Function

Regulator subunit of pancreatic ATP-sensitive potassium channel (KATP), playing a major role in the regulation of insulin release. In pancreatic cells, it forms KATP channels with KCNJ11; KCNJ11 forms the channel pore while ABCC8 is required for activation and regulation.

Classification

Family (Pfam)

PF00664 ABC_membrane, PF00005 ABC_tran

InterPro

AAA+_ATPase, ABC1_TM_dom, ABC1_TM_sf, ABC_transporter-like_ATP-bd, ABC_transporter-like_CS, ABC_transporter_C-like, ABCC8, ABCC8/9, P-loop_NTPase

Functional cluster

G Protein-Coupled Receptors

Experimental structures · PDB · 8

• 6C3O EM 3.90A
• 6C3P EM 5.60A
• 7S5V EM 3.30A
• 7S5X EM 3.70A
• 7S5Y EM 3.90A
• 7S5Z EM 3.90A
• 7S60 EM 3.70A
• 7S61 EM 4.00A

A predicted model is available from AlphaFold.

Gene Ontology · 41

• GO:0008282 inward rectifying potassium channel
• GO:0005886 plasma membrane
• GO:0031004 potassium ion-transporting ATPase complex
• GO:0042734 presynaptic membrane
• GO:0042383 sarcolemma
• GO:0030672 synaptic vesicle membrane
• GO:0140359 ABC-type transporter activity
• GO:0043531 ADP binding
• GO:0005524 ATP binding
• GO:0016887 ATP hydrolysis activity
• GO:0015272 ATP-activated inward rectifier potassium channel activity
• GO:0019829 ATPase-coupled monoatomic cation transmembrane transporter activity
• GO:0046872 metal ion binding
• GO:0005267 potassium channel activity
• GO:0008281 sulfonylurea receptor activity
• GO:0044325 transmembrane transporter binding
• GO:0007565 female pregnancy
• GO:0001678 intracellular glucose homeostasis
• GO:0007613 memory
• GO:0016525 negative regulation of angiogenesis
• GO:1905604 negative regulation of blood-brain barrier permeability
• GO:0060253 negative regulation of glial cell proliferation
• GO:0046676 negative regulation of insulin secretion
• GO:0010989 negative regulation of low-density lipoprotein particle clearance
• GO:0061855 negative regulation of neuroblast migration
• GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus
• GO:0043268 positive regulation of potassium ion transport
• GO:1905075 positive regulation of tight junction disassembly
• GO:0032760 positive regulation of tumor necrosis factor production
• GO:1900721 positive regulation of uterine smooth muscle relaxation
• GO:1990573 potassium ion import across plasma membrane
• GO:0071805 potassium ion transmembrane transport
• GO:0006813 potassium ion transport
• GO:0050796 regulation of insulin secretion
• GO:0032868 response to insulin
• GO:0032496 response to lipopolysaccharide
• GO:0009268 response to pH
• GO:0009410 response to xenobiotic stimulus
• GO:0010043 response to zinc ion
• GO:0055085 transmembrane transport
• GO:0008542 visual learning

Disease associations

• hypoglycemia, leucine-induced MONDO:0009415
• hyperinsulinemic hypoglycemia, familial, 1 MONDO:0009734
• hyperinsulinemic hypoglycemia, familial, 3 MONDO:0011236
• diabetes mellitus, transient neonatal, 2 MONDO:0012480
• diabetes mellitus, permanent neonatal 3 MONDO:0030088
• maturity-onset diabetes of the young, type 12 MONDO:0978299

Drugs targeting this protein · 14

• GLIPIZIDE blocker
• TOLBUTAMIDE SODIUM blocker
• REPAGLINIDE blocker
• GLIMEPIRIDE blocker
• ACETOHEXAMIDE blocker
• SARAKALIM opener
• NAMINIDIL opener
• GLICLAZIDE blocker
• MITIGLINIDE blocker
• GLYBURIDE blocker
• CHLORPROPAMIDE blocker
• TOLBUTAMIDE blocker
• NATEGLINIDE blocker
• TOLAZAMIDE blocker

Related proteins · sequence + function similarity

• ATP-binding cassette sub-family C member 8 0.99
• ATP-binding cassette sub-family C member 8 0.99
• ATP-binding cassette sub-family C member 9 0.94
• ATP-binding cassette sub-family C member 9 0.93
• ATP-binding cassette sub-family C member 9 0.92
• ATP-binding cassette sub-family C member 9 0.91
• Multidrug resistance-associated protein 1 0.85
• ATP-binding cassette sub-family C member 12 0.85
• Multidrug resistance-associated protein 1 0.84
• ATP-binding cassette sub-family C member 5 0.84
• ABC transporter C family member 12 0.84
• ATP-binding cassette sub-family C member 12 0.84

Co-cited proteins · studied together in the literature

• ATP-sensitive inward rectifier potassium channel 11 11 shared papers
• ATP-binding cassette sub-family C member 8 1 shared papers

Literature · 42 cited papers

• Molecular structure of an open human KATP channel. Proc. Natl. Acad. Sci. U.S.A. · 2021
• ABCC8 variants in MODY12: Review of the literature and report of a case with severe complications. Diabetes Metab. Res. Rev. · 2021
• Molecular structure of human KATP in complex with ATP and ADP. Elife · 2017
• Alternating hypoglycemia and hyperglycemia in a toddler with a homozygous p.R1419H ABCC8 mutation: an unusual clinical picture. J. Pediatr. Endocrinol. Metab. · 2015
• Monoallelic ABCC8 mutations are a common cause of diazoxide-unresponsive diffuse form of congenital hyperinsulinism. Clin. Genet. · 2015
• Heterozygous ABCC8 mutations are a cause of MODY. Diabetologia · 2012
• Transient neonatal diabetes mellitus caused by a de novoABCC8 gene mutation. Korean J. Pediatr. · 2011
• An abundant, truncated human sulfonylurea receptor 1 splice variant has prodiabetic properties and impairs sulfonylurea action. Cell. Mol. Life Sci. · 2012
• Transient neonatal diabetes due to activating mutation in the ABCC8 gene encoding SUR1. Indian J. Pediatr. · 2009
• Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. Am. J. Hum. Genet. · 2007
• Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers. J. Clin. Endocrinol. Metab. · 2007
• Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N. Engl. J. Med. · 2006
• … and 30 more in the literature graph