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sulfonylurea receptor 1; ATP-binding cassette transporter sub-family C member 8; ATP-binding cassette C8 (ABCC8, HRINS, SUR SUR1)
Function:
- putative subunit of the beta-cell ATP-sensitive K+ channel (KATP)
- regulator of ATP-sensitive K+ channels & insulin release
- associates with KCNJ11
- because of the presence of 2 ATP-binding cassettes, the sulfonylurea receptor may not function physiologically as a receptor, but may sense ATP/ADP status of beta cells, thus modifiying K+ channel activity & insulin release
Structure:
- belongs to the ABC transporter family, conjugate
- transporter (TC 3.A.1.208) subfamily
- contains 2 ABC transmembrane type-1 domains
- contains 2 ABC transporter domains
Compartment: membrane
Alternative splicing: named isoforms=2
Pathology:
- defects in ABCC8 are a cause of
a) leucine-induced hypoglycemia
b) familial hyperinsulinemic hypoglycemia type 1
c) permanent neonatal diabetes mellitus
d) transient neonatal diabetes mellitus type 2
- defects in ABCC8 may contribute to diabetes mellitus type 2 in Northern European Caucasians
Pharmacology:
- sulfonylureas represent a class of drugs used clinically to promote insulin secretion in the treatment of type 2 diabetes
- these drugs interact with the sulfonylurea receptor of pancreatic beta cells & inhibit the conductance of ATP-dependent K+ channels
Related
ATP-sensitive K+ channel (inwardly-rectifying K+ channel)
inwardly-rectifying K+ channel J11; ATP-sensitive inward rectifier K+ channel 11; K+ channel, inwardly rectifying subfamily J member 11; inward rectifier K+ channel Kir6.2; IKATP (KCNJ11)
sulfonylurea
General
ATP-binding cassette sub-family C (ABC transporter-C, ABCC)
cell surface receptor
phosphoprotein
transmembrane 13 protein
Properties
SIZE: MW = 140 kD
calculated = 177 kD
entity length = 1582 aa
COMPARTMENT: plasma membrane
CELL: beta cell
WITHIN: islets of Langerhans
MOTIF: exoplasmic domain {N-TERMINAL}
N-glycosylation site {N-TERMINAL}
ligand-binding site
membrane region
Ser phosphorylation site {cytoplasmic loop
LOOP#: 1}
FOR-PHOSPHORYLATION-BY: protein kinase C
active site
MOTIF: adenine nucleotide-binding site
ATP-binding site
NAME: ATP-binding site
SITE: cytoplasmic loop
LOOP#: 5
MOTIF: Thr phosphorylation site {cytoplasmic loop {T5.2}
LOOP#: 5}
FOR-PHOSPHORYLATION-BY: protein kinase C
Ser phosphorylation site {cytoplasmic loop {S5.3}
LOOP#: 5}
FOR-PHOSPHORYLATION-BY: protein kinase C
Ser phosphorylation site {cytoplasmic loop {S5.4}
LOOP#: 5}
FOR-PHOSPHORYLATION-BY: protein kinase C
Thr phosphorylation site {cytoplasmic loop {T5.5}
LOOP#: 5}
FOR-PHOSPHORYLATION-BY: protein kinase C
Thr phosphorylation site {cytoplasmic loop {T4.1}
LOOP#: 4}
FOR-PHOSPHORYLATION-BY: protein kinase C
Ser phosphorylation site {cytoplasmic loop {S4.2}
LOOP#: 4}
FOR-PHOSPHORYLATION-BY: protein kinase C
Thr phosphorylation site {cytoplasmic loop {T5.1}
LOOP#: 5}
FOR-PHOSPHORYLATION-BY: protein kinase C
Thr phosphorylation site {cytoplasmic loop {T5.6}
LOOP#: 5}
FOR-PHOSPHORYLATION-BY: protein kinase C
Ser phosphorylation site {cytoplasmic loop {S5.7}
LOOP#: 5}
FOR-PHOSPHORYLATION-BY: protein kinase C
Ser phosphorylation site {CYTOPLASMIC-TAIL}
FOR-PHOSPHORYLATION-BY: protein kinase C
Ser phosphorylation site {CYTOPLASMIC-TAIL}
FOR-PHOSPHORYLATION-BY: protein kinase C
ATP-binding site
NAME: ATP-binding site
SITE: CYTOPLASMIC-TAIL
MOTIF: Thr phosphorylation site {CYTOPLASMIC-TAIL}
FOR-PHOSPHORYLATION-BY: protein kinase C
Thr phosphorylation site {CYTOPLASMIC-TAIL}
FOR-PHOSPHORYLATION-BY: protein kinase C
Thr phosphorylation site {CYTOPLASMIC-TAIL}
FOR-PHOSPHORYLATION-BY: protein kinase C
Ser phosphorylation site {CYTOPLASMIC-TAIL}
FOR-PHOSPHORYLATION-BY: cAMP kinase
Ser phosphorylation site {CYTOPLASMIC-TAIL}
FOR-PHOSPHORYLATION-BY: cAMP kinase
Ser phosphorylation site {CYTOPLASMIC-TAIL}
FOR-PHOSPHORYLATION-BY: protein kinase C
cytoplasmic domain {C-TERMINAL}
Database Correlations
OMIM correlations
MORBIDMAP 600509
UniProt Q09428
PFAM correlations
Entrez Gene 6833
Kegg hsa:6833
References
- UniProt :accession Q09428
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=ABCC8
- Raab-Graham KF et al
Membrane topology of the amino-terminal region of the
sulfonylurea receptor
J Biol Chem. 1999 Oct 8;274(41):29122-9.
PMID: 10506167
- Aguilar-Bryan L et al
Cloning of the beta cell high-affinity sulfonylurea receptor:
a regulator of insulin secretion.
Science. 1995 Apr 21;268(5209):423-6.
PMID: 7716547
Component-of
ATP-sensitive K+ channel (inwardly-rectifying K+ channel)