ATP-binding cassette, sub-family C (CFTR/MRP), member 8

Target id: 2594

Nomenclature: ATP-binding cassette, sub-family C (CFTR/MRP), member 8

Abbreviated Name: SUR1

Systematic Nomenclature: ABCC8

Family: ABCC subfamily

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1581 11p15.1 ABCC8 ATP-binding cassette, sub-family C (CFTR/MRP), member 8
Mouse - 1588 7 B4 Abcc8 ATP-binding cassette, sub-family C (CFTR/MRP), member 8
Rat - 1582 1q22 Abcc8 ATP-binding cassette, subfamily C (CFTR/MRP), member 8
Previous and Unofficial Names
TNDM2
ABC36
HHF1
HI
MRP8
PHHI
SUR1
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
InterPro
KEGG Gene
NeXtProt
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
repaglinide Hs Inhibition 6.97 pIC50 5
pIC50 6.97 (IC50 1.06x10-7 M) [5]
Inhibitor Comments
KATP channels are composed of a small inwardly rectifying K+ channel subunit (Kir6.1 or Kir6.2) plus a sulfonylurea receptor (SUR1, SUR2A or SUR2B) belonging to the ATP-binding cassette superfamily [1]. Repaglinide is a member of the carbamoylmethylbenzoic acid chemical family, which inhibits SUR1 [5].
Clinically-Relevant Mutations and Pathophysiology
Disease:  Autosomal dominant hyperinsulinism due to SUR1 deficiency
Synonyms: Hyperinsulinemic hypoglycemia [Disease Ontology: DOID:13317]
Hyperinsulinemic hypoglycemia, familial, 1; HHF1 [OMIM: 256450]
Disease Ontology: DOID:13317
OMIM: 256450
Orphanet: ORPHA276575
Disease:  Autosomal recessive hyperinsulinism due to SUR1 deficiency
Synonyms: Hyperinsulinemic hypoglycemia [Disease Ontology: DOID:13317]
Hyperinsulinemic hypoglycemia, familial, 1; HHF1 [OMIM: 256450]
Disease Ontology: DOID:13317
OMIM: 256450
Orphanet: ORPHA79643
Disease:  Diabetes mellitus, permanent neonatal; PNDM
Synonyms: DEND syndrome [Orphanet: ORPHA79134]
Developmental delay-epilepsy-neonatal diabetes syndrome [Orphanet: ORPHA79134]
Permanent neonatal diabetes mellitus [Orphanet: ORPHA99885]
OMIM: 606176
Orphanet: ORPHA99885, ORPHA79134
Disease:  Diabetes mellitus, transient neonatal, 2
Synonyms: Transient neonatal diabetes mellitus [Orphanet: ORPHA99886]
OMIM: 610374
Orphanet: ORPHA99886
Disease:  Diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency
Synonyms: Hyperinsulinemic hypoglycemia, familial, 1; HHF1 [OMIM: 256450]
OMIM: 256450
Orphanet: ORPHA276598
Drugs: 
Disease:  Hypoglycemia, Leucine-Induced; LIH
OMIM: 240800
Disease:  Maturity-onset diabetes of the young; MODY
Disease Ontology: DOID:0050524
OMIM: 606391
Orphanet: ORPHA552
General Comments
The sulfonyurea drugs (acetohexamide, tolbutamide and glibenclamide) appear to bind sulfonylurea receptors and it has been shown experimentally that tritiated glibenclamide can be used to pull out a 140 kDa protein identified as SUR1 (now known as ABCC8) [4]. SUR2 (ABCC9) has also been identified [2]. However, this is not the full mechanism of action and the functional channel has been characterised as a hetero-octamer formed by four SUR and four Kir6.2 subunits, with the Kir6.2 subunits forming the core ion pore and the SUR subunits providing the regulatory properties [3]. Co-expression of Kir6.2 with SUR1, reconstitutes the ATP-dependent K+ conductivity inhibited by the sulfonyureas [2].

References

Show »

1. Aguilar-Bryan L, Clement JP, Gonzalez G, Kunjilwar K, Babenko A, Bryan J. (1998) Toward understanding the assembly and structure of KATP channels. Physiol. Rev.78 (1): 227-45. [PMID:9457174]

2. Inagaki N, Gonoi T, Clement JP, Namba N, Inazawa J, Gonzalez G, Aguilar-Bryan L, Seino S, Bryan J. (1995) Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science270 (5239): 1166-70. [PMID:7502040]

3. Miki T, Nagashima K, Seino S. (1999) The structure and function of the ATP-sensitive K+ channel in insulin-secreting pancreatic beta-cells. J. Mol. Endocrinol.22 (2): 113-23. [PMID:10194514]

4. Rehmann H. (2012) Epac2: a sulfonylurea receptor?. Biochem. Soc. Trans.40 (1): 6-10. [PMID:22260657]

5. Wängler B, Beck C, Shiue CY, Schneider S, Schwanstecher C, Schwanstecher M, Feilen PJ, Alavi A, Rösch F, Schirrmacher R. (2004) Synthesis and in vitro evaluation of (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic acid ([11C]methoxy-repaglinide): a potential beta-cell imaging agent. Bioorg. Med. Chem. Lett.14 (20): 5205-9. [PMID:15380228]

How to cite this page

ABCC subfamily: ATP-binding cassette, sub-family C (CFTR/MRP), member 8. Last modified on 02/03/2015. Accessed on 06/07/2015. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2594.