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

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

Family: ATP-binding cassette transporter family

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
HI
PHHI
MRP8
ABC36
HHF1
TNDM2
SUR1
ATP-binding cassette sub-family C member 8
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
InterPro
KEGG Gene
OMIM
Orphanet Gene
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:  Diabetes mellitus, permanent neonatal
OMIM:  606176
Orphanet:  99885
References: 
Mutations not determined
Disease:  Diabetes mellitus, transient neonatal 2
OMIM:  610374
Orphanet:  99886
References: 
Mutations not determined
Disease:  Hyperinsulinemic hypoglycemia, familial, 1; autosomal dominant
OMIM:  256450
Orphanet:  276575
References: 
Mutations not determined
Disease:  Hyperinsulinemic hypoglycemia, familial, 1; autosomal recessive
OMIM:  256450
Orphanet:  79643
References: 
Mutations not determined
Disease:  MODY syndrome
Orphanet:  552
References: 
Mutations not determined
Disease:  Hyperinsulinemic hypoglycemia, familial, 1; diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency
OMIM:  256450
Orphanet:  276598
Drugs: 
References: 
Mutations not determined
Disease:  Hypoglycemia of infancy, leucine-induced
OMIM:  240800
References: 
Mutations not determined
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

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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

ATP-binding cassette transporter family: ATP-binding cassette, sub-family C (CFTR/MRP), member 8. Last modified on 28/04/2014. Accessed on 01/10/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2594.