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

   GtoImmuPdb view: OFF:     Currently no data for ATP-binding cassette, sub-family C (CFTR/MRP), member 8 in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1581 11p15.1 ABCC8 ATP binding cassette subfamily C 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 member 8
Previous and Unofficial Names
TNDM2
ABC36
HHF1
HI
MRP8
PHHI
SUR1
ATP-binding cassette, subfamily C (CFTR/MRP), member 8
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
repaglinide Hs Inhibition 7.0 pIC50 5
pIC50 7.0 (IC50 1.06x10-7 M) [5]
chlorpropamide Hs Inhibition - -
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

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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

ABCC subfamily: ATP-binding cassette, sub-family C (CFTR/MRP), member 8. Last modified on 21/09/2015. Accessed on 26/05/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2594.