title: Organization of the human glucokinase regulator gene GCKR.
abstract: Glucokinase plays an important role in regulating insulin secretion in response to changes in blood glucose levels. As a result, one form of maturity onset diabetes of the young (MODY) results from haploinsufficiency of glucokinase. In both liver and pancreatic islet, glucokinase is allosterically regulated by an inhibitory protein (glucokinase regulatory protein, GCKR). GCKR has therefore become an important gene for functional analysis in type 2 diabetes. To allow genetic assessment of any such role, we have determined the structure of the human GCKR gene. Characterization of P1 and YAC clones containing GCKR shows it to consist of 19 exons spanning 27 kb. RT-PCR, RACE, and RNase protection experiments defined a transcriptional start site for GCKR 66 bp upstream of the initiation codon, but provided no evidence for islet cell specific alternative splicing in the rat. By SSCP screening, a common polymorphic sequence variant has been defined within exon 15 of human GCKR, at nt 1400 of the cDNA. This alters amino acid residue 446 from proline, conserved in rat and Xenopus, to leucine.
authors.affiliation: University of Edinburgh, Department of Medicine, Western General Hospital, United Kingdom.
authors.forename: B E
authors.initials: BE
authors.lastname: Hayward
authors.forename: N
authors.initials: N
authors.lastname: Dunlop
authors.forename: S
authors.initials: S
authors.lastname: Intody
authors.forename: J P
authors.initials: JP
authors.lastname: Leek
authors.forename: A F
authors.initials: AF
authors.lastname: Markham
authors.forename: J P
authors.initials: JP
authors.lastname: Warner
authors.forename: D T
authors.initials: DT
authors.lastname: Bonthron
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins; D018076:DNA, Complementary; D005941:Glucokinase / Q000037:antagonists & inhibitors*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics*; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018076:DNA, Complementary; C485100:GCKR protein, human; C499484:Gckr protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C080906:glucokinase regulatory protein; D005941:Glucokinase