HUMAN GLUCOKINASE REGULATORY PROTEIN (GCKR) - CDNA AND GENOMIC CLONING, COMPLETE PRIMARY STRUCTURE, AND CHROMOSOMAL LOCALIZATION

Null mutations in the glucokinase (GCK) gene can cause autosomal domin ant type 2 diabetes (maturity onset diabetes of the young, MODY); howe ver, MODY is genetically heterogeneous. In both liver and pancreatic i slet, glucokinase is subject to inhibition by a regulatory protein (GC KR). Given the role of GCK in MODY, GCKR is itself a candidate type 2 diabetes susceptibility gene. Here we describe the structure of full-l ength (2.2 kb) cDNA for human GCKR, from the hepatoblastoma cell line HepG2. The human GCKR translation product has 625 amino acids and a pr edicted molecular weight of 68,700. It has 88% amino acid identity to rat GCKR. Yeast artificial chromosomes (YAC clones) containing human G CKR were isolated, and the gene was mapped to Chromosome (Chr) 2p23 by fluorescent in situ hybridization and somatic cell hybrid analysis.