GCKR

This gene encodes a protein belonging to the GCKR subfamily of the SIS (Sugar ISomerase) family of proteins. The gene product is a regulatory protein that inhibits glucokinase in liver and pancreatic islet cells by binding non-covalently to form an inactive complex with the enzyme. This gene is considered a susceptibility gene candidate for a form of maturity-onset diabetes of the young (MODY).

glucokinase regulator

Regulates glucokinase (GCK) by forming an inactive complex with this enzyme (PubMed:23621087, PubMed:23733961).

Acts by promoting GCK recruitment to the nucleus, possibly to provide a reserve of GCK that can be quickly released in the cytoplasm after a meal (PubMed:10456334).

The affinity of GCKR for GCK is modulated by fructose metabolites: GCKR with bound fructose 6-phosphate has increased affinity for GCK, while GCKR with bound fructose 1-phosphate has strongly decreased affinity for GCK and does not inhibit GCK activity (PubMed:23621087, PubMed:23733961).

Carbohydrate derivative metabolic process Source: InterPro
Carbohydrate metabolic process Source: UniProtKB-KW
Glucose homeostasis Source: GO_Central
Negative regulation of glucokinase activity Source: UniProtKB
Protein import into nucleus Source: BHF-UCL
Response to fructose Source: BHF-UCL
Triglyceride homeostasis Source: BHF-UCL
Urate metabolic process Source: BHF-UCL

Cytoplasm; Mitochondrion; Nucleus. Under low glucose concentrations, GCKR associates with GCK and the inactive complex is recruited to the hepatocyte nucleus.