Class 1 Glucose transporters (GLUTs) of the Major Facilitator Superfamily
GLUTs, also called Solute carrier family 2, facilitated glucose transporters (SLC2A), are a family of proteins that facilitate the transport of hexoses such as glucose and fructose. There are fourteen GLUTs found in humans; they display different substrate specificities and tissue expression. They have been categorized into three classes based on sequence similarity: Class 1 (GLUTs 1-4, 14); Class 2 (GLUTs 5, 7, 9, and 11); and Class 3 (GLUTs 6, 8, 10, 12, and HMIT). GLUTs 1-4 are well-established as glucose and/or fructose transporters in various tissues and cell types. GLUT1, also called solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1), displays broad substrate specificity and can transport a wide range of pentoses and hexoses including glucose, galactose, mannose, and glucosamine. It is found in the brain, erythrocytes, and in many fetal tissues. GLUT2 (or SLC2A2) is found in the liver, islet of Langerhans, intestine, and kidney, and is the isoform that likely mediates the bidirectional transfer of glucose across the plasma membrane of hepatocytes and is responsible for uptake of glucose by beta cells. GLUT3 (or SLC2A3) is found in the brain and can mediates the uptake of glucose, 2-deoxyglucose, galactose, mannose, xylose and fucose, and dehydroascorbate. GLUT4 (or SLC2A4) is an insulin-regulated facilitative glucose transporter found in adipose tissues, and in skeletal and cardiac muscle. GLUT14 (or SLC2A14) is an orphan transporter expressed mainly in the testis. GLUT proteins are comprised of about 500 amino acid residues, possess a single N-linked oligosaccharide, and have 12 transmembrane segments. They belong to the Glucose transporter -like (GLUT-like) family of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.