Sodium- and chloride-dependent creatine transporter 1
creatine:sodium symporter activity
Cloning, pharmacological characterization, and genomic localization of the human creatine transporter.
The complete coding sequence from a human creatine transporter cDNA was isolated from a kidney library. This transporter is a member of a superfamily of proteins which includes the family of Na(+)- and Cl(-)-dependent transporters responsible for the uptake of certain neurotransmitters (e.g. dopamine, GABA, serotonin, and norepinephrine), and amino acids (e.g. glycine). Within this family, the human creatine transporter is strongly related to a subfamily of sequences which includes the transporters for taurine, GABA, and betaine, and this cDNA is approximately 98% amino acid identical to sequences that have been reported from rat and rabbit as choline and creatine transporters respectively. Pharmacological characterization demonstrated that the protein product of this cDNA mediated high affinity (Km = 77 +/- 6 microM) creatine uptake, which was blocked by creatine analogs with high affinity. There was no specific transport of choline. Northern analysis demonstrated highest levels of mRNA expression in human skeletal muscle, kidney, and heart, with lower levels in brain and other tissues. Expression within the kidney was evenly distributed between cortex and medulla. Genetic mapping in the mouse localizes the creatine transporter to a region on the X chromosome in linkage conservation with the human region Xq28, the location of the genes for several neuromuscular diseases.