This region, sometimes called the S1 domain, is the luminal domain just upstream of the first, M1, transmembrane region of transmembrane ion-channel proteins, and binds L-glutamate and glycine in the ionotropic glutamate receptor NMDA. It is found in association with . Ionotropic Receptors (IRs) are a variant subfamily of the Ionotropic glutamate receptors (iGluRs). In IRs, the ligand binding domain lacks one or more residues that directly contact the glutamate ligand in iGluRs.