This entry includes glutamate carboxypeptidase 2 (FOLH1) and its homologues from peptidase family M28 subfamily B. Not all members of this subfamily are peptidases, and non-peptidase homologues include transferrin receptor proteins.FOLH1 is a zinc-dependent carboxypeptidase that also acts as a folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase). It has a preference for tri-alpha-glutamate peptides []. It is required for the uptake of folate in the intestine, and in the brain modulates excitatory neurotransmission through the hydrolysis of the neuropeptide, N-aceylaspartylglutamate (NAAG), releasing glutamate. Two zinc ions are bound per molecule []. NAALADL1 and NAALAD2 are also included in this entry. NAALAD2 has both N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) and dipeptidyl-peptidase IV type activity []. The structure of NAALADase has been solved []. The transferrin receptor (TfR) assists iron uptake into vertebrate cells through a cycle of endo- and exocytosis of the iron transport protein transferrin (Tf). TfR binds iron-loaded (diferric) Tf at the cell surface and carries it to the endosome, where the iron dissociates from Tf. The apo-Tf remains bound to TfR until it reaches the cell surface, where apo-Tf is replaced by diferric Tf from the serum to begin the cycle again. Human TfR is a homodimeric type II transmembrane protein. The crystal structure of a TfR monomer reveals a 3-domain structure: a protease-like domain that closely resembles carboxy- and amino-peptidases; an apical domain consisting of a β-sandwich; and a helical dimerisation domain. The dimerisation domain consists of a 4-helical bundle that makes contact with each of the three domains in the dimer partner [].
