FOLH1

Folate hydrolase 1 (FOLH1), also known as PSMA, is a type II transmembrane glycoprotein belonging to the M28 peptidase family. Typically, FOLH1 function as a glutamate carboxypeptidase. In the intestines, the enzyme is termed folate hydrolase, and is expressed on brush border membranes where it is associated with the sequential cleavage of terminal γ-linked glutamate residues from dietary polyglutamyl folates to allow the absorption of folate. Apart from the gut, the enzyme is also highly expressed in the neovasculature of solid tumors and prostate cancer, in which it is called prostate-specific membrane antigen (PSMA) and acts as a cancer biomarker.
In addition, in the brain and peripheral nervous system, the enzyme is referred to as glutamate carboxypeptidase II (GCPII), which cleaves the abundant dipeptide neurotransmitter N-acetylaspartylglutamate (NAAG) to liberate glutamate. Importantly, many classes of strong and selective small-molecule GCPII inhibitors have been synthesized and proven to have profound therapeutic effects in various preclinical models of neurological disorders wherein excess glutamate is implicated. It has also demonstrated that a mutation of the FOLH1 gene may be related to impaired intestinal absorption of dietary folates, leading to low blood folate levels and consequent hyperhomocysteinemia.
Gene ID: 2346
UniProt ID: Q04609