FOLH1
Description
The FOLH1 (folate hydrolase 1) is a protein-coding gene located on chromosome 11.
FOLH1 (folate hydrolase 1) encodes a protein known as TAH, also called N-acetyl-L-aspartyl-L-glutamate peptidase I (NAALADase I), NAAG peptidase, or prostate-specific membrane antigen (PSMA). This enzyme, consisting of 750 amino acids and weighing approximately 84 kDa, is a zinc metalloenzyme that resides in membranes. Most of the enzyme is found in the extracellular space. GCPII, as it is also called, is a class II membrane glycoprotein. It catalyzes the hydrolysis of N-acetylaspartylglutamate (NAAG) to glutamate and N-acetylaspartate (NAA). Neuroscientists typically use the term NAALADase, while those studying folate metabolism use folate hydrolase, and those researching prostate cancer or oncology use PSMA, all referring to the same protein, glutamate carboxypeptidase II. FOLH1 is predominantly expressed in four tissues: prostate epithelium, the proximal tubules of the kidney, the jejunal brush border of the small intestine, and ganglia of the nervous system. The initial cloning of the cDNA encoding the gene expressing PSMA was done using RNA from a prostate tumor cell line, LNCaP. PSMA was first detected in the LNCaP cell line using the murine monoclonal antibody 7E11-C5.3 (also known as capromab), generated from murine spleen cells treated with LNCaP cell membranes. However, 7E11-C5.3 exclusively targets an intracellular epitope of PSMA, thus only binding to dead or dying cells. PSMA shares homology with the transferrin receptor and undergoes endocytosis but the ligand for inducing internalization has not been identified.
FOLH1 exhibits both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. It preferentially hydrolyzes tri-alpha-glutamate peptides. In the intestines, FOLH1 is essential for the absorption of folate. Within the brain, FOLH1 regulates excitatory neurotransmission by hydrolyzing the neuropeptide N-acetylaspartylglutamate (NAAG), leading to the release of glutamate. FOLH1 has been implicated in prostate tumor progression.
FOLH1 is also known as FGCP, FOLH, GCP2, GCPII, NAALAD1, PSM, PSMA, mGCP.
