Gene Summary: This gene encodes a type II transmembrane glycoprotein belonging to the M28 peptidase family. The protein acts as a glutamate carboxypeptidase on different alternative substrates, including the nutrient folate and the neuropeptide N-acetyl-l-aspartyl-l-glutamate and is expressed in a number of tissues such as prostate, central and peripheral nervous system and kidney. A mutation in this gene may be associated with impaired intestinal absorption of dietary folates, resulting in low blood folate levels and consequent hyperhomocysteinemia. Expression of this protein in the brain may be involved in a number of pathological conditions associated with glutamate excitotoxicity. In the prostate the protein is up-regulated in cancerous cells and is used as an effective diagnostic and prognostic indicator of prostate cancer. This gene likely arose from a duplication event of a nearby chromosomal region. Alternative splicing gives rise to multiple transcript variants encoding several different isoforms.General information above from NCBI
Catalytic activity: Release of an unsubstituted, C-terminal glutamyl residue, typically from Ac-Asp-Glu or folylpoly-gamma- glutamates.
Cofactor: Binds 2 zinc ions per subunit. Required for NAALADase activity.
Enzyme regulation: The NAALADase activity is inhibited by beta- NAAG, quisqualic acid, 2-(phosphonomethyl) pentanedioic acid (PMPA) and EDTA. Activated by cobalt.
Subunit structure: Homodimer.
Domain: The NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal.
Subcellular location: Cell membrane; Single-pass type II membrane protein.
Isoform PSMA': Cytoplasm.
Tissue specificity: Highly expressed in prostate epithelium. Detected in urinary bladder, kidney, testis, ovary, fallopian tube, breast, adrenal gland, liver, esophagus, stomach, small intestine, colon and brain (at protein level). Detected in the small intestine, brain, kidney, liver, spleen, colon, trachea, spinal cord and the capillary endothelium of a variety of tumors. Expressed specifically in jejunum brush border membranes. In the brain, highly expressed in the ventral striatum and brain stem. Also expressed in fetal liver and kidney. Isoform PSMA' is the most abundant form in normal prostate. Isoform PSMA-1 is the most abundant form in primary prostate tumors. Isoform PSMA-2 is also found in normal prostate as well as in brain and liver. Isoform PSMA-9 is specifically expressed in prostate cancer.
Induction: In the prostate, up-regulated in response to androgen deprivation.
Post-translational: The first two amino acids at the N-terminus of isoform PSMA' appear to be cleaved by limited proteolysis.
The N-terminus is blocked.
Sequence similarity: Belongs to the peptidase M28 family. M28B subfamily.
General information above from UniProt