Prostate Specific Membrane Antigen 1

Function

folate hydrolase
acetylated-alpha-linked-acidic dipeptidase (NAALADase)
preference for tri-alpha- glutamate peptides
in the intestine, required for uptake of folate
in brain, modulates excitatory neurotransmission through hydrolysis of the neuropeptide NAAG, endogenous ligand of mGluR3, thus releasing glutamate
isoforms PSM-4 & PSM-5 would appear to be physiologically irrelevant
exhibits a dipeptidyl-peptidase IV type activity in vitro, cleaves Gly- Pro-AMC
release of an unsubstituted, C-terminal glutamyl residue, typically from Ac- Asp-Glu or folylpoly-gamma- glutamates
the NAALADase activity is inhibited by beta- NAAG, quisqualic acid, 2-(phosphonomethyl) pentanedioic acid (PMPA) & EDTA
activated by cobalt

the N-terminus is blocked
the first two amino acids at the N-terminus of isoform PSMA' appear to be cleaved by limited proteolysis
the NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal
belongs to the peptidase M28 family, M28B subfamily

highly expressed in prostate epithelium
also expressed, in the small intestine, brain, kidney, liver, spleen, colon, trachea, spinal cord & the capillary endothelium of a variety of tumors
expressed specifically in jejunum brush border membranes
in the brain, highly expressed in the ventral striatum & brain stem
also expressed in fetal liver & kidney
in the prostate, the PSMA' cytosolic isoform is the most abundant form in normal tissue, the membrane-bound PSMA-1 form in primary prostate tumors
the PSMA-2 isoform also found in normal prostate as well as in brain & liver
in the prostate, up-regulated in response to androgen deprivation

role in prostate tumor progression
PSMA is used as a diagnostic & prognostic indicator of prostate cancer, & as a possible marker for various neurological disorders including:

genetic variation in FOLH1 may be associated with low folate levels & consequent hyperhomocysteinemia

UniProt: [1]
Entrez gene: 2346
Kegg: [2]
OMIM: 600934

UniProt [3]