Human Gene FOLH1 (ENST00000256999.7) from GENCODE V44
Description: Homo sapiens folate hydrolase 1 (FOLH1), transcript variant 1, mRNA. (from RefSeq NM_004476) RefSeq Summary (NM_004476): 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. [provided by RefSeq, Jul 2010]. Gencode Transcript: ENST00000256999.7 Gencode Gene: ENSG00000086205.18 Transcript (Including UTRs) Position: hg38 chr11:49,145,092-49,208,602 Size: 63,511 Total Exon Count: 19 Strand: - Coding Region Position: hg38 chr11:49,146,756-49,208,409 Size: 61,654 Coding Exon Count: 19
ID:FOLH1_HUMAN DESCRIPTION: RecName: Full=Glutamate carboxypeptidase 2; EC=3.4.17.21; AltName: Full=Cell growth-inhibiting gene 27 protein; AltName: Full=Folate hydrolase 1; AltName: Full=Folylpoly-gamma-glutamate carboxypeptidase; Short=FGCP; AltName: Full=Glutamate carboxypeptidase II; Short=GCPII; AltName: Full=Membrane glutamate carboxypeptidase; Short=mGCP; AltName: Full=N-acetylated-alpha-linked acidic dipeptidase I; Short=NAALADase I; AltName: Full=Prostate-specific membrane antigen; Short=PSM; Short=PSMA; AltName: Full=Pteroylpoly-gamma-glutamate carboxypeptidase; FUNCTION: Has both folate hydrolase and N-acetylated-alpha-linked- acidic dipeptidase (NAALADase) activity. Has a preference for tri- alpha-glutamate peptides. In the intestine, required for the uptake of folate. In the brain, modulates excitatory neurotransmission through the hydrolysis of the neuropeptide, N- aceylaspartylglutamate (NAAG), thereby releasing glutamate. Isoform PSM-4 and isoform PSM-5 would appear to be physiologically irrelevant. Involved in prostate tumor progression. FUNCTION: Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC. 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. BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Stable at pH greater than 6.5; SUBUNIT: Homodimer. SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein. SUBCELLULAR LOCATION: 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. DOMAIN: The NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal. PTM: The first two amino acids at the N-terminus of isoform PSMA' appear to be cleaved by limited proteolysis. PTM: The N-terminus is blocked. POLYMORPHISM: Genetic variation in FOLH1 may be associated with low folate levels and consequent hyperhomocysteinemia. This condition can result in increased risk of cardiovascular disease, neural tube defects, and cognitive deficits. MISCELLANEOUS: PSMA is used as a diagnostic and prognostic indicator of prostate cancer, and as a possible marker for various neurological disorders such as schizophrenia, Alzheimer disease and Huntington disease. SIMILARITY: Belongs to the peptidase M28 family. M28B subfamily. SEQUENCE CAUTION: Sequence=AAF31167.1; Type=Erroneous gene model prediction;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q04609
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.