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 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:49,145,092-49,208,602)mRNA (may differ from genome)Protein (750 aa)
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-  Comments and Description Text from UniProtKB
  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;

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: FOLH1
Diseases sorted by gene-association score: hyperhomocysteinemia (32), prostate cancer (20), prostate disease (16), prostate adenocarcinoma (14), canavan disease (11), male reproductive organ cancer (11), villous adenoma (9), anthracosilicosis (8), reproductive organ cancer (8), lymph node cancer (7), marantic endocarditis (6), lipid pneumonia (4), cardiomyopathy, dilated, 1p (4), neural tube defects (4), schizophrenia (3), amyotrophic lateral sclerosis 1 (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 25.48 RPKM in Brain - Spinal cord (cervical c-1)
Total median expression: 134.05 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -70.50193-0.365 Picture PostScript Text
3' UTR -410.401664-0.247 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007484 - Peptidase_M28
IPR003137 - Protease-assoc_domain
IPR007365 - TFR-like_dimer_dom

Pfam Domains:
PF02225 - PA domain
PF04389 - Peptidase family M28
PF04253 - Transferrin receptor-like dimerisation domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1Z8L - X-ray MuPIT 2C6C - X-ray 2C6G - X-ray 2C6P - X-ray 2CIJ - X-ray 2JBJ - X-ray 2JBK - X-ray 2OOT - X-ray 2OR4 - X-ray 2PVV - X-ray 2PVW - X-ray 2XEF - X-ray MuPIT 2XEG - X-ray MuPIT 2XEI - X-ray MuPIT 2XEJ - X-ray MuPIT 3BHX - X-ray 3BI0 - X-ray 3BI1 - X-ray 3BXM - X-ray 3D7D - X-ray 3D7F - X-ray 3D7G - X-ray 3D7H - X-ray 3IWW - X-ray 3RBU - X-ray MuPIT 3SJE - X-ray 3SJF - X-ray 3SJG - X-ray 3SJX - X-ray


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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
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Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003824 catalytic activity
GO:0004180 carboxypeptidase activity
GO:0004181 metallocarboxypeptidase activity
GO:0008233 peptidase activity
GO:0008237 metallopeptidase activity
GO:0016787 hydrolase activity
GO:0016805 dipeptidase activity
GO:0046872 metal ion binding
GO:1904492 Ac-Asp-Glu binding
GO:1904493 tetrahydrofolyl-poly(glutamate) polymer binding

Biological Process:
GO:0006508 proteolysis
GO:0006760 folic acid-containing compound metabolic process
GO:0008152 metabolic process
GO:0008652 cellular amino acid biosynthetic process
GO:0035609 C-terminal protein deglutamylation

Cellular Component:
GO:0005737 cytoplasm
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AF176574 - Homo sapiens folylpoly-gamma-glutamate carboxypeptidase (FGCP) mRNA, complete cds.
BC025672 - Homo sapiens folate hydrolase (prostate-specific membrane antigen) 1, mRNA (cDNA clone MGC:34488 IMAGE:5202715), complete cds.
M99487 - Human prostate-specific membrane antigen (PSM) mRNA, complete cds.
AK295368 - Homo sapiens cDNA FLJ60551 complete cds.
AK295470 - Homo sapiens cDNA FLJ54681 complete cds.
BC108719 - Homo sapiens folate hydrolase (prostate-specific membrane antigen) 1, mRNA (cDNA clone IMAGE:6196956), partial cds.
DQ088979 - Homo sapiens cell growth-inhibiting protein 27 mRNA, complete cds.
AF254358 - Homo sapiens prostate-specific membrane antigen PSM mRNA, exon 18 alternative splice variant, partial cds.
EF488811 - Homo sapiens prostate specific membrane antigen variant E mRNA, complete cds, alternatively spliced.
EF488812 - Homo sapiens prostate specific membrane antigen variant F mRNA, complete cds, alternatively spliced.
AY101595 - Homo sapiens prostate-specific membrane antigen mRNA, complete cds.
AK312366 - Homo sapiens cDNA, FLJ92688, Homo sapiens folate hydrolase (prostate-specific membrane antigen)1 (FOLH1), mRNA.
DQ891167 - Synthetic construct clone IMAGE:100003797; FLH177902.01X; RZPDo839F03126D folate hydrolase (prostate-specific membrane antigen) 1 (FOLH1) gene, encodes complete protein.
DQ894349 - Synthetic construct Homo sapiens clone IMAGE:100008809; FLH177898.01L; RZPDo839F03125D folate hydrolase (prostate-specific membrane antigen) 1 (FOLH1) gene, encodes complete protein.
AF027824 - Homo sapiens prostate-specific membrane protein 1 (FOLH1) pseudogene mRNA, partial sequence.
JD441998 - Sequence 423022 from Patent EP1572962.
AK300532 - Homo sapiens cDNA FLJ57056 partial cds.
AF254357 - Homo sapiens prostate-specific membrane antigen PSM mRNA, exon 6 alternative splice variant, partial cds.
JD229592 - Sequence 210616 from Patent EP1572962.
AB231784 - Homo sapiens mRNA for hypothetical protein, partial cds, clone:Hsa11-digit35-15-11-R.
AJ007318 - Homo sapiens mRNA for prostate-specific membrane antigen, splice variant, partial.
S76978 - Homo sapiens prostate-specific membrane antigen (prostate-specific membrane antigen, PSM) mRNA, partial cds.
JD217514 - Sequence 198538 from Patent EP1572962.
JD494022 - Sequence 475046 from Patent EP1572962.
JD039796 - Sequence 20820 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q04609 (Reactome details) participates in the following event(s):

R-HSA-5693783 NAALADases hydrolyse NAAG
R-HSA-70614 Amino acid synthesis and interconversion (transamination)
R-HSA-71291 Metabolism of nitrogenous molecules
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: A4UU12, A9CB79, B7Z312, B7Z343, D3DQS5, E9PDX8, ENST00000256999.1, ENST00000256999.2, ENST00000256999.3, ENST00000256999.4, ENST00000256999.5, ENST00000256999.6, FOLH, FOLH1_HUMAN, GIG27, NAALAD1, NM_004476, O43748, PSM, PSMA, Q04609, Q16305, Q541A4, Q8TAY3, Q9NP15, Q9NYE2, Q9P1P8, uc001ngy.1, uc001ngy.2, uc001ngy.3, uc001ngy.4
UCSC ID: ENST00000256999.7
RefSeq Accession: NM_004476
Protein: Q04609 (aka FOLH1_HUMAN or FOH1_HUMAN)
CCDS: CCDS7946.1, CCDS31493.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.