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Aliases for FOLH1 Gene

Aliases for FOLH1 Gene

  • Folate Hydrolase (Prostate-Specific Membrane Antigen) 1 2 3 5
  • Glutamate Carboxypeptidase II 2 3 4
  • N-Acetylated-Alpha-Linked Acidic Dipeptidase I 3 4
  • Pteroylpoly-Gamma-Glutamate Carboxypeptidase 3 4
  • Folylpoly-Gamma-Glutamate Carboxypeptidase 3 4
  • Cell Growth-Inhibiting Gene 27 Protein 3 4
  • Membrane Glutamate Carboxypeptidase 3 4
  • Glutamate Carboxylase II 2 3
  • EC 3.4.17.21 4 63
  • NAALADase I 3 4
  • NAALAD1 3 4
  • GCPII 3 4
  • FOLH 3 4
  • FGCP 3 4
  • PSMA 3 4
  • MGCP 3 4
  • PSM 3 4
  • N-Acetylated Alpha-Linked Acidic Dipeptidase 1 3
  • Prostate Specific Membrane Antigen Variant F 3
  • Prostate-Specific Membrane Antigen 4
  • Folate Hydrolase 1 4
  • NAALAdase 3
  • GCP2 3

External Ids for FOLH1 Gene

Previous HGNC Symbols for FOLH1 Gene

  • FOLH

Previous GeneCards Identifiers for FOLH1 Gene

  • GC11M051274
  • GC11M050361
  • GC11M049199
  • GC11M049132
  • GC11M049124
  • GC11M048888
  • GC11M049168
  • GC11M049596
  • GC11M049622

Summaries for FOLH1 Gene

Entrez Gene Summary for FOLH1 Gene

  • 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]

GeneCards Summary for FOLH1 Gene

FOLH1 (Folate Hydrolase (Prostate-Specific Membrane Antigen) 1) is a Protein Coding gene. Diseases associated with FOLH1 include hyperhomocysteinemia and prostate cancer. Among its related pathways are Alanine, aspartate and glutamate metabolism and Metabolism. GO annotations related to this gene include peptidase activity and carboxypeptidase activity. An important paralog of this gene is NAALAD2.

UniProtKB/Swiss-Prot for FOLH1 Gene

  • 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. Involved in prostate tumor progression.

  • Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC.

Tocris Summary for FOLH1 Gene

  • Carboxypeptidases are a group of enzymes that cleave amino acids from the C'-terminal of proteins and peptides by hydrolysis. There are three subgroups; serine-type carboxypeptidases, metallocarboxypeptidases, and cysteine-type carboxypeptidases.

Gene Wiki entry for FOLH1 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for FOLH1 Gene

Genomics for FOLH1 Gene

Regulatory Elements for FOLH1 Gene

Enhancers for FOLH1 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around FOLH1 on UCSC Golden Path with GeneCards custom track

Promoters for FOLH1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around FOLH1 on UCSC Golden Path with GeneCards custom track

Genomic Location for FOLH1 Gene

Chromosome:
11
Start:
49,146,635 bp from pter
End:
49,208,670 bp from pter
Size:
62,036 bases
Orientation:
Minus strand

Genomic View for FOLH1 Gene

Genes around FOLH1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FOLH1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FOLH1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FOLH1 Gene

Proteins for FOLH1 Gene

  • Protein details for FOLH1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q04609-FOLH1_HUMAN
    Recommended name:
    Glutamate carboxypeptidase 2
    Protein Accession:
    Q04609
    Secondary Accessions:
    • A4UU12
    • A9CB79
    • B7Z312
    • B7Z343
    • D3DQS5
    • E9PDX8
    • O43748
    • Q16305
    • Q541A4
    • Q8TAY3
    • Q9NP15
    • Q9NYE2
    • Q9P1P8

    Protein attributes for FOLH1 Gene

    Size:
    750 amino acids
    Molecular mass:
    84331 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Homodimer.
    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.
    SequenceCaution:
    • Sequence=AAF31167.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for FOLH1 Gene

    Alternative splice isoforms for FOLH1 Gene

neXtProt entry for FOLH1 Gene

Proteomics data for FOLH1 Gene at MOPED

Post-translational modifications for FOLH1 Gene

  • The first two amino acids at the N-terminus of isoform PSMA appear to be cleaved by limited proteolysis.
  • The N-terminus is blocked.
  • Glycosylation at Asn 51, Asn 76, Asn 121, Asn 140, Asn 153, Asn 195, Asn 336, Asn 459, Asn 476, and Asn 638
  • Modification sites at PhosphoSitePlus

Antibody Products

  • R&D Systems Antibodies for FOLH1 (PSMA/FOLH1/NAALADase I)
  • Cell Signaling Technology (CST) Antibodies for FOLH1 (FOLH1)
  • Cloud-Clone Corp. Antibodies for FOLH1

Domains & Families for FOLH1 Gene

Gene Families for FOLH1 Gene

Suggested Antigen Peptide Sequences for FOLH1 Gene

Graphical View of Domain Structure for InterPro Entry

Q04609

UniProtKB/Swiss-Prot:

FOLH1_HUMAN :
  • 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.
Domain:
  • The NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal.
Family:
  • Belongs to the peptidase M28 family. M28B subfamily.
genes like me logo Genes that share domains with FOLH1: view

Function for FOLH1 Gene

Molecular function for FOLH1 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
pH dependence: Stable at pH greater than 6.5.;
UniProtKB/Swiss-Prot CatalyticActivity:
Release of an unsubstituted, C-terminal glutamyl residue, typically from Ac-Asp-Glu or folylpoly-gamma-glutamates.
UniProtKB/Swiss-Prot EnzymeRegulation:
The NAALADase activity is inhibited by beta-NAAG, quisqualic acid, 2-(phosphonomethyl) pentanedioic acid (PMPA) and EDTA. Activated by cobalt.
UniProtKB/Swiss-Prot 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. Involved in prostate tumor progression.
UniProtKB/Swiss-Prot Function:
Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC.
UniProtKB/Swiss-Prot Induction:
In the prostate, up-regulated in response to androgen deprivation.

Enzyme Numbers (IUBMB) for FOLH1 Gene

Gene Ontology (GO) - Molecular Function for FOLH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004181 metallocarboxypeptidase activity IDA 12949938
genes like me logo Genes that share ontologies with FOLH1: view
genes like me logo Genes that share phenotypes with FOLH1: view

Animal Model Products

CRISPR Products

miRNA for FOLH1 Gene

miRTarBase miRNAs that target FOLH1

In Situ Assay Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for FOLH1 Gene

Localization for FOLH1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FOLH1 Gene

Cell membrane; Single-pass type II membrane protein.
Isoform PSMA: Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for FOLH1 Gene COMPARTMENTS Subcellular localization image for FOLH1 gene
Compartment Confidence
extracellular 5
plasma membrane 5
cytoskeleton 2
cytosol 2
nucleus 2
mitochondrion 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for FOLH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0016020 membrane NAS 9375657
genes like me logo Genes that share ontologies with FOLH1: view

Pathways & Interactions for FOLH1 Gene

genes like me logo Genes that share pathways with FOLH1: view

Gene Ontology (GO) - Biological Process for FOLH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0034641 cellular nitrogen compound metabolic process TAS --
GO:0044281 small molecule metabolic process TAS --
genes like me logo Genes that share ontologies with FOLH1: view

No data available for SIGNOR curated interactions for FOLH1 Gene

Drugs & Compounds for FOLH1 Gene

(28) Drugs for FOLH1 Gene - From: DrugBank, PharmGKB, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Capromab Approved Pharma antibody, Target, other/unknown 0
Docetaxel Approved May 1996, Investigational Pharma Inhibition, inhibitor, Biomarker Microtubulin disassembly inhibitor, Tubulin and VEGF inhibitor, Taxanes 1859
Methotrexate Approved Pharma Folate antagonist,inhibits DFHR, Cytotoxic agent 1466
Mercaptopurine Approved Pharma 0
(2S)-2-{[HYDROXY(4-IODOBENZYL)PHOSPHORYL]METHYL}PENTANEDIOIC ACID Experimental Pharma Target 0

(25) Additional Compounds for FOLH1 Gene - From: Novoseek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
2-MPPA
254737-29-6
PMPA (NAALADase inhibitor)
173039-10-6
ZJ 43
723331-20-2

(3) Tocris Compounds for FOLH1 Gene

Compound Action Cas Number
2-MPPA Selective glutamate carboxypeptidase II (GCP II) inhibitor; orally bioavailable 254737-29-6
PMPA (NAALADase inhibitor) GCP II inhibitor 173039-10-6
ZJ 43 Glutamate carboxypeptidase II and III (NAALADase, NAAG peptidase) inhibitor 723331-20-2
genes like me logo Genes that share compounds with FOLH1: view

Transcripts for FOLH1 Gene

Unigene Clusters for FOLH1 Gene

Folate hydrolase (prostate-specific membrane antigen) 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for FOLH1 Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2a · 2b · 2c ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b ^ 9
SP1: - - - - - -
SP2: - - - -
SP3: - - - - - - - -
SP4: - - - -
SP5: - - -
SP6: - - -

Relevant External Links for FOLH1 Gene

GeneLoc Exon Structure for
FOLH1
ECgene alternative splicing isoforms for
FOLH1

Expression for FOLH1 Gene

mRNA expression in normal human tissues for FOLH1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for FOLH1 Gene

This gene is overexpressed in Brain - Spinal cord (cervical c-1) (x9.8), Prostate (x7.3), Brain - Substantia nigra (x5.7), and Brain - Hippocampus (x4.3).

Protein differential expression in normal tissues from HIPED for FOLH1 Gene

This gene is overexpressed in Pancreatic juice (18.5), Fetal gut (16.9), Salivary gland (9.2), and Platelet (8.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for FOLH1 Gene



SOURCE GeneReport for Unigene cluster for FOLH1 Gene Hs.654487

mRNA Expression by UniProt/SwissProt for FOLH1 Gene

Q04609-FOLH1_HUMAN
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-3 is also found in normal prostate as well as in brain and liver. Isoform PSMA-9 is specifically expressed in prostate cancer.
genes like me logo Genes that share expression patterns with FOLH1: view

Primer Products

In Situ Assay Products

No data available for Protein tissue co-expression partners for FOLH1 Gene

Orthologs for FOLH1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for FOLH1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia FOLH1 35
  • 99.16 (n)
  • 98.8 (a)
FOLH1 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia FOLH1 36
  • 90 (a)
OneToOne
dog
(Canis familiaris)
Mammalia FOLH1 36
  • 94 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia FOLH1 36
  • 79 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Folh1 36
  • 85 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia FOLH1 36
  • 77 (a)
OneToOne
chicken
(Gallus gallus)
Aves FOLH1 36
  • 74 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia FOLH1 36
  • 72 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.8739 35
zebrafish
(Danio rerio)
Actinopterygii zgc56429 35
naalad2 36
  • 66 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea C35C5.2 37
  • 32 (a)
gcp-2.1 36
  • 32 (a)
ManyToMany
gcp-2.2 36
  • 29 (a)
ManyToMany
gcp-2.3 36
  • 28 (a)
ManyToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes VPS70 36
  • 22 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 44 (a)
ManyToMany
-- 36
  • 44 (a)
ManyToMany
-- 36
  • 37 (a)
ManyToMany
-- 36
  • 37 (a)
ManyToMany
Species with no ortholog for FOLH1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for FOLH1 Gene

ENSEMBL:
Gene Tree for FOLH1 (if available)
TreeFam:
Gene Tree for FOLH1 (if available)

Paralogs for FOLH1 Gene

Paralogs for FOLH1 Gene

(4) SIMAP similar genes for FOLH1 Gene using alignment to 6 proteins:

genes like me logo Genes that share paralogs with FOLH1: view

Variants for FOLH1 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for FOLH1 Gene

Q04609-FOLH1_HUMAN
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.

Sequence variations from dbSNP and Humsavar for FOLH1 Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
rs61886492 - 49,164,722(+) GTTGT(A/G)TACCA reference, missense
rs202676 - 49,206,068(-) TCTTA(C/T)AGTAA reference, missense, utr-variant-5-prime
VAR_028882 -
VAR_036398 A colorectal cancer sample
rs583850 -- 49,180,264(+) TTAGC(A/C)CTCCA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for FOLH1 Gene

Variant ID Type Subtype PubMed ID
esv542 CNV CNV 17122850
nsv467874 CNV Gain 19166990
essv4365 CNV CNV 17122850
nsv469956 CNV Gain 18288195
esv2744485 CNV Deletion 23290073
esv2666171 CNV Deletion 23128226
nsv832145 CNV Gain 17160897
nsv525454 CNV Loss 19592680
nsv518571 CNV Gain 19592680
essv23230 CNV CNV 17122850
dgv367e1 CNV Complex 17122850

Variation tolerance for FOLH1 Gene

Residual Variation Intolerance Score: 52.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.81; 86.85% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for FOLH1 Gene

HapMap Linkage Disequilibrium report
FOLH1
Human Gene Mutation Database (HGMD)
FOLH1

Disorders for FOLH1 Gene

MalaCards: The human disease database

(12) MalaCards diseases for FOLH1 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hyperhomocysteinemia
prostate cancer
  • prostate cancer, hereditary, 5
prostate disease
  • prostatic diseases
canavan disease
  • canavan-van bogaert-bertrand disease
lipid pneumonia
  • exogenous lipoid pneumonia
- elite association - COSMIC cancer census association via MalaCards
Search FOLH1 in MalaCards View complete list of genes associated with diseases

Relevant External Links for FOLH1

Genetic Association Database (GAD)
FOLH1
Human Genome Epidemiology (HuGE) Navigator
FOLH1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
FOLH1
genes like me logo Genes that share disorders with FOLH1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for FOLH1 Gene

Publications for FOLH1 Gene

  1. Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene. (PMID: 9838072) O'Keefe D.S. … Heston W.D.W. (Biochim. Biophys. Acta 1998) 2 3 4 23 67
  2. Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase. (PMID: 15837926) Davis M.I. … Bjorkman P.J. (Proc. Natl. Acad. Sci. U.S.A. 2005) 3 23 25 26
  3. Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates. (PMID: 15336276) Maung J. … Berkman C.E. (Bioorg. Med. Chem. 2004) 23 25 26
  4. Inhibition of glutamate carboxypeptidase II by phosphonamidothionate derivatives of glutamic acid. (PMID: 11916141) Rodriguez C.E. … Berkman C.E. (J. Enzym. Inhib. 2001) 23 25 26
  5. PSMA expression in Schwannoma: a potential clinical mimicker of metastatic prostate carcinoma. (PMID: 18534872) Wang W. … Netto G.J. (Urol. Oncol. 2009) 3 23

Products for FOLH1 Gene

Sources for FOLH1 Gene

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