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Aliases for FOLH1 Gene

Aliases for FOLH1 Gene

  • Folate Hydrolase (Prostate-Specific Membrane Antigen) 1 2 3
  • Glutamate Carboxypeptidase II 2 3 4
  • FOLH 3 4 6
  • PSMA 3 4 6
  • PSM 3 4 6
  • 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
  • FGCP 3 4
  • MGCP 3 4
  • N-Acetylated Alpha-Linked Acidic Dipeptidase 1 3
  • Prostate Specific Membrane Antigen Variant F 3
  • Prostate-Specific Membrane Antigen 4
  • Glutamate Carboxypeptidase 2 3
  • 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

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 villous adenoma. Among its related pathways are Vitamin digestion and absorption and Circadian entrainment. GO annotations related to this gene include metallopeptidase 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. Isoform PSM-4 and isoform PSM-5 would appear to be physiologically irrelevant. Involved in prostate tumor progression

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

Tocris Summary for FOLH1 Gene

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

Genomic Location for FOLH1 Gene

Start:
49,146,631 bp from pter
End:
49,208,670 bp from pter
Size:
62,040 bases
Orientation:
Minus strand

Genomic View for FOLH1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
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; Note=Binds 2 Zn(2+) ions per subunit. Required for NAALADase activity.;
    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 Asn76, Asn121, Asn140, Asn153, Asn195, Asn336, Asn459, Asn476, and Asn638
  • Modification sites at PhosphoSitePlus

Antibody Products

  • R&D Systems Antibodies for FOLH1 (PSMA/FOLH1/NAALADase I)
  • Cell Signaling Technology (CST) Antibodies for FOLH1 (FOLH1)

Domains for FOLH1 Gene

Suggested Antigen Peptide Sequences for FOLH1 Gene

Graphical View of Domain Structure for InterPro Entry

Q04609

UniProtKB/Swiss-Prot:

FOLH1_HUMAN :
  • Q04609
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. Isoform PSM-4 and isoform PSM-5 would appear to be physiologically irrelevant. 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:0004180 carboxypeptidase activity IEA --
GO:0008233 peptidase activity NAS 9375657
GO:0008237 metallopeptidase activity IEA --
GO:0016805 dipeptidase activity IEA --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with FOLH1: view
genes like me logo Genes that share phenotypes with FOLH1: view

Animal Models for FOLH1 Gene

MGI Knock Outs for FOLH1:

Animal Model Products

CRISPR Products

miRNA for FOLH1 Gene

miRTarBase miRNAs that target FOLH1

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for FOLH1

In Situ Assay Products

Flow Cytometry Products

No data available for Transcription Factor Targeting 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
plasma membrane 5
nucleus 4
cytosol 3
extracellular 2
cytoskeleton 1
endosome 1
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:0005887 integral component of plasma membrane IEA --
GO:0016020 membrane NAS 9375657
GO:0016021 integral component of membrane --
GO:0070062 extracellular exosome IDA 23533145
genes like me logo Genes that share ontologies with FOLH1: view

Pathways for FOLH1 Gene

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

Pathways by source for FOLH1 Gene

1 BioSystems pathway for FOLH1 Gene
1 KEGG pathway for FOLH1 Gene
1 R&D Systems pathway for FOLH1 Gene

Gene Ontology (GO) - Biological Process for FOLH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis NAS 9375657
GO:0006760 folic acid-containing compound metabolic process IEA --
genes like me logo Genes that share ontologies with FOLH1: view

Compounds for FOLH1 Gene

(2) 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]

(2) HMDB Compounds for FOLH1 Gene

Compound Synonyms Cas Number PubMed IDs
Cobalt
  • Co
7440-48-4
L-Glutamic acid
  • (2S)-2-Aminopentanedioate
56-86-0

(4) Drugbank Compounds for FOLH1 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
(2S)-2-{[HYDROXY(4-IODOBENZYL)PHOSPHORYL]METHYL}PENTANEDIOIC ACID
target
Capromab
  • Capromab pendetide
145464-28-4 target other/unknown
L-Glutamic Acid
  • (2S)-2-Aminopentanedioic acid
56-86-0 target
N-({(1R)-1-carboxy-2-[(4-fluorobenzyl)sulfanyl]ethyl}carbamoyl)-L-glutamic acid
target

(41) Novoseek inferred chemical compound relationships for FOLH1 Gene

Compound -log(P) Hits PubMed IDs
naag 93.7 77
n-acetyl-aspartyl-glutamate 93.3 32
prostascint 90.3 12
pmsa 72.1 3
glutamate 65.8 163
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:

CRISPR Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for FOLH1

Primer Products

  • OriGene qSTAR qPCR primer pairs in human,mouse,rat for FOLH1
  • QuantiTect SYBR Green Assays in human,mouse,rat
  • Pre-validated RT² qPCR Primer Assay in human,mouse,rat
  • QuantiFast Probe-based Assays in human,mouse,rat

Flow Cytometry Products

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) (9.8), Prostate (7.3), Brain - Substantia nigra (5.7), and Brain - Hippocampus (4.3).

Integrated Proteomics: protein expression 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-2 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 expressions with FOLH1: view

In Situ Assay Products

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
mouse
(Mus musculus)
Mammalia Folh1 16
Folh1 36
  • 85 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia FOLH1 36
  • 79 (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 naalad2 36
  • 66 (a)
OneToMany
zgc56429 35
worm
(Caenorhabditis elegans)
Secernentea gcp-2.1 36
  • 32 (a)
ManyToMany
gcp-2.2 36
  • 29 (a)
ManyToMany
gcp-2.3 36
  • 28 (a)
ManyToMany
C35C5.2 37
  • 32 (a)
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

Selected 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 MAF
rs149894 -- 49,187,383(-) AGGGG(G/T)ACATT intron-variant
rs169366 -- 49,170,540(+) AACCC(A/G)GGATG intron-variant
rs172129 -- 49,198,374(-) ctccc(G/T)agtag intron-variant
rs175849 -- 49,173,342(+) TTGCT(A/G)TTTGT intron-variant
rs182168 -- 49,204,632(-) CGTTT(C/T)AAATG 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

Relevant External Links for FOLH1 Gene

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

Disorders for FOLH1 Gene

(1) University of Copenhagen DISEASES for FOLH1 Gene

(42) Novoseek inferred disease relationships for FOLH1 Gene

Disease -log(P) Hits PubMed IDs
prostate cancer 89 243
prostate carcinoma 76 53
prostatic adenocarcinoma 70.8 19
recurrent prostate cancer 64.2 3
benign prostatic hyperplasia 59.2 13

Relevant External Links for FOLH1

Genetic Association Database (GAD)
FOLH1
Human Genome Epidemiology (HuGE) Navigator
FOLH1
genes like me logo Genes that share disorders with FOLH1: view

No data available for UniProtKB/Swiss-Prot 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
  2. Glutamate carboxypeptidase II: a polymorphism associated with lower levels of serum folate and hyperhomocysteinemia. (PMID: 11092759) Devlin A.M. … Halsted C.H. (Hum. Mol. Genet. 2000) 3 4 23 48
  3. Effect of glutamate carboxypeptidase II and reduced folate carrier polymorphisms on folate and total homocysteine concentrations in dialysis patients. (PMID: 12707400) FAPdinger M. … Sunder-Plassmann G. (J. Am. Soc. Nephrol. 2003) 3 23 48
  4. The H475Y polymorphism in the glutamate carboxypeptidase II gene increases plasma folate without affecting the risk for neural tube defects in humans. (PMID: 12514270) Afman L.A. … Blom H.J. (J. Nutr. 2003) 3 23 48
  5. Influence of a glutamate carboxypeptidase II (GCPII) polymorphism (1561C-->T) on plasma homocysteine, folate and vitamin B(12) levels and its relationship to cardiovascular disease risk. (PMID: 12204797) Lievers K.J. … Blom H.J. (Atherosclerosis 2002) 3 23 48

Products for FOLH1 Gene

  • Addgene plasmids for FOLH1

Sources for FOLH1 Gene

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