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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]
FOLH1 (Folate Hydrolase 1) is a Protein Coding gene. Diseases associated with FOLH1 include Prostate Cancer and Canavan Disease. Among its related pathways are Circadian entrainment and One carbon pool by folate. Gene Ontology (GO) annotations related to this gene include peptidase activity and carboxypeptidase activity. An important paralog of this gene is NAALAD2.
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.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH11J049206 | Promoter/Enhancer | 1.9 | EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER | 624.3 | +0.6 | 611 | 2.5 | SP1 YY1 POLR2A RAD21 HNF4A REST TAF1 EZH2 | FOLH1 HSALNG0084130 RF00017-919 TRIM64C | |
GH11J049166 | Enhancer | 0.5 | dbSUPER | 36.5 | +36.4 | 36391 | 10.7 | CTCF SP1 NFE2 RAD21 SMC3 ZNF654 HNF4A MAFK | FOLH1 GTF2IP11 RF00017-919 UBTFL9 TRIM64C | |
GH11J049226 | Enhancer | 0.6 | Ensembl dbSUPER | 22.1 | -21.0 | -20958 | 0.4 | CTCF RAD21 SMC3 ZNF654 TRIM22 | FOLH1 RF00004-023 lnc-TRIM49B-7 ENSG00000255532 OR4C13 | |
GH11J049183 | Enhancer | 0.5 | dbSUPER | 25.7 | +19.7 | 19729 | 11.6 | CTCF SP1 SOX13 POLR2A HNF4A SMARCA4 SOX5 CREB1 | FOLH1 RF00017-919 HSALNG0084130 TRIM64C | |
GH11J049233 | Enhancer | 0.7 | Ensembl ENCODE | 16.2 | -24.9 | -24859 | 2.6 | TFE3 GABPA CTCF CEBPB FOXA2 CREB1 GABPB1 FOXA1 JUN HNF4A | FOLH1 ENSG00000205035 RF00004-023 lnc-TRIM49B-7 ENSG00000255532 OR4C13 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0003824 | catalytic activity | IEA | -- |
GO:0004180 | carboxypeptidase activity | IBA | 21873635 |
GO:0004181 | metallocarboxypeptidase activity | IDA | 12949938 |
GO:0008233 | peptidase activity | NAS | -- |
GO:0008237 | metallopeptidase activity | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005737 | cytoplasm | IEA | -- |
GO:0005886 | plasma membrane | IDA,TAS | -- |
GO:0005887 | integral component of plasma membrane | TAS,IEA | -- |
GO:0009986 | cell surface | IDA | 12949938 |
GO:0016020 | membrane | IEA,NAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Metabolism |
.40
|
|
2 | Alanine, aspartate and glutamate metabolism | ||
3 | Vitamin digestion and absorption | ||
4 | Circadian entrainment | ||
5 | Amino acid synthesis and interconversion (transamination) |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0006508 | proteolysis | IDA,NAS | -- |
GO:0006760 | folic acid-containing compound metabolic process | IEA | -- |
GO:0008152 | metabolic process | IEA | -- |
GO:0008652 | cellular amino acid biosynthetic process | TAS | -- |
GO:0035609 | C-terminal protein deglutamylation | IDA | 12949938 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Glutamic acid | Approved | Nutra | Agonist, Full agonist, Target | 304 | ||
Docetaxel | Approved, Investigational | Pharma | Inhibition, inhibitor, Biomarker | Microtubulin disassembly inhibitor, Tubulin and VEGF inhibitor, Taxanes | 2330 | |
Methotrexate | Approved | Pharma | Folate antagonist,inhibits DFHR | 1825 | ||
Capromab pendetide | Approved | Pharma | Target, other/unknown | 0 | ||
Mercaptopurine | Approved | Pharma | 232 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
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 |
Compound | Action | Cas Number |
---|---|---|
2-MPPA | 254737-29-6 | |
PMPA (NAALADase inhibitor) | Glutamate carboxypeptidase 2 inhibitor | 173039-10-6 |
ZJ 43 | GCP II and III/NAAG peptidase/NAALADase inhibitor | 723331-20-2 |
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: | - | - | - |
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | FOLH1 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | FOLH1 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | FOLH1 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Folh1 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | FOLH1 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | FOLH1 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | FOLH1 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | FOLH1 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | Str.8739 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | naalad2 31 |
|
OneToMany | |
zgc56429 30 |
|
||||
Worm (Caenorhabditis elegans) |
Secernentea | gcp-2.1 31 |
|
ManyToMany | |
C35C5.2 32 |
|
|
|||
gcp-2.2 31 |
|
ManyToMany | |||
gcp-2.3 31 |
|
ManyToMany | |||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | VPS70 31 |
|
OneToMany | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
ManyToMany | |
-- 31 |
|
ManyToMany | |||
-- 31 |
|
ManyToMany | |||
-- 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 11 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
768447 | Likely Benign: not provided | 49,185,763(-) | A/G | SYNONYMOUS_VARIANT,INTRON_VARIANT | |
787594 | Benign: not provided | 49,192,828(-) | G/C | MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT | |
789798 | Benign: not provided | 49,192,842(-) | G/A | MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT | |
rs79155991 | Benign: not specified | 49,186,767(-) | G/A | SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT | |
VAR_036398 | A colorectal cancer sample | p.Ala23Thr |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv2666171 | CNV | deletion | 23128226 |
esv2744485 | CNV | deletion | 23290073 |
esv2759824 | CNV | gain+loss | 17122850 |
esv2759825 | CNV | gain+loss | 17122850 |
esv3891984 | CNV | gain | 25118596 |
esv3891986 | CNV | gain | 25118596 |
esv3891995 | CNV | gain | 25118596 |
esv3891996 | CNV | gain | 25118596 |
nsv1044070 | CNV | loss | 25217958 |
nsv467874 | CNV | gain | 19166990 |
nsv469956 | CNV | gain | 18288195 |
nsv518571 | CNV | gain | 19592680 |
nsv525454 | CNV | loss | 19592680 |
nsv554223 | CNV | gain | 21841781 |
nsv554347 | CNV | gain | 21841781 |
nsv832145 | CNV | gain | 17160897 |
nsv972015 | CNV | duplication | 23825009 |
nsv975176 | CNV | duplication | 23825009 |
Disorder | Aliases | PubMed IDs |
---|---|---|
prostate cancer |
|
|
canavan disease |
|
|
bladder lateral wall cancer |
|
|
neural tube defects |
|
|
prostate disease |
|