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FOLH1 folate hydrolase 1 [ Homo sapiens (human) ]

Gene ID: 2346, updated on 2-Nov-2024

Summary

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Official Symbol
FOLH1provided by HGNC
Official Full Name
folate hydrolase 1provided by HGNC
Primary source
HGNC:HGNC:3788
See related
Ensembl:ENSG00000086205 MIM:600934; AllianceGenome:HGNC:3788
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PSM; FGCP; FOLH; GCP2; PSMA; mGCP; GCPII; NAALAD1
Summary
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]
Expression
Biased expression in duodenum (RPKM 94.9), prostate (RPKM 43.3) and 6 other tissues See more
Orthologs
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Genomic context

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See FOLH1 in Genome Data Viewer
Location:
11p11.12
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (49145092..49208602, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (49322228..49385778, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (49166644..49230154, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene tripartite motif containing 77B, pseudogene Neighboring gene UBTF like 9 (pseudogene) Neighboring gene uncharacterized LOC124902845 Neighboring gene NOX4 pseudogene 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen. Rajasekaran SA, et al. Mol Biol Cell, 2003 Dec. PMID 14528023, Free PMC Article
  2. Prostate-specific membrane antigen as a potential novel vascular target for treatment of glioblastoma multiforme. Wernicke AG, et al. Arch Pathol Lab Med, 2011 Nov. PMID 22032578
  3. Glutamate carboxypeptidase II gene polymorphisms and neural tube defects in a high-risk Chinese population. Xie H, et al. Metab Brain Dis, 2012 Mar. PMID 22124883
  4. GCPII imaging and cancer. Foss CA, et al. Curr Med Chem, 2012. PMID 22304713, Free PMC Article
  5. Paradoxical role of C1561T glutamate carboxypeptidase II (GCPII) genetic polymorphism in altering disease susceptibility. Divyya S, et al. Gene, 2012 Apr 15. PMID 22310383

See all (217) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Expression of PSMA in Tumor-Associated Vasculature Predicts Poorer Survival in Patients With Hepatocellular Carcinoma and Is Likely Associated With PD-L1.
    Title: Expression of PSMA in Tumor-Associated Vasculature Predicts Poorer Survival in Patients With Hepatocellular Carcinoma and Is Likely Associated With PD-L1.
  2. Frequent Amplification and Overexpression of PSMA in Basallike Breast Cancer from Analysis of The Cancer Genome Atlas.
    Title: Frequent Amplification and Overexpression of PSMA in Basallike Breast Cancer from Analysis of The Cancer Genome Atlas.
  3. Prostate-specific membrane antigen (PSMA) glycoforms in prostate cancer patients seminal plasma.
    Title: Prostate-specific membrane antigen (PSMA) glycoforms in prostate cancer patients seminal plasma.
  4. Logistical, technical, and radiation safety aspects of establishing a radiopharmaceutical therapy program: A case in Lutetium-177 prostate-specific membrane antigen (PSMA) therapy.
    Title: Logistical, technical, and radiation safety aspects of establishing a radiopharmaceutical therapy program: A case in Lutetium-177 prostate-specific membrane antigen (PSMA) therapy.
  5. PSMA-heterogeneity in metastatic castration-resistant prostate cancer: Circulating tumor cells, metastatic tumor burden, and response to targeted radioligand therapy.
    Title: PSMA-heterogeneity in metastatic castration-resistant prostate cancer: Circulating tumor cells, metastatic tumor burden, and response to targeted radioligand therapy.
  6. Prostate-Specific Membrane Antigen (PSMA) Expression in The Neovasculature of High Grade Gliomas (Histopathological and Immunohistochemical Study).
    Title: Prostate-Specific Membrane Antigen (PSMA) Expression in The Neovasculature of High Grade Gliomas (Histopathological and Immunohistochemical Study).
  7. Secreted phosphoprotein 1 promotes angiogenesis of glioblastoma through upregulating PSMA expression via transcription factor HIF1alpha.
    Title: Secreted phosphoprotein 1 promotes angiogenesis of glioblastoma through upregulating PSMA expression via transcription factor HIF1α.
  8. Diagnostic Efficacy of PSMA and PSCA mRNAs Combined to PSA in Prostate Cancer Patients.
    Title: Diagnostic Efficacy of PSMA and PSCA mRNAs Combined to PSA in Prostate Cancer Patients.
  9. STAT3, VEGF, and PSMA Expression Patterns in Malignant Peripheral Nerve Sheath Tumors, Malignant Melanomas, and Glioblastomas: Does Staining Percentage and Intensity Have an Effect on Survival?
    Title: STAT3, VEGF, and PSMA Expression Patterns in Malignant Peripheral Nerve Sheath Tumors, Malignant Melanomas, and Glioblastomas: Does Staining Percentage and Intensity Have an Effect on Survival?
  10. Impact of Androgen Receptor Activity on Prostate-Specific Membrane Antigen Expression in Prostate Cancer Cells.
    Title: Impact of Androgen Receptor Activity on Prostate-Specific Membrane Antigen Expression in Prostate Cancer Cells.
Submit: New GeneRIF Correction See all GeneRIFs (157)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
EBI GWAS Catalog
Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables Ac-Asp-Glu binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables carboxypeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables dipeptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables metallocarboxypeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables peptidase activity NAS
Non-traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables tetrahydrofolyl-poly(glutamate) polymer binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in C-terminal protein deglutamylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in folic acid-containing compound metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in proteolysis NAS
Non-traceable Author Statement
more info
  
Component Evidence Code Pubs
located_in cell surface IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular exosome HDA PubMed 
located_in membrane NAS
Non-traceable Author Statement
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
glutamate carboxypeptidase 2
Names
N-acetylated alpha-linked acidic dipeptidase 1
N-acetylated-alpha-linked acidic dipeptidase I
NAALADase I
cell growth-inhibiting gene 27 protein
folylpoly-gamma-glutamate carboxypeptidase
glutamate carboxylase II
glutamate carboxypeptidase II
membrane glutamate carboxypeptidase
pteroylpoly-gamma-glutamate carboxypeptidase
NP_001014986.1
NP_001180400.1
NP_001180401.1
NP_001180402.1
NP_001338165.1
NP_004467.1
XP_011518260.2
XP_016872921.1
XP_016872922.1
XP_016872923.1
XP_047282634.1
XP_047282635.1
XP_047282636.1
XP_047282637.1
XP_047282638.1
XP_054224215.1
XP_054224216.1
XP_054224217.1
XP_054224218.1
XP_054224219.1
XP_054224220.1
XP_054224221.1
XP_054224222.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_029170.1 RefSeqGene

    Range
    5069..68579
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001014986.3 → NP_001014986.1  glutamate carboxypeptidase 2 isoform 2

    See identical proteins and their annotated locations for NP_001014986.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AC118273, BC025672, CA432757, M99487
    Consensus CDS
    CCDS31493.1
    UniProtKB/TrEMBL
    A4UU13
    Related
    ENSP00000349129.3, ENST00000356696.7
    Conserved Domains (4) summary
    cd08022
    Location:348 → 595
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:120 → 346
    PA_GCPII_like; PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to ...
    pfam04253
    Location:632 → 716
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:58 → 114
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42

  2. NM_001193471.3 → NP_001180400.1  glutamate carboxypeptidase 2 isoform 3

    See identical proteins and their annotated locations for NP_001180400.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) has a shorter and distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AC118273, CA432757, EF488811, M99487
    Consensus CDS
    CCDS53628.1
    UniProtKB/TrEMBL
    A4UU13
    Related
    ENSP00000344131.7, ENST00000340334.11
    Conserved Domains (4) summary
    cd08022
    Location:333 → 580
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:105 → 331
    PA_GCPII_like; PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to ...
    pfam04253
    Location:617 → 732
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:43 → 99
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42

  3. NM_001193472.3 → NP_001180401.1  glutamate carboxypeptidase 2 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (4) has a shorter and distinct N-terminus and lacks an internal segment compared to isoform 1.
    Source sequence(s)
    AC118273, BC025672, CA432757, EF488811, M99487
    Consensus CDS
    CCDS53627.1
    UniProtKB/TrEMBL
    A4UU13
    Related
    ENSP00000431463.1, ENST00000533034.1
    Conserved Domains (4) summary
    cd08022
    Location:333 → 580
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:105 → 331
    PA_GCPII_like; PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to ...
    pfam04253
    Location:617 → 701
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:43 → 99
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42

  4. NM_001193473.3 → NP_001180402.1  glutamate carboxypeptidase 2 isoform 5

    See identical proteins and their annotated locations for NP_001180402.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (5) is shorter at the N-terminus compared to isoform 1.
    Source sequence(s)
    AC118273, AK295368, CA432757, M99487
    UniProtKB/Swiss-Prot
    Q9HBA9
    Conserved Domains (3) summary
    cd08022
    Location:40 → 287
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    pfam04253
    Location:324 → 439
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl10459
    Location:1 → 38
    Peptidases_S8_S53; Peptidase domain in the S8 and S53 families

  5. NM_001351236.2 → NP_001338165.1  glutamate carboxypeptidase 2 isoform 6

    Status: REVIEWED

    Source sequence(s)
    AC110742, AC118273, CA432757
    UniProtKB/TrEMBL
    Q2VPJ0
    Conserved Domains (4) summary
    cd08022
    Location:291 → 538
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:63 → 289
    PA_GCPII_like; PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to ...
    pfam04253
    Location:575 → 655
    TFR_dimer; Transferrin receptor-like dimerisation domain
    cl14876
    Location:1 → 57
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42

  6. NM_004476.3 → NP_004467.1  glutamate carboxypeptidase 2 isoform 1

    See identical proteins and their annotated locations for NP_004467.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AC118273, CA432757, M99487
    Consensus CDS
    CCDS7946.1
    UniProtKB/Swiss-Prot
    A4UU12, A9CB79, B7Z312, B7Z343, D3DQS5, E9PDX8, O43748, Q04609, Q16305, Q541A4, Q8TAY3, Q9NP15, Q9NYE2, Q9P1P8
    UniProtKB/TrEMBL
    A4UU13
    Related
    ENSP00000256999.2, ENST00000256999.7
    Conserved Domains (4) summary
    cd08022
    Location:348 → 595
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:120 → 346
    PA_GCPII_like; PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to ...
    pfam04253
    Location:632 → 747
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:58 → 114
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    49145092..49208602 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047426681.1 → XP_047282637.1  glutamate carboxypeptidase 2 isoform X5

  2. XM_047426678.1 → XP_047282634.1  glutamate carboxypeptidase 2 isoform X4

  3. XM_017017434.2 → XP_016872923.1  glutamate carboxypeptidase 2 isoform X3

    UniProtKB/TrEMBL
    A4UU13
    Conserved Domains (4) summary
    cd08022
    Location:333 → 580
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:105 → 331
    PA_GCPII_like; PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to ...
    pfam04253
    Location:617 → 732
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:43 → 99
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42

  4. XM_047426682.1 → XP_047282638.1  glutamate carboxypeptidase 2 isoform X5

  5. XM_047426679.1 → XP_047282635.1  glutamate carboxypeptidase 2 isoform X4

  6. XM_017017433.3 → XP_016872922.1  glutamate carboxypeptidase 2 isoform X2

    UniProtKB/TrEMBL
    A4UU13

  7. XM_017017432.2 → XP_016872921.1  glutamate carboxypeptidase 2 isoform X1

    UniProtKB/TrEMBL
    A4UU13
    Conserved Domains (4) summary
    cd08022
    Location:403 → 650
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:175 → 401
    PA_GCPII_like; PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to ...
    pfam04253
    Location:687 → 802
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:113 → 169
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42

  8. XM_047426680.1 → XP_047282636.1  glutamate carboxypeptidase 2 isoform X4

  9. XM_011519958.4 → XP_011518260.2  glutamate carboxypeptidase 2 isoform X6

    UniProtKB/TrEMBL
    B7Z6L3, E9PG45

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    49322228..49385778 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054368241.1 → XP_054224216.1  glutamate carboxypeptidase 2 isoform X2

  2. XM_054368240.1 → XP_054224215.1  glutamate carboxypeptidase 2 isoform X1

  3. XM_054368245.1 → XP_054224220.1  glutamate carboxypeptidase 2 isoform X5

  4. XM_054368243.1 → XP_054224218.1  glutamate carboxypeptidase 2 isoform X4

  5. XM_054368242.1 → XP_054224217.1  glutamate carboxypeptidase 2 isoform X3

  6. XM_054368246.1 → XP_054224221.1  glutamate carboxypeptidase 2 isoform X5

  7. XM_054368244.1 → XP_054224219.1  glutamate carboxypeptidase 2 isoform X4

  8. XM_054368247.1 → XP_054224222.1  glutamate carboxypeptidase 2 isoform X6

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q04609.1 GenPept UniProtKB/Swiss-Prot:Q04609

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