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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
    mouse all
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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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    NEW Try the new Transcript table

    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

    Gene LinkOut

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