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FOLH1 folate hydrolase 1 [ Homo sapiens (human) ]

Gene ID: 2346, updated on 10-Oct-2024

Summary

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

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

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

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

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)

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_001014986.3NP_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:348595
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:120346
    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:632716
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:58114
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42
  2. NM_001193471.3NP_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:333580
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:105331
    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:617732
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:4399
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42
  3. NM_001193472.3NP_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:333580
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:105331
    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:617701
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:4399
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42
  4. NM_001193473.3NP_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:40287
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    pfam04253
    Location:324439
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl10459
    Location:138
    Peptidases_S8_S53; Peptidase domain in the S8 and S53 families
  5. NM_001351236.2NP_001338165.1  glutamate carboxypeptidase 2 isoform 6

    Status: REVIEWED

    Source sequence(s)
    AC110742, AC118273, CA432757
    UniProtKB/TrEMBL
    Q2VPJ0
    Conserved Domains (4) summary
    cd08022
    Location:291538
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:63289
    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:575655
    TFR_dimer; Transferrin receptor-like dimerisation domain
    cl14876
    Location:157
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42
  6. NM_004476.3NP_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:348595
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:120346
    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:632747
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:58114
    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_047426681.1XP_047282637.1  glutamate carboxypeptidase 2 isoform X5

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

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

    UniProtKB/TrEMBL
    A4UU13
    Conserved Domains (4) summary
    cd08022
    Location:333580
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:105331
    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:617732
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:4399
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42
  4. XM_047426682.1XP_047282638.1  glutamate carboxypeptidase 2 isoform X5

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

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

    UniProtKB/TrEMBL
    A4UU13
  7. XM_017017432.2XP_016872921.1  glutamate carboxypeptidase 2 isoform X1

    UniProtKB/TrEMBL
    A4UU13
    Conserved Domains (4) summary
    cd08022
    Location:403650
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:175401
    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:687802
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:113169
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42
  8. XM_047426680.1XP_047282636.1  glutamate carboxypeptidase 2 isoform X4

  9. XM_011519958.4XP_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_054368241.1XP_054224216.1  glutamate carboxypeptidase 2 isoform X2

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

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

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

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

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

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

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