Folh1 folate hydrolase 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Folh1provided by MGI
Official Full Name: folate hydrolase 1provided by MGI
Primary source: MGI:MGI:1858193
See related: Ensembl:ENSMUSG00000001773 AllianceGenome:MGI:1858193
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: GCP2; mopsm
Summary: Enables carboxypeptidase activity and dipeptidase activity. Acts upstream of or within folic acid-containing compound metabolic process and proteolysis. Is integral component of plasma membrane. Is expressed in central nervous system; male reproductive gland or organ; metanephros; and submandibular gland. Orthologous to several human genes including FOLH1 (folate hydrolase 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in kidney adult (RPKM 9.1), genital fat pad adult (RPKM 4.5) and 4 other tissues See more
Orthologs: human all
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Genomic context

Location:: 7; 7 D3

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
109	current	GRCm39 (GCF_000001635.27)	7	NC_000073.7 (86365733..86425171, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	7	NC_000073.6 (86716525..86776053, complement)

Chromosome 7 - NC_000073.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

decrease in both glutamate and N-acetylaspartate levels in the ipsilateral hippocampus at 24 h post-traumatic brain injury (TBI); however, the reduction in glutamate and N-acetylaspartate levels was less marked in GCP II-KO mice than in WT mice. T2 MR data and brain water-content analysis demonstrated that the extent of cortical edema and brain swelling was less in KO than in WT mice after TBI .
Title: Metabolite differences between glutamate carboxypeptidase II gene knockout mice and their wild-type littermates after traumatic brain injury: a 7-tesla <sup>1</sup>H-MRS study.
Data support the hypothesis that the neuroprotective efficacy of glutamate carboxypeptidase II knockout in traumatic brain injury is mediated via a reduction in oxidative stress.
Title: Glutamate carboxypeptidase II gene knockout attenuates oxidative stress and cortical apoptosis after traumatic brain injury.
Knockout of the GCPII gene is not embryonic lethal and affords histopathological protection with improved long-term behavioral outcomes after traumatic brain injury
Title: Mice lacking glutamate carboxypeptidase II develop normally, but are less susceptible to traumatic brain injury.
Inhibition of glutamate carboxypeptidase II (GCPII) activity as a treatment for cognitive impairment in multiple sclerosis.
Title: Inhibition of glutamate carboxypeptidase II (GCPII) activity as a treatment for cognitive impairment in multiple sclerosis.
PSMA plays a VEGF-independent role in retinal angiogenesis
Title: Prostate specific membrane antigen (PSMA) regulates angiogenesis independently of VEGF during ocular neovascularization.
The combined effects of a haplo-insufficiency of glutamate carboxypeptidase II and dietary folic acid deficiency esult in reciprocal protection against cognitive and social deficits.
Title: Glutamate carboxypeptidase II and folate deficiencies result in reciprocal protection against cognitive and social deficits in mice: implications for neurodevelopmental disorders.
analysis of GCP2 and GCP3; beta-citrylglutamate hydrolase is glutamate carboxypeptidase 3
Title: Molecular identification of β-citrylglutamate hydrolase as glutamate carboxypeptidase 3.
This study demenestrated that the heterozygous mice,glutamate carboxypeptidase II, however, developed normally to adulthood and exhibited increased locomotor activity, reduced social interaction, and a subtle cognitive deficit in working memory.
Title: Phenotypic characterization of mice heterozygous for a null mutation of glutamate carboxypeptidase II.
active PSMA facilitates integrin signaling and PAK activation, leading to both productive invasion and downregulation of integrin beta(1) signaling via reduced PSMA activity
Title: Prostate-specific membrane antigen regulates angiogenesis by modulating integrin signal transduction.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (6) 1 citation
Endonuclease-mediated (4)

General gene information

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Homology

Homologs of the Folh1 gene: The Folh1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, rat, chicken, zebrafish, K.lactis, M.oryzae, N.crassa, and frog.
Orthologs from Annotation Pipeline: 178 organisms have orthologs with human gene Folh1
Orthologs

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables Ac-Asp-Glu binding	ISO Inferred from Sequence Orthology more info
enables carboxypeptidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables carboxypeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables catalytic activity	IEA Inferred from Electronic Annotation more info
enables dipeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables metallocarboxypeptidase activity	ISO Inferred from Sequence Orthology more info
enables metallopeptidase activity	IEA Inferred from Electronic Annotation more info
enables peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables tetrahydrofolyl-poly(glutamate) polymer binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within folic acid-containing compound metabolic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within metabolic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in protein catabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within proteolysis	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cell surface	ISO Inferred from Sequence Orthology more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: glutamate carboxypeptidase 2

Names: FGCP; GCPII; N-acetylated-alpha-linked acidic dipeptidase I; NAALADase I; folylpoly-gamma-glutamate carboxypeptidase; glutamate carboxypeptidase II; mGCP; membrane glutamate carboxypeptidase; prostate-specific membrane antigen homolog; pteroylpoly-gamma-glutamate carboxypeptidase

NP_001153178.1

EC 3.4.17.21

NP_058050.3

EC 3.4.17.21

XP_006508086.1

EC 3.4.17.21

XP_011240163.1

EC 3.4.17.21

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.

mRNA and Protein(s)

NM_001159706.1 → NP_001153178.1 glutamate carboxypeptidase 2 isoform 2

See identical proteins and their annotated locations for NP_001153178.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an exon in the coding region compared to variant 1. The resulting protein (isoform 2) is shorter but has the same N- and C-termini compared to isoform 1.

Source sequence(s)

AK002920, BB179784, BB872570, BC119604, BC119605

Consensus CDS

CCDS52300.1

UniProtKB/Swiss-Prot

O35409

UniProtKB/TrEMBL

Q0VDM6

Related

ENSMUSP00000102892.4, ENSMUST00000107271.10

Conserved Domains (3) summary

cd08022
Location:275 → 564

M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen

cd02121
Location:122 → 365

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:601 → 716

TFR_dimer; Transferrin receptor-like dimerization domain
NM_016770.3 → NP_058050.3 glutamate carboxypeptidase 2 isoform 1

See identical proteins and their annotated locations for NP_058050.3

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AK002920, BB179784, BB872570, BC119605

Consensus CDS

CCDS21436.1

UniProtKB/Swiss-Prot

O35409, Q9DCC2

Related

ENSMUSP00000001824.6, ENSMUST00000001824.7

Conserved Domains (4) summary

cd08022
Location:356 → 597

M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen

cd02121
Location:122 → 348

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:634 → 749

TFR_dimer; Transferrin receptor-like dimerization domain

cl14876
Location:70 → 116

Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42

RefSeqs of Annotated Genomes: Mus musculus Annotation Release 109 details...

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

Reference GRCm39 C57BL/6J

Genomic

NC_000073.7 Reference GRCm39 C57BL/6J

Range

86365733..86425171 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006508023.5 → XP_006508086.1 glutamate carboxypeptidase 2 isoform X1

Conserved Domains (3) summary

cd02121
Location:122 → 306

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 the peptidase ...

cd08022
Location:314 → 555

M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen

pfam04253
Location:587 → 707

TFR_dimer; Transferrin receptor-like dimerization domain
XM_011241861.4 → XP_011240163.1 glutamate carboxypeptidase 2 isoform X2

Conserved Domains (2) summary

cd02121
Location:122 → 348

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 the peptidase ...

cl14876
Location:356 → 438

Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42