FOLH1 (folate hydrolase 1)

Gene

• Entrez ID: 2346
• Gene name: Folate hydrolase 1
• Gene symbol: FOLH1
• Synonyms: FGCP, FOLH, GCP2, GCPII, NAALAD1, NAALAdase, PSM, PSMA, mGCP
• Chromosome: 11
• Chromosome location: 11p11.12
• 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]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029538	hsa-miR-26b-5p	Microarray	19088304

Transcription factors

Transcription factor	Regulation	Reference
AR	Unknown	12539223

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004180	Function	Carboxypeptidase activity	IBA	21873635
GO:0004181	Function	Metallocarboxypeptidase activity	IDA	12949938, 17241121, 24863754
GO:0005737	Component	Cytoplasm	IEA
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	IDA	12949938
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	TAS	8417812
GO:0006508	Process	Proteolysis	IDA	12949938
GO:0006508	Process	Proteolysis	NAS
GO:0008233	Function	Peptidase activity	NAS
GO:0008652	Process	Cellular amino acid biosynthetic process	TAS
GO:0009986	Component	Cell surface	IDA	12949938
GO:0016020	Component	Membrane	NAS
GO:0016805	Function	Dipeptidase activity	IEA
GO:0035609	Process	C-terminal protein deglutamylation	IDA	12949938, 17241121, 24863754
GO:0046872	Function	Metal ion binding	IEA
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:1904492	Function	Ac-Asp-Glu binding	IDA	24863754
GO:1904493	Function	Tetrahydrofolyl-poly(glutamate) polymer binding	IDA	24863754

Other IDs

• MIM: 600934
• HGNC: 3788
• e!Ensembl: ENSG00000086205

Protein

• UniProt ID: Q04609
• Protein name: Glutamate carboxypeptidase 2 (EC 3.4.17.21) (Cell growth-inhibiting gene 27 protein) (Folate hydrolase 1) (Folylpoly-gamma-glutamate carboxypeptidase) (FGCP) (Glutamate carboxypeptidase II) (GCPII) (Membrane glutamate carboxypeptidase) (mGCP) (N-acetylated-alpha-linked acidic dipeptidase I) (NAALADase I) (Prostate-specific membrane antigen) (PSM) (PSMA) (Pteroylpoly-gamma-glutamate carboxypeptidase)
• Protein function: Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate. In the brain, modulates excitatory neurotransmission through the hydrolysis of the neuropeptide, N-aceylaspartylglutamate (NAAG), thereby releasing glutamate. Involved in prostate tumor progression.; Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC.
• PDB: 1Z8L, 2C6C, 2C6G, 2C6P, 2CIJ, 2JBJ, 2JBK, 2OOT, 2OR4, 2PVV, 2PVW, 2XEF, 2XEG, 2XEI, 2XEJ, 3BHX, 3BI0, 3BI1, 3BXM, 3D7D, 3D7F, 3D7G, 3D7H, 3IWW, 3RBU, 3SJE, 3SJF, 3SJG, 3SJX, 4JYW, 4JZ0, 4LQG, 4MCP, 4MCQ, 4MCR, 4MCS, 4NGM, 4NGN, 4NGP, 4NGQ, 4NGR, 4NGS, 4NGT, 4OC0, 4OC1, 4OC2, 4OC3, 4OC4, 4OC5, 4OME, 4P44
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02225	PA	170 → 261	PA domain	Family
  PF04389	Peptidase_M28	357 → 564	Peptidase family M28	Family
  PF04253	TFR_dimer	627 → 747	Transferrin receptor-like dimerisation domain	Domain

• Sequence:

  MWNLLHETDSAVATARRPRWLCAGALVLAGGFFLLGFLFGWFIKSSNEATNITPKHNMKA
  FLDELKAENIKKFLYNFTQIPHLAGTEQNFQLAKQIQSQWKEFGLDSVELAHYDVLLSYP
  NKTHPNYISIINEDGNEIFNTSLFEPPPPGYENVSDIVPPFSAFSPQGMPEGDLVYVNYA
  RTEDFFKLERDMKINCSGKIVIARYGKVFRGNKVKNAQLAGAKGVILYSDPADYFAPGVK
  SYPDGWNLPGGGVQRGNILNLNGAGDPLTPGYPANEYAYRRGIAEAVGLPSIPVHPIGYY
  DAQKLLEKMGGSAPPDSSWRGSLKVPYNVGPGFTGNFSTQKVKMHIHSTNEVTRIYNVIG
  TLRGAVEPDRYVILGGHRDSWVFGGIDPQSGAAVVHEIVRSFGTLKKEGWRPRRTILFAS
  WDAEEFGLLGSTEWAEENSRLLQERGVAYINADSSIEGNYTLRVDCTPLMYSLVHNLTKE
  LKSPDEGFEGKSLYESWTKKSPSPEFSGMPRISKLGSGNDFEVFFQRLGIASGRARYTKN
  WETNKFSGYPLYHSVYETYELVEKFYDPMFKYHLTVAQVRGGMVFELANSIVLPFDCRDY
  AVVLRKYADKIYSISMKHPQEMKTYSVSFDSLFSAVKNFTEIASKFSERLQDFDKSNPIV
  LRMMNDQLMFLERAFIDPLGLPDRPFYRHVIYAPSSHNKYAGESFPGIYDALFDIESKVD
  PSKAWGEVKRQIYVAAFTVQAAAETLSEVA

• Sequence length: 750