TISIDB

Summary
Symbol	FOLH1
Name	folate hydrolase (prostate-specific membrane antigen) 1
Aliases	PSMA; NAALAD1; GCPII; glutamate carboxylase II; glutamate carboxypeptidase II; FOLH; FGCP; mGCP; N-acetylate ......
Chromosomal Location	11p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cell membrane Single-pass type II membrane protein ; SUBCELLULAR LOCATION: Isoform PSMA': Cytoplasm
Domain	PF02225 PA domain PF04389 Peptidase family M28 PF04253 Transferrin receptor-like dimerisation domain
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.; FUNCTION: Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC.

> Gene Ontology [ TOP ]
Biological Process	GO:0006520 cellular amino acid metabolic process GO:0006575 cellular modified amino acid metabolic process GO:0006732 coenzyme metabolic process GO:0006760 folic acid-containing compound metabolic process GO:0008652 cellular amino acid biosynthetic process GO:0016053 organic acid biosynthetic process GO:0018200 peptidyl-glutamic acid modification GO:0018410 C-terminal protein amino acid modification GO:0035608 protein deglutamylation GO:0035609 C-terminal protein deglutamylation GO:0042558 pteridine-containing compound metabolic process GO:0043687 post-translational protein modification GO:0044283 small molecule biosynthetic process GO:0046394 carboxylic acid biosynthetic process GO:0051186 cofactor metabolic process
Molecular Function	GO:0004180 carboxypeptidase activity GO:0004181 metallocarboxypeptidase activity GO:0008235 metalloexopeptidase activity GO:0008237 metallopeptidase activity GO:0008238 exopeptidase activity GO:0016805 dipeptidase activity GO:0033218 amide binding GO:0042277 peptide binding GO:1900750 oligopeptide binding GO:1904492 Ac-Asp-Glu binding GO:1904493 tetrahydrofolyl-poly(glutamate) polymer binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04977 Vitamin digestion and absorption hsa00250 Alanine, aspartate and glutamate metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-70614: Amino acid synthesis and interconversion (transamination) R-HSA-1430728: Metabolism R-HSA-71291: Metabolism of amino acids and derivatives

Summary
Symbol	FOLH1
Name	folate hydrolase (prostate-specific membrane antigen) 1
Aliases	PSMA; NAALAD1; GCPII; glutamate carboxylase II; glutamate carboxypeptidase II; FOLH; FGCP; mGCP; N-acetylate ......
Chromosomal Location	11p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between FOLH1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between FOLH1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
18272481	Prostate carcinoma	Promote immunity	NPs were formulated by the self-assembly of an amphiphilic triblock copolymer composed of end-to-end linkage of poly(lactic-co-glycolic-acid) (PLGA), polyethyleneglycol (PEG), and the A10 aptamer (Apt), which binds to the prostate-specific membrane antigen (PSMA) on the surface of prostate cancer (PCa) cells, enabling, respectively, controlled drug release, "stealth" properties for immune evasion, and cell-specific targeting.
27406985	Prostate carcinoma	Promote immunity (T cell function)	In vitro cross-linking of T cells with PSMA-expressing tumor cells by MOR209/ES414 triggered potent target-dependent tumor lysis and induction of target-dependent T-cell activation and proliferation.
29229829	Prostate Carcinoma	Promote immunity	Prostate tumors invariably overexpress prostate surface membrane antigen (PSMA). PPD selectively delivered polyIC into PSMA-overexpressing PC cells, inducing apoptosis, cytokine secretion, and the recruitment of human peripheral blood mononuclear cells (PBMCs).
16243819	Metastatic Prostate Carcinoma	Promote immunity	Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein primarily expressed on benign and malignant prostatic epithelial cells. J591 is an IgG1 monoclonal antibody that targets the external domain of the PSMA.
21829171	colon carcinoma	Promote immunity	Tumor inhibition was dependent on homing to PSMA-expressing tumor cells and 4-1BB costimulation. Aptamer targeted costimulation is a broadly applicable and clinically feasible approach to enhance the costimulatory environment of disseminated tumor lesions

Summary
Symbol	FOLH1
Name	folate hydrolase (prostate-specific membrane antigen) 1
Aliases	PSMA; NAALAD1; GCPII; glutamate carboxylase II; glutamate carboxypeptidase II; FOLH; FGCP; mGCP; N-acetylate ......
Chromosomal Location	11p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of FOLH1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	FOLH1
Name	folate hydrolase (prostate-specific membrane antigen) 1
Aliases	PSMA; NAALAD1; GCPII; glutamate carboxylase II; glutamate carboxypeptidase II; FOLH; FGCP; mGCP; N-acetylate ......
Chromosomal Location	11p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of FOLH1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.104	0.852
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.496	0.633
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.541	0.533
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.49	0.398
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.702	0.646
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.214	0.9
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.848	0.151
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.159	0.865
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.547	0.133
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.157	0.441
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	2.009	0.342
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.005	0.975

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of FOLH1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	4.1	-0.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	9.1	-1.4	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	18.8	-7.7	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	22.2	-2.2	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	7.1	-0.9	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	FOLH1
Name	folate hydrolase (prostate-specific membrane antigen) 1
Aliases	PSMA; NAALAD1; GCPII; glutamate carboxylase II; glutamate carboxypeptidase II; FOLH; FGCP; mGCP; N-acetylate ......
Chromosomal Location	11p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FOLH1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	FOLH1
Name	folate hydrolase (prostate-specific membrane antigen) 1
Aliases	PSMA; NAALAD1; GCPII; glutamate carboxylase II; glutamate carboxypeptidase II; FOLH; FGCP; mGCP; N-acetylate ......
Chromosomal Location	11p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FOLH1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FOLH1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	FOLH1
Name	folate hydrolase (prostate-specific membrane antigen) 1
Aliases	PSMA; NAALAD1; GCPII; glutamate carboxylase II; glutamate carboxypeptidase II; FOLH; FGCP; mGCP; N-acetylate ......
Chromosomal Location	11p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FOLH1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	FOLH1
Name	folate hydrolase (prostate-specific membrane antigen) 1
Aliases	PSMA; NAALAD1; GCPII; glutamate carboxylase II; glutamate carboxypeptidase II; FOLH; FGCP; mGCP; N-acetylate ......
Chromosomal Location	11p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of FOLH1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	FOLH1
Name	folate hydrolase (prostate-specific membrane antigen) 1
Aliases	PSMA; NAALAD1; GCPII; glutamate carboxylase II; glutamate carboxypeptidase II; FOLH; FGCP; mGCP; N-acetylate ......
Chromosomal Location	11p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between FOLH1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	FOLH1
Name	folate hydrolase (prostate-specific membrane antigen) 1
Aliases	PSMA; NAALAD1; GCPII; glutamate carboxylase II; glutamate carboxypeptidase II; FOLH; FGCP; mGCP; N-acetylate ......
Chromosomal Location	11p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting FOLH1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting FOLH1.

ID	Name	Drug Type	Targets	#Targets
DB00089	Capromab pendetide	Biotech	FOLH1	1
DB00142	Glutamic Acid	Small Molecule	AADAT, AASS, ABAT, ALDH18A1, ASNS, BCAT1, BCAT2, CCBL2, CPQ, DNPEP ......	69
DB06928	(2S)-2-{[HYDROXY(4-IODOBENZYL)PHOSPHORYL]METHYL}PENTANEDIOIC ACID	Small Molecule	FOLH1	1
DB07754	N-({(1R)-1-carboxy-2-[(4-fluorobenzyl)sulfanyl]ethyl}carbamoyl)-L-glutamic acid	Small Molecule	FOLH1	1
DB08835	Spaglumic Acid	Small Molecule	FOLH1	1

Browse FOLH1