TISIDB

Summary
Symbol	GGH
Name	gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)
Aliases	gamma-Glu-X carboxypeptidase; Conjugase; Gamma-glutamyl hydrolase
Chromosomal Location	8q12.3
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	Secreted, extracellular space Lysosome Melanosome Note=While its intracellular location is primarily the lysosome, most of the enzyme activity is secreted. Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
Domain	PF07722 Peptidase C26
Function	Hydrolyzes the polyglutamate sidechains of pteroylpolyglutamates. Progressively removes gamma-glutamyl residues from pteroylpoly-gamma-glutamate to yield pteroyl-alpha-glutamate (folic acid) and free glutamate. May play an important role in the bioavailability of dietary pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates and antifolates.

> Gene Ontology [ TOP ]
Biological Process	GO:0006520 cellular amino acid metabolic process GO:0006541 glutamine metabolic process GO:0006575 cellular modified amino acid metabolic process GO:0006732 coenzyme metabolic process GO:0006760 folic acid-containing compound metabolic process GO:0009064 glutamine family amino acid metabolic process GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0010043 response to zinc ion GO:0032868 response to insulin GO:0042493 response to drug GO:0042558 pteridine-containing compound metabolic process GO:0043434 response to peptide hormone GO:0045471 response to ethanol GO:0046900 tetrahydrofolylpolyglutamate metabolic process GO:0051186 cofactor metabolic process GO:0097305 response to alcohol GO:1901605 alpha-amino acid metabolic process GO:1901652 response to peptide GO:1990267 response to transition metal nanoparticle
Molecular Function	GO:0008238 exopeptidase activity GO:0008242 omega peptidase activity GO:0034722 gamma-glutamyl-peptidase activity
Cellular Component	GO:0042470 melanosome GO:0048770 pigment granule

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00790 Folate biosynthesis
Reactome	R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-6798695: Neutrophil degranulation

Summary
Symbol	GGH
Name	gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)
Aliases	gamma-Glu-X carboxypeptidase; Conjugase; Gamma-glutamyl hydrolase
Chromosomal Location	8q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between GGH 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 [ TOP ]
There is no record.

Summary
Symbol	GGH
Name	gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)
Aliases	gamma-Glu-X carboxypeptidase; Conjugase; Gamma-glutamyl hydrolase
Chromosomal Location	8q12.3
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 GGH 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	GGH
Name	gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)
Aliases	gamma-Glu-X carboxypeptidase; Conjugase; Gamma-glutamyl hydrolase
Chromosomal Location	8q12.3
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 GGH 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	-0.634	0.0335
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.125	0.663
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.272	0.882
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.356	0.505
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.383	0.732
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.32	0.805
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.211	0.688
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.699	0.679
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.318	0.866
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.036	0.981
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	0.47	0.834
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.567	0.000404

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of GGH 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	0	3.7	0.27
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	0	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	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	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	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	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	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	GGH
Name	gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)
Aliases	gamma-Glu-X carboxypeptidase; Conjugase; Gamma-glutamyl hydrolase
Chromosomal Location	8q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GGH. 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	GGH
Name	gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)
Aliases	gamma-Glu-X carboxypeptidase; Conjugase; Gamma-glutamyl hydrolase
Chromosomal Location	8q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GGH. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GGH. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	GGH
Name	gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)
Aliases	gamma-Glu-X carboxypeptidase; Conjugase; Gamma-glutamyl hydrolase
Chromosomal Location	8q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GGH. 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	GGH
Name	gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)
Aliases	gamma-Glu-X carboxypeptidase; Conjugase; Gamma-glutamyl hydrolase
Chromosomal Location	8q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of GGH expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	GGH
Name	gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)
Aliases	gamma-Glu-X carboxypeptidase; Conjugase; Gamma-glutamyl hydrolase
Chromosomal Location	8q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between GGH and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	GGH
Name	gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)
Aliases	gamma-Glu-X carboxypeptidase; Conjugase; Gamma-glutamyl hydrolase
Chromosomal Location	8q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting GGH collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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