TISIDB

Summary
Symbol	GZMA
Name	granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)
Aliases	CTL tryptase; Granzyme A (Cytotoxic T-lymphocyte-associated serine esterase-3; Hanukah factor serine proteas ......
Chromosomal Location	5q11-q12
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	Isoform alpha: Secreted. Cytoplasmic granule.
Domain	PF00089 Trypsin
Function	Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent cell death with morphological features of apoptosis when delivered into the target cell through the immunological synapse. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. Cleaves the nucleosome assembly protein SET after 'Lys-189', which disrupts its nucleosome assembly activity and allows the SET complex to translocate into the nucleus to nick and degrade the DNA.

> Gene Ontology [ TOP ]
Biological Process	GO:0019835 cytolysis GO:0032069 regulation of nuclease activity GO:0032070 regulation of deoxyribonuclease activity GO:0032071 regulation of endodeoxyribonuclease activity GO:0032074 negative regulation of nuclease activity GO:0032076 negative regulation of deoxyribonuclease activity GO:0032078 negative regulation of endodeoxyribonuclease activity GO:0043392 negative regulation of DNA binding GO:0051052 regulation of DNA metabolic process GO:0051053 negative regulation of DNA metabolic process GO:0051098 regulation of binding GO:0051100 negative regulation of binding GO:0051101 regulation of DNA binding GO:0051341 regulation of oxidoreductase activity GO:0051346 negative regulation of hydrolase activity GO:0051354 negative regulation of oxidoreductase activity
Molecular Function	GO:0004175 endopeptidase activity GO:0004252 serine-type endopeptidase activity GO:0008236 serine-type peptidase activity GO:0017171 serine hydrolase activity
Cellular Component	GO:0001772 immunological synapse

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04080 Neuroactive ligand-receptor interaction
Reactome	-

Summary
Symbol	GZMA
Name	granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)
Aliases	CTL tryptase; Granzyme A (Cytotoxic T-lymphocyte-associated serine esterase-3; Hanukah factor serine proteas ......
Chromosomal Location	5q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between GZMA 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 GZMA and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29668679	breast carcinoma; ovarian carcinoma and glioblastoma	Promote immunity (T cell function)	In contrast to exposure to mf, exposure to cancer cell lines increased the phagocytic ability of monocytes and reduced their ability to induce T cell proliferation and to expand Granzyme A+ CD8+ T cells.
23851682	Lung Adenocarcinoma; Non-Small Cell Lung Carcinoma	Promote immunity (infiltration)	Because mice bearing early NSCLC treated with anti-CD25 mAb exhibited increased tumor cell death associated with infiltration by CD8(+) T cells expressing elevated levels of granzyme A, granzyme B, perforin, and IFN-γ, we therefore evaluated carboplatin combination therapy resulting in a significantly extended survival beyond that observed with chemotherapy alone, indicating that Treg depletion in combination with cytotoxic therapy may be beneficial as a treatment strategy for advanced NSCLC.
17015756	colon carcinoma	Promote immunity	Notably, redirected CD4+ T cells mediate cytolysis of CEA+ tumor cells with high efficiencies. Lysis by redirected CD4+ T cells is independent of death receptor signaling via TNF-alpha or Fas, but mediated by perforin and granzyme because cytolysis is inhibited by blocking the release of cytotoxic granules, but not by blocking of Fas ligand or TNF-alpha.

Summary
Symbol	GZMA
Name	granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)
Aliases	CTL tryptase; Granzyme A (Cytotoxic T-lymphocyte-associated serine esterase-3; Hanukah factor serine proteas ......
Chromosomal Location	5q11-q12
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 GZMA 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	GZMA
Name	granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)
Aliases	CTL tryptase; Granzyme A (Cytotoxic T-lymphocyte-associated serine esterase-3; Hanukah factor serine proteas ......
Chromosomal Location	5q11-q12
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 GZMA 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	-0.534	0.382
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.511	0.768
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.551	0.682
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.614	0.379
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.716	0.529
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.477	0.704
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.694	0.331
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.553	0.198
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.255	0.846
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	2.042	0.258
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	1.315	0.653
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.373	0.118

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of GZMA 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	0	0	0	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	0	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	0	9.5	0.492
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	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	0	0	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	4.5	7.7	-3.2	1
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	GZMA
Name	granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)
Aliases	CTL tryptase; Granzyme A (Cytotoxic T-lymphocyte-associated serine esterase-3; Hanukah factor serine proteas ......
Chromosomal Location	5q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GZMA. 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	GZMA
Name	granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)
Aliases	CTL tryptase; Granzyme A (Cytotoxic T-lymphocyte-associated serine esterase-3; Hanukah factor serine proteas ......
Chromosomal Location	5q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GZMA. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GZMA. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	GZMA
Name	granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)
Aliases	CTL tryptase; Granzyme A (Cytotoxic T-lymphocyte-associated serine esterase-3; Hanukah factor serine proteas ......
Chromosomal Location	5q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GZMA. 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	GZMA
Name	granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)
Aliases	CTL tryptase; Granzyme A (Cytotoxic T-lymphocyte-associated serine esterase-3; Hanukah factor serine proteas ......
Chromosomal Location	5q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of GZMA expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	GZMA
Name	granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)
Aliases	CTL tryptase; Granzyme A (Cytotoxic T-lymphocyte-associated serine esterase-3; Hanukah factor serine proteas ......
Chromosomal Location	5q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between GZMA and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	GZMA
Name	granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)
Aliases	CTL tryptase; Granzyme A (Cytotoxic T-lymphocyte-associated serine esterase-3; Hanukah factor serine proteas ......
Chromosomal Location	5q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting GZMA collected from DrugBank database.

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

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