Browse GZMA

Summary
SymbolGZMA
Namegranzyme 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 Location5q11-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
 
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
 
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
 
KEGG hsa04080 Neuroactive ligand-receptor interaction
Reactome -
Summary
SymbolGZMA
Namegranzyme 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 Location5q11-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
 
  Literatures describing the relation between GZMA and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
29668679breast carcinoma; ovarian carcinoma and glioblastomaPromote 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.
23851682Lung Adenocarcinoma; Non-Small Cell Lung CarcinomaPromote 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.
17015756colon carcinomaPromote immunityNotably, 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
SymbolGZMA
Namegranzyme 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 Location5q11-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
  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
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolGZMA
Namegranzyme 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 Location5q11-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
 
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 Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.5340.382
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.5110.768
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.5510.682
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.6140.379
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.7160.529
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.4770.704
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.6940.331
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15111.5530.198
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.2550.846
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 482.0420.258
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.3150.653
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.3730.118
> Mutation difference between responders and non-responders
 
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 Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.509.50.492
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.63.7-1.11
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.57.7-3.21
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolGZMA
Namegranzyme 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 Location5q11-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
 
Summary
SymbolGZMA
Namegranzyme 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 Location5q11-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
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolGZMA
Namegranzyme 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 Location5q11-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
 
> Receptor
 
Summary
SymbolGZMA
Namegranzyme 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 Location5q11-q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of GZMA expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolGZMA
Namegranzyme 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 Location5q11-q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between GZMA and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolGZMA
Namegranzyme 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 Location5q11-q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting GZMA collected from DrugBank database.
> Drugs from DrugBank database
 

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