Cytolytic T lymphocytes (CTL) and natural killer (NK) cells share the remarkable ability to recognize, bind, and lyse specific target cells. They are thought to protect their host by lysing cells bearing on their surface 'nonself' antigens, usually peptides or proteins resulting from infection by intracellular pathogens. The protein described here is a T cell- and natural kille... See more...

Aliases for GZMA Gene

Aliases for GZMA Gene

  • Granzyme A 2 3 4 5
  • CTL Tryptase 2 3 4
  • Granzyme A (Granzyme 1, Cytotoxic T-Lymphocyte-Associated Serine Esterase 3) 2 3
  • Cytotoxic T-Lymphocyte-Associated Serine Esterase-3 2 3
  • Cytotoxic T-Lymphocyte Proteinase 1 3 4
  • Hanukah Factor Serine Protease) 2 3
  • Fragmentin-1 3 4
  • Granzyme 1 2 3
  • H Factor 3 4
  • CTLA3 3 4
  • HFSP 3 4
  • HF 3 4
  • Granzyme A (Cytotoxic T-Lymphocyte-Associated Serine Esterase-3; Hanukah Factor Serine Protease) 3
  • Hanukkah Factor 4
  • EC 3.4.21'); 50
  • EC 3.4.21.78 4
  • Granzyme-1 4
  • EC 3.4.21 50
  • GZMA 5

External Ids for GZMA Gene

Previous HGNC Symbols for GZMA Gene

  • HFSP
  • CTLA3

Previous GeneCards Identifiers for GZMA Gene

  • GC05P054561
  • GC05P055827
  • GC05P054352
  • GC05P054414
  • GC05P054434
  • GC05P051373
  • GC05P054398

Summaries for GZMA Gene

Entrez Gene Summary for GZMA Gene

  • Cytolytic T lymphocytes (CTL) and natural killer (NK) cells share the remarkable ability to recognize, bind, and lyse specific target cells. They are thought to protect their host by lysing cells bearing on their surface 'nonself' antigens, usually peptides or proteins resulting from infection by intracellular pathogens. The protein described here is a T cell- and natural killer cell-specific serine protease that may function as a common component necessary for lysis of target cells by cytotoxic T lymphocytes and natural killer cells. [provided by RefSeq, Jul 2008]

GeneCards Summary for GZMA Gene

GZMA (Granzyme A) is a Protein Coding gene. Diseases associated with GZMA include Chediak-Higashi Syndrome and Smallpox. Among its related pathways are Innate Lymphoid Cell Differentiation Pathways and Common Cytokine Receptor Gamma-Chain Family Signaling Pathways. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and serine-type peptidase activity. An important paralog of this gene is GZMK.

UniProtKB/Swiss-Prot Summary for GZMA Gene

  • Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent pyroptosis when delivered into the target cell through the immunological synapse (PubMed:3257574, PubMed:3262682, PubMed:3263427, PubMed:32299851, PubMed:12819770). It cleaves after Lys or Arg (PubMed:32299851, PubMed:12819770). Once delivered into the target cell, acts by catalyzing cleavage of gasdermin-B (GSDMB), releasing the pore-forming moiety of GSDMB, thereby triggering pyroptosis and target cell death (PubMed:32299851). Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity (PubMed:12524539). 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 (PubMed:11555662, PubMed:12628186, PubMed:16818237).

Gene Wiki entry for GZMA Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GZMA Gene

Genomics for GZMA Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for GZMA Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH05J055101 Promoter/Enhancer 1 EPDnew Ensembl ENCODE 250.7 -0.5 -503 1.8 PKNOX1 RUNX3 GZMA CDC20B piR-47402-030 GZMK
GH05J055103 Promoter/Enhancer 0.5 Ensembl ENCODE 250.7 +1.6 1597 1.5 GZMA FJ601678-025 GPX8
GH05J054982 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE dbSUPER 10.6 -118.6 -118619 5.7 ZNF600 JUND ZSCAN16 ZIC2 ZNF513 STAT3 PRDM6 ZNF2 ZNF189 ZFP37 ESM1 ENSG00000249016 GZMA GZMK ENSG00000240535 GPX8 CCNO piR-57135-004 LOC102467081 SNX18
GH05J055146 Enhancer 0.9 Ensembl ENCODE 11.8 +44.0 43974 0.8 ZNF654 CTCF REST TRIM22 ZNF639 ELF1 SP2 RAD21 RFX5 SMC3 CCNO GZMA ENSG00000226810 ENSG00000249016 CCNO-DT GPX8 FJ601678-025 CDC20B
GH05J055036 Enhancer 0.7 Ensembl ENCODE 11.2 -65.2 -65245 3.6 MAFF YY1 ZNF316 MAFK CTCF MAFG CEBPB RAD21 EP300 EMSY GZMA ENSG00000249016 GPX8 CDC20B ENSG00000207229 LOC102467081 ENSG00000240535 LOC105378971 GZMK
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GZMA on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GZMA

Top Transcription factor binding sites by QIAGEN in the GZMA gene promoter:
  • aMEF-2
  • AML1a
  • C/EBPalpha
  • FOXJ2
  • FOXJ2 (long isoform)
  • FOXO4
  • GATA-1
  • MEF-2
  • MEF-2A
  • YY1

Genomic Locations for GZMA Gene

Latest Assembly
chr5:55,102,646-55,110,252
(GRCh38/hg38)
Size:
7,607 bases
Orientation:
Plus strand

Previous Assembly
chr5:54,398,474-54,406,080
(GRCh37/hg19 by Entrez Gene)
Size:
7,607 bases
Orientation:
Plus strand

chr5:54,398,476-54,406,080
(GRCh37/hg19 by Ensembl)
Size:
7,605 bases
Orientation:
Plus strand

Genomic View for GZMA Gene

Genes around GZMA on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GZMA Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GZMA Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GZMA Gene

Proteins for GZMA Gene

  • Protein details for GZMA Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P12544-GRAA_HUMAN
    Recommended name:
    Granzyme A
    Protein Accession:
    P12544
    Secondary Accessions:
    • A4PHN1
    • Q6IB36

    Protein attributes for GZMA Gene

    Size:
    262 amino acids
    Molecular mass:
    28999 Da
    Quaternary structure:
    • Homodimer; disulfide-linked (PubMed:12819769, PubMed:12819770). Interacts with APEX1 (PubMed:12524539).

    Three dimensional structures from OCA and Proteopedia for GZMA Gene

    Alternative splice isoforms for GZMA Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GZMA Gene

Selected DME Specific Peptides for GZMA Gene

P12544:
  • VLTAAHC
  • WVLTAAH
  • GDSGSPL

Post-translational modifications for GZMA Gene

  • Glycosylation at Asn170
  • Modification sites at PhosphoSitePlus

Other Protein References for GZMA Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

Domains & Families for GZMA Gene

Gene Families for GZMA Gene

Protein Domains for GZMA Gene

InterPro:
Blocks:
  • Serine protease, trypsin family
  • Chymotrypsin serine protease family (S1) signature

Suggested Antigen Peptide Sequences for GZMA Gene

GenScript: Design optimal peptide antigens:
  • Hanukkah factor (GRAA_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P12544

UniProtKB/Swiss-Prot:

GRAA_HUMAN :
  • Belongs to the peptidase S1 family. Granzyme subfamily.
Family:
  • Belongs to the peptidase S1 family. Granzyme subfamily.
genes like me logo Genes that share domains with GZMA: view

Function for GZMA Gene

Molecular function for GZMA Gene

UniProtKB/Swiss-Prot Function:
Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent pyroptosis when delivered into the target cell through the immunological synapse (PubMed:3257574, PubMed:3262682, PubMed:3263427, PubMed:32299851, PubMed:12819770). It cleaves after Lys or Arg (PubMed:32299851, PubMed:12819770). Once delivered into the target cell, acts by catalyzing cleavage of gasdermin-B (GSDMB), releasing the pore-forming moiety of GSDMB, thereby triggering pyroptosis and target cell death (PubMed:32299851). Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity (PubMed:12524539). 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 (PubMed:11555662, PubMed:12628186, PubMed:16818237).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Hydrolysis of proteins, including fibronectin, type IV collagen and nucleolin. Preferential cleavage: -Arg-|-Xaa-, -Lys-|-Xaa- >> -Phe-|-Xaa- in small molecule substrates.; EC=3.4.21.78; Evidence={ECO:0000269|PubMed:12819770, ECO:0000269|PubMed:32299851};.
UniProtKB/Swiss-Prot Induction:
Dexamethasone (DEX) induces expression of isoform beta and represses expression of isoform alpha. The alteration in expression is mediated by binding of glucocorticoid receptor to independent promoters adjacent to the alternative first exons of isoform alpha and isoform beta.
GENATLAS Biochemistry:
cytotoxic T-lymphocyte-associated granule serine protease 3,Hanuka factor,lymphocyte tryptase 1

Enzyme Numbers (IUBMB) for GZMA Gene

Phenotypes From GWAS Catalog for GZMA Gene

Gene Ontology (GO) - Molecular Function for GZMA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity IDA 11331782
GO:0005515 protein binding IPI 12524539
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with GZMA: view
genes like me logo Genes that share phenotypes with GZMA: view

Animal Models for GZMA Gene

MGI Knock Outs for GZMA:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GZMA

No data available for Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for GZMA Gene

Localization for GZMA Gene

Subcellular locations from UniProtKB/Swiss-Prot for GZMA Gene

[Isoform alpha]: Secreted. Cytoplasmic granule. Note=Delivered into the target cell by perforin. {ECO:0000269 PubMed:20038786, ECO:0000269 PubMed:32299851}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GZMA gene
Compartment Confidence
plasma membrane 5
nucleus 5
extracellular 4
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
endosome 2
cytosol 2
lysosome 2
golgi apparatus 2

Gene Ontology (GO) - Cellular Components for GZMA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001772 immunological synapse TAS 12524539
GO:0005576 extracellular region IEA --
GO:0005634 nucleus IEA,TAS 11909973
genes like me logo Genes that share ontologies with GZMA: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for GZMA Gene

Pathways & Interactions for GZMA Gene

genes like me logo Genes that share pathways with GZMA: view

Pathways by source for GZMA Gene

3 Qiagen pathways for GZMA Gene
  • Granzyme Pathway
  • Granzyme-A Pathway
  • IL-9 Pathway
2 Cell Signaling Technology pathways for GZMA Gene

SIGNOR curated interactions for GZMA Gene

Inactivates:

Gene Ontology (GO) - Biological Process for GZMA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0006915 apoptotic process TAS 12524539
GO:0006955 immune response TAS 12524539
GO:0009617 response to bacterium IEA --
GO:0019835 cytolysis IEA --
genes like me logo Genes that share ontologies with GZMA: view

Drugs & Compounds for GZMA Gene

(10) Drugs for GZMA Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(6) Additional Compounds for GZMA Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with GZMA: view

Transcripts for GZMA Gene

mRNA/cDNA for GZMA Gene

1 REFSEQ mRNAs :
5 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GZMA

Alternative Splicing Database (ASD) splice patterns (SP) for GZMA Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5
SP1:
SP2: -

Relevant External Links for GZMA Gene

GeneLoc Exon Structure for
GZMA

Expression for GZMA Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GZMA Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GZMA Gene

This gene is overexpressed in Whole Blood (x28.2) and Spleen (x7.5).

Protein differential expression in normal tissues from HIPED for GZMA Gene

This gene is overexpressed in NK cells (40.0), Tlymphocyte (9.7), and CD8 Tcells (7.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GZMA Gene



Protein tissue co-expression partners for GZMA Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GZMA

SOURCE GeneReport for Unigene cluster for GZMA Gene:

Hs.90708

Evidence on tissue expression from TISSUES for GZMA Gene

  • Blood(4.7)
  • Liver(4.4)
  • Lymph node(3.1)
  • Spleen(3)
  • Bone marrow(2.5)
  • Intestine(2.4)
  • Heart(2.4)
  • Lung(2.3)
  • Muscle(2.1)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with GZMA: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for GZMA Gene

Orthologs for GZMA Gene

This gene was present in the common ancestor of chordates.

Orthologs for GZMA Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia GZMA 29 30
  • 99.24 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia GZMA 29 30
  • 82.75 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia GZMA 29 30
  • 81.67 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Gzma 29
  • 78.84 (n)
Mouse
(Mus musculus)
Mammalia Gzma 29 16 30
  • 77.78 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia GZMA 30
  • 62 (a)
OneToOne
Chicken
(Gallus gallus)
Aves GZMA 29 30
  • 62.15 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 30
  • 48 (a)
OneToMany
-- 30
  • 45 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100497188 29
  • 55.12 (n)
Species where no ortholog for GZMA was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for GZMA Gene

ENSEMBL:
Gene Tree for GZMA (if available)
TreeFam:
Gene Tree for GZMA (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GZMA: view image
Alliance of Genome Resources:
Additional Orthologs for GZMA

Paralogs for GZMA Gene

Variants for GZMA Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GZMA Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
rs61730831 Benign: not provided 55,108,350(+) A/G
NM_006144.4(GZMA):c.583A>G (p.Met195Val)
MISSENSE
rs3104233 -- p.Met121Thr

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for GZMA Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for GZMA Gene

Variant ID Type Subtype PubMed ID
esv2503041 CNV deletion 19546169
nsv1117557 CNV deletion 24896259
nsv4833 CNV deletion 18451855
nsv830301 CNV gain 17160897
nsv830302 CNV gain 17160897
nsv956462 CNV deletion 24416366

Variation tolerance for GZMA Gene

Residual Variation Intolerance Score: 87.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.94; 49.18% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GZMA Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
GZMA
Leiden Open Variation Database (LOVD)
GZMA

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GZMA Gene

Disorders for GZMA Gene

MalaCards: The human disease database

(7) MalaCards diseases for GZMA Gene - From: COP and GCD

Disorder Aliases PubMed IDs
chediak-higashi syndrome
  • chs
smallpox
  • ordinary smallpox
ankylosing spondylitis 3
t-cell large granular lymphocyte leukemia
  • large granular lymphocytic leukaemia
chilblain lupus 1
  • chbl1
- elite association - COSMIC cancer census association via MalaCards
Search GZMA in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GZMA

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with GZMA: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GZMA Gene

Publications for GZMA Gene

  1. Glucocorticoid-induced alternative promoter usage for a novel 5' variant of granzyme A. (PMID: 17180578) Ruike Y … Tsujimoto G (Journal of human genetics 2007) 3 4 22
  2. Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A. (PMID: 12524539) Fan Z … Lieberman J (Nature immunology 2003) 3 4 22
  3. Crystal structure of the apoptosis-inducing human granzyme A dimer. (PMID: 12819770) Hink-Schauer C … Jenne DE (Nature structural biology 2003) 3 4 22
  4. The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity. (PMID: 12819769) Bell JK … Craik CS (Nature structural biology 2003) 3 4 22
  5. Granzyme A activates an endoplasmic reticulum-associated caspase-independent nuclease to induce single-stranded DNA nicks. (PMID: 11555662) Beresford PJ … Lieberman J (The Journal of biological chemistry 2001) 3 4 22

Products for GZMA Gene

  • Addgene plasmids for GZMA

Sources for GZMA Gene