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'); 52
  • EC 3.4.21.78 4
  • Granzyme-1 4
  • EC 3.4.21 52

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 Peptide ligand-binding receptors and Innate Lymphoid Cell Differentiation 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 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 Wiki entry for GZMA Gene

Additional gene information 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 for GZMA Gene

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 1.1 EPDnew Ensembl ENCODE 500.7 -0.5 -503 1.8 SPI1 PKNOX1 RUNX3 GZMA CDC20B piR-47402-030
GH05J055103 Promoter/Enhancer 0.5 Ensembl ENCODE 500.7 +1.6 1597 1.5 GZMA FJ601678-026
GH05J054982 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE dbSUPER 10.6 -118.6 -118619 5.7 JUND FOS ZIC2 TRIM28 OSR2 MYC ZBTB17 CTCF ZNF76 JUN ESM1 ENSG00000249016 GZMA GZMK ENSG00000240535 GPX8 CCNO piR-57135-004
GH05J055146 Enhancer 0.9 Ensembl ENCODE 11.8 +44.0 43974 0.8 CTCF ZNF639 REST RAD21 TRIM22 SMC3 SP2 ZBTB17 ELF1 IKZF3 CCNO GZMA ENSG00000226810 ENSG00000249016 ENSG00000251307 GPX8 FJ601678-026 CDC20B
GH05J054989 Enhancer 0.8 Ensembl ENCODE dbSUPER 10.8 -112.5 -112546 4.2 ZIC2 EZH2 FOS GATA2 JUN STAT3 ENSG00000249016 GZMK GZMA ENSG00000240535 GPX8 CCNO piR-57135-004 ESM1
- 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 UCSC Golden Path with GeneCards custom track

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

Genomic Locations for GZMA Gene
chr5:55,102,646-55,110,252
(GRCh38/hg38)
Size:
7,607 bases
Orientation:
Plus strand
chr5:54,398,474-54,406,080
(GRCh37/hg19)
Size:
7,607 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. Interacts with APEX1.

    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:

Antibody Products

  • Boster Bio Antibodies for GZMA

Domains & Families for GZMA Gene

Gene Families for GZMA Gene

Protein Domains for GZMA Gene

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

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 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.
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;.
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:

Animal Model Products

CRISPR Products

Clone Products

  • Addgene plasmids 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.

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
extracellular 5
nucleus 5
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 TAS,IEA 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

1 BioSystems pathway for GZMA Gene
1 KEGG pathway for GZMA Gene
1 R&D Systems pathway 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 :

CRISPR Products

Clone Products

  • Addgene plasmids 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(4.6)
  • Liver(4.3)
  • Spleen(2.5)
  • Lymph node(2.3)
  • Lung(2)
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 31 30
  • 99.24 (n)
OneToOne
cow
(Bos Taurus)
Mammalia GZMA 31 30
  • 82.75 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GZMA 31 30
  • 81.67 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Gzma 30
  • 78.84 (n)
mouse
(Mus musculus)
Mammalia Gzma 17 31 30
  • 77.78 (n)
oppossum
(Monodelphis domestica)
Mammalia GZMA 31
  • 62 (a)
OneToOne
chicken
(Gallus gallus)
Aves GZMA 31 30
  • 62.15 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 48 (a)
OneToMany
-- 31
  • 45 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100497188 30
  • 55.12 (n)
Species where no ortholog for GZMA was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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 squirt (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

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
786056 Benign: not provided 55,108,350(+) A/G MISSENSE_VARIANT
rs3104233 - p.Met121Thr

Additional dbSNP identifiers (rs#s) for GZMA Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for GZMA Gene

MalaCards: The human disease database

(8) MalaCards diseases for GZMA Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
chediak-higashi syndrome
  • chs
smallpox
  • ordinary smallpox
cutaneous leishmaniasis
  • asian desert cutaneous leishmaniasis
t-cell large granular lymphocyte leukemia
  • large granular lymphocytic leukemia
leishmaniasis
  • post kala-azar dermal leishmaniasis
- 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

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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 23 54
  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 23 54
  3. Crystal structure of the apoptosis-inducing human granzyme A dimer. (PMID: 12819770) Hink-Schauer C … Jenne DE (Nature structural biology 2003) 3 4 23 54
  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 23 54
  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 23 54

Products for GZMA Gene

  • Addgene plasmids for GZMA
  • Boster Bio Antibodies for GZMA
  • Boster Bio ELISA Kits for GZMA

Sources for GZMA Gene