GZMA

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.

Full Name

granzyme A

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).

Biological Process

Apoptotic process Source: UniProtKB
Cytolysis Source: UniProtKB-KW
Cytotoxic T cell pyroptotic process Source: UniProtKB
Granzyme-mediated programmed cell death signaling pathway Source: UniProtKB
Immune response Source: UniProtKB
Negative regulation of DNA binding Source: UniProtKB
Negative regulation of endodeoxyribonuclease activity Source: UniProtKB
Negative regulation of oxidoreductase activity Source: UniProtKB
Positive regulation of apoptotic process Source: UniProtKB
Proteolysis involved in cellular protein catabolic process Source: UniProtKB
Pyroptosis Source: UniProtKB
Response to bacterium Source: Ensembl

Cellular Location

Isoform alpha: Secreted; Cytoplasmic granule. Delivered into the target cell by perforin.