GSDML

This gene encodes a member of the gasdermin-domain containing protein family. Other gasdermin-family genes are implicated in the regulation of apoptosis in epithelial cells, and are linked to cancer. Multiple transcript variants encoding different isoforms have been found for this gene. Additional variants have been described, but they are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to be protein-coding. [provided by RefSeq]

Full Name

gasdermin B

Function

Gasdermin-B:
Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death (PubMed:32299851).

This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-B, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:32299851).

Gasdermin-B, N-terminal:
Pore-forming protein produced by cleavage by granzyme A (GZMA), which causes membrane permeabilization and pyroptosis in target cells of cytotoxic T and natural killer (NK) cells (PubMed:27281216, PubMed:32299851).

Key downstream mediator of granzyme-mediated cell death: (1) granzyme A (GZMA), delivered to target cells from cytotoxic T- and NK-cells, (2) specifically cleaves Gasdermin-B to generate this form (PubMed:32299851).

After cleavage, moves to the plasma membrane, homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:32299851).

Binds to membrane inner leaflet lipids, such as phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, and more weakly to phosphatidic acid (PubMed:28154144).

Also binds sufatide, a component of the apical membrane of epithelial cells (PubMed:28154144).

Biological Process

Cytolysis Source: UniProtKB-KW
Cytotoxic T cell pyroptotic process Source: UniProtKB
Defense response to bacterium Source: GO_Central
Granzyme-mediated programmed cell death signaling pathway Source: UniProtKB
Pyroptosis Source: UniProtKB

Cellular Location

Gasdermin-B: Cytoplasm. Vesicular localization in the apical region of gastric chief cells and colonic surface mucous cells, and the basal region of neuroendocrine cells.
Gasdermin-B, N-terminal: Cell membrane

PTM

Cleavage by granzyme A (GZMA) relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-B, N-terminal) that initiates pyroptosis (PubMed:32299851). Not cleaved by other granzymes (PubMed:32299851). Major cleavage site takes places after Lys-239; a minor cleavage site takes place after Lys-233 (PubMed:32299851).