Recombinant Human GSDMB protein

Specifications

Form

Liquid

Additional notes

> 80% as determined by SDS-PAGE and Coomassie blue staining

General info

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). Also acts as a regulator of epithelial cell repair independently of programmed cell death : translocates to the plasma membrane and promotes epithelial maintenance and repair by regulating PTK2/FAK-mediated phosphorylation of PDGFA (PubMed : 35021065).. 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, PubMed : 36599845, PubMed : 36991122, PubMed : 36991125). The different isoforms recognize and bind different phospholipids on membranes, promoting cell death of different target cells (PubMed : 34022140, PubMed : 36157507, PubMed : 36991122, PubMed : 36991125).. Isoform 4. Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death and mediates pyroptosis (PubMed : 28154144, PubMed : 36157507, PubMed : 36899106, PubMed : 36991122, PubMed : 36991125). Following cleavage and activation by granzyme A (GZMA), the N-terminal part binds to membrane inner leaflet lipids, homooligomerizes within the human plasma membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed : 28154144, PubMed : 36157507, PubMed : 36899106, PubMed : 36991122, PubMed : 36991125). Recognizes and binds membrane inner leaflet lipids of human cells, such as phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, and more weakly to phosphatidic acid (PubMed : 28154144, PubMed : 36157507). Also binds sufatide, a component of the apical membrane of epithelial cells (PubMed : 28154144).. Isoform 6. Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death and mediates pyroptosis of human cells (PubMed : 36899106, PubMed : 36991122, PubMed : 36991125). Following cleavage and activation by granzyme A (GZMA), the N-terminal part binds to membrane inner leaflet lipids, homooligomerizes within the human plasma membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed : 36899106, PubMed : 36991122, PubMed : 36991125).. Isoform 1. Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death and specifically mediates cell death of Gram-negative bacteria in response to infection (PubMed : 34022140). Following cleavage and activation by granzyme A (GZMA), the N-terminal part recognizes and binds phospholipids found on Gram-negative bacterial membranes, such as lipid A and cariolipin, homooligomerizes within the bacterial membranes and forms pores, triggering pyroptosis followed by cell death (PubMed : 34022140). In contrast to isoform 4, does not bind to membrane inner leaflet lipids of host human cell, such as phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate (PubMed : 34022140).. Isoform 2. Not able to trigger pyroptosis.. Isoform 3. Not able to trigger pyroptosis.

Sequence similarities

Belongs to the gasdermin family.

Post-translational modifications

Cleavage by granzyme A (GZMA) relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-B, N-terminal) that initiates pyroptosis (PubMed:32299851, PubMed:34022140, PubMed:36157507, PubMed:36899106, PubMed:36991125). Not cleaved by other granzymes (PubMed:32299851). Major cleavage site takes places after Lys-244; a minor cleavage site takes place after Lys-229 (PubMed:32299851). Cleavage by neutrophil elastase ELANE, inhibits its ability to trigger pyroptosis (PubMed:36899106).. Palmitoylated.. (Microbial infection) Ubiquitinated by S.flexneri IpaH7.8, leading to its degradation by the proteasome, thereby preventing its ability to form pores in bacterial-derived membranes.