Recombinant Human Gasdermin-D (GSDMD)

Uniprot Id

P57764

Target Species

Human

Target Name

GSDMD

Target Full Name

Gasdermin-D

Target Function

Precursor of a pore-forming protein that plays a key role in host defense against pathogen infection and danger signals. This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-D, N-terminal) binds to membranes and forms pores, triggering pyroptosis.; Promotes pyroptosis in response to microbial infection and danger signals. Produced by the cleavage of gasdermin-D by inflammatory caspases CASP1, CASP4 or CASP5 in response to canonical, as well as non-canonical (such as cytosolic LPS) inflammasome activators. After cleavage, moves to the plasma membrane where it strongly binds to inner leaflet lipids, including monophosphorylated phosphatidylinositols, such as phosphatidylinositol 4-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, as well as phosphatidylinositol (3,4,5)-bisphosphate, and more weakly to phosphatidic acid and phosphatidylserine. Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the release of mature IL1B and triggering pyroptosis. Exhibits bactericidal activity. Gasdermin-D, N-terminal released from pyroptotic cells into the extracellular milieu rapidly binds to and kills both Gram-negative and Gram-positive bacteria, without harming neighboring mammalian cells, as it does not disrupt the plasma membrane from the outside due to lipid-binding specificity. Under cell culture conditions, also active against intracellular bacteria, such as Listeria monocytogenes. Also active in response to MAP3K7/TAK1 inactivation by Yersinia toxin YopJ, which triggers cleavage by CASP8 and subsequent activation. Strongly binds to bacterial and mitochondrial lipids, including cardiolipin. Does not bind to unphosphorylated phosphatidylinositol, phosphatidylethanolamine nor phosphatidylcholine.

Target Subcellular Location

[Gasdermin-D]: Cytoplasm, cytosol. Inflammasome.; [Gasdermin-D, N-terminal]: Cell membrane; Multi-pass membrane protein. Secreted.; [Gasdermin-D, C-terminal]: Cytoplasm, cytosol.

Target Protein Families

Gasdermin family

Target Tissue Specificity

Expressed in the suprabasal cells of esophagus, as well as in the isthmus/neck, pit, and gland of the stomach, suggesting preferential expression in differentiating cells.

Target Research Area

Cell Biology

Target Synonyms

C-terminal; Gasdermin domain-containing protein 1; Gasdermin-D; GSDMD; GSDMD-CT; GSDMD-NT; GSDMD_HUMAN

Target Background

Enables phospholipid binding activity and wide pore channel activity. Involved in several processes, including defense response to bacterium; positive regulation of interleukin-1 beta production; and protein-containing complex assembly. Acts upstream of or within cellular response to extracellular stimulus. Located in cytosol; extracellular space; and plasma membrane. Part of NLRP3 inflammasome complex. Is expressed in several structures, including gut; liver; lung; metanephros; and spleen. Orthologous to human GSDMD (gasdermin D).