Tchem GSDMD Gasdermin-D

Protein Summary

Description

Gasdermin-D, N-terminal: Promotes pyroptosis in response to microbial infection and danger signals. Produced by the cleavage of gasdermin-D by inflammatory caspases CASP1 or CASP4 in response to canonical, as well as non-canonical (such as cytosolic LPS) inflammasome activators (PubMed:26375003, PubMed:26375259, PubMed:27418190). 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 (PubMed:27281216). Homooligomerizes within the membrane and forms pores of 10 - 15 nanometers (nm) of inner diameter, possibly allowing the release of mature IL1B and triggering pyroptosis (PubMed:27418190, PubMed:27281216). 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 (PubMed:27281216). Under cell culture conditions, also active against intracellular bacteria, such as Listeria monocytogenes (By similarity). Strongly binds to bacterial and mitochondrial lipids, including cardiolipin. Does not bind to unphosphorylated phosphatidylinositol, phosphatidylethanolamine nor phosphatidylcholine (PubMed:27281216). Gasdermin D is a member of the gasdermin family. Members of this family appear to play a role in regulation of epithelial proliferation. Gasdermin D has been suggested to act as a tumor suppressor. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2009]

Uniprot Accession IDs

• P57764
• A8K702
• D3DWJ9
• Q96Q98

Gene Name

• GSDMD

Ensembl ID

• ENST00000262580
• ENSP00000262580
• ENSG00000104518
• ENST00000526406
• ENSP00000433209
• ENST00000615119
• ENSP00000482096
• ENSG00000278718
• ENST00000631751
• ENSP00000488012

Symbol

• DFNA5L
• GSDMDC1
• DF5L
• DFNA5L
• FKSG10
• GSDMDC1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
histone modification site profile	0.76
kinase perturbation	0.76
transcription factor	0.66
tissue	0.61
tissue sample	0.59

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 513.24   (req: < 5)

Gene RIFs: 87   (req: <= 3)

Antibodies: 126   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 513.24   (req: >= 5)

Gene RIFs: 87   (req: > 3)

Antibodies: 126   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 17

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2