GSDMC
Domain
Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal (By similarity). The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain (By similarity).
Function
Gasdermin-C
This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-C, N-terminal) binds to membranes and forms pores, triggering pyroptosis.
Gasdermin-C, N-terminal
Pore-forming protein that causes membrane permeabilization and pyroptosis (PubMed:27281216, PubMed:32929201, PubMed:34012073). Produced by the cleavage of gasdermin-C by caspase CASP8 in response to death signals (PubMed:32929201, PubMed:34012073). After cleavage, moves to the plasma membrane where it strongly binds to membrane inner leaflet lipids (PubMed:32929201, PubMed:34012073). Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:32929201, PubMed:34012073).
Post-translational modifications
Cleavage by CASP8 relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-C, N-terminal) that initiates pyroptosis (PubMed:32929201, PubMed:34012073). The cleavage site is unclear (PubMed:32929201, PubMed:34012073). According to a publication, it takes place after Asp-240 in response to alpha-ketoglutarate (PubMed:34012073). Another paper reports cleavage by CASP8 after Asp-365 (PubMed:32929201).
Palmitoylated.
Sequence Similarities
Belongs to the gasdermin family.
Tissue Specificity
Expressed mainly in trachea and spleen (PubMed:11223543). In the esophagus, expressed in differentiating cells and probably in differentiated cells. Also detected in gastric epithelium (PubMed:19051310).
Cellular localization
- Gasdermin-C
- Cytoplasm
- Cytosol
- Gasdermin-C, N-terminal
- Cell membrane
- Multi-pass membrane protein
Alternative names
MLZE, GSDMC, Gasdermin-C, Melanoma-derived leucine zipper-containing extranuclear factor