General Information of Drug Off-Target (DOT) (ID: OTVM43E3)

DOT Name Gasdermin-C (GSDMC)
Synonyms Melanoma-derived leucine zipper-containing extranuclear factor
Gene Name GSDMC
Related Disease
Glioma ( )
Colorectal carcinoma ( )
Gastric cancer ( )
Neoplasm ( )
UniProt ID
GSDMC_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF04598 ; PF17708
Sequence
MPSMLERISKNLVKEIGSKDLTPVKYLLSATKLRQFVILRKKKDSRSSFWEQSDYVPVEF
SLNDILEPSSSVLETVVTGPFHFSDIMIQKHKADMGVNVGIEVSVSGEASVDHGCSLEFQ
IVTIPSPNLEDFQKRKLLDPEPSFLKECRRRGDNLYVVTEAVELINNTVLYDSSSVNILG
KIALWITYGKGQGQGESLRVKKKALTLQKGMVMAYKRKQLVIKEKAILISDDDEQRTFQD
EYEISEMVGYCAARSEGLLPSFHTISPTLFNASSNDMKLKPELFLTQQFLSGHLPKYEQV
HILPVGRIEEPFWQNFKHLQEEVFQKIKTLAQLSKDVQDVMFYSILAMLRDRGALQDLMN
MLELDSSGHLDGPGGAILKKLQQDSNHAWFNPKDPILYLLEAIMVLSDFQHDLLACSMEK
RILLQQQELVRSILEPNFRYPWSIPFTLKPELLAPLQSEGLAITYGLLEECGLRMELDNP
RSTWDVEAKMPLSALYGTLSLLQQLAEA
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. Produced by the cleavage of gasdermin-D by caspase CASP8 in response to death signals. After cleavage, moves to the plasma membrane where it strongly binds to membrane inner leaflet lipids. Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis.
Tissue Specificity Expressed mainly in trachea and spleen . In the esophagus, expressed in differentiating cells and probably in differentiated cells. Also detected in gastric epithelium .

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Glioma DIS5RPEH Definitive Genetic Variation [1]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [2]
Gastric cancer DISXGOUK Strong Genetic Variation [3]
Neoplasm DISZKGEW Strong Altered Expression [2]
------------------------------------------------------------------------------------
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Gasdermin-C (GSDMC). [4]
------------------------------------------------------------------------------------
1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Gasdermin-C (GSDMC). [5]
------------------------------------------------------------------------------------

References

1 Associations of high-grade glioma with glioma risk alleles and histories of allergy and smoking.Am J Epidemiol. 2011 Sep 1;174(5):574-81. doi: 10.1093/aje/kwr124. Epub 2011 Jul 8.
2 Gasdermin C Is Upregulated by Inactivation of Transforming Growth Factor Receptor Type II in the Presence of Mutated Apc, Promoting Colorectal Cancer Proliferation.PLoS One. 2016 Nov 11;11(11):e0166422. doi: 10.1371/journal.pone.0166422. eCollection 2016.
3 Distinctive expression and function of four GSDM family genes (GSDMA-D) in normal and malignant upper gastrointestinal epithelium.Genes Chromosomes Cancer. 2009 Mar;48(3):261-71. doi: 10.1002/gcc.20636.
4 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
5 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.