Gasdermin-A (GSDMA)

The protein contains 445 amino acids for an estimated molecular weight of 49365 Da.

 

This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-A, N-terminal) binds to membranes and forms pores, triggering cell death.', 'Pore-forming protein that causes membrane permeabilization and pyroptosis (PubMed:17471240, PubMed:27281216). Released upon cleavage in vitro of genetically engineered GSDMA, and binds to membrane inner leaflet lipids (PubMed:27281216). Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:27281216). Binds to membrane inner leaflet lipids, such as phosphatidylinositol (4,5)-bisphosphate (PubMed:27281216). The functional mechanisms and physiological proteases that cleave and activate this pore-forming protein are unknown (PubMed:27281216). (updated: Feb. 10, 2021)

Protein identification was indicated in the following studies:

  1. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 0%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs3894194
dbSNP:rs7212938
dbSNP:rs7212944
dbSNP:rs56030650

No binding partner found

The reference OMIM entry for this protein is 611218

Gasdermin a; gsdma
Gasdermin 1; gsdm1
Gsdm

CLONING

Saeki et al. (2000) cloned Gsdma, which they called Gsdm1, from newborn mouse skin. The deduced 446-amino acid protein contains a leucine zipper motif. Northern blot analysis detected Gsdm1 expression in mouse stomach, skin, and esophagus, but not in other tissues examined. Northern blot analysis of human tissues detected GSDM1 expression in stomach only. By database and sequence analysis, Tamura et al. (2007) identified several members of the gasdermin family, including GSDMA, GSDMB (611221), and GSDMC (608384). By RT-PCR of human stomach RNA, Saeki et al. (2007) cloned GSDM1. GSDM1 mRNA was detected in epithelium of stomach, esophagus, mammary gland, and skin. Both GSDM1 mRNA and protein were preferentially expressed in differentiated gastric pit cells and not in proliferating cells.

GENE FUNCTION

Using Northern blot analysis, Saeki et al. (2000) found reduced expression of GSDM1 in several human gastric cancer cell lines. Saeki et al. (2007) found that the GSDM gene was frequently silenced in primary gastric cancers and in gastric cancer cell lines. GSDM showed apoptotic activity upon expression in a human gastric cancer cell line. LMO1 (186921), RUNX3 (600210), and TGF-beta receptor II (TGFBR2; 190182) were coexpressed with GSDM in pit cells, and both LMO1 and RUNX3 bound to the GSDM promoter in vitro. TGF-beta (TGFB1; 190180) upregulated LMO1 and GSDM expression and induced apoptosis, and induction of apoptosis was inhibited by suppression of LMO1, RUNX3, and GSDM expression. Saeki et al. (2007) concluded that GSDM is a component of TGF-beta signaling that induces apoptosis in gastric pit cells.

MAPPING

By genomic sequence analysis, Saeki et al. (2000) mapped the GSDMA gene to chromosome 17q12. They mapped the mouse gene to a region of chromosome 11 that shows homology of synteny to human chromosome 17q12. By genomic sequence analysis, Tamura et al. (2007) mapped the GSDMA gene to chromosome 17q21. On mouse chromosome 11, they identified 3 GSDMA orthologs, which they called Gsdma1, Gsdma2, and Gsdma3, respectively. ... More on the omim web site

Subscribe to this protein entry history

Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 611218 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).