DFNA5
entrez
1687
canonical
uniprot
O60443
canonical
ensembl
ENSG00000105928
resolver
ensp
ENSP00000339587
resolver
ensp
ENSP00000387119
resolver
ensp
ENSP00000401332
resolver
ensp
ENSP00000494186
resolver
genesymbol
DFNA5
resolver
genesymbol
GSDME
resolver
genesymbol_syn
DFNA5
resolver
genesymbol_syn
ICERE1
resolver
hgnc
HGNC:2810
resolver
uniprot
A4D156
resolver
uniprot
A4FVA8
resolver
uniprot
B2RAX9
resolver
uniprot
B3KT05
resolver
uniprot
O14590
resolver
uniprot
Q08AQ8
resolver
uniprot
Q9UBV3
resolver
uniprot_entry
A4FVA8_HUMAN
resolver
uniprot_entry
GSDME_HUMAN
resolver
uniprot_sec
A4D156
resolver
uniprot_sec
B2RAX9
resolver
uniprot_sec
B3KT05
resolver
uniprot_sec
O14590
resolver
uniprot_sec
Q08AQ8
resolver
uniprot_sec
Q9UBV3
resolver
activity_regulation
ACTIVITY REGULATION: [Gasdermin-E]: The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (PubMed:28045099, PubMed:28459430). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-E, N-terminal) following cleavage by CASP3 or granzyme B (GZMB) (PubMed:28459430, PubMed:31953257, PubMed:32188940, PubMed:35594856). Activated by NLRP1 in the absence of GSDMD expression: NLRP1 cleaves and activates CASP8, promoting downstream activation of CASP3 and subsequent activation of GSDME (PubMed:33852854, PubMed:35594856). {ECO:0000269|PubMed:28045099, ECO:0000269|PubMed:28459430, ECO:0000269|PubMed:31953257, ECO:0000269|PubMed:32188940, ECO:0000269|PubMed:33852854, ECO:0000269|PubMed:35594856}.; ACTIVITY REGULATION: (Microbial infection) Activated upon human coronavirus SARS-CoV-2 infection, leading to lung epithelial cell death (PubMed:35594856). Activation takes place in response to (1) activation of NLRP1 and (2) inactivation of GSDMD following NLRP1 and GSDMD cleavage by the SARS-CoV-2 3C-like proteinase nsp5 (PubMed:35594856). {ECO:0000269|PubMed:35594856}.
uniprot
proteins
amino_acid_sequence
MFAKATRNFLREVDADGDLIAVSNLNDSDKLQLLSLVTKKKRFWCWQRPKYQFLSLTLGDVLIEDQFPSPVVVESDFVKYEGKFANHVSGTLETALGKVKLNLGGSSRVESQSSFGTLRKQEVDLQQLIRDSAERTINLRNPVLQQVLEGRNEVLCVLTQKITTMQKCVISEHMQVEEKCGGIVGIQTKTVQVSATEDGNVTKDSNVVLEIPAATTIAYGVIELYVKLDGQFEFCLLRGKQGGFENKKRIDSVYLDPLVFREFAFIDMPDAAHGISSQDGPLSVLKQATLLLERNFHPFAELPEPQQTALSDIFQAVLFDDELLMVLEPVCDDLVSGLSPTVAVLGELKPRQQQDLVAFLQLVGCSLQGGCPGPEDAGSKQLFMTAYFLVSALAEMPDSAAALLGTCCKLQIIPTLCHLLRALSDDGVSDLEDPTLTPLKDTERFGIVQRLFASADISLERLKSSVKAVILKDSKVFPLLLCITLNGLCALGREHS
uniprot
proteins
disease_involvement
DISEASE: Deafness, autosomal dominant, 5 (DFNA5) [MIM:600994]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:19911014, ECO:0000269|PubMed:24506266, ECO:0000269|PubMed:26236191, ECO:0000269|PubMed:9771715}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=Is a tumor suppressor gene with an important role in colorectal cancer (CRC). {ECO:0000303|PubMed:18223688}.
uniprot
proteins
function
FUNCTION: [Gasdermin-E]: Precursor of a pore-forming protein that converts non-inflammatory apoptosis to pyroptosis (PubMed:27281216, PubMed:28459430, PubMed:33852854, PubMed:35594856, PubMed:36607699). This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-E, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:28459430). {ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:28459430, ECO:0000269|PubMed:33852854, ECO:0000269|PubMed:35594856, ECO:0000269|PubMed:36607699}.; FUNCTION: [Gasdermin-E, N-terminal]: Pore-forming protein produced by cleavage by CASP3 or granzyme B (GZMB), which converts non-inflammatory apoptosis to pyroptosis or promotes granzyme-mediated pyroptosis, respectively (PubMed:27281216, PubMed:28459430, PubMed:32188940, PubMed:33852854, PubMed:35594856). After cleavage, moves to the plasma membrane, homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the release of mature interleukins (IL1B and IL16) and triggering pyroptosis (PubMed:28459430, PubMed:32188940, PubMed:33852854, PubMed:35594856). Binds to inner leaflet lipids, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate (PubMed:28459430). Cleavage by CASP3 switches CASP3-mediated apoptosis induced by TNF or danger signals, such as chemotherapy drugs, to pyroptosis (PubMed:27281216, PubMed:28459430, PubMed:32188940). Mediates secondary necrosis downstream of the mitochondrial apoptotic pathway and CASP3 activation as well as in response to viral agents (PubMed:28045099). Exhibits bactericidal activity (PubMed:27281216). Cleavage by GZMB promotes tumor suppressor activity by triggering robust anti-tumor immunity (PubMed:21522185, PubMed:32188940). Suppresses tumors by mediating granzyme-mediated pyroptosis in target cells of natural killer (NK) cells: cleavage by granzyme B (GZMB), delivered to target cells from NK-cells, triggers pyroptosis of tumor cells and tumor suppression (PubMed:31953257, PubMed:32188940). May play a role in the p53/TP53-regulated cellular response to DNA damage (PubMed:16897187). {ECO:0000269|PubMed:16897187, ECO:0000269|PubMed:21522185, ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:28045099, ECO:0000269|PubMed:28459430, ECO:0000269|PubMed:31953257, ECO:0000269|PubMed:32188940, ECO:0000269|PubMed:33852854, ECO:0000269|PubMed:35594856}.; FUNCTION: [Gasdermin-E, N-terminal]: (Microbial infection) Pore-forming protein, which promotes maternal placental pyroptosis in response to Zika virus infection, contributing to adverse fetal outcomes. {ECO:0000269|PubMed:35972780}.
uniprot
proteins
mass_dalton
54555
uniprot
proteins
mutagenesis
MUTAGEN 2; /note="F->A: No effect on plasma membrane targeting. Decreases induction of necrotic activity. Disrupts plasma membrane targeting and induction of necrotic activity; when associated with A-40."; /evidence="ECO:0000269|PubMed:28045099, ECO:0000269|PubMed:32188940"; MUTAGEN 39; /note="K->A: Disrupts plasma membrane targeting and induction of necrotic activity; when associated with A-40 and/or A-41."; /evidence="ECO:0000269|PubMed:28045099"; MUTAGEN 40; /note="K->A: No effect on plasma membrane targeting. No effect on induction of cytotoxivity. Disrupts plasma membrane targeting and induction of necrotic activity; when associated with A-2 or A-39 and A-41."; /evidence="ECO:0000269|PubMed:28045099"; MUTAGEN 41; /note="K->A: Disrupts plasma membrane targeting and induction of necrotic activity; when associated with A-39 and/or A-41."; /evidence="ECO:0000269|PubMed:28045099"; MUTAGEN 267; /note="D->A: Abolishes cleavage by CASP3. Abolishes pyroptosis induction."; /evidence="ECO:0000269|PubMed:28459430"; MUTAGEN 270; /note="D->A,E: Abolishes cleavage by CASP3 or granzyme B. Abolishes pyroptosis induction."; /evidence="ECO:0000269|PubMed:28045099, ECO:0000269|PubMed:28459430, ECO:0000269|PubMed:32188940, ECO:0000269|PubMed:33852854"; MUTAGEN 313; /note="I->D: No spontaneous pyroptosis-inducing activity."; /evidence="ECO:0000269|PubMed:27281216"; MUTAGEN 388; /note="F->D: Low spontaneous pyroptosis-inducing activity."; /evidence="ECO:0000269|PubMed:27281216"; MUTAGEN 392; /note="A->D: Low spontaneous pyroptosis-inducing activity."; /evidence="ECO:0000269|PubMed:27281216
uniprot
proteins
post_translational_modification
PTM: Cleavage at Asp-270 by CASP3 (mature and uncleaved precursor forms) or granzyme B (GZMB) relieves autoinhibition and is sufficient to initiate pyroptosis. {ECO:0000269|PubMed:28045099, ECO:0000269|PubMed:28459430, ECO:0000269|PubMed:31953257, ECO:0000269|PubMed:32188940}.; PTM: (Microbial infection) The 3C-like proteinase nsp5 from human coronavirus SARS-CoV-2 cleaves and activates GSDME at Asp-270, thereby promoting unconventional secretion of the viral 3C-like proteinase nsp5 through gasdermin pores into the host extracellular space. {ECO:0000269|PubMed:39673710}.; PTM: [Gasdermin-E]: Succination by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits processing by caspases, and ability to initiate pyroptosis (PubMed:32820063). Succination modification is catalyzed by a non-enzymatic reaction caused by an accumulation of fumarate (PubMed:32820063). {ECO:0000269|PubMed:32820063}.; PTM: [Gasdermin-E]: Ubiquitinated at Lys-120 and Lys-189 via 'Lys-48'-linked polyubiquitin chains, leading to proteasomal degradation. Deubiquitinated by USP48, leading to increased stability. {ECO:0000269|PubMed:36607699}.; PTM: Palmitoylated. {ECO:0000269|PubMed:38599239}.
uniprot
proteins
protein_family
Gasdermin family
uniprot
proteins
pubmed
12690205
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16897187
uniprot
proteins
pubmed
18223688
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19911014
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21522185
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
24506266
uniprot
proteins
pubmed
26236191
uniprot
proteins
pubmed
27281216
uniprot
proteins
pubmed
28045099
uniprot
proteins
pubmed
28459430
uniprot
proteins
pubmed
31953257
uniprot
proteins
pubmed
32188940
uniprot
proteins
pubmed
32820063
uniprot
proteins
pubmed
33852854
uniprot
proteins
pubmed
35594856
uniprot
proteins
pubmed
35972780
uniprot
proteins
pubmed
36607699
uniprot
proteins
pubmed
38599239
uniprot
proteins
pubmed
39673710
uniprot
proteins
pubmed
9523727
uniprot
proteins
pubmed
9771715
uniprot
proteins
sequence_length
496
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Gasdermin-E, N-terminal]: Cell membrane {ECO:0000269|PubMed:28045099, ECO:0000269|PubMed:28459430}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q5Y4Y6}.; SUBCELLULAR LOCATION: [Gasdermin-E]: Cytoplasm, cytosol {ECO:0000269|PubMed:28045099}.
uniprot
proteins