GSDA3_MOUSE
ID GSDA3_MOUSE Reviewed; 464 AA.
AC Q5Y4Y6; A2A4X5;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Gasdermin-A3 {ECO:0000305};
DE AltName: Full=Gasdermin-3 {ECO:0000303|PubMed:15475261};
DE Contains:
DE RecName: Full=Gasdermin-A3, N-terminal {ECO:0000305};
DE Short=GSDMA3-NT {ECO:0000305};
DE Contains:
DE RecName: Full=Gasdermin-A3, C-terminal {ECO:0000305};
DE Short=GSDMA3-CT {ECO:0000305};
GN Name=Gsdma3 {ECO:0000303|PubMed:17572385, ECO:0000312|MGI:MGI:3044668};
GN Synonyms=Gsdm3 {ECO:0000303|PubMed:15475261, ECO:0000312|MGI:MGI:3044668};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LEU-343; TYR-344 AND
RP ALA-412.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAU95732.1};
RC TISSUE=Skin {ECO:0000312|EMBL:AAU95732.1};
RX PubMed=15475261; DOI=10.1016/j.ygeno.2004.07.003;
RA Runkel F., Marquardt A., Stoeger C., Kochmann E., Simon D., Kohnke B.,
RA Korthaus D., Wattler F., Fuchs H., Hrabe de Angelis M., Stumm G., Nehls M.,
RA Wattler S., Franz T., Augustin M.;
RT "The dominant alopecia phenotypes Bareskin, Rex-denuded, and Reduced Coat 2
RT are caused by mutations in gasdermin 3.";
RL Genomics 84:824-835(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP IDENTIFICATION.
RX PubMed=17350798; DOI=10.1016/j.ygeno.2007.01.003;
RA Tamura M., Tanaka S., Fujii T., Aoki A., Komiyama H., Ezawa K.,
RA Sumiyama K., Sagai T., Shiroishi T.;
RT "Members of a novel gene family, Gsdm, are expressed exclusively in the
RT epithelium of the skin and gastrointestinal tract in a highly tissue-
RT specific manner.";
RL Genomics 89:618-629(2007).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 262-GLU--SER-464 AND
RP THR-278.
RX PubMed=15737203; DOI=10.1111/j.0022-202x.2005.23623.x;
RA Lunny D.P., Weed E., Nolan P.M., Marquardt A., Augustin M., Porter R.M.;
RT "Mutations in gasdermin 3 cause aberrant differentiation of the hair
RT follicle and sebaceous gland.";
RL J. Invest. Dermatol. 124:615-621(2005).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ALA-348.
RX PubMed=17572385; DOI=10.1016/j.bbrc.2007.05.209;
RA Tanaka S., Tamura M., Aoki A., Fujii T., Komiyama H., Sagai T.,
RA Shiroishi T.;
RT "A new Gsdma3 mutation affecting anagen phase of first hair cycle.";
RL Biochem. Biophys. Res. Commun. 359:902-907(2007).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF TYR-344.
RX PubMed=22155111; DOI=10.1016/j.ajpath.2011.10.034;
RA Zhou Y., Jiang X., Gu P., Chen W., Zeng X., Gao X.;
RT "Gsdma3 mutation causes bulge stem cell depletion and alopecia mediated by
RT skin inflammation.";
RL Am. J. Pathol. 180:763-774(2012).
RN [7]
RP MUTAGENESIS OF ILE-359.
RX PubMed=22682752; DOI=10.1016/j.jdermsci.2012.05.001;
RA Kumar S., Rathkolb B., Budde B.S., Nuernberg P., de Angelis M.H.,
RA Aigner B., Schneider M.R.;
RT "Gsdma3(I359N) is a novel ENU-induced mutant mouse line for studying the
RT function of Gasdermin A3 in the hair follicle and epidermis.";
RL J. Dermatol. Sci. 67:190-192(2012).
RN [8]
RP ACTIVITY REGULATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF TYR-344.
RX PubMed=25825937; DOI=10.1042/bj20150204;
RA Shi P., Tang A., Xian L., Hou S., Zou D., Lv Y., Huang Z., Wang Q.,
RA Song A., Lin Z., Gao X.;
RT "Loss of conserved Gsdma3 self-regulation causes autophagy and cell
RT death.";
RL Biochem. J. 468:325-336(2015).
RN [9]
RP ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=26100518; DOI=10.1186/s12929-015-0152-0;
RA Lin P.H., Lin H.Y., Kuo C.C., Yang L.T.;
RT "N-terminal functional domain of Gasdermin A3 regulates mitochondrial
RT homeostasis via mitochondrial targeting.";
RL J. Biomed. Sci. 22:44-44(2015).
RN [10]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF THR-278; LEU-343;
RP TYR-344; ALA-348 AND ALA-412.
RX PubMed=26375003; DOI=10.1038/nature15514;
RA Shi J., Zhao Y., Wang K., Shi X., Wang Y., Huang H., Zhuang Y., Cai T.,
RA Wang F., Shao F.;
RT "Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell
RT death.";
RL Nature 526:660-665(2015).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF TYR-344.
RX PubMed=28168650; DOI=10.1007/s00418-017-1542-z;
RA Guo H., Xu S., Liu Y., Yang Y., Deng F., Xing Y., Lian X., Li Y.;
RT "Gsdma3 is required for mammary gland development in mice.";
RL Histochem. Cell Biol. 147:575-583(2017).
RN [12]
RP FUNCTION.
RX PubMed=32302611; DOI=10.1016/j.jid.2020.02.033;
RA Li S.T., Suen W.J., Kao C.H., Yang M.K., Yang L.T.;
RT "Gasdermin A3-mediated cell death causes niche collapse and precocious
RT activation of hair follicle stem cells.";
RL J. Invest. Dermatol. 140:2117-2128(2020).
RN [13]
RP BIOTECHNOLOGY.
RX PubMed=32188939; DOI=10.1038/s41586-020-2079-1;
RA Wang Q., Wang Y., Ding J., Wang C., Zhou X., Gao W., Huang H., Shao F.,
RA Liu Z.;
RT "A bioorthogonal system reveals antitumour immune function of pyroptosis.";
RL Nature 579:421-426(2020).
RN [14]
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF 41-ARG--LYS-44; 47-LEU--TRP-49;
RP 62-ASP--ASP-75 AND 86-ASP--GLU-94.
RX PubMed=33883744; DOI=10.1038/s41586-021-03478-3;
RA Xia S., Zhang Z., Magupalli V.G., Pablo J.L., Dong Y., Vora S.M., Wang L.,
RA Fu T.M., Jacobson M.P., Greka A., Lieberman J., Ruan J., Wu H.;
RT "Gasdermin D pore structure reveals preferential release of mature
RT interleukin-1.";
RL Nature 593:607-611(2021).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS), FUNCTION, LIPID-BINDING,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-14; LEU-184; LEU-270; TYR-344
RP AND ALA-348.
RX PubMed=27281216; DOI=10.1038/nature18590;
RA Ding J., Wang K., Liu W., She Y., Sun Q., Shi J., Sun H., Wang D.C.,
RA Shao F.;
RT "Pore-forming activity and structural autoinhibition of the gasdermin
RT family.";
RL Nature 535:111-116(2016).
RN [16] {ECO:0007744|PDB:6CB8}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) OF 1-262 IN COMPLEX WITH
RP CARDIOLIPIN, FUNCTION, SUBUNIT, AND MUTAGENESIS OF 9-ARG--ARG-18; ARG-132;
RP ARG-145 AND LEU-186.
RX PubMed=29695864; DOI=10.1038/s41586-018-0058-6;
RA Ruan J., Xia S., Liu X., Lieberman J., Wu H.;
RT "Cryo-EM structure of the gasdermin A3 membrane pore.";
RL Nature 557:62-67(2018).
CC -!- FUNCTION: [Gasdermin-A3]: Precursor of a pore-forming protein involved
CC in the transition from catagen to telogen at the end of hair follicle
CC morphogenesis (PubMed:15475261, PubMed:26375003, PubMed:27281216). This
CC form constitutes the precursor of the pore: upon cleavage, the released
CC N-terminal moiety (Gasdermin-A3, N-terminal) binds to membranes and
CC forms pores, triggering cell death (PubMed:26375003, PubMed:27281216).
CC {ECO:0000269|PubMed:15475261, ECO:0000269|PubMed:26375003,
CC ECO:0000269|PubMed:27281216}.
CC -!- FUNCTION: [Gasdermin-A3, N-terminal]: Pore-forming protein that causes
CC membrane permeabilization and pyroptosis (PubMed:26375003,
CC PubMed:27281216). Released upon cleavage in vitro of genetically
CC engineered Gsdma3, and binds to membrane inner leaflet lipids
CC (PubMed:27281216). Homooligomerizes within the membrane and forms pores
CC of 10-15 nanometers (nm) of inner diameter, allowing the release of
CC mature interleukin-1 (IL1B and IL18) and triggering pyroptosis
CC (PubMed:27281216, PubMed:33883744). Binds to membrane inner leaflet
CC lipids, including bisphosphorylated phosphatidylinositols, such as
CC phosphatidylinositol (4,5)-bisphosphate, as well as
CC phosphatidylinositol (3,4,5)-bisphosphate, and more weakly to
CC monophosphorylated phosphatidylinositols (PubMed:27281216). Also binds
CC to bacterial and mitochondrial lipids, including cardiolipin, and
CC exhibits bactericidal activity (PubMed:27281216, PubMed:29695864). The
CC functional mechanisms and physiological proteases that cleave and
CC activate this pore-forming protein are unknown (Probable). Plays a role
CC in the transition from catagen to telogen at the end of hair follicle
CC morphogenesis, possibly by regulating hair follicle stem cell niche
CC maintenance (PubMed:15475261, PubMed:15737203, PubMed:17572385,
CC PubMed:22155111, PubMed:32302611). Also required for mammary gland
CC development (PubMed:28168650). {ECO:0000269|PubMed:15475261,
CC ECO:0000269|PubMed:15737203, ECO:0000269|PubMed:17572385,
CC ECO:0000269|PubMed:22155111, ECO:0000269|PubMed:26375003,
CC ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:28168650,
CC ECO:0000269|PubMed:29695864, ECO:0000269|PubMed:32302611,
CC ECO:0000269|PubMed:33883744, ECO:0000305}.
CC -!- ACTIVITY REGULATION: [Gasdermin-A3]: The full-length protein before
CC cleavage is inactive: intramolecular interactions between N- and C-
CC terminal domains mediate autoinhibition in the absence of activation
CC signal (PubMed:25825937, PubMed:26100518, PubMed:26375003). The
CC intrinsic pyroptosis-inducing activity is carried by the released N-
CC terminal moiety (Gasdermin-A3, N-terminal) (PubMed:26100518,
CC PubMed:26375003). {ECO:0000269|PubMed:25825937,
CC ECO:0000269|PubMed:26100518, ECO:0000269|PubMed:26375003}.
CC -!- SUBUNIT: [Gasdermin-A3, N-terminal]: Homooligomer; homooligomeric ring-
CC shaped pore complex containing 27-28 subunits when inserted in the
CC membrane. {ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:29695864}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-A3]: Cytoplasm, cytosol
CC {ECO:0000269|PubMed:27281216}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-A3, N-terminal]: Cell membrane
CC {ECO:0000269|PubMed:27281216}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29695864}. Mitochondrion membrane
CC {ECO:0000305|PubMed:26100518}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29695864}.
CC -!- TISSUE SPECIFICITY: Highest levels in skin with weak expression in
CC placenta and testis. Not detected in the gastrointestinal tract. In
CC skin, expressed in postnatal hair follicles and epidermis as well as
CC sebaceous gland basal cells. {ECO:0000269|PubMed:15475261}.
CC -!- DEVELOPMENTAL STAGE: Not detected at postnatal day 1. Expressed on
CC subsequent postnatal days up to day 20 and throughout adulthood.
CC {ECO:0000269|PubMed:15475261}.
CC -!- DOMAIN: Intramolecular interactions between N- and C-terminal domains
CC are important for autoinhibition in the absence of activation signal
CC (PubMed:26375003). The intrinsic pyroptosis-inducing activity is
CC carried by the N-terminal domain (PubMed:26375003).
CC {ECO:0000269|PubMed:26375003}.
CC -!- DOMAIN: [Gasdermin-A3, N-terminal]: Forms a ring-shaped pore complex
CC containing 27-28 subunits that inserts into the membrane
CC (PubMed:33883744). The pore conduit is predominantly negatively
CC charged, facilitating the release of mature interleukin-1 (IL1B and
CC IL18). In contrast interleukin-1 precursors are not released, due to
CC the presence of an acidic region that is proteolytically removed by
CC CASP1 during maturation (PubMed:33883744).
CC {ECO:0000269|PubMed:33883744}.
CC -!- PTM: Cleavage relieves autoinhibition by releasing the N-terminal
CC moiety (Gasdermin-A3, N-terminal) that initiates pyroptosis.
CC {ECO:0000250|UniProtKB:P57764}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype (PubMed:25825937). A number
CC of gain-of-function mutations, such as alopecia and excoriation (AE),
CC bareskin (Bsk), defolliculated (Dfl), finnegan (Fgn) reduced coat 2
CC (Rco2), Rex-denuded (Re-den) and recombination induced mutation 3
CC (Rim3), have been identified: they cause progressive hair loss
CC (alopecia) accompanied with hyperkeratosis and chronic skin
CC inflammation (PubMed:15475261, PubMed:15737203, PubMed:17572385,
CC PubMed:22155111). Gain-of-function mutations cause bulge stem cell
CC depletion, leading to skin inflammation and alopecia (PubMed:22155111).
CC {ECO:0000269|PubMed:15475261, ECO:0000269|PubMed:15737203,
CC ECO:0000269|PubMed:17572385, ECO:0000269|PubMed:22155111,
CC ECO:0000269|PubMed:25825937}.
CC -!- BIOTECHNOLOGY: Pyroptosis-induced inflammation mediated by Gsdma3
CC triggers robust anti-tumor immunity and may be used in therapies to
CC suppress tumor growth (PubMed:32188939). Use of a nanoparticle-mediated
CC delivery system that selectively directs release of N-terminal moiety
CC (Gasdermin-A3, N-terminal) into tumor cells, triggers pyroptosis and
CC robust anti-tumor immunity (PubMed:32188939). Pyroptosis of less than
CC 15% of tumor cells is sufficient to clear the entire tumor in a mammary
CC tumor graft (PubMed:32188939). {ECO:0000269|PubMed:32188939}.
CC -!- SIMILARITY: Belongs to the gasdermin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAM24379.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AY679090; AAU95732.1; -; mRNA.
DR EMBL; AL591125; CAM24379.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS25356.1; -.
DR RefSeq; NP_001007462.1; NM_001007461.1.
DR RefSeq; XP_006533737.1; XM_006533674.2.
DR PDB; 5B5R; X-ray; 1.90 A; A=1-464.
DR PDB; 6CB8; EM; 3.80 A; A=1-262.
DR PDBsum; 5B5R; -.
DR PDBsum; 6CB8; -.
DR AlphaFoldDB; Q5Y4Y6; -.
DR SMR; Q5Y4Y6; -.
DR STRING; 10090.ENSMUSP00000073022; -.
DR iPTMnet; Q5Y4Y6; -.
DR PhosphoSitePlus; Q5Y4Y6; -.
DR PaxDb; Q5Y4Y6; -.
DR PeptideAtlas; Q5Y4Y6; -.
DR PRIDE; Q5Y4Y6; -.
DR ProteomicsDB; 271445; -.
DR DNASU; 450219; -.
DR Ensembl; ENSMUST00000073295; ENSMUSP00000073022; ENSMUSG00000064224.
DR GeneID; 450219; -.
DR KEGG; mmu:450219; -.
DR UCSC; uc007lgs.1; mouse.
DR CTD; 450219; -.
DR MGI; MGI:3044668; Gsdma3.
DR VEuPathDB; HostDB:ENSMUSG00000064224; -.
DR eggNOG; ENOG502S0IQ; Eukaryota.
DR GeneTree; ENSGT00950000183140; -.
DR InParanoid; Q5Y4Y6; -.
DR OMA; VICHIAL; -.
DR OrthoDB; 747086at2759; -.
DR PhylomeDB; Q5Y4Y6; -.
DR TreeFam; TF331886; -.
DR BioGRID-ORCS; 450219; 0 hits in 75 CRISPR screens.
DR PRO; PR:Q5Y4Y6; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q5Y4Y6; protein.
DR Bgee; ENSMUSG00000064224; Expressed in stomach glandular region mucosa and 22 other tissues.
DR ExpressionAtlas; Q5Y4Y6; baseline and differential.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:1901612; F:cardiolipin binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IBA:GO_Central.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IBA:GO_Central.
DR GO; GO:0001786; F:phosphatidylserine binding; IBA:GO_Central.
DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB.
DR GO; GO:0022829; F:wide pore channel activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR GO; GO:0036331; P:avascular cornea development in camera-type eye; IMP:MGI.
DR GO; GO:0042742; P:defense response to bacterium; IBA:GO_Central.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0042633; P:hair cycle; IMP:MGI.
DR GO; GO:0001942; P:hair follicle development; IMP:UniProtKB.
DR GO; GO:0031069; P:hair follicle morphogenesis; IMP:MGI.
DR GO; GO:0030879; P:mammary gland development; IMP:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:MGI.
DR GO; GO:0051886; P:negative regulation of timing of anagen; IDA:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB.
DR GO; GO:0012501; P:programmed cell death; IMP:UniProtKB.
DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; IDA:UniProtKB.
DR GO; GO:0001949; P:sebaceous gland cell differentiation; IMP:MGI.
DR GO; GO:0043588; P:skin development; IMP:MGI.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IMP:MGI.
DR InterPro; IPR007677; Gasdermin.
DR InterPro; IPR040460; Gasdermin_pore.
DR InterPro; IPR041263; Gasdermin_PUB.
DR PANTHER; PTHR16399; PTHR16399; 1.
DR Pfam; PF04598; Gasdermin; 1.
DR Pfam; PF17708; Gasdermin_C; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Coiled coil; Cytoplasm; Developmental protein;
KW Membrane; Mitochondrion; Necrosis; Reference proteome; Transmembrane;
KW Transmembrane beta strand.
FT CHAIN 1..464
FT /note="Gasdermin-A3"
FT /id="PRO_0000347272"
FT CHAIN 1..?262
FT /note="Gasdermin-A3, N-terminal"
FT /evidence="ECO:0000305|PubMed:29695864"
FT /id="PRO_0000451670"
FT CHAIN ?263..464
FT /note="Gasdermin-A3, C-terminal"
FT /evidence="ECO:0000305|PubMed:29695864"
FT /id="PRO_0000451671"
FT TRANSMEM 78..95
FT /note="Beta stranded"
FT /evidence="ECO:0000305|PubMed:29695864,
FT ECO:0007744|PDB:6CB8"
FT TRANSMEM 99..120
FT /note="Beta stranded"
FT /evidence="ECO:0000305|PubMed:29695864,
FT ECO:0007744|PDB:6CB8"
FT TRANSMEM 164..180
FT /note="Beta stranded"
FT /evidence="ECO:0000305|PubMed:29695864,
FT ECO:0007744|PDB:6CB8"
FT TRANSMEM 184..198
FT /note="Beta stranded"
FT /evidence="ECO:0000305|PubMed:29695864,
FT ECO:0007744|PDB:6CB8"
FT REGION 1..261
FT /note="Triggers pyroptosis"
FT /evidence="ECO:0000269|PubMed:27281216"
FT COILED 255..327
FT /evidence="ECO:0000255"
FT BINDING 9..13
FT /ligand="a cardiolipin"
FT /ligand_id="ChEBI:CHEBI:62237"
FT /evidence="ECO:0000269|PubMed:29695864"
FT MUTAGEN 9..18
FT /note="RALVRELNPR->AALVAELNPAA: Impaired pore-formation."
FT /evidence="ECO:0000269|PubMed:29695864"
FT MUTAGEN 14
FT /note="E->K: No spontaneous pyroptosis-inducing activity;
FT when associated with D-184."
FT /evidence="ECO:0000269|PubMed:27281216"
FT MUTAGEN 41..44
FT /note="RKRK->EEEE: Abolished ability to form a pore."
FT /evidence="ECO:0000269|PubMed:33883744"
FT MUTAGEN 47..49
FT /note="LFW->EEE: Abolished ability to form a pore."
FT /evidence="ECO:0000269|PubMed:33883744"
FT MUTAGEN 62..75
FT /note="DLLEPGSSPSDLTD->ALLAPGSSPSALTA: In AP1; promotes
FT ability to release of interleukin-1 (IL1B and IL18)
FT precursors."
FT /evidence="ECO:0000269|PubMed:33883744"
FT MUTAGEN 86..94
FT /note="DVQVQGLVE->AVQVQGLVA: In AP2; promotes ability to
FT release of interleukin-1 (IL1B and IL18) precursors."
FT /evidence="ECO:0000269|PubMed:33883744"
FT MUTAGEN 132
FT /note="R->A: Weak or no effect on ability to induce
FT pyroptosis. Impaired ability to induce pyroptosis; when
FT associated with A-145."
FT /evidence="ECO:0000269|PubMed:29695864"
FT MUTAGEN 145
FT /note="R->A: Impaired ability to induce pyroptosis; when
FT associated with A-132."
FT /evidence="ECO:0000269|PubMed:29695864"
FT MUTAGEN 184
FT /note="L->D: Markedly decreased induction of pyroptosis and
FT defects in liposome-binding. No spontaneous pyroptosis-
FT inducing activity; when associated with K-14."
FT /evidence="ECO:0000269|PubMed:27281216"
FT MUTAGEN 186
FT /note="L->E: Impaired pore-formation."
FT /evidence="ECO:0000269|PubMed:29695864"
FT MUTAGEN 262..464
FT /note="Missing: In Dfl mutant; gain-of-function mutation;
FT causes an alopecia phenotype."
FT /evidence="ECO:0000269|PubMed:15737203"
FT MUTAGEN 270
FT /note="L->D: Spontaneous pyroptosis-inducing activity."
FT /evidence="ECO:0000269|PubMed:27281216"
FT MUTAGEN 278
FT /note="T->P: In Fgn mutant; gain-of-function mutation;
FT causes an alopecia phenotype. Attenuates intramolecular
FT interaction between the N- and C-terminal domains, hence
FT may relieve autoinhibition; constitutively active in
FT triggering pyroptosis."
FT /evidence="ECO:0000269|PubMed:15737203,
FT ECO:0000269|PubMed:26375003"
FT MUTAGEN 343
FT /note="L->P: In Rco2 mutant; gain-of-function mutation;
FT causes an alopecia phenotype. Attenuates intramolecular
FT interaction between the N- and C-terminal domains, hence
FT may relieve autoinhibition; constitutively active in
FT triggering pyroptosis."
FT /evidence="ECO:0000269|PubMed:15475261,
FT ECO:0000269|PubMed:26375003"
FT MUTAGEN 344
FT /note="Y->C: In Bsk mutant; gain-of-function mutation;
FT causes an alopecia phenotype. Attenuates intramolecular
FT interaction between the N- and C-terminal domains, hence
FT may relieve autoinhibition; constitutively active in
FT triggering pyroptosis."
FT /evidence="ECO:0000269|PubMed:15475261,
FT ECO:0000269|PubMed:26375003"
FT MUTAGEN 344
FT /note="Y->D: Spontaneous pyroptosis-inducing activity."
FT /evidence="ECO:0000269|PubMed:27281216"
FT MUTAGEN 344
FT /note="Y->H: In AE mutant; gain-of-function mutation;
FT causes an alopecia phenotype; constitutively active in
FT triggering cell death. Mice also display hypoplastic
FT mammary glands, impairing lactation function."
FT /evidence="ECO:0000269|PubMed:22155111,
FT ECO:0000269|PubMed:25825937, ECO:0000269|PubMed:28168650"
FT MUTAGEN 348
FT /note="A->D: Spontaneous pyroptosis-inducing activity."
FT /evidence="ECO:0000269|PubMed:27281216"
FT MUTAGEN 348
FT /note="A->T: In Rim3 mutant; gain-of-function mutation;
FT causes an alopecia phenotype. Attenuates intramolecular
FT interaction between the N- and C-terminal domains, hence
FT may relieve autoinhibition; constitutively active in
FT triggering pyroptosis."
FT /evidence="ECO:0000269|PubMed:17572385,
FT ECO:0000269|PubMed:26375003"
FT MUTAGEN 359
FT /note="I->T: Gain-of-function mutation; causes an alopecia
FT phenotype."
FT /evidence="ECO:0000269|PubMed:22682752"
FT MUTAGEN 412
FT /note="A->AEA: In Re-den mutant; gain-of-function mutation;
FT causes an alopecia phenotype. Attenuates intramolecular
FT interaction between the N- and C-terminal domains, hence
FT may relieve autoinhibition; constitutively active in
FT triggering pyroptosis."
FT /evidence="ECO:0000269|PubMed:15475261,
FT ECO:0000269|PubMed:26375003"
FT HELIX 2..15
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 30..33
FT /evidence="ECO:0007829|PDB:5B5R"
FT STRAND 37..41
FT /evidence="ECO:0007829|PDB:5B5R"
FT STRAND 52..59
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:5B5R"
FT STRAND 85..94
FT /evidence="ECO:0007829|PDB:5B5R"
FT STRAND 99..105
FT /evidence="ECO:0007829|PDB:5B5R"
FT STRAND 110..120
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 122..131
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 139..147
FT /evidence="ECO:0007829|PDB:5B5R"
FT STRAND 152..162
FT /evidence="ECO:0007829|PDB:5B5R"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 180..184
FT /evidence="ECO:0007829|PDB:5B5R"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:5B5R"
FT STRAND 203..210
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 267..282
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 286..300
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 303..319
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 336..349
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 354..366
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 369..383
FT /evidence="ECO:0007829|PDB:5B5R"
FT STRAND 390..393
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 396..398
FT /evidence="ECO:0007829|PDB:5B5R"
FT TURN 399..401
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 404..415
FT /evidence="ECO:0007829|PDB:5B5R"
FT TURN 416..418
FT /evidence="ECO:0007829|PDB:5B5R"
FT STRAND 420..422
FT /evidence="ECO:0007829|PDB:5B5R"
FT TURN 423..426
FT /evidence="ECO:0007829|PDB:5B5R"
FT STRAND 427..430
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 432..434
FT /evidence="ECO:0007829|PDB:5B5R"
FT HELIX 435..452
FT /evidence="ECO:0007829|PDB:5B5R"
SQ SEQUENCE 464 AA; 52020 MW; 112C6F81F26AD1E0 CRC64;
MPVFEDVTRA LVRELNPRGD LTPLDSLIDF KHFRPFCLVL RKRKSTLFWG ARYVRTDYTL
LDLLEPGSSP SDLTDSGNFS FKNMLDVQVQ GLVEVPKTVK VKGTAGLSQS STLEVQTLSV
APSALENLKK ERKLSADHSF LNEMRYHEKN LYVVMEAVEA KQEVTVEQTG NANAIFSLPS
LALLGLQGSL NNNKAVTIPK GCVLAYRVRL LRVFLFNLWD IPYICNDSMQ TFPKIRRVPC
SAFISPTQMI SEEPEEEKLI GEMHEDFKTL KEEVQRETQE VEKLSPVGRS SLLTSLSHLL
GKKKELQDLE QKLEGALDKG QKVTLEALPK DVLLSKDAMD AILYFLGALT ELTEEQLKIL
VKSLEKKILP VQLKLVESTL EQNFLQDKEG VFPLQPDLLS SLGEEELTLT EALVGLSGLE
VQRSGPQYAW DPDTRHNLCA LYAGLSLLHL LSRKSNALTY CALS
