GSDMA_MOUSE
ID GSDMA_MOUSE Reviewed; 446 AA.
AC Q9EST1; A3KFN3;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Gasdermin-A;
DE AltName: Full=Gasdermin-1;
DE AltName: Full=Gasdermin-A1;
DE Contains:
DE RecName: Full=Gasdermin-A, N-terminal {ECO:0000305};
DE Short=GSDMA-NT {ECO:0000305};
DE Contains:
DE RecName: Full=Gasdermin-A, C-terminal {ECO:0000305};
DE Short=GSDMA-CT {ECO:0000305};
GN Name=Gsdma; Synonyms=Gsdm {ECO:0000303|PubMed:10967128}, Gsdm1, Gsdma1;
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/10J; TISSUE=Skin;
RX PubMed=10967128; DOI=10.1007/s003350010138;
RA Saeki N., Kuwahara Y., Sasaki H., Satoh H., Shiroishi T.;
RT "Gasdermin (Gsdm) localizing to mouse chromosome 11 is predominantly
RT expressed in upper gastrointestinal tract but significantly suppressed in
RT human gastric cancer cells.";
RL Mamm. Genome 11:718-724(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
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 [4]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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).
CC -!- FUNCTION: [Gasdermin-A]: This form constitutes the precursor of the
CC pore-forming protein: upon cleavage, the released N-terminal moiety
CC (Gasdermin-A, N-terminal) binds to membranes and forms pores,
CC triggering cell death. {ECO:0000250|UniProtKB:Q96QA5}.
CC -!- FUNCTION: [Gasdermin-A, N-terminal]: Pore-forming protein that causes
CC membrane permeabilization and pyroptosis. Released upon cleavage of
CC Gasdermin-A, and binds to membrane inner leaflet lipids.
CC Homooligomerizes within the membrane and forms pores of 10-15
CC nanometers (nm) of inner diameter, triggering pyroptosis. Binds to
CC membrane inner leaflet lipids, such as phosphatidylinositol (4,5)-
CC bisphosphate. The functional mechanisms and physiological proteases
CC that cleave and activate this pore-forming protein are unknown.
CC {ECO:0000250|UniProtKB:Q96QA5}.
CC -!- ACTIVITY REGULATION: [Gasdermin-A]: 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. The intrinsic pyroptosis-inducing activity is carried by the
CC released N-terminal moiety (Gasdermin-A, N-terminal).
CC {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- SUBUNIT: [Gasdermin-A, N-terminal]: Homooligomer; homooligomeric ring-
CC shaped pore complex containing 27-28 subunits when inserted in the
CC membrane. {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-A]: Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q96QA5}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-A, N-terminal]: Cell membrane
CC {ECO:0000250|UniProtKB:Q5Y4Y6}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in the gastrointestinal
CC (GI) tract and in the skin at a lower level. In the GI tract, the
CC expression is highly restricted to the esophagus and forestomach.
CC {ECO:0000269|PubMed:10967128, ECO:0000269|PubMed:17350798}.
CC -!- DEVELOPMENTAL STAGE: Expression is first detected at 12.5 dpc.
CC {ECO:0000269|PubMed:17350798}.
CC -!- DOMAIN: Intramolecular interactions between N- and C-terminal domains
CC are important for autoinhibition in the absence of activation signal.
CC The intrinsic pyroptosis-inducing activity is carried by the N-terminal
CC domain. {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- PTM: Cleavage relieves autoinhibition by releasing the N-terminal
CC moiety (Gasdermin-A, N-terminal) that initiates pyroptosis.
CC {ECO:0000250|UniProtKB:P57764}.
CC -!- SIMILARITY: Belongs to the gasdermin family. {ECO:0000305}.
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DR EMBL; AB033595; BAB13697.1; -; mRNA.
DR EMBL; AK028645; BAC26045.1; -; mRNA.
DR EMBL; AK028698; BAC26073.1; -; mRNA.
DR EMBL; AK029062; BAC26272.1; -; mRNA.
DR EMBL; AL590963; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS25358.1; -.
DR RefSeq; NP_067322.1; NM_021347.4.
DR AlphaFoldDB; Q9EST1; -.
DR SMR; Q9EST1; -.
DR BioGRID; 208361; 1.
DR IntAct; Q9EST1; 1.
DR MINT; Q9EST1; -.
DR STRING; 10090.ENSMUSP00000017348; -.
DR iPTMnet; Q9EST1; -.
DR PhosphoSitePlus; Q9EST1; -.
DR SwissPalm; Q9EST1; -.
DR MaxQB; Q9EST1; -.
DR PaxDb; Q9EST1; -.
DR PRIDE; Q9EST1; -.
DR ProteomicsDB; 271467; -.
DR DNASU; 57911; -.
DR Ensembl; ENSMUST00000017348; ENSMUSP00000017348; ENSMUSG00000017204.
DR GeneID; 57911; -.
DR KEGG; mmu:57911; -.
DR UCSC; uc007lgv.1; mouse.
DR CTD; 284110; -.
DR MGI; MGI:1889509; Gsdma.
DR VEuPathDB; HostDB:ENSMUSG00000017204; -.
DR eggNOG; ENOG502S0IQ; Eukaryota.
DR GeneTree; ENSGT00950000183140; -.
DR HOGENOM; CLU_040752_0_0_1; -.
DR InParanoid; Q9EST1; -.
DR OMA; HICNDSM; -.
DR OrthoDB; 747086at2759; -.
DR PhylomeDB; Q9EST1; -.
DR TreeFam; TF331886; -.
DR BioGRID-ORCS; 57911; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Gsdma; mouse.
DR PRO; PR:Q9EST1; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9EST1; protein.
DR Bgee; ENSMUSG00000017204; Expressed in esophagus and 46 other tissues.
DR Genevisible; Q9EST1; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IBA:GO_Central.
DR GO; GO:0070269; P:pyroptosis; IBA:GO_Central.
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 2: Evidence at transcript level;
KW Cell membrane; Cytoplasm; Membrane; Necrosis; Reference proteome;
KW Transmembrane; Transmembrane beta strand.
FT CHAIN 1..446
FT /note="Gasdermin-A"
FT /id="PRO_0000148174"
FT CHAIN 1..?
FT /note="Gasdermin-A, N-terminal"
FT /evidence="ECO:0000305"
FT /id="PRO_0000451666"
FT CHAIN ?..446
FT /note="Gasdermin-A, C-terminal"
FT /evidence="ECO:0000305"
FT /id="PRO_0000451667"
FT TRANSMEM 78..95
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"
FT TRANSMEM 99..120
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"
FT TRANSMEM 164..180
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"
FT TRANSMEM 184..198
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"
FT REGION 1..252
FT /note="Triggers pyroptosis"
FT /evidence="ECO:0000250|UniProtKB:Q96QA5"
FT BINDING 9..13
FT /ligand="a cardiolipin"
FT /ligand_id="ChEBI:CHEBI:62237"
FT /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"
SQ SEQUENCE 446 AA; 49593 MW; 603673EC007CB305 CRC64;
MTMFENVTRA LARQLNPRGD LTPLDSLIDF KRFHPFCLVL RKRKSTLFWG ARYVHTDYTL
LDVLEPGSSP SDPTDSGNFS FKNMLDARVE GDVDVPKTVK VKGTAGLSRS STLEVQTLSV
APTALENLHK ERKLSADHPF LKEMRERGEN LYVVMEVVET LQEVTLERAG KAEGCFSLPF
FAPLGLQGSV NHKEAVTIPK GCVLAYRVRQ LMVNGKDEWG IPHICNDSMQ TFPPGEKPGE
GKFILIQASD VGEMHEDFKT LKEEVQRETQ EVEKLSPVGR SSLLTSLSHL LGKKKELQDL
EQTLEGALDK GHEVTLEALP KDVLLSKDAM DAILYFLGAL TVLSEAQQKL LVKSLEKKIL
PVQLKLVEST MEKNFLQDKE GVFPLQPDLL SSLGEEELIL TEALVGLSGL EVQRSGPQYT
WDPDTLPHLC ALYAGLSLLQ LLSKNS
