GSDA2_MOUSE
ID GSDA2_MOUSE Reviewed; 443 AA.
AC Q32M21; Q8CF01; Q9D810;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Gasdermin-A2;
DE AltName: Full=Gasdermin-2;
DE Contains:
DE RecName: Full=Gasdermin-A2, N-terminal {ECO:0000305};
DE Short=GSDMA2-NT {ECO:0000305};
DE Contains:
DE RecName: Full=Gasdermin-A2, C-terminal {ECO:0000305};
DE Short=GSDMA2-CT {ECO:0000305};
GN Name=Gsdma2 {ECO:0000312|MGI:MGI:1921490};
GN Synonyms=Gsdm2 {ECO:0000312|MGI:MGI:1921490};
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] {ECO:0000305, ECO:0000312|EMBL:BAB25778.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAB25778.1};
RC TISSUE=Stomach {ECO:0000312|EMBL:BAB25778.1};
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 [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] {ECO:0000305, ECO:0000312|EMBL:AAI09336.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4] {ECO:0000305}
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-A2]: This form constitutes the precursor of the
CC pore-forming protein: upon cleavage, the released N-terminal moiety
CC (Gasdermin-A2, N-terminal) binds to membranes and forms pores,
CC triggering cell death. {ECO:0000250|UniProtKB:Q96QA5}.
CC -!- FUNCTION: [Gasdermin-A2, N-terminal]: Pore-forming protein that causes
CC membrane permeabilization and pyroptosis. Released upon cleavage of
CC Gasdermin-A2, 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-A2]: 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-A2, N-terminal).
CC {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- SUBUNIT: [Gasdermin-A2, 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-A2]: Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q96QA5}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin-A2, N-terminal]: Cell membrane
CC {ECO:0000250|UniProtKB:Q5Y4Y6}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q5Y4Y6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1 {ECO:0000269|PubMed:15489334};
CC IsoId=Q32M21-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:16141072};
CC IsoId=Q32M21-2; Sequence=VSP_052880, VSP_052882;
CC Name=3 {ECO:0000269|PubMed:16141072};
CC IsoId=Q32M21-3; Sequence=VSP_052881;
CC -!- TISSUE SPECIFICITY: Expressed in the gastrointestinal tract,
CC specifically from the middle to the upper region of the gastric mucosa
CC in the glandular stomach. {ECO:0000269|PubMed:17350798}.
CC -!- DEVELOPMENTAL STAGE: Expression is first detected at 16.6-17.5 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-A2, N-terminal) that initiates pyroptosis.
CC {ECO:0000250|UniProtKB:P57764}.
CC -!- SIMILARITY: Belongs to the gasdermin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK008613; BAB25778.1; -; mRNA.
DR EMBL; AK008685; BAC25228.1; -; mRNA.
DR EMBL; AL591125; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC109335; AAI09336.1; -; mRNA.
DR EMBL; BC109336; AAI09337.1; -; mRNA.
DR CCDS; CCDS36301.1; -. [Q32M21-1]
DR CCDS; CCDS88246.1; -. [Q32M21-2]
DR RefSeq; NP_084003.2; NM_029727.2. [Q32M21-1]
DR RefSeq; XP_006534519.1; XM_006534456.3.
DR AlphaFoldDB; Q32M21; -.
DR SMR; Q32M21; -.
DR STRING; 10090.ENSMUSP00000091470; -.
DR iPTMnet; Q32M21; -.
DR PhosphoSitePlus; Q32M21; -.
DR SwissPalm; Q32M21; -.
DR EPD; Q32M21; -.
DR MaxQB; Q32M21; -.
DR PaxDb; Q32M21; -.
DR PeptideAtlas; Q32M21; -.
DR PRIDE; Q32M21; -.
DR ProteomicsDB; 271442; -. [Q32M21-1]
DR ProteomicsDB; 271443; -. [Q32M21-2]
DR ProteomicsDB; 271444; -. [Q32M21-3]
DR Ensembl; ENSMUST00000017355; ENSMUSP00000017355; ENSMUSG00000017211. [Q32M21-2]
DR Ensembl; ENSMUST00000093938; ENSMUSP00000091470; ENSMUSG00000017211. [Q32M21-1]
DR GeneID; 76758; -.
DR KEGG; mmu:76758; -.
DR UCSC; uc007lgt.1; mouse. [Q32M21-3]
DR UCSC; uc007lgu.1; mouse. [Q32M21-1]
DR UCSC; uc011yef.1; mouse. [Q32M21-2]
DR CTD; 76758; -.
DR MGI; MGI:1921490; Gsdma2.
DR VEuPathDB; HostDB:ENSMUSG00000017211; -.
DR eggNOG; ENOG502S0IQ; Eukaryota.
DR GeneTree; ENSGT00950000183140; -.
DR HOGENOM; CLU_040752_0_0_1; -.
DR InParanoid; Q32M21; -.
DR OMA; EEEWDIT; -.
DR OrthoDB; 747086at2759; -.
DR PhylomeDB; Q32M21; -.
DR TreeFam; TF331886; -.
DR BioGRID-ORCS; 76758; 0 hits in 74 CRISPR screens.
DR PRO; PR:Q32M21; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q32M21; protein.
DR Bgee; ENSMUSG00000017211; Expressed in mucosa of stomach and 65 other tissues.
DR Genevisible; Q32M21; MM.
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; ISO:MGI.
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; ISO:MGI.
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 Alternative splicing; Cell membrane; Coiled coil; Cytoplasm; Membrane;
KW Necrosis; Reference proteome; Transmembrane; Transmembrane beta strand.
FT CHAIN 1..443
FT /note="Gasdermin-A2"
FT /id="PRO_0000347271"
FT CHAIN 1..?
FT /note="Gasdermin-A2, N-terminal"
FT /evidence="ECO:0000305"
FT /id="PRO_0000451668"
FT CHAIN ?..443
FT /note="Gasdermin-A2, C-terminal"
FT /evidence="ECO:0000305"
FT /id="PRO_0000451669"
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..179
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"
FT TRANSMEM 183..197
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"
FT REGION 1..249
FT /note="Triggers pyroptosis"
FT /evidence="ECO:0000250|UniProtKB:Q96QA5"
FT COILED 249..312
FT /evidence="ECO:0000255"
FT BINDING 9..13
FT /ligand="a cardiolipin"
FT /ligand_id="ChEBI:CHEBI:62237"
FT /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"
FT VAR_SEQ 1..167
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_052880"
FT VAR_SEQ 133..443
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_052881"
FT VAR_SEQ 168..185
FT /note="RASNAISKFSLNLPSLGL -> MCAPTTLSWMCWSRAAPP (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_052882"
SQ SEQUENCE 443 AA; 49844 MW; 1E88C27EF8D21A51 CRC64;
MSMFEDVTRA LARQLNPRGD LTPLDSLIDF KRFHPFCLVL RKRKSTLFWG ARYVRTDYTL
LDVLEPGSSP SDPTLLGNFS FKNMLDVRVE GDVEVPTMMK VKGTVGLSQS STLEVQMLSV
APTALENLHM ERKLSADHPF LKEMREYKQN LYVVMEVVKA KQEVTLKRAS NAISKFSLNL
PSLGLQGSVN HKEAVTIPKG CVLAYRVRQL IIYGKDEWGI PYICTDNMPT FNPLCVLQRQ
GSTVQMISGE MHEDFKTLKK EVQQETQEVE KLSPVGRSSL LTSLSHLLGK KKELQDLEQM
LEGALDKGHE VTLEALPKDV LLLKDAMDAI LYFLGALTEL SEEQLKILVK SLENKVLPVQ
LKLVESILEQ NFLQDKEDVF PLRPDLLSSL GEEDQILTEA LVGLSGLEVQ RSGPQYTWNP
DTCHNLCALY AGLSLLHLLS RDS
