AIM2_MOUSE
ID AIM2_MOUSE Reviewed; 354 AA.
AC Q91VJ1;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Interferon-inducible protein AIM2;
DE AltName: Full=Interferon-inducible protein 210 {ECO:0000303|PubMed:15896773};
DE Short=Ifi-210 {ECO:0000303|PubMed:15896773};
DE AltName: Full=Interferon-inducible protein p210 {ECO:0000303|PubMed:15896773};
GN Name=Aim2 {ECO:0000303|PubMed:19158676, ECO:0000312|MGI:MGI:2686159};
GN Synonyms=Gm1313 {ECO:0000312|MGI:MGI:2686159},
GN Ifi210 {ECO:0000303|PubMed:15896773};
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 219-354.
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [3]
RP IDENTIFICATION.
RX PubMed=15896773; DOI=10.1016/j.yexcr.2005.03.032;
RA Ludlow L.E.A., Johnstone R.W., Clarke C.J.P.;
RT "The HIN-200 family: more than interferon-inducible genes?";
RL Exp. Cell Res. 308:1-17(2005).
RN [4]
RP FUNCTION.
RX PubMed=19158676; DOI=10.1038/nature07710;
RA Fernandes-Alnemri T., Yu J.W., Datta P., Wu J., Alnemri E.S.;
RT "AIM2 activates the inflammasome and cell death in response to cytoplasmic
RT DNA.";
RL Nature 458:509-513(2009).
RN [5]
RP FUNCTION.
RX PubMed=19158675; DOI=10.1038/nature07725;
RA Hornung V., Ablasser A., Charrel-Dennis M., Bauernfeind F., Horvath G.,
RA Caffrey D.R., Latz E., Fitzgerald K.A.;
RT "AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating
RT inflammasome with ASC.";
RL Nature 458:514-518(2009).
RN [6]
RP FUNCTION.
RX PubMed=19131592; DOI=10.1126/science.1169841;
RA Roberts T.L., Idris A., Dunn J.A., Kelly G.M., Burnton C.M., Hodgson S.,
RA Hardy L.L., Garceau V., Sweet M.J., Ross I.L., Hume D.A., Stacey K.J.;
RT "HIN-200 proteins regulate caspase activation in response to foreign
RT cytoplasmic DNA.";
RL Science 323:1057-1060(2009).
RN [7]
RP FUNCTION.
RX PubMed=20417169; DOI=10.1016/j.chom.2010.04.004;
RA Sauer J.D., Witte C.E., Zemansky J., Hanson B., Lauer P., Portnoy D.A.;
RT "Listeria monocytogenes triggers AIM2-mediated pyroptosis upon infrequent
RT bacteriolysis in the macrophage cytosol.";
RL Cell Host Microbe 7:412-419(2010).
RN [8]
RP FUNCTION.
RX PubMed=20351693; DOI=10.1038/ni.1859;
RA Fernandes-Alnemri T., Yu J.W., Juliana C., Solorzano L., Kang S., Wu J.,
RA Datta P., McCormick M., Huang L., McDermott E., Eisenlohr L., Landel C.P.,
RA Alnemri E.S.;
RT "The AIM2 inflammasome is critical for innate immunity to Francisella
RT tularensis.";
RL Nat. Immunol. 11:385-393(2010).
RN [9]
RP FUNCTION.
RX PubMed=20351692; DOI=10.1038/ni.1864;
RA Rathinam V.A., Jiang Z., Waggoner S.N., Sharma S., Cole L.E., Waggoner L.,
RA Vanaja S.K., Monks B.G., Ganesan S., Latz E., Hornung V., Vogel S.N.,
RA Szomolanyi-Tsuda E., Fitzgerald K.A.;
RT "The AIM2 inflammasome is essential for host defense against cytosolic
RT bacteria and DNA viruses.";
RL Nat. Immunol. 11:395-402(2010).
RN [10]
RP FUNCTION.
RX PubMed=20457908; DOI=10.1073/pnas.1003738107;
RA Jones J.W., Kayagaki N., Broz P., Henry T., Newton K., O'Rourke K.,
RA Chan S., Dong J., Qu Y., Roose-Girma M., Dixit V.M., Monack D.M.;
RT "Absent in melanoma 2 is required for innate immune recognition of
RT Francisella tularensis.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:9771-9776(2010).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22555457; DOI=10.1038/cdd.2012.51;
RA Pierini R., Juruj C., Perret M., Jones C.L., Mangeot P., Weiss D.S.,
RA Henry T.;
RT "AIM2/ASC triggers caspase-8-dependent apoptosis in Francisella-infected
RT caspase-1-deficient macrophages.";
RL Cell Death Differ. 19:1709-1721(2012).
RN [12]
RP FUNCTION.
RX PubMed=21902795; DOI=10.1111/j.1462-5822.2011.01700.x;
RA Belhocine K., Monack D.M.;
RT "Francisella infection triggers activation of the AIM2 inflammasome in
RT murine dendritic cells.";
RL Cell. Microbiol. 14:71-80(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS) OF 158-349 IN COMPLEX WITH DNA,
RP FUNCTION, DOMAIN, AND DNA-BINDING.
RX PubMed=23567559; DOI=10.1038/cr.2013.52;
RA Ru H., Ni X., Zhao L., Crowley C., Ding W., Hung L.W., Shaw N., Cheng G.,
RA Liu Z.J.;
RT "Structural basis for termination of AIM2-mediated signaling by p202.";
RL Cell Res. 23:855-858(2013).
RN [14]
RP FUNCTION, AND IDENTIFICATION IN THE AIM2 PANOPTOSOME COMPLEX.
RX PubMed=34471287; DOI=10.1038/s41586-021-03875-8;
RA Lee S., Karki R., Wang Y., Nguyen L.N., Kalathur R.C., Kanneganti T.D.;
RT "AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host
RT defence.";
RL Nature 597:415-419(2021).
CC -!- FUNCTION: Involved in innate immune response by recognizing cytosolic
CC double-stranded DNA and inducing caspase-1-activating inflammasome
CC formation in macrophages (PubMed:19131592, PubMed:19158675,
CC PubMed:19158676, PubMed:20351692, PubMed:20351693, PubMed:20417169,
CC PubMed:20457908, PubMed:21902795, PubMed:23567559). Upon binding to DNA
CC is thought to undergo oligomerization and to associate with PYCARD
CC initiating the recruitment of caspase-1 precursor and processing of
CC interleukin-1 beta and interleukin-18 (PubMed:19131592,
CC PubMed:19158675, PubMed:19158676, PubMed:20351692, PubMed:20351693,
CC PubMed:20417169, PubMed:20457908, PubMed:21902795, PubMed:23567559).
CC Detects cytosolic dsDNA of viral and bacterial origin in a non-
CC sequence-specific manner (PubMed:19131592, PubMed:19158675,
CC PubMed:20351692, PubMed:23567559). Also acts as a mediator of
CC pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of
CC host defense against pathogens, in response to bacterial infection
CC (PubMed:34471287). Can also trigger PYCARD-dependent, caspase-1-
CC independent cell death that involves caspase-8 (PubMed:22555457).
CC {ECO:0000269|PubMed:19131592, ECO:0000269|PubMed:19158675,
CC ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:20351692,
CC ECO:0000269|PubMed:20351693, ECO:0000269|PubMed:20417169,
CC ECO:0000269|PubMed:20457908, ECO:0000269|PubMed:21902795,
CC ECO:0000269|PubMed:22555457, ECO:0000269|PubMed:23567559,
CC ECO:0000269|PubMed:34471287}.
CC -!- ACTIVITY REGULATION: In absence of dsDNA pyrin and HIN-20 domain can
CC interact inducing a closed conformation; an autoinhibitory mechanism is
CC proposed in which binding to dsDNA liberates the pyrin domain for
CC homotypic downstream signaling interactions with PYCARD.
CC {ECO:0000250|UniProtKB:O14862}.
CC -!- SUBUNIT: Self-associates; forms homooligomers in response to cytosolic
CC dsDNA and the dsDNA seems to serve as oligomerization platform (By
CC similarity). Component of the AIM2 inflammasome complex (By
CC similarity). Interacts with PYCARD (By similarity). Interacts with
CC IFI16 (By similarity). Interacts with EIF2AK2/PKR (By similarity).
CC Interacts with PYDC5; disrupts assembly of the ALR inflammasome complex
CC (By similarity). Component of the AIM2 PANoptosome complex, a
CC multiprotein complex that drives inflammatory cell death (PANoptosis)
CC (PubMed:34471287). {ECO:0000250|UniProtKB:O14862,
CC ECO:0000269|PubMed:34471287}.
CC -!- INTERACTION:
CC Q91VJ1; Q91VJ1: Aim2; NbExp=2; IntAct=EBI-6253384, EBI-6253384;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O14862}. Cytoplasm
CC {ECO:0000269|PubMed:22555457}.
CC -!- DOMAIN: The HIN-20 domain mediates dsDNA binding via electrostatic
CC interactions. {ECO:0000269|PubMed:23567559}.
CC -!- DOMAIN: The pyrin domain mediates homotypic interaction with PYCARD.
CC {ECO:0000250|UniProtKB:O14862}.
CC -!- SIMILARITY: Belongs to the HIN-200 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH09664.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AC084073; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009664; AAH09664.1; ALT_INIT; mRNA.
DR CCDS; CCDS15529.2; -.
DR RefSeq; NP_001013801.2; NM_001013779.2.
DR RefSeq; XP_006496982.1; XM_006496919.2.
DR RefSeq; XP_006496989.1; XM_006496926.1.
DR RefSeq; XP_011237133.1; XM_011238831.2.
DR RefSeq; XP_011237137.1; XM_011238835.1.
DR RefSeq; XP_011237144.1; XM_011238842.1.
DR RefSeq; XP_017176969.1; XM_017321480.1.
DR RefSeq; XP_017176971.1; XM_017321482.1.
DR RefSeq; XP_017176972.1; XM_017321483.1.
DR RefSeq; XP_017176975.1; XM_017321486.1.
DR RefSeq; XP_017176976.1; XM_017321487.1.
DR RefSeq; XP_017176977.1; XM_017321488.1.
DR RefSeq; XP_017176981.1; XM_017321492.1.
DR RefSeq; XP_017176983.1; XM_017321494.1.
DR RefSeq; XP_017176985.1; XM_017321496.1.
DR RefSeq; XP_017176987.1; XM_017321498.1.
DR RefSeq; XP_017176990.1; XM_017321501.1.
DR RefSeq; XP_017176994.1; XM_017321505.1.
DR RefSeq; XP_017176996.1; XM_017321507.1.
DR RefSeq; XP_017176999.1; XM_017321510.1.
DR PDB; 2N00; NMR; -; A=1-95.
DR PDB; 4JBM; X-ray; 2.22 A; A/B=158-349.
DR PDBsum; 2N00; -.
DR PDBsum; 4JBM; -.
DR AlphaFoldDB; Q91VJ1; -.
DR BMRB; Q91VJ1; -.
DR SMR; Q91VJ1; -.
DR BioGRID; 238833; 1.
DR ComplexPortal; CPX-4243; AIM2 inflammasome.
DR IntAct; Q91VJ1; 3.
DR MINT; Q91VJ1; -.
DR STRING; 10090.ENSMUSP00000119465; -.
DR ChEMBL; CHEMBL4295911; -.
DR PhosphoSitePlus; Q91VJ1; -.
DR EPD; Q91VJ1; -.
DR MaxQB; Q91VJ1; -.
DR PaxDb; Q91VJ1; -.
DR PeptideAtlas; Q91VJ1; -.
DR PRIDE; Q91VJ1; -.
DR ProteomicsDB; 296217; -.
DR Antibodypedia; 34257; 629 antibodies from 42 providers.
DR DNASU; 383619; -.
DR Ensembl; ENSMUST00000147604; ENSMUSP00000119465; ENSMUSG00000037860.
DR Ensembl; ENSMUST00000166137; ENSMUSP00000132253; ENSMUSG00000037860.
DR GeneID; 383619; -.
DR KEGG; mmu:383619; -.
DR UCSC; uc011wws.1; mouse.
DR CTD; 9447; -.
DR MGI; MGI:2686159; Aim2.
DR VEuPathDB; HostDB:ENSMUSG00000037860; -.
DR eggNOG; ENOG502QTQS; Eukaryota.
DR GeneTree; ENSGT00390000013296; -.
DR HOGENOM; CLU_020123_2_0_1; -.
DR InParanoid; Q91VJ1; -.
DR OMA; MKCKEGD; -.
DR OrthoDB; 1304994at2759; -.
DR PhylomeDB; Q91VJ1; -.
DR TreeFam; TF337385; -.
DR Reactome; R-MMU-1834949; Cytosolic sensors of pathogen-associated DNA.
DR Reactome; R-MMU-844615; The AIM2 inflammasome.
DR BioGRID-ORCS; 383619; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Aim2; mouse.
DR PRO; PR:Q91VJ1; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q91VJ1; protein.
DR Bgee; ENSMUSG00000037860; Expressed in granulocyte and 90 other tissues.
DR ExpressionAtlas; Q91VJ1; baseline and differential.
DR Genevisible; Q91VJ1; MM.
DR GO; GO:0097169; C:AIM2 inflammasome complex; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0002218; P:activation of innate immune response; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0035458; P:cellular response to interferon-beta; IDA:MGI.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0051607; P:defense response to virus; IC:ComplexPortal.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0044546; P:NLRP3 inflammasome complex assembly; ISO:MGI.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:2001056; P:positive regulation of cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IMP:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:ComplexPortal.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0070269; P:pyroptosis; IDA:UniProtKB.
DR GO; GO:1904270; P:pyroptosome complex assembly; ISO:MGI.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISO:MGI.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 2.40.50.140; -; 2.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR040205; HIN-200.
DR InterPro; IPR004021; HIN200/IF120x.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR PANTHER; PTHR12200; PTHR12200; 1.
DR Pfam; PF02760; HIN; 1.
DR Pfam; PF02758; PYRIN; 1.
DR SMART; SM01289; PYRIN; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50824; DAPIN; 1.
DR PROSITE; PS50834; HIN_200; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Cytoplasm; DNA-binding; Immunity;
KW Inflammatory response; Innate immunity; Nucleus; Reference proteome.
FT CHAIN 1..354
FT /note="Interferon-inducible protein AIM2"
FT /id="PRO_0000334528"
FT DOMAIN 1..87
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT DOMAIN 144..341
FT /note="HIN-200"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00106"
FT REGION 95..124
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 106..124
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT HELIX 2..14
FT /evidence="ECO:0007829|PDB:2N00"
FT HELIX 19..29
FT /evidence="ECO:0007829|PDB:2N00"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:2N00"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:2N00"
FT TURN 42..46
FT /evidence="ECO:0007829|PDB:2N00"
FT HELIX 47..55
FT /evidence="ECO:0007829|PDB:2N00"
FT HELIX 58..72
FT /evidence="ECO:0007829|PDB:2N00"
FT TURN 73..77
FT /evidence="ECO:0007829|PDB:2N00"
FT HELIX 78..91
FT /evidence="ECO:0007829|PDB:2N00"
FT STRAND 160..167
FT /evidence="ECO:0007829|PDB:4JBM"
FT STRAND 181..188
FT /evidence="ECO:0007829|PDB:4JBM"
FT STRAND 193..199
FT /evidence="ECO:0007829|PDB:4JBM"
FT HELIX 202..206
FT /evidence="ECO:0007829|PDB:4JBM"
FT STRAND 212..217
FT /evidence="ECO:0007829|PDB:4JBM"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:4JBM"
FT STRAND 231..235
FT /evidence="ECO:0007829|PDB:4JBM"
FT HELIX 244..251
FT /evidence="ECO:0007829|PDB:4JBM"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:4JBM"
FT STRAND 267..279
FT /evidence="ECO:0007829|PDB:4JBM"
FT STRAND 281..290
FT /evidence="ECO:0007829|PDB:4JBM"
FT STRAND 293..301
FT /evidence="ECO:0007829|PDB:4JBM"
FT STRAND 313..324
FT /evidence="ECO:0007829|PDB:4JBM"
FT STRAND 327..331
FT /evidence="ECO:0007829|PDB:4JBM"
FT STRAND 337..341
FT /evidence="ECO:0007829|PDB:4JBM"
SQ SEQUENCE 354 AA; 40155 MW; E860C5D902AA5D35 CRC64;
MESEYREMLL LTGLDHITEE ELKRFKYFAL TEFQIARSTL DVADRTELAD HLIQSAGAAS
AVTKAINIFQ KLNYMHIANA LEEKKKEAER KLMTNTKKRG TQKVENRSQA ENCSAASATR
SDNDFKEQAA TEVCPQAKPQ KKQMVAEQEA IREDLQKDPL VVTVLKAINP FECETQEGRQ
EIFHATVATE TDFFFVKVLN AQFKDKFIPK RTIKISNYLW HSNFMEVTSS SVVVDVESNH
EVPNNVVKRA RETPRISKLK IQPCGTIVNG LFKVQKITEE KDRVLYGIHD KTGTMEVLVL
GNPSKTKCEE GDKIRLTFFE VSKNGVKIQL KSGPCSFFKV IKAAKPKTDM KSVE
