AIM2_HUMAN
ID AIM2_HUMAN Reviewed; 343 AA.
AC O14862; A8K7M7; Q5T3V9; Q96FG9;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Interferon-inducible protein AIM2 {ECO:0000303|PubMed:9242382};
DE AltName: Full=Absent in melanoma 2 {ECO:0000303|PubMed:9242382};
GN Name=AIM2 {ECO:0000303|PubMed:9242382, ECO:0000312|HGNC:HGNC:357};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION BY IFNG.
RX PubMed=9242382; DOI=10.1038/sj.onc.1201206;
RA DeYoung K.L., Ray M.E., Su Y.A., Anzick S.L., Johnstone R.W., Trapani J.A.,
RA Meltzer P.S., Trent J.M.;
RT "Cloning a novel member of the human interferon-inducible gene family
RT associated with control of tumorigenicity in a model of human melanoma.";
RL Oncogene 15:453-457(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP SUBCELLULAR LOCATION, INDUCTION BY IFNG, AND SUBUNIT.
RX PubMed=15582594; DOI=10.1016/j.bbrc.2004.11.048;
RA Cresswell K.S., Clarke C.J.P., Jackson J.T., Darcy P.K., Trapani J.A.,
RA Johnstone R.W.;
RT "Biochemical and growth regulatory activities of the HIN-200 family member
RT and putative tumor suppressor protein, AIM2.";
RL Biochem. Biophys. Res. Commun. 326:417-424(2005).
RN [6]
RP FUNCTION.
RX PubMed=16432157; DOI=10.1158/1535-7163.mct-05-0310;
RA Chen I.-F., Ou-Yang F., Hung J.-Y., Liu J.-C., Wang H., Wang S.-C.,
RA Hou M.-F., Hortobagyi G.N., Hung M.-C.;
RT "AIM2 suppresses human breast cancer cell proliferation in vitro and
RT mammary tumor growth in a mouse model.";
RL Mol. Cancer Ther. 5:1-7(2006).
RN [7]
RP ROLE IN COLON CANCER, AND VARIANTS LYS-32 AND TYR-304.
RX PubMed=17726700; DOI=10.1002/gcc.20493;
RA Woerner S.M., Kloor M., Schwitalle Y., Youmans H., Doeberitz M.K.,
RA Gebert J., Dihlmann S.;
RT "The putative tumor suppressor AIM2 is frequently affected by different
RT genetic alterations in microsatellite unstable colon cancers.";
RL Genes Chromosomes Cancer 46:1080-1089(2007).
RN [8]
RP FUNCTION, INDUCTION, DNA-BINDING, SUBCELLULAR LOCATION, INTERACTION WITH
RP PYCARD, AND MUTAGENESIS OF LEU-14 AND PHE-165.
RX PubMed=19158679; DOI=10.1038/ni.1702;
RA Burckstummer T., Baumann C., Bluml S., Dixit E., Durnberger G., Jahn H.,
RA Planyavsky M., Bilban M., Colinge J., Bennett K.L., Superti-Furga G.;
RT "An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic
RT DNA sensor for the inflammasome.";
RL Nat. Immunol. 10:266-272(2009).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PYCARD, AND
RP SELF-ASSOCIATION.
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 [10]
RP FUNCTION, SUBCELLULAR LOCATION, DNA-BINDING, AND INTERACTION WITH PYCARD.
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 [11]
RP FUNCTION.
RX PubMed=20566831; DOI=10.4049/jimmunol.1001058;
RA Tsuchiya K., Hara H., Kawamura I., Nomura T., Yamamoto T., Daim S.,
RA Dewamitta S.R., Shen Y., Fang R., Mitsuyama M.;
RT "Involvement of absent in melanoma 2 in inflammasome activation in
RT macrophages infected with Listeria monocytogenes.";
RL J. Immunol. 185:1186-1195(2010).
RN [12]
RP INTERACTION WITH IFI16.
RX PubMed=22046441; DOI=10.1371/journal.pone.0027040;
RA Veeranki S., Duan X., Panchanathan R., Liu H., Choubey D.;
RT "IFI16 protein mediates the anti-inflammatory actions of the type-I
RT interferons through suppression of activation of caspase-1 by
RT inflammasomes.";
RL PLoS ONE 6:E27040-E27040(2011).
RN [13]
RP INTERACTION WITH MAPRE1.
RX PubMed=22869553; DOI=10.1074/mcp.m112.020594;
RA Wang L.J., Hsu C.W., Chen C.C., Liang Y., Chen L.C., Ojcius D.M.,
RA Tsang N.M., Hsueh C., Wu C.C., Chang Y.S.;
RT "Interactome-wide analysis identifies end-binding protein 1 as a crucial
RT component for the speck-like particle formation of activated AIM2
RT inflammasomes.";
RL Mol. Cell. Proteomics 11:1230-1244(2012).
RN [14]
RP INTERACTION WITH EIF2AK2.
RX PubMed=22801494; DOI=10.1038/nature11290;
RA Lu B., Nakamura T., Inouye K., Li J., Tang Y., Lundbaeck P.,
RA Valdes-Ferrer S.I., Olofsson P.S., Kalb T., Roth J., Zou Y.,
RA Erlandsson-Harris H., Yang H., Ting J.P., Wang H., Andersson U.,
RA Antoine D.J., Chavan S.S., Hotamisligil G.S., Tracey K.J.;
RT "Novel role of PKR in inflammasome activation and HMGB1 release.";
RL Nature 488:670-674(2012).
RN [15]
RP INTERACTION WITH PYDC5.
RX PubMed=24531343; DOI=10.1038/ni.2829;
RA Khare S., Ratsimandresy R.A., de Almeida L., Cuda C.M., Rellick S.L.,
RA Misharin A.V., Wallin M.C., Gangopadhyay A., Forte E., Gottwein E.,
RA Perlman H., Reed J.C., Greaves D.R., Dorfleutner A., Stehlik C.;
RT "The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and
RT regulates responses to infection with DNA viruses.";
RL Nat. Immunol. 15:343-353(2014).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 144-343 IN COMPLEX WITH
RP DOUBLE-STRANDED DNA, ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-160;
RP LYS-162; LYS-163; LYS-198; LYS-204; ARG-244; LYS-251; LYS-309; ARG-311;
RP LYS-335 AND ILE-337.
RX PubMed=22483801; DOI=10.1016/j.immuni.2012.02.014;
RA Jin T., Perry A., Jiang J., Smith P., Curry J.A., Unterholzner L.,
RA Jiang Z., Horvath G., Rathinam V.A., Johnstone R.W., Hornung V., Latz E.,
RA Bowie A.G., Fitzgerald K.A., Xiao T.S.;
RT "Structures of the HIN domain:DNA complexes reveal ligand binding and
RT activation mechanisms of the AIM2 inflammasome and IFI16 receptor.";
RL Immunity 36:561-571(2012).
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:17726700, PubMed:19158675,
CC PubMed:19158676, PubMed:19158679, PubMed:20566831). 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:17726700,
CC PubMed:19158675, PubMed:19158676, PubMed:19158679, PubMed:20566831).
CC Detects cytosolic dsDNA of viral and bacterial origin in a non-
CC sequence-specific manner (PubMed:17726700, PubMed:19158675,
CC PubMed:19158676, PubMed:19158679, PubMed:20566831). Also acts as a
CC mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an
CC integral part of host defense against pathogens, in response to
CC bacterial infection (By similarity). Can also trigger PYCARD-dependent,
CC caspase-1-independent cell death that involves caspase-8 (By
CC similarity). Tumor suppressor which may act by repressing NF-kappa-B
CC transcriptional activity (PubMed:16432157).
CC {ECO:0000250|UniProtKB:Q91VJ1, ECO:0000269|PubMed:16432157,
CC ECO:0000269|PubMed:17726700, ECO:0000269|PubMed:19158675,
CC ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19158679,
CC ECO:0000269|PubMed:20566831}.
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:0000269|PubMed:22483801}.
CC -!- SUBUNIT: Self-associates; forms homooligomers in response to cytosolic
CC dsDNA and the dsDNA seems to serve as oligomerization platform
CC (PubMed:15582594, PubMed:19158676). Component of the AIM2 inflammasome
CC (PubMed:22869553, PubMed:22483801). Interacts with PYCARD, IFI16,
CC EIF2AK2/PKR and MAPRE1 (PubMed:19158676, PubMed:19158675,
CC PubMed:19158679, PubMed:22046441, PubMed:22801494, PubMed:22869553).
CC Interacts with PYDC5; disrupts assembly of the ALR inflammasome complex
CC (PubMed:24531343). Component of the AIM2 PANoptosome complex, a
CC multiprotein complex that drives inflammatory cell death (PANoptosis)
CC (By similarity). {ECO:0000250|UniProtKB:Q91VJ1,
CC ECO:0000269|PubMed:15582594, ECO:0000269|PubMed:19158675,
CC ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19158679,
CC ECO:0000269|PubMed:22046441, ECO:0000269|PubMed:22483801,
CC ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:22869553,
CC ECO:0000269|PubMed:24531343}.
CC -!- INTERACTION:
CC O14862; O14862: AIM2; NbExp=3; IntAct=EBI-6253193, EBI-6253193;
CC O14862; Q9ULZ3: PYCARD; NbExp=13; IntAct=EBI-6253193, EBI-751215;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Activated inflammasomes
CC can aggregate in the cytosol as speck-like particles.
CC -!- TISSUE SPECIFICITY: Expressed in spleen, small intestine, peripheral
CC blood leukocytes, and testis. {ECO:0000269|PubMed:9242382}.
CC -!- INDUCTION: By IFNG/IFN-gamma and IFNB1/IFN-beta.
CC {ECO:0000269|PubMed:15582594, ECO:0000269|PubMed:19158679,
CC ECO:0000269|PubMed:9242382}.
CC -!- DOMAIN: The pyrin domain mediates homotypic interaction with PYCARD
CC (PubMed:19158676, PubMed:19158675). {ECO:0000269|PubMed:19158675,
CC ECO:0000269|PubMed:19158676}.
CC -!- DOMAIN: The HIN-20 domain mediates dsDNA binding via electrostatic
CC interactions. {ECO:0000269|PubMed:22483801}.
CC -!- MISCELLANEOUS: Defects in AIM2 may be a cause of microsatellite
CC unstable colon cancers.
CC -!- SIMILARITY: Belongs to the HIN-200 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH10940.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF024714; AAB81613.1; -; mRNA.
DR EMBL; AK292042; BAF84731.1; -; mRNA.
DR EMBL; AL359753; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010940; AAH10940.1; ALT_FRAME; mRNA.
DR CCDS; CCDS1181.1; -.
DR RefSeq; NP_004824.1; NM_004833.2.
DR RefSeq; XP_016858337.1; XM_017002848.1.
DR PDB; 3RN2; X-ray; 2.55 A; A/B=144-343.
DR PDB; 3RN5; X-ray; 2.50 A; A/B/C/D=144-343.
DR PDB; 3VD8; X-ray; 2.07 A; A=1-107.
DR PDB; 4O7Q; X-ray; 1.82 A; A=1-93.
DR PDB; 6MB2; EM; 5.00 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O=1-93.
DR PDB; 7K3R; EM; 3.20 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U=1-117.
DR PDBsum; 3RN2; -.
DR PDBsum; 3RN5; -.
DR PDBsum; 3VD8; -.
DR PDBsum; 4O7Q; -.
DR PDBsum; 6MB2; -.
DR PDBsum; 7K3R; -.
DR AlphaFoldDB; O14862; -.
DR SMR; O14862; -.
DR BioGRID; 114837; 111.
DR ComplexPortal; CPX-4142; AIM2 inflammasome.
DR DIP; DIP-59741N; -.
DR IntAct; O14862; 111.
DR MINT; O14862; -.
DR STRING; 9606.ENSP00000357112; -.
DR ChEMBL; CHEMBL4630802; -.
DR iPTMnet; O14862; -.
DR PhosphoSitePlus; O14862; -.
DR BioMuta; AIM2; -.
DR MassIVE; O14862; -.
DR MaxQB; O14862; -.
DR PaxDb; O14862; -.
DR PeptideAtlas; O14862; -.
DR PRIDE; O14862; -.
DR ProteomicsDB; 48275; -.
DR Antibodypedia; 34257; 629 antibodies from 42 providers.
DR DNASU; 9447; -.
DR Ensembl; ENST00000368130.9; ENSP00000357112.4; ENSG00000163568.15.
DR GeneID; 9447; -.
DR KEGG; hsa:9447; -.
DR MANE-Select; ENST00000368130.9; ENSP00000357112.4; NM_004833.3; NP_004824.1.
DR UCSC; uc001ftj.2; human.
DR CTD; 9447; -.
DR DisGeNET; 9447; -.
DR GeneCards; AIM2; -.
DR HGNC; HGNC:357; AIM2.
DR HPA; ENSG00000163568; Tissue enhanced (intestine, lymphoid tissue, urinary bladder).
DR MIM; 604578; gene.
DR neXtProt; NX_O14862; -.
DR OpenTargets; ENSG00000163568; -.
DR PharmGKB; PA24651; -.
DR VEuPathDB; HostDB:ENSG00000163568; -.
DR eggNOG; ENOG502QTQS; Eukaryota.
DR GeneTree; ENSGT00390000013296; -.
DR HOGENOM; CLU_020123_2_0_1; -.
DR InParanoid; O14862; -.
DR OMA; MKCKEGD; -.
DR OrthoDB; 1304994at2759; -.
DR PhylomeDB; O14862; -.
DR TreeFam; TF337385; -.
DR PathwayCommons; O14862; -.
DR Reactome; R-HSA-1834949; Cytosolic sensors of pathogen-associated DNA.
DR Reactome; R-HSA-844615; The AIM2 inflammasome.
DR SignaLink; O14862; -.
DR SIGNOR; O14862; -.
DR BioGRID-ORCS; 9447; 14 hits in 1076 CRISPR screens.
DR ChiTaRS; AIM2; human.
DR GeneWiki; AIM2; -.
DR GenomeRNAi; 9447; -.
DR Pharos; O14862; Tbio.
DR PRO; PR:O14862; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O14862; protein.
DR Bgee; ENSG00000163568; Expressed in lymph node and 124 other tissues.
DR ExpressionAtlas; O14862; baseline and differential.
DR Genevisible; O14862; HS.
DR GO; GO:0097169; C:AIM2 inflammasome complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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; IBA:GO_Central.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:MGI.
DR GO; GO:0051607; P:defense response to virus; IC:ComplexPortal.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
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; IDA:UniProtKB.
DR GO; GO:0044546; P:NLRP3 inflammasome complex assembly; IDA:UniProtKB.
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; ISS: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; IDA:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; IDA:UniProtKB.
DR GO; GO:1904270; P:pyroptosome complex assembly; IDA:GO_Central.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB.
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;
KW Tumor suppressor.
FT CHAIN 1..343
FT /note="Interferon-inducible protein AIM2"
FT /id="PRO_0000153726"
FT DOMAIN 1..87
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT DOMAIN 138..337
FT /note="HIN-200"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00106"
FT VARIANT 32
FT /note="E -> K (in dbSNP:rs2276405)"
FT /evidence="ECO:0000269|PubMed:17726700"
FT /id="VAR_022022"
FT VARIANT 304
FT /note="C -> Y (in dbSNP:rs778047649)"
FT /evidence="ECO:0000269|PubMed:17726700"
FT /id="VAR_043379"
FT MUTAGEN 14
FT /note="L->A: Fails to activate interleukin-1 beta
FT production."
FT /evidence="ECO:0000269|PubMed:19158679"
FT MUTAGEN 160
FT /note="K->A: Impairs DNA binding; when associated with A-
FT 160; A-K162; A-163; A-198; A-204. Impairs DNA binding; when
FT associated with A-160; A-162; A-163; A-198; A-204; A-244;
FT A-251; A-309; A-311; A-355 and A-337."
FT /evidence="ECO:0000269|PubMed:22483801"
FT MUTAGEN 162
FT /note="K->A: Impairs DNA binding; when associated with A-
FT 160; A-162; A-163; A-198; A-204. Impairs DNA binding; when
FT associated with A-160; A-162; A-163; A-198; A-204; A-244;
FT A-251; A-309; A-311; A-355 and A-337."
FT /evidence="ECO:0000269|PubMed:22483801"
FT MUTAGEN 163
FT /note="K->A: Impairs DNA binding; when associated with A-
FT 160; A-162; A-163; A-198; A-204. Impairs DNA binding; when
FT associated with A-160; A-162; A-163; A-198; A-204; A-244;
FT A-251; A-309; A-311; A-355 and A-337."
FT /evidence="ECO:0000269|PubMed:22483801"
FT MUTAGEN 165
FT /note="F->A: Impairs DNA binding."
FT /evidence="ECO:0000269|PubMed:19158679"
FT MUTAGEN 198
FT /note="K->A: Impairs DNA binding; when associated with A-
FT 160; A-162; A-163; A-198; A-204. Impairs DNA binding; when
FT associated with A-160; A-162; A-163; A-198; A-204; A-244;
FT A-251; A-309; A-311; A-355 and A-337."
FT /evidence="ECO:0000269|PubMed:22483801"
FT MUTAGEN 204
FT /note="K->A: Impairs DNA binding; when associated with A-
FT 160; A-162; A-163; A-198; A-204. Impairs DNA binding; when
FT associated with A-160; A-162; A-163; A-198; A-204; A-244;
FT A-251; A-309; A-311; A-355 and A-337."
FT /evidence="ECO:0000269|PubMed:22483801"
FT MUTAGEN 244
FT /note="R->A: Impairs DNA binding; when associated with A-
FT 160; A-162; A-163; A-198; A-204. Impairs DNA binding; when
FT associated with A-160; A-162; A-163; A-198; A-204; A-244;
FT A-251; A-309; A-311; A-355 and A-337."
FT /evidence="ECO:0000269|PubMed:22483801"
FT MUTAGEN 251
FT /note="K->A: Impairs DNA binding; when associated with A-
FT 160; A-162; A-163; A-198; A-204. Impairs DNA binding; when
FT associated with A-160; A-162; A-163; A-198; A-204; A-244;
FT A-251; A-309; A-311; A-355 and A-337."
FT /evidence="ECO:0000269|PubMed:22483801"
FT MUTAGEN 309
FT /note="K->A: Impairs DNA binding; when associated with A-
FT 160; A-162; A-163; A-198; A-204. Impairs DNA binding; when
FT associated with A-160; A-162; A-163; A-198; A-204; A-244;
FT A-251; A-309; A-311; A-355 and A-337."
FT /evidence="ECO:0000269|PubMed:22483801"
FT MUTAGEN 311
FT /note="R->A: Impairs DNA binding; when associated with A-
FT 160; A-162; A-163; A-198; A-204. Impairs DNA binding; when
FT associated with A-160; A-162; A-163; A-198; A-204; A-244;
FT A-251; A-309; A-311; A-355 and A-337."
FT /evidence="ECO:0000269|PubMed:22483801"
FT MUTAGEN 335
FT /note="K->A: Impairs DNA binding; when associated with A-
FT 160; A-162; A-163; A-198; A-204. Impairs DNA binding; when
FT associated with A-160; A-162; A-163; A-198; A-204; A-244;
FT A-251; A-309; A-311; A-355 and A-337."
FT /evidence="ECO:0000269|PubMed:22483801"
FT MUTAGEN 337
FT /note="I->A: Impairs DNA binding; when associated with A-
FT 160; A-162; A-163; A-198; A-204. Impairs DNA binding; when
FT associated with A-160; A-162; A-163; A-198; A-204; A-244;
FT A-251; A-309; A-311; A-355 and A-337."
FT /evidence="ECO:0000269|PubMed:22483801"
FT CONFLICT 253
FT /note="N -> D (in Ref. 2; BAF84731)"
FT /evidence="ECO:0000305"
FT HELIX 1..11
FT /evidence="ECO:0007829|PDB:4O7Q"
FT HELIX 14..16
FT /evidence="ECO:0007829|PDB:4O7Q"
FT HELIX 19..29
FT /evidence="ECO:0007829|PDB:4O7Q"
FT TURN 30..32
FT /evidence="ECO:0007829|PDB:4O7Q"
FT HELIX 37..40
FT /evidence="ECO:0007829|PDB:4O7Q"
FT HELIX 45..56
FT /evidence="ECO:0007829|PDB:4O7Q"
FT HELIX 58..71
FT /evidence="ECO:0007829|PDB:4O7Q"
FT HELIX 75..91
FT /evidence="ECO:0007829|PDB:4O7Q"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:3RN2"
FT STRAND 154..161
FT /evidence="ECO:0007829|PDB:3RN5"
FT STRAND 165..169
FT /evidence="ECO:0007829|PDB:3RN5"
FT STRAND 172..182
FT /evidence="ECO:0007829|PDB:3RN5"
FT STRAND 187..192
FT /evidence="ECO:0007829|PDB:3RN5"
FT HELIX 195..199
FT /evidence="ECO:0007829|PDB:3RN5"
FT STRAND 206..214
FT /evidence="ECO:0007829|PDB:3RN5"
FT STRAND 219..221
FT /evidence="ECO:0007829|PDB:3RN5"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:3RN5"
FT HELIX 240..247
FT /evidence="ECO:0007829|PDB:3RN5"
FT HELIX 252..256
FT /evidence="ECO:0007829|PDB:3RN5"
FT STRAND 263..275
FT /evidence="ECO:0007829|PDB:3RN5"
FT STRAND 277..286
FT /evidence="ECO:0007829|PDB:3RN5"
FT STRAND 289..296
FT /evidence="ECO:0007829|PDB:3RN5"
FT HELIX 300..302
FT /evidence="ECO:0007829|PDB:3RN5"
FT STRAND 309..319
FT /evidence="ECO:0007829|PDB:3RN5"
FT STRAND 321..327
FT /evidence="ECO:0007829|PDB:3RN5"
FT STRAND 333..337
FT /evidence="ECO:0007829|PDB:3RN5"
SQ SEQUENCE 343 AA; 38954 MW; 92EC418AB28CE1E6 CRC64;
MESKYKEILL LTGLDNITDE ELDRFKFFLS DEFNIATGKL HTANRIQVAT LMIQNAGAVS
AVMKTIRIFQ KLNYMLLAKR LQEEKEKVDK QYKSVTKPKP LSQAEMSPAA SAAIRNDVAK
QRAAPKVSPH VKPEQKQMVA QQESIREGFQ KRCLPVMVLK AKKPFTFETQ EGKQEMFHAT
VATEKEFFFV KVFNTLLKDK FIPKRIIIIA RYYRHSGFLE VNSASRVLDA ESDQKVNVPL
NIIRKAGETP KINTLQTQPL GTIVNGLFVV QKVTEKKKNI LFDLSDNTGK MEVLGVRNED
TMKCKEGDKV RLTFFTLSKN GEKLQLTSGV HSTIKVIKAK KKT
