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 27-MAR-2024, entry version 170. 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. RX PubMed=8454910; DOI=10.1089/jir.1993.13.43; RA Choubey D., Lengyel P.; RT "Interferon action: cytoplasmic and nuclear localization of the interferon- RT inducible 52-kD protein that is encoded by the Ifi 200 gene from the gene RT 200 cluster."; RL J. Interferon Res. 13:43-52(1993). RN [6] 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 [7] RP FUNCTION, AND ACTIVITY REGULATION. 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 [8] 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 [9] 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 [10] RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, INTERACTION WITH RP PYCARD, AND 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 [11] RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, DNA-BINDING, AND RP 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] RP SUBCELLULAR LOCATION, AND 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 [17] RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF 10-LEU-LEU-11; RP 19-ASP--ASP-23; THR-50; GLU-147; PHE-167; LYS-173; GLN-258 AND LYS-272. RX PubMed=26197926; DOI=10.1038/ncomms8827; RA Morrone S.R., Matyszewski M., Yu X., Delannoy M., Egelman E.H., Sohn J.; RT "Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a RT polymerization template for downstream ASC."; RL Nat. Commun. 6:7827-7827(2015). RN [18] RP ACTIVITY REGULATION, AND INTERACTION WITH TRIM11. RX PubMed=27498865; DOI=10.1016/j.celrep.2016.07.019; RA Liu T., Tang Q., Liu K., Xie W., Liu X., Wang H., Wang R.F., Cui J.; RT "TRIM11 suppresses AIM2 inflammasome by degrading AIM2 via p62-dependent RT selective autophagy."; RL Cell Rep. 16:1988-2002(2016). RN [19] RP INTERACTION WITH IFI16-BETA, AND ACTIVITY REGULATION. RX PubMed=30104205; DOI=10.15252/embr.201845737; RA Wang P.H., Ye Z.W., Deng J.J., Siu K.L., Gao W.W., Chaudhary V., Cheng Y., RA Fung S.Y., Yuen K.S., Ho T.H., Chan C.P., Zhang Y., Kok K.H., Yang W., RA Chan C.P., Jin D.Y.; RT "Inhibition of AIM2 inflammasome activation by a novel transcript isoform RT of IFI16."; RL EMBO Rep. 19:0-0(2018). RN [20] RP FUNCTION, ACTIVITY REGULATION, AND INTERACTION WITH PYCARD. RX PubMed=29440442; DOI=10.1073/pnas.1712860115; RA Matyszewski M., Morrone S.R., Sohn J.; RT "Digital signaling network drives the assembly of the AIM2-ASC RT inflammasome."; RL Proc. Natl. Acad. Sci. U.S.A. 115:E1963-E1972(2018). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HUMAN HERPES VIRUS 8 RP PROTEIN SOX/ORF37 (MICROBIAL INFECTION), AND SUBUNIT. RX PubMed=37364111; DOI=10.1073/pnas.2300204120; RA Zhang X., Lan Q., Zhang M., Wang F., Shi K., Li X., Kuang E.; RT "Inhibition of AIM2 inflammasome activation by SOX/ORF37 promotes lytic RT replication of Kaposi's sarcoma-associated herpesvirus."; RL Proc. Natl. Acad. Sci. U.S.A. 120:e2300204120-e2300204120(2023). RN [22] 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). RN [23] {ECO:0007744|PDB:3VD8} RP X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) OF 1-107, FUNCTION, INTERACTION WITH RP PYCARD, AND MUTAGENESIS OF 19-ASP--ASP-23 AND 27-PHE-PHE-28. RX PubMed=23530044; DOI=10.1074/jbc.m113.468033; RA Jin T., Perry A., Smith P., Jiang J., Xiao T.S.; RT "Structure of the absent in melanoma 2 (AIM2) pyrin domain provides RT insights into the mechanisms of AIM2 autoinhibition and inflammasome RT assembly."; RL J. Biol. Chem. 288:13225-13235(2013). RN [24] {ECO:0007744|PDB:4O7Q} RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 1-93, SUBUNIT, AND MUTAGENESIS OF RP PHE-27. RX PubMed=24406744; DOI=10.1016/j.jmb.2013.12.029; RA Lu A., Kabaleeswaran V., Fu T., Magupalli V.G., Wu H.; RT "Crystal structure of the F27G AIM2 PYD mutant and similarities of its RT self-association to DED/DED interactions."; RL J. Mol. Biol. 426:1420-1427(2014). RN [25] {ECO:0007744|PDB:6MB2} RP STRUCTURE BY ELECTRON MICROSCOPY (5.00 ANGSTROMS) OF 1-93, FUNCTION, AND RP SUBUNIT. RX PubMed=26583071; DOI=10.1038/celldisc.2015.13; RA Lu A., Li Y., Yin Q., Ruan J., Yu X., Egelman E., Wu H.; RT "Plasticity in PYD assembly revealed by cryo-EM structure of the PYD RT filament of AIM2."; RL Cell Discov. 1:15013-15013(2015). RN [26] {ECO:0007744|PDB:7K3R} RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) OF 1-117, FUNCTION, RP ACTIVITY REGULATION, INTERACTION WITH PYCARD, AND MUTAGENESIS OF LEU-11; RP GLU-21; ASP-23; ALA-36; ILE-46; ASN-73 AND MET-75. RX PubMed=33980849; DOI=10.1038/s41467-021-23045-8; RA Matyszewski M., Zheng W., Lueck J., Mazanek Z., Mohideen N., Lau A.Y., RA Egelman E.H., Sohn J.; RT "Distinct axial and lateral interactions within homologous filaments RT dictate the signaling specificity and order of the AIM2-ASC inflammasome."; RL Nat. Commun. 12:2735-2735(2021). CC -!- FUNCTION: Sensor component of the AIM2 inflammasome, which mediates CC inflammasome activation in response to the presence of double-stranded CC DNA (dsDNA) in the cytosol, leading to subsequent pyroptosis CC (PubMed:17726700, PubMed:19158675, PubMed:19158676, PubMed:19158679, CC PubMed:20566831, PubMed:26197926, PubMed:29440442, PubMed:23530044, CC PubMed:26583071, PubMed:33980849, PubMed:37364111). Inflammasomes are CC supramolecular complexes that assemble in the cytosol in response to CC pathogens and other damage-associated signals and play critical roles CC in innate immunity and inflammation (PubMed:17726700, PubMed:19158675, CC PubMed:19158676, PubMed:19158679, PubMed:20566831, PubMed:26197926, CC PubMed:29440442, PubMed:33980849). Acts as a recognition receptor CC (PRR): specifically recognizes and binds dsDNA in the cytosol, and CC mediates the formation of the inflammasome polymeric complex composed CC of AIM2, CASP1 and PYCARD/ASC (PubMed:17726700, PubMed:19158675, CC PubMed:19158676, PubMed:19158679, PubMed:20566831, PubMed:26197926, CC PubMed:29440442, PubMed:33980849). Recruitment of pro-caspase-1 CC (proCASP1) to the AIM2 inflammasome promotes caspase-1 (CASP1) CC activation, which subsequently cleaves and activates inflammatory CC cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine CC secretion (PubMed:17726700, PubMed:19158675, PubMed:19158676, CC PubMed:19158679, PubMed:20566831). In some cells, CASP1 activation CC mediates cleavage and activation of GSDMD, triggering pyroptosis CC without promoting cytokine secretion (PubMed:19158675, CC PubMed:19158676). Detects cytosolic dsDNA of viral and bacterial origin CC in a non-sequence-specific manner (PubMed:17726700, PubMed:19158675, CC PubMed:19158676, PubMed:19158679, PubMed:20566831, PubMed:26197926, CC PubMed:29440442, PubMed:26583071, PubMed:33980849). Involved in the DNA CC damage response caused by acute ionizing radiation by mediating CC pyroptosis of intestinal epithelial cells and bone marrow cells in CC response to double-strand DNA breaks (By similarity). Mechanistically, CC AIM2 senses DNA damage in the nucleus to mediate inflammasome assembly CC and inflammatory cell death (By similarity). Also acts as a regulator CC of neurodevelopment via its role in the DNA damage response: acts by CC promoting neural cell death in response to DNA damage in the developing CC brain, thereby purging genetically compromised cells of the central CC nervous system (By similarity). Pyroptosis mediated by the AIM2 CC inflammasome in response to DNA damage is dependent on GSDMD without CC involving IL1B and IL18 cytokine secretion (By similarity). Also acts CC as a 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/ASC- CC dependent, caspase-1-independent cell death that involves caspase-8 CC (CASP8) (By similarity). {ECO:0000250|UniProtKB:Q91VJ1, CC ECO:0000269|PubMed:17726700, ECO:0000269|PubMed:19158675, CC ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19158679, CC ECO:0000269|PubMed:20566831, ECO:0000269|PubMed:23530044, CC ECO:0000269|PubMed:26197926, ECO:0000269|PubMed:26583071, CC ECO:0000269|PubMed:29440442, ECO:0000269|PubMed:33980849, CC ECO:0000269|PubMed:37364111}. CC -!- FUNCTION: Also acts as a tumor suppressor independently of its role in CC inflammatory response (PubMed:16432157). Able to suppress overt cell CC proliferation in enterocytes: restricts stem cell proliferation in the CC intestinal mucosa in an inflammasome-independent manner, contributing CC to a decrease in the likelihood of colorectal cancer development (By CC similarity). AIM2 suppresses cell proliferation by inhibiting CC phosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and CC AKT-mTOR signaling pathway (By similarity). Inhibits AKT1 CC phosphorylation both by inhibiting the activity of PRKDC/DNA-PK kinase CC and promoting dephosphorylation by PP2A phosphatase (By similarity). CC Also acts as a key regulator of regulatory T-cells (Treg) homeostasis CC by promoting their stability: acts by preventing AKT1 activation (By CC similarity). Its role in Treg homeostasis is important to restain CC autoimmune diseases (By similarity). {ECO:0000250|UniProtKB:Q91VJ1, CC ECO:0000269|PubMed:16432157}. CC -!- ACTIVITY REGULATION: Inactive in absence of double-stranded DNA (dsDNA) CC (PubMed:26197926, PubMed:22483801). Homooligomerizes upon binding to CC dsDNA, dsDNA serving as an oligomerization platform (PubMed:26197926, CC PubMed:33980849). AIM2 requires large dsDNA to generate a structural CC template that couples dsDNA ligand-binding and homooligomerization CC (PubMed:26197926). Homooligomerization is followed by recruitment of CC PYCARD/ASC to initiate speck formation (nucleation) (PubMed:26197926, CC PubMed:29440442, PubMed:22483801, PubMed:33980849). AIM2 and PYCARD/ASC CC homooligomer filaments assemble bidirectionally and the recognition CC between AIM2 and PYCARD/ASC oligomers occurs in a head-to-tail manner CC (PubMed:33980849). Clustered PYCARD/ASC nucleates the formation of CC CASP1 filaments through the interaction of their respective CARD CC domains, acting as a platform for CASP1 polymerization and activation CC (PubMed:19158675, PubMed:19158676). Active CASP1 then specifically CC processes protein precursors, such as gasdermin-D (GSDMD), IL1B and CC IL18, leading to the release of mature cytokines in the extracellular CC milieu or pyroptosis, depending on cell type (PubMed:16432157, CC PubMed:19158676, PubMed:19158675). AIM2 can be activated in response to CC events that cause genomic DNA (HIV protease inhibitor nelfinavir) or CC mitochondrial DNA release in the cytoplasm (such as Perfluoroalkyl CC substance pollutants or cholesterol overload) (By similarity). CC Activation of the AIM2 inflammasome is inhibited by isoform IFI16-beta CC of IFI16, which prevents the interaction between AIM2 and PYCARD/ASC CC (PubMed:30104205). Activation of the AIM2 inflammasome is inhibited by CC TRIM11, which promotes autophagy-dependent degradation of AIM2 CC (PubMed:27498865). {ECO:0000250|UniProtKB:Q91VJ1, CC ECO:0000269|PubMed:16432157, ECO:0000269|PubMed:19158675, CC ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:22483801, CC ECO:0000269|PubMed:26197926, ECO:0000269|PubMed:27498865, CC ECO:0000269|PubMed:29440442, ECO:0000269|PubMed:30104205, CC ECO:0000269|PubMed:33980849}. CC -!- SUBUNIT: Self-associates; forms homooligomers in response to cytosolic CC double-stranded DNA (dsDNA) and the dsDNA seems to serve as CC oligomerization platform (PubMed:15582594, PubMed:19158676, CC PubMed:26197926, PubMed:29440442, PubMed:24406744, PubMed:26583071, CC PubMed:33980849). Component of AIM2 inflammasome, which consists of a CC signal sensor component (AIM2), an adapter (PYCARD/ASC), which recruits CC an effector pro-inflammatory caspase (CASP1) (PubMed:22869553, CC PubMed:22483801, PubMed:33980849). Interacts (via pyrin domain) with CC PYCARD/ASC (via pyrin domain); interaction is direct (PubMed:19158675, CC PubMed:19158679, PubMed:29440442, PubMed:23530044, PubMed:33980849). CC Component of the AIM2 PANoptosome complex, a multiprotein complex that CC drives inflammatory cell death (PANoptosis) (By similarity). Interacts CC with PYDC5; disrupts assembly of the AIM2 inflammasome complex CC (PubMed:24531343). Interacts with EIF2AK2/PKR (PubMed:22801494). CC Interacts with MAPRE1 (PubMed:22869553). Interacts with IFI16 CC (PubMed:22046441). Interacts with isoform IFI16-beta of IFI16; CC preventing the interaction between AIM2 and PYCARD/ASC CC (PubMed:30104205). Interacts with RACK1; promoting association with CC PP2A phosphatase and dephosphorylation of AKT1 (By similarity). CC Interacts with TRIM11; promoting AIM2 recruitment to autophagosomes and CC autophagy-dependent degradation (PubMed:27498865). CC {ECO:0000250|UniProtKB:Q91VJ1, ECO:0000269|PubMed:15582594, CC ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, CC ECO:0000269|PubMed:19158679, ECO:0000269|PubMed:22046441, CC ECO:0000269|PubMed:22483801, ECO:0000269|PubMed:22801494, CC ECO:0000269|PubMed:22869553, ECO:0000269|PubMed:23530044, CC ECO:0000269|PubMed:24406744, ECO:0000269|PubMed:24531343, CC ECO:0000269|PubMed:26197926, ECO:0000269|PubMed:26583071, CC ECO:0000269|PubMed:27498865, ECO:0000269|PubMed:29440442, CC ECO:0000269|PubMed:30104205, ECO:0000269|PubMed:33980849}. CC -!- SUBUNIT: (Microbial infection) Interacts with human herpesvirus 8 CC protein SOX/ORF37; this interaction inhibits AIM2 polymerization and CC subsequent inflammasome activation. {ECO:0000269|PubMed:37364111}. 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: Cytoplasm {ECO:0000269|PubMed:19158675, CC ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19158679, CC ECO:0000269|PubMed:24531343, ECO:0000269|PubMed:8454910}. Inflammasome CC {ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19158679}. Nucleus CC {ECO:0000269|PubMed:15582594}. Note=Activated inflammasomes can CC aggregate in the cytosol as speck-like particles (PubMed:19158679, CC PubMed:19158676, PubMed:19158675). Activated inflammasomes can also CC aggregate in the nucleus in response to DNA damage: AIM2 is recruited CC to double-strand DNA breaks and mediates activation of the AIM2 CC inflammasome (By similarity). {ECO:0000250|UniProtKB:Q91VJ1, CC ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, CC ECO:0000269|PubMed:19158679}. 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/ASC CC (PubMed:19158676, PubMed:19158675). {ECO:0000269|PubMed:19158675, CC ECO:0000269|PubMed:19158676}. CC -!- DOMAIN: The HIN-200 domain mediates dsDNA binding via electrostatic CC interactions. {ECO:0000269|PubMed:22483801}. CC -!- PTM: Degraded via selective autophagy following interaction with CC TRIM11. {ECO:0000269|PubMed:27498865}. CC -!- MISCELLANEOUS: Defects in AIM2 may be a cause of microsatellite CC unstable colon cancers. {ECO:0000269|PubMed:17726700}. CC -!- SIMILARITY: Belongs to the HIN-200 family. {ECO:0000305}. CC -!- CAUTION: According to a report, AIM2 is autoinhibited in absence of CC double-stranded DNA (dsDNA) due to an interaction between the pyrin and CC HIN-200 domains that induce a closed conformation (PubMed:22483801). CC However, it was later shown that AIM2 is not autoinhibited and that CC dsDNA acts as a molecular ruler to promote its homooligomerization CC (PubMed:26197926). {ECO:0000269|PubMed:22483801, CC ECO:0000269|PubMed:26197926}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH10940.1; Type=Frameshift; Evidence={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; 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 EMDB; EMD-22656; -. DR EMDB; EMD-9064; -. DR SMR; O14862; -. DR BioGRID; 114837; 113. 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; 9606-ENSP00000357112; -. DR PeptideAtlas; O14862; -. DR ProteomicsDB; 48275; -. DR Antibodypedia; 34257; 683 antibodies from 42 providers. DR DNASU; 9447; -. DR Ensembl; ENST00000368130.9; ENSP00000357112.4; ENSG00000163568.16. DR Ensembl; ENST00000411768.2; ENSP00000512039.1; ENSG00000163568.16. DR Ensembl; ENST00000695580.1; ENSP00000512040.1; ENSG00000163568.16. 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 AGR; HGNC:357; -. DR DisGeNET; 9447; -. DR GeneCards; AIM2; -. DR HGNC; HGNC:357; AIM2. DR HPA; ENSG00000163568; Tissue enhanced (intestine, lymphoid tissue). 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; 5264770at2759; -. 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; 15 hits in 1154 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 125 other cell types or tissues. DR ExpressionAtlas; O14862; baseline and differential. 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:0035861; C:site of double-strand break; ISS:UniProtKB. DR GO; GO:0140608; F:cysteine-type endopeptidase activator activity; IDA:UniProt. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0038187; F:pattern recognition receptor activity; IDA:UniProt. DR GO; GO:0035591; F:signaling adaptor activity; IDA:UniProtKB. DR GO; GO:0002218; P:activation of innate immune response; IDA:UniProtKB. DR GO; GO:0140970; P:AIM2 inflammasome complex assembly; IDA:UniProtKB. DR GO; GO:0007420; P:brain development; ISS:UniProtKB. 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; NAS:ComplexPortal. DR GO; GO:0006974; P:DNA damage response; ISS:UniProtKB. 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:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB. DR GO; GO:0070050; P:neuron cellular homeostasis; ISS:UniProtKB. DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; NAS: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; NAS: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:0050795; P:regulation of behavior; ISS:UniProtKB. DR GO; GO:0043029; P:T cell homeostasis; ISS:UniProtKB. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB. DR CDD; cd08305; Pyrin; 1. DR Gene3D; 1.10.533.10; Death Domain, Fas; 1. DR Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 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:SF17; INTERFERON-INDUCIBLE PROTEIN AIM2; 1. DR PANTHER; PTHR12200; INTERFERON-INDUCIBLE PROTEIN AIM2 FAMILY MEMBER; 1. DR Pfam; PF02760; HIN; 1. DR Pfam; PF02758; PYRIN; 1. DR SMART; SM01289; PYRIN; 1. DR SUPFAM; SSF47986; DEATH domain; 1. DR SUPFAM; SSF159141; HIN-2000 domain-like; 2. DR PROSITE; PS50824; DAPIN; 1. DR PROSITE; PS50834; HIN_200; 1. DR Genevisible; O14862; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; DNA damage; DNA-binding; Immunity; Inflammasome; 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 10..11 FT /note="LL->AA: Impaired double-stranded DNA FT (dsDNA)-binding, preventing homooligomerization." FT /evidence="ECO:0000269|PubMed:26197926" FT MUTAGEN 11 FT /note="L->A: Impaired homooligomerization." FT /evidence="ECO:0000269|PubMed:33980849" FT MUTAGEN 14 FT /note="L->A: Fails to activate interleukin-1 beta FT production." FT /evidence="ECO:0000269|PubMed:19158679" FT MUTAGEN 19..23 FT /note="DEELD->AAALA: In Mut2; abolished interaction with FT PYCARD/ASC. Abolished ability to bind double-stranded DNA FT (dsDNA)." FT /evidence="ECO:0000269|PubMed:23530044, FT ECO:0000269|PubMed:26197926" FT MUTAGEN 21 FT /note="E->K: Impaired ability to nucleate with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33980849" FT MUTAGEN 23 FT /note="D->K: Impaired homooligomerization." FT /evidence="ECO:0000269|PubMed:33980849" FT MUTAGEN 27..28 FT /note="FF->AA: In Mut1; abolished interaction with FT PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:23530044" FT MUTAGEN 27 FT /note="F->G: Abolished ability to homooligomerize." FT /evidence="ECO:0000269|PubMed:24406744" FT MUTAGEN 27 FT /note="F->L: Strongly impaired ability to homooligomerize." FT /evidence="ECO:0000269|PubMed:24406744" FT MUTAGEN 27 FT /note="F->W,Y: Impaired ability to homooligomerize." FT /evidence="ECO:0000269|PubMed:24406744" FT MUTAGEN 36 FT /note="A->R,D: Impaired homooligomerization." FT /evidence="ECO:0000269|PubMed:33980849" FT MUTAGEN 46 FT /note="I->D: Impaired homooligomerization." FT /evidence="ECO:0000269|PubMed:33980849" FT MUTAGEN 50 FT /note="T->A: Impaired double-stranded DNA (dsDNA)-binding, FT preventing homooligomerization." FT /evidence="ECO:0000269|PubMed:26197926" FT MUTAGEN 73 FT /note="N->L: Impaired ability to form AIM2 inflammasome FT filaments in response to double-stranded DNA (dsDNA)." FT /evidence="ECO:0000269|PubMed:33980849" FT MUTAGEN 75 FT /note="M->D: Impaired ability to nucleate with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33980849" FT MUTAGEN 147 FT /note="E->A: Strongly reduced ability to homooligomerize FT upon double-stranded DNA (dsDNA)-binding." FT /evidence="ECO:0000269|PubMed:26197926" FT MUTAGEN 160 FT /note="K->A: Impairs DNA binding; when associated with FT A-160; A-K162; A-163; A-198; A-204. Impairs DNA binding; FT when associated with A-160; A-162; A-163; A-198; A-204; FT A-244; 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 FT A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; FT when associated with A-160; A-162; A-163; A-198; A-204; FT A-244; 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 FT A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; FT when associated with A-160; A-162; A-163; A-198; A-204; FT A-244; 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 167 FT /note="F->A: Strongly reduced ability to homooligomerize FT upon double-stranded DNA (dsDNA)-binding." FT /evidence="ECO:0000269|PubMed:26197926" FT MUTAGEN 173 FT /note="K->A: Impaired double-stranded DNA (dsDNA)-binding, FT preventing homooligomerization." FT /evidence="ECO:0000269|PubMed:26197926" FT MUTAGEN 198 FT /note="K->A: Impairs DNA binding; when associated with FT A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; FT when associated with A-160; A-162; A-163; A-198; A-204; FT A-244; 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 FT A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; FT when associated with A-160; A-162; A-163; A-198; A-204; FT A-244; 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 FT A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; FT when associated with A-160; A-162; A-163; A-198; A-204; FT A-244; 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 FT A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; FT when associated with A-160; A-162; A-163; A-198; A-204; FT A-244; A-251; A-309; A-311; A-355 and A-337." FT /evidence="ECO:0000269|PubMed:22483801" FT MUTAGEN 258 FT /note="Q->A: Impaired double-stranded DNA (dsDNA)-binding, FT preventing homooligomerization." FT /evidence="ECO:0000269|PubMed:26197926" FT MUTAGEN 272 FT /note="K->A: Strongly reduced ability to homooligomerize FT upon double-stranded DNA (dsDNA)-binding." FT /evidence="ECO:0000269|PubMed:26197926" FT MUTAGEN 309 FT /note="K->A: Impairs DNA binding; when associated with FT A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; FT when associated with A-160; A-162; A-163; A-198; A-204; FT A-244; 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 FT A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; FT when associated with A-160; A-162; A-163; A-198; A-204; FT A-244; 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 FT A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; FT when associated with A-160; A-162; A-163; A-198; A-204; FT A-244; 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 FT A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; FT when associated with A-160; A-162; A-163; A-198; A-204; FT A-244; 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 //