ID C2TA_HUMAN Reviewed; 1130 AA. AC P33076; A0N0N9; D3DUG0; E9PFE0; Q29675; Q8SNB8; Q96KL4; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 3. DT 28-JUN-2023, entry version 208. DE RecName: Full=MHC class II transactivator {ECO:0000305}; DE Short=CIITA {ECO:0000305}; DE EC=2.3.1.- {ECO:0000269|PubMed:24036077}; DE EC=2.7.11.1 {ECO:0000269|PubMed:24036077}; GN Name=CIITA {ECO:0000312|HGNC:HGNC:7067}; Synonyms=MHC2TA; 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] (ISOFORM 1), VARIANTS BLS2 LYS-120 DEL ILE-GLU RP INS AND 940-THR--ALA-963 DEL, AND VARIANTS GLY-174; ALA-500 AND ARG-900. RX PubMed=8402893; DOI=10.1016/s0092-8674(05)80090-x; RA Steimle V., Otten L.A., Zufferey M., Mach B.; RT "Complementation cloning of an MHC class II transactivator mutated in RT hereditary MHC class II deficiency (or bare lymphocyte syndrome)."; RL Cell 75:135-146(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS BLS2 LYS-120 DEL RP ILE-GLU INS; GLY-174; ALA-500 AND ARG-900, AND ALTERNATIVE SPLICING. RX PubMed=7749984; DOI=10.1016/1074-7613(95)90033-0; RA Riley J.L., Westerheide S.D., Price J.A., Brown J.A., Boss J.M.; RT "Activation of class II MHC genes requires both the X box region and the RT class II transactivator (CIITA)."; RL Immunity 2:533-543(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), VARIANT ARG-900, AND ALTERNATIVE RP SPLICING. RX PubMed=12919287; DOI=10.1046/j.1365-2370.2003.00397.x; RA Quinn G., Bower R., Dos-Santos Cruz G., Giovino M., Xu Y., Patience C., RA Schuurman H.J.; RT "Structural and functional characteristics of a dominant-negative isoform RT of porcine MHC class II transactivator."; RL Eur. J. Immunogenet. 30:259-270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), VARIANTS GLY-174 AND ALA-500, AND RP ALTERNATIVE SPLICING. RX PubMed=12859996; DOI=10.1016/s0145-2126(03)00072-9; RA Day N.E., Ugai H., Yokoyama K.K., Ichiki A.T.; RT "K-562 cells lack MHC class II expression due to an alternatively spliced RT CIITA transcript with a truncated coding region."; RL Leuk. Res. 27:1027-1038(2003). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-174 AND ARG-900. RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., RA Nickerson D.A.; RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP GTP-BINDING, AND MUTAGENESIS OF 420-GLY-LYS-421 AND ASP-561. RX PubMed=10464099; DOI=10.1126/science.285.5432.1402; RA Harton J.A., Cressman D.E., Chin K.C., Der C.J., Ting J.P.; RT "GTP binding by class II transactivator: role in nuclear import."; RL Science 285:1402-1405(1999). RN [9] RP FUNCTION AS ACETYLTRANSFERASE, GTP-BINDING, AND ACETYLTRANSFERASE REGION. RX PubMed=11172716; DOI=10.1016/s1097-2765(01)00159-9; RA Raval A., Howcroft T.K., Weissman J.D., Kirshner S., Zhu X.S., Yokoyama K., RA Ting J., Singer D.S.; RT "Transcriptional coactivator, CIITA, is an acetyltransferase that bypasses RT a promoter requirement for TAF(II)250."; RL Mol. Cell 7:105-115(2001). RN [10] RP FUNCTION, AND INTERACTION WITH ZXDA AND ZXDC. RX PubMed=17493635; DOI=10.1016/j.jmb.2007.04.033; RA Al-Kandari W., Koneni R., Navalgund V., Aleksandrova A., Jambunathan S., RA Fontes J.D.; RT "The zinc finger proteins ZXDA and ZXDC form a complex that binds CIITA and RT regulates MHC II gene transcription."; RL J. Mol. Biol. 369:1175-1187(2007). RN [11] RP FUNCTION, AND INTERACTION WITH ZXDC. RX PubMed=16600381; DOI=10.1016/j.molimm.2006.02.029; RA Al-Kandari W., Jambunathan S., Navalgund V., Koneni R., Freer M., RA Parimi N., Mudhasani R., Fontes J.D.; RT "ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene RT transcription."; RL Mol. Immunol. 44:311-321(2007). RN [12] RP INTERACTION WITH TAF7. RX PubMed=20937824; DOI=10.1074/jbc.m110.173864; RA Devaiah B.N., Lu H., Gegonne A., Sercan Z., Zhang H., Clifford R.J., RA Lee M.P., Singer D.S.; RT "Novel functions for TAF7, a regulator of TAF1-independent transcription."; RL J. Biol. Chem. 285:38772-38780(2010). RN [13] RP SUBCELLULAR LOCATION, AND INTERACTION WITH PML. RX PubMed=23007646; DOI=10.1083/jcb.201112015; RA Ulbricht T., Alzrigat M., Horch A., Reuter N., von Mikecz A., Steimle V., RA Schmitt E., Kraemer O.H., Stamminger T., Hemmerich P.; RT "PML promotes MHC class II gene expression by stabilizing the class II RT transactivator."; RL J. Cell Biol. 199:49-63(2012). RN [14] RP FUNCTION AS KINASE, CATALYTIC ACTIVITY, AND AUTOPHOSPHORYLATION. RX PubMed=24036077; DOI=10.1016/j.bbagrm.2013.09.001; RA Soe K.C., Devaiah B.N., Singer D.S.; RT "Transcriptional coactivator CIITA, a functional homolog of TAF1, has RT kinase activity."; RL Biochim. Biophys. Acta 1829:1184-1190(2013). RN [15] RP FUNCTION. RX PubMed=32855215; DOI=10.1126/science.abb3753; RA Bruchez A., Sha K., Johnson J., Chen L., Stefani C., McConnell H., RA Gaucherand L., Prins R., Matreyek K.A., Hume A.J., Muehlberger E., RA Schmidt E.V., Olinger G.G., Stuart L.M., Lacy-Hulbert A.; RT "MHC class II transactivator CIITA induces cell resistance to Ebola virus RT and SARS-like coronaviruses."; RL Science 370:241-247(2020). RN [16] RP VARIANT BLS2 GROUP A SER-962. RX PubMed=10501838; DOI=10.1007/s002510050579; RA Quan V., Towey M., Sacks S., Kelly A.P.; RT "Absence of MHC class II gene expression in a patient with a single amino RT acid substitution in the class II transactivator protein CIITA."; RL Immunogenetics 49:957-963(1999). RN [17] RP VARIANT BLS2 GROUP A PRO-469. RX PubMed=11466404; DOI=10.4049/jimmunol.167.3.1787; RA Wiszniewski W., Fondaneche M.-C., Le Deist F., Kanariou M., Selz F., RA Brousse N., Steimle V., Barbieri G., Alcaide-Loridan C., Charron D., RA Fischer A., Lisowska-Grospierre B.; RT "Mutation in the class II trans-activator leading to a mild RT immunodeficiency."; RL J. Immunol. 167:1787-1794(2001). RN [18] RP ERRATUM OF PUBMED:11466404. RA Wiszniewski W., Fondaneche M.-C., Le Deist F., Kanariou M., Selz F., RA Brousse N., Steimle V., Barbieri G., Alcaide-Loridan C., Charron D., RA Fischer A., Lisowska-Grospierre B.; RL J. Immunol. 169:607-607(2002). RN [19] RP VARIANTS BLS2 GROUP A 964-LEU--ASP-991 DEL AND ILE-1027 DEL. RX PubMed=11862382; DOI=10.1007/s00251-001-0395-7; RA Dziembowska M., Fondaneche M.-C., Vedrenne J., Barbieri G., Wiszniewski W., RA Picard C., Cant A.J., Steimle V., Charron D., Alcaide-Loridan C., RA Fischer A., Lisowska-Grospierre B.; RT "Three novel mutations of the CIITA gene in MHC class II-deficient patients RT with a severe immunodeficiency."; RL Immunogenetics 53:821-829(2002). CC -!- FUNCTION: Essential for transcriptional activity of the HLA class II CC promoter; activation is via the proximal promoter. No DNA binding of in CC vitro translated CIITA was detected. May act in a coactivator-like CC fashion through protein-protein interactions by contacting factors CC binding to the proximal MHC class II promoter, to elements of the CC transcription machinery, or both. Alternatively it may activate HLA CC class II transcription by modifying proteins that bind to the MHC class CC II promoter. Also mediates enhanced MHC class I transcription; the CC promoter element requirements for CIITA-mediated transcription are CC distinct from those of constitutive MHC class I transcription, and CC CIITA can functionally replace TAF1 at these genes. Activates CD74 CC transcription (PubMed:32855215). Exhibits intrinsic GTP-stimulated CC acetyltransferase activity. Exhibits serine/threonine protein kinase CC activity: can phosphorylate the TFIID component TAF7, the RAP74 subunit CC of the general transcription factor TFIIF, histone H2B at 'Ser-37' and CC other histones (in vitro). Has antiviral activity against Ebola virus CC and coronaviruses, including SARS-CoV-2. Induces resistance by up- CC regulation of the p41 isoform of CD74, which blocks cathepsin-mediated CC cleavage of viral glycoproteins, thereby preventing viral fusion CC (PubMed:32855215). {ECO:0000269|PubMed:11172716, CC ECO:0000269|PubMed:16600381, ECO:0000269|PubMed:17493635, CC ECO:0000269|PubMed:24036077, ECO:0000269|PubMed:32855215}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:24036077}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:24036077}; CC -!- SUBUNIT: Interacts with ZXDA and ZXDC (PubMed:17493635). Interacts with CC PML (isoform PML-2) (PubMed:23007646). Interacts with TAF7; interaction CC inhibits CIITA acetyltransferase activity, thereby repressing CC transcription (PubMed:20937824). {ECO:0000269|PubMed:17493635, CC ECO:0000269|PubMed:20937824, ECO:0000269|PubMed:23007646}. CC -!- INTERACTION: CC P33076; P48382: RFX5; NbExp=2; IntAct=EBI-1538819, EBI-923266; CC P33076; Q96EB6: SIRT1; NbExp=4; IntAct=EBI-1538819, EBI-1802965; CC P33076; P98168: ZXDA; NbExp=4; IntAct=EBI-1538819, EBI-1538980; CC P33076; Q2QGD7: ZXDC; NbExp=6; IntAct=EBI-1538819, EBI-1538838; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23007646}. Nucleus, CC PML body {ECO:0000269|PubMed:23007646}. Note=Recruited to PML body by CC PML. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=P33076-1; Sequence=Displayed; CC Name=2; CC IsoId=P33076-2; Sequence=VSP_055099, VSP_055102, VSP_055103; CC Name=3; Synonyms=hCIITA'; CC IsoId=P33076-3; Sequence=VSP_055099, VSP_055100, VSP_055101; CC Name=4; CC IsoId=P33076-4; Sequence=VSP_055102, VSP_055103; CC -!- DOMAIN: The acetyltransferase domain is necessary for activation of CC both class I and class II transcription. CC -!- DOMAIN: The GTP-binding motif doesn't confer GTPase activity but CC promotes nuclear localization. CC -!- PTM: Autophosphorylated, affecting interaction with TAF7. CC -!- DISEASE: Bare lymphocyte syndrome 2 (BLS2) [MIM:209920]: A severe CC combined immunodeficiency disease with early onset. It is characterized CC by a profound defect in constitutive and interferon-gamma induced MHC CC II expression, absence of cellular and humoral T-cell response to CC antigen challenge, hypogammaglobulinemia and impaired antibody CC production. The consequence include extreme susceptibility to viral, CC bacterial and fungal infections. {ECO:0000269|PubMed:10501838, CC ECO:0000269|PubMed:11466404, ECO:0000269|PubMed:11862382, CC ECO:0000269|PubMed:7749984, ECO:0000269|PubMed:8402893}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 3]: Exhibits dominant-negative suppression of CC MHC class II gene expression. {ECO:0000305}. CC -!- WEB RESOURCE: Name=CIITAbase; Note=CIITA mutation db; CC URL="http://structure.bmc.lu.se/idbase/CIITAbase/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/260/MHC2TA"; 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; X74301; CAA52354.1; -; mRNA. DR EMBL; U18259; AAA88861.1; -; mRNA. DR EMBL; U18288; AAA88862.1; -; mRNA. DR EMBL; AY084054; AAM15723.1; -; mRNA. DR EMBL; AF410154; AAL04118.1; -; mRNA. DR EMBL; EF064747; ABK41930.1; -; Genomic_DNA. DR EMBL; AC133065; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471112; EAW85169.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85172.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85173.1; -; Genomic_DNA. DR CCDS; CCDS10544.1; -. [P33076-1] DR CCDS; CCDS66943.1; -. [P33076-3] DR PIR; A48843; A48843. DR RefSeq; NP_000237.2; NM_000246.3. DR RefSeq; NP_001273332.1; NM_001286403.1. [P33076-3] DR AlphaFoldDB; P33076; -. DR SMR; P33076; -. DR BioGRID; 110416; 31. DR ELM; P33076; -. DR IntAct; P33076; 4. DR STRING; 9606.ENSP00000485010; -. DR GlyGen; P33076; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P33076; -. DR PhosphoSitePlus; P33076; -. DR BioMuta; CIITA; -. DR DMDM; 317373472; -. DR jPOST; P33076; -. DR MassIVE; P33076; -. DR MaxQB; P33076; -. DR PaxDb; P33076; -. DR PeptideAtlas; P33076; -. DR ProteomicsDB; 20081; -. DR ProteomicsDB; 54897; -. [P33076-1] DR Antibodypedia; 4234; 217 antibodies from 35 providers. DR DNASU; 4261; -. DR Ensembl; ENST00000381835.9; ENSP00000371257.5; ENSG00000179583.21. [P33076-3] DR GeneID; 4261; -. DR KEGG; hsa:4261; -. DR UCSC; uc002dak.5; human. [P33076-1] DR AGR; HGNC:7067; -. DR CTD; 4261; -. DR DisGeNET; 4261; -. DR GeneCards; CIITA; -. DR HGNC; HGNC:7067; CIITA. DR HPA; ENSG00000179583; Tissue enhanced (lymphoid). DR MalaCards; CIITA; -. DR MIM; 209920; phenotype. DR MIM; 600005; gene. DR neXtProt; NX_P33076; -. DR OpenTargets; ENSG00000179583; -. DR Orphanet; 572; Immunodeficiency by defective expression of MHC class II. DR PharmGKB; PA30795; -. DR VEuPathDB; HostDB:ENSG00000179583; -. DR eggNOG; KOG4308; Eukaryota. DR GeneTree; ENSGT00940000161578; -. DR HOGENOM; CLU_498699_0_0_1; -. DR InParanoid; P33076; -. DR OrthoDB; 5311112at2759; -. DR PhylomeDB; P33076; -. DR TreeFam; TF352118; -. DR PathwayCommons; P33076; -. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR SignaLink; P33076; -. DR SIGNOR; P33076; -. DR BioGRID-ORCS; 4261; 17 hits in 1148 CRISPR screens. DR ChiTaRS; CIITA; human. DR GeneWiki; CIITA; -. DR GenomeRNAi; 4261; -. DR Pharos; P33076; Tbio. DR PRO; PR:P33076; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; P33076; protein. DR Bgee; ENSG00000179583; Expressed in monocyte and 127 other tissues. DR ExpressionAtlas; P33076; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:BHF-UCL. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL. DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central. DR GO; GO:0032966; P:negative regulation of collagen biosynthetic process; IC:BHF-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0046597; P:negative regulation of viral entry into host cell; IDA:UniProtKB. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0045345; P:positive regulation of MHC class I biosynthetic process; IDA:BHF-UCL. DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; IBA:GO_Central. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0046677; P:response to antibiotic; IDA:MGI. DR GO; GO:0034341; P:response to type II interferon; IDA:UniProtKB. DR CDD; cd00116; LRR_RI; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR008095; MHC_II_transact. DR InterPro; IPR007111; NACHT_NTPase. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR47189; MHC CLASS II TRANSACTIVATOR; 1. DR PANTHER; PTHR47189:SF1; MHC CLASS II TRANSACTIVATOR; 1. DR Pfam; PF13516; LRR_6; 3. DR Pfam; PF05729; NACHT; 1. DR PRINTS; PR01719; MHCIIACTVATR. DR SMART; SM00368; LRR_RI; 4. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF52047; RNI-like; 1. DR PROSITE; PS51450; LRR; 4. DR PROSITE; PS50837; NACHT; 1. PE 1: Evidence at protein level; KW Activator; Acyltransferase; Alternative splicing; ATP-binding; KW Disease variant; GTP-binding; Kinase; Leucine-rich repeat; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW SCID; Transcription; Transcription regulation; Transferase. FT CHAIN 1..1130 FT /note="MHC class II transactivator" FT /id="PRO_0000089241" FT DOMAIN 414..724 FT /note="NACHT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136" FT REPEAT 985..1008 FT /note="LRR 1" FT REPEAT 1016..1037 FT /note="LRR 2" FT REPEAT 1045..1066 FT /note="LRR 3" FT REPEAT 1073..1093 FT /note="LRR 4" FT REGION 94..132 FT /note="Required for acetyltransferase activity" FT REGION 269..303 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 280..294 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 420..427 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT VAR_SEQ 161..210 FT /note="AEPPTVVTGSLLVRPVSDCSTLPCLPLPALFNQEPASGQMRLEKTDQIPM FT -> V (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:12919287, FT ECO:0000303|PubMed:7749984" FT /id="VSP_055099" FT VAR_SEQ 336..350 FT /note="EPVEQFYRSLQDTYG -> GLAWSPCLGLRPSLH (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12919287" FT /id="VSP_055100" FT VAR_SEQ 351..885 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12919287" FT /id="VSP_055101" FT VAR_SEQ 887..930 FT /note="AALSDTVALWESLQQHGETKLLQAAEEKFTIEPFKAKSLKDVED -> WGEG FT LGRDILVLGINCGLGAKPSALWGPFSMQSSRVGQNGFSPF (in isoform 2 and FT isoform 4)" FT /evidence="ECO:0000303|PubMed:12859996, FT ECO:0000303|PubMed:7749984" FT /id="VSP_055102" FT VAR_SEQ 931..1128 FT /note="Missing (in isoform 2 and isoform 4)" FT /evidence="ECO:0000303|PubMed:12859996, FT ECO:0000303|PubMed:7749984" FT /id="VSP_055103" FT VARIANT 45 FT /note="L -> V (in dbSNP:rs2229317)" FT /id="VAR_029270" FT VARIANT 120 FT /note="K -> IE (in BLS2)" FT /id="VAR_005127" FT VARIANT 174 FT /note="R -> G (in dbSNP:rs8046121)" FT /evidence="ECO:0000269|PubMed:12859996, FT ECO:0000269|PubMed:7749984, ECO:0000269|PubMed:8402893, FT ECO:0000269|Ref.5" FT /id="VAR_047907" FT VARIANT 469 FT /note="L -> P (in BLS2; mild immunodeficiency; has residual FT MHC class II trans activation activity)" FT /evidence="ECO:0000269|PubMed:11466404" FT /id="VAR_015551" FT VARIANT 500 FT /note="G -> A (in dbSNP:rs4774)" FT /evidence="ECO:0000269|PubMed:12859996, FT ECO:0000269|PubMed:7749984, ECO:0000269|PubMed:8402893" FT /id="VAR_005128" FT VARIANT 658 FT /note="A -> G (in dbSNP:rs2229319)" FT /id="VAR_015552" FT VARIANT 781 FT /note="S -> L (in dbSNP:rs13330686)" FT /id="VAR_060104" FT VARIANT 782 FT /note="V -> A (in dbSNP:rs13336804)" FT /id="VAR_057711" FT VARIANT 900 FT /note="Q -> R (in dbSNP:rs7197779)" FT /evidence="ECO:0000269|PubMed:12919287, FT ECO:0000269|PubMed:7749984, ECO:0000269|PubMed:8402893, FT ECO:0000269|Ref.5" FT /id="VAR_047908" FT VARIANT 940..963 FT /note="Missing (in BLS2)" FT /evidence="ECO:0000269|PubMed:8402893" FT /id="VAR_005129" FT VARIANT 962 FT /note="F -> S (in BLS2)" FT /evidence="ECO:0000269|PubMed:10501838" FT /id="VAR_015553" FT VARIANT 964..991 FT /note="Missing (in BLS2)" FT /id="VAR_015554" FT VARIANT 1027 FT /note="Missing (in BLS2)" FT /evidence="ECO:0000269|PubMed:11862382" FT /id="VAR_015555" FT MUTAGEN 420..421 FT /note="Missing: Strongly reduces GTP-binding and abolishes FT transactivation at MHC promoters." FT /evidence="ECO:0000269|PubMed:10464099" FT MUTAGEN 561 FT /note="D->A: Strongly reduces GTP-binding and abolishes FT transactivation at MHC promoters." FT /evidence="ECO:0000269|PubMed:10464099" FT CONFLICT 1020..1021 FT /note="LN -> RS (in Ref. 4; ABK41930)" FT /evidence="ECO:0000305" SQ SEQUENCE 1130 AA; 123514 MW; 7A61CAA4F3FFECE0 CRC64; MRCLAPRPAG SYLSEPQGSS QCATMELGPL EGGYLELLNS DADPLCLYHF YDQMDLAGEE EIELYSEPDT DTINCDQFSR LLCDMEGDEE TREAYANIAE LDQYVFQDSQ LEGLSKDIFK HIGPDEVIGE SMEMPAEVGQ KSQKRPFPEE LPADLKHWKP AEPPTVVTGS LLVRPVSDCS TLPCLPLPAL FNQEPASGQM RLEKTDQIPM PFSSSSLSCL NLPEGPIQFV PTISTLPHGL WQISEAGTGV SSIFIYHGEV PQASQVPPPS GFTVHGLPTS PDRPGSTSPF APSATDLPSM PEPALTSRAN MTEHKTSPTQ CPAAGEVSNK LPKWPEPVEQ FYRSLQDTYG AEPAGPDGIL VEVDLVQARL ERSSSKSLER ELATPDWAER QLAQGGLAEV LLAAKEHRRP RETRVIAVLG KAGQGKSYWA GAVSRAWACG RLPQYDFVFS VPCHCLNRPG DAYGLQDLLF SLGPQPLVAA DEVFSHILKR PDRVLLILDG FEELEAQDGF LHSTCGPAPA EPCSLRGLLA GLFQKKLLRG CTLLLTARPR GRLVQSLSKA DALFELSGFS MEQAQAYVMR YFESSGMTEH QDRALTLLRD RPLLLSHSHS PTLCRAVCQL SEALLELGED AKLPSTLTGL YVGLLGRAAL DSPPGALAEL AKLAWELGRR HQSTLQEDQF PSADVRTWAM AKGLVQHPPR AAESELAFPS FLLQCFLGAL WLALSGEIKD KELPQYLALT PRKKRPYDNW LEGVPRFLAG LIFQPPARCL GALLGPSAAA SVDRKQKVLA RYLKRLQPGT LRARQLLELL HCAHEAEEAG IWQHVVQELP GRLSFLGTRL TPPDAHVLGK ALEAAGQDFS LDLRSTGICP SGLGSLVGLS CVTRFRAALS DTVALWESLQ QHGETKLLQA AEEKFTIEPF KAKSLKDVED LGKLVQTQRT RSSSEDTAGE LPAVRDLKKL EFALGPVSGP QAFPKLVRIL TAFSSLQHLD LDALSENKIG DEGVSQLSAT FPQLKSLETL NLSQNNITDL GAYKLAEALP SLAASLLRLS LYNNCICDVG AESLARVLPD MVSLRVMDVQ YNKFTAAGAQ QLAASLRRCP HVETLAMWTP TIPFSVQEHL QQQDSRISLR //