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 09-APR-2025, entry version 217.
DE RecName: Full=MHC class II transactivator {ECO:0000305};
DE Short=CIITA {ECO:0000305};
DE EC=2.3.1.- {ECO:0000269|PubMed:11172716};
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), FUNCTION, VARIANTS MHC2D1 LYS-120
RP DELINS ILE-GLU AND 940-THR--ALA-963 DEL, AND VARIANTS GLY-174; ALA-500 AND
RP 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), FUNCTION, VARIANTS MHC2D1
RP LYS-120 DELINS ILE-GLU; GLY-174; ALA-500 AND ARG-900, AND ALTERNATIVE
RP 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), FUNCTION (ISOFORM 3), VARIANT
RP ARG-900, AND ALTERNATIVE 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, SUBCELLULAR LOCATION, GTP-BINDING, AND
RP 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 MHC2D1 SER-962, AND INVOLVEMENT IN MHC2D1.
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 MHC2D1 PRO-469, AND INVOLVEMENT IN MHC2D1.
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 MHC2D1 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 (PubMed:16600381,
CC PubMed:17493635, PubMed:7749984, PubMed:8402893). Does not bind DNA
CC (PubMed:16600381, PubMed:17493635, PubMed:7749984, PubMed:8402893). May
CC act in a coactivator-like fashion through protein-protein interactions
CC by contacting factors binding to the proximal MHC class II promoter, to
CC elements of the transcription machinery, or both PubMed:8402893,
CC PubMed:7749984, (PubMed:16600381, PubMed:17493635). Alternatively it
CC may activate HLA class II transcription by modifying proteins that bind
CC to the MHC class II promoter (PubMed:16600381, PubMed:17493635,
CC PubMed:7749984, PubMed:8402893). Also mediates enhanced MHC class I
CC transcription; the promoter element requirements for CIITA-mediated
CC transcription are distinct from those of constitutive MHC class I
CC transcription, and CIITA can functionally replace TAF1 at these genes.
CC Activates CD74 transcription (PubMed:32855215). Exhibits intrinsic GTP-
CC stimulated acetyltransferase activity (PubMed:11172716). Exhibits
CC serine/threonine protein kinase activity: can phosphorylate the TFIID
CC component TAF7, the RAP74 subunit of the general transcription factor
CC TFIIF, histone H2B at 'Ser-37' and other histones (in vitro)
CC (PubMed:24036077). Has antiviral activity against Ebola virus and
CC coronaviruses, including SARS-CoV-2 (PubMed:32855215). Induces
CC resistance by up-regulation of the p41 isoform of CD74, which blocks
CC cathepsin-mediated cleavage of viral glycoproteins, thereby preventing
CC viral fusion (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 ECO:0000269|PubMed:7749984, ECO:0000269|PubMed:8402893}.
CC -!- FUNCTION: [Isoform 3]: Exhibits dominant-negative suppression of MHC
CC class II gene expression. {ECO:0000269|PubMed:12919287}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP +
CC H(+); 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=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] +
CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC 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:11172716,
CC ECO:0000269|PubMed:23007646}. Nucleus, PML body
CC {ECO:0000269|PubMed:23007646}. Note=Recruited to PML body by PML.
CC {ECO:0000269|PubMed:23007646}.
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. {ECO:0000269|PubMed:11172716}.
CC -!- DOMAIN: The GTP-binding motif doesn't confer GTPase activity but
CC promotes nuclear localization. {ECO:0000269|PubMed:11172716}.
CC -!- PTM: Autophosphorylated, affecting interaction with TAF7.
CC {ECO:0000269|PubMed:24036077}.
CC -!- DISEASE: MHC class II deficiency 1 (MHC2D1) [MIM:209920]: An autosomal
CC recessive immunologic disorder characterized by the loss of expression
CC of MHC class II antigens on antigen-presenting cells. Affected
CC individuals present in early infancy with severe recurrent bacterial,
CC viral, fungal and parasitic infections, usually affecting the
CC gastrointestinal and respiratory tracts. {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 -!- WEB RESOURCE: Name=CIITAbase; Note=CIITA mutation db;
CC URL="https://databases.lovd.nl/shared/genes/CIITA";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/260/MHC2TA";
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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_001286403.2. [P33076-3]
DR AlphaFoldDB; P33076; -.
DR SMR; P33076; -.
DR BioGRID; 110416; 39.
DR ELM; P33076; -.
DR IntAct; P33076; 4.
DR STRING; 9606.ENSP00000485010; -.
DR GlyGen; P33076; 5 sites, 1 O-linked glycan (5 sites).
DR iPTMnet; P33076; -.
DR PhosphoSitePlus; P33076; -.
DR BioMuta; CIITA; -.
DR DMDM; 317373472; -.
DR jPOST; P33076; -.
DR MassIVE; P33076; -.
DR PaxDb; 9606-ENSP00000485010; -.
DR PeptideAtlas; P33076; -.
DR ProteomicsDB; 20081; -.
DR ProteomicsDB; 54897; -. [P33076-1]
DR Antibodypedia; 4234; 226 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; 120976at2759; -.
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 CD-CODE; B5B9A610; PML body.
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 129 other cell types or 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:0004676; F:3-phosphoinositide-dependent protein kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0004679; F:AMP-activated protein kinase activity; IEA:UniProtKB-EC.
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:0004677; F:DNA-dependent protein kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004694; F:eukaryotic translation initiation factor 2alpha kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0044024; F:histone H2AS1 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0072371; F:histone H2AS121 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:1990244; F:histone H2AT120 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0035979; F:histone H2AXS139 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0044025; F:histone H2BS14 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0140823; F:histone H2BS36 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0035175; F:histone H3S10 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0044022; F:histone H3S28 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0140855; F:histone H3S57 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0035402; F:histone H3T11 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0072354; F:histone H3T3 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0140857; F:histone H3T45 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0035403; F:histone H3T6 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0044023; F:histone H4S1 kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR GO; GO:0072518; F:Rho-dependent protein serine/threonine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004711; F:ribosomal protein S6 kinase activity; IEA:UniProtKB-EC.
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:0046597; P:host-mediated suppression of symbiont invasion; IDA:UniProtKB.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
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: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 FunFam; 3.40.50.300:FF:001028; Class II major histocompatibility complex transactivator; 1.
DR FunFam; 3.80.10.10:FF:000157; Class II major histocompatibility complex transactivator; 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; 2.
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; Proteomics identification;
KW Reference proteome; Repeat; SCID; Transcription; Transcription regulation;
KW 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 /evidence="ECO:0000269|PubMed:11172716"
FT REGION 269..303
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 420..427
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:11172716"
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 MHC2D1)"
FT /evidence="ECO:0000269|PubMed:7749984,
FT ECO:0000269|PubMed:8402893"
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 MHC2D1; mild immunodeficiency; has
FT residual 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 MHC2D1)"
FT /evidence="ECO:0000269|PubMed:8402893"
FT /id="VAR_005129"
FT VARIANT 962
FT /note="F -> S (in MHC2D1)"
FT /evidence="ECO:0000269|PubMed:10501838"
FT /id="VAR_015553"
FT VARIANT 964..991
FT /note="Missing (in MHC2D1)"
FT /id="VAR_015554"
FT VARIANT 1027
FT /note="Missing (in MHC2D1)"
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
//