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
//