C2TA_MOUSE
ID C2TA_MOUSE Reviewed; 1155 AA.
AC P79621; O46787; O78036; O78109; Q31115; Q9TPP1;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=MHC class II transactivator {ECO:0000305};
DE Short=CIITA;
DE EC=2.3.1.-;
DE EC=2.7.11.1;
GN Name=Ciita {ECO:0000312|MGI:MGI:108445}; Synonyms=C2ta, Mhc2ta;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3), TISSUE
RP SPECIFICITY, AND INDUCTION.
RC STRAIN=BALB/cJ;
RX PubMed=9184229; DOI=10.1093/emboj/16.10.2851;
RA Muhlethaler-Mottet A., Otten L.A., Steimle V., Mach B.;
RT "Expression of MHC class II molecules in different cellular and functional
RT compartments is controlled by differential usage of multiple promoters of
RT the transactivator CIITA.";
RL EMBO J. 16:2851-2860(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=NOD; TISSUE=Spleen;
RX PubMed=8995190; DOI=10.1007/s002510050193;
RA Sims T.N., Elliott J.F., Ramassar V., Denney D.W. Jr., Halloran P.F.;
RT "Mouse class II transactivator: cDNA sequence and amino acid comparison
RT with the human class II transactivator.";
RL Immunogenetics 45:220-222(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 955-1097.
RC STRAIN=BALB/cJ; TISSUE=Thymus;
RX PubMed=8620527; DOI=10.1007/s002620050258;
RA Panelli M.C., Wang E., Shen S., Schluter S.F., Bernstein R.M., Hersh E.M.,
RA Stopeck A., Gangavalli R., Barber J., Jolly D., Akporiaye E.T.;
RT "Interferon gamma (IFNgamma) gene transfer of an EMT6 tumor that is poorly
RT responsive to IFNgamma stimulation: increase in tumor immunogenicity is
RT accompanied by induction of a mouse class II transactivator and class II
RT MHC.";
RL Cancer Immunol. Immunother. 42:99-107(1996).
RN [4]
RP INDUCTION BY LPS, AND 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).
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 (By similarity).
CC Activates CD74 transcription (By similarity) (PubMed:32855215).
CC Exhibits intrinsic GTP-stimulated acetyltransferase activity. Exhibits
CC serine/threonine protein kinase activity: phosphorylates the TFIID
CC component TAF7, the RAP74 subunit of the general transcription factor
CC TFIIF, histone H2B at 'Ser-37' and other histones (By similarity).
CC {ECO:0000250|UniProtKB:P33076, 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:0000250|UniProtKB:P33076};
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:0000250|UniProtKB:P33076};
CC -!- SUBUNIT: Interacts with ZXDA and ZXDC. Interacts with PML (isoform PML-
CC 2). Interacts with TAF7; interaction inhibits CIITA acetyltransferase
CC activity, thereby repressing transcription.
CC {ECO:0000250|UniProtKB:P33076}.
CC -!- INTERACTION:
CC P79621; Q07279: Nfe2; NbExp=2; IntAct=EBI-26668013, EBI-6554737;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P33076}. Nucleus,
CC PML body {ECO:0000250|UniProtKB:P33076}. Note=Recruited to PML body by
CC PML. {ECO:0000250|UniProtKB:P33076}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=I;
CC IsoId=P79621-1; Sequence=Displayed;
CC Name=2; Synonyms=III;
CC IsoId=P79621-2; Sequence=VSP_007214, VSP_007215;
CC Name=3; Synonyms=IV;
CC IsoId=P79621-3; Sequence=VSP_007216;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed at very high levels in
CC dendritic cells, at very low levels in spleen and thymus and is not
CC detected in other tissues. Isoform 2 is detected at high levels in
CC spleen and tonsil as well as in a number of B-lymphocyte cell lines,
CC and at very low levels in dendritic cells.
CC {ECO:0000269|PubMed:9184229}.
CC -!- INDUCTION: By IFNG and LPS. {ECO:0000269|PubMed:32855215,
CC ECO:0000269|PubMed:9184229}.
CC -!- DOMAIN: The acetyltransferase domain is necessary for activation of
CC both class I and class II transcription.
CC {ECO:0000250|UniProtKB:P33076}.
CC -!- DOMAIN: The GTP-binding motif doesn't confer GTPase activity but
CC promotes nuclear localization. {ECO:0000250|UniProtKB:P33076}.
CC -!- PTM: Autophosphorylated, affecting interaction with TAF7.
CC {ECO:0000250|UniProtKB:P33076}.
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DR EMBL; AF000006; AAB92364.2; -; Genomic_DNA.
DR EMBL; AF000007; AAB92365.1; -; Genomic_DNA.
DR EMBL; AF042158; AAC34366.1; -; mRNA.
DR EMBL; AF042159; AAC34367.1; -; mRNA.
DR EMBL; AF100709; AAF06838.1; -; mRNA.
DR EMBL; AF100710; AAF06839.1; -; mRNA.
DR EMBL; U60653; AAB48859.1; -; mRNA.
DR EMBL; U46562; AAB05004.1; -; mRNA.
DR CCDS; CCDS27950.1; -. [P79621-2]
DR CCDS; CCDS88875.1; -. [P79621-1]
DR CCDS; CCDS88877.1; -. [P79621-3]
DR RefSeq; NP_001230690.1; NM_001243761.2.
DR RefSeq; NP_001289547.1; NM_001302618.1. [P79621-1]
DR RefSeq; NP_001289548.1; NM_001302619.1. [P79621-3]
DR RefSeq; NP_031601.1; NM_007575.4. [P79621-2]
DR RefSeq; XP_006521788.1; XM_006521725.3.
DR RefSeq; XP_011244112.1; XM_011245810.2. [P79621-3]
DR AlphaFoldDB; P79621; -.
DR SMR; P79621; -.
DR BioGRID; 198417; 11.
DR IntAct; P79621; 8.
DR STRING; 10090.ENSMUSP00000023147; -.
DR iPTMnet; P79621; -.
DR PhosphoSitePlus; P79621; -.
DR PaxDb; P79621; -.
DR PRIDE; P79621; -.
DR ProteomicsDB; 265408; -. [P79621-1]
DR ProteomicsDB; 265409; -. [P79621-2]
DR ProteomicsDB; 265410; -. [P79621-3]
DR Antibodypedia; 4234; 192 antibodies from 35 providers.
DR DNASU; 12265; -.
DR Ensembl; ENSMUST00000023147; ENSMUSP00000023147; ENSMUSG00000022504. [P79621-2]
DR Ensembl; ENSMUST00000230395; ENSMUSP00000155517; ENSMUSG00000022504. [P79621-1]
DR Ensembl; ENSMUST00000230450; ENSMUSP00000155002; ENSMUSG00000022504. [P79621-3]
DR GeneID; 12265; -.
DR KEGG; mmu:12265; -.
DR UCSC; uc007ydr.2; mouse. [P79621-1]
DR CTD; 4261; -.
DR MGI; MGI:108445; Ciita.
DR VEuPathDB; HostDB:ENSMUSG00000022504; -.
DR eggNOG; KOG4308; Eukaryota.
DR GeneTree; ENSGT00940000161578; -.
DR HOGENOM; CLU_010691_1_0_1; -.
DR InParanoid; P79621; -.
DR OMA; CEYLFSH; -.
DR PhylomeDB; P79621; -.
DR TreeFam; TF352118; -.
DR BioGRID-ORCS; 12265; 4 hits in 76 CRISPR screens.
DR ChiTaRS; Ciita; mouse.
DR PRO; PR:P79621; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; P79621; protein.
DR Bgee; ENSMUSG00000022504; Expressed in mesenteric lymph node and 70 other tissues.
DR ExpressionAtlas; P79621; baseline and differential.
DR Genevisible; P79621; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0016605; C:PML body; ISS: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; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0071257; P:cellular response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; IEA:Ensembl.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:MGI.
DR GO; GO:0046597; P:negative regulation of viral entry into host cell; ISO:MGI.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0045345; P:positive regulation of MHC class I biosynthetic process; ISO:MGI.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0046677; P:response to antibiotic; ISO:MGI.
DR GO; GO:0034341; P:response to interferon-gamma; IDA:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 2.
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 Pfam; PF13516; LRR_6; 3.
DR Pfam; PF05729; NACHT; 1.
DR PRINTS; PR01719; MHCIIACTVATR.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50837; NACHT; 1.
PE 1: Evidence at protein level;
KW Activator; Acyltransferase; Alternative splicing; ATP-binding; GTP-binding;
KW Kinase; Leucine-rich repeat; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Transferase.
FT CHAIN 1..1155
FT /note="MHC class II transactivator"
FT /id="PRO_0000089242"
FT DOMAIN 439..749
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 1010..1033
FT /note="LRR 1"
FT REPEAT 1041..1062
FT /note="LRR 2"
FT REPEAT 1070..1091
FT /note="LRR 3"
FT REPEAT 1098..1119
FT /note="LRR 4"
FT REGION 171..210
FT /note="Required for acetyltransferase activity"
FT /evidence="ECO:0000250"
FT REGION 217..237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 297..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 297..320
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..349
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 445..452
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..101
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9184229"
FT /id="VSP_007216"
FT VAR_SEQ 1..77
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8995190,
FT ECO:0000303|PubMed:9184229"
FT /id="VSP_007214"
FT VAR_SEQ 78..94
FT /note="SLQAPTVERGTSYRDHG -> MRCLVPGPSGSYLPELQ (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:8995190,
FT ECO:0000303|PubMed:9184229"
FT /id="VSP_007215"
FT CONFLICT 994
FT /note="G -> R (in Ref. 3; AAB05004)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1155 AA; 127528 MW; F3FF05DEBFB0CE71 CRC64;
MNHFQAILAQ VQTLLSSQKP RQVRALLDGL LEEELLSREY HCALLHEPDG DALARKISLT
LLEKGDLDLT FLSWVCNSLQ APTVERGTSY RDHGDHSLCA TMDLGSPEGS YLELLNSDAD
PLHLYHLYDQ MDLAGEEEIE LSSEPDTDTI NCDQFSKLLQ DMELDEETRE AYANIAELDQ
YVFQDTQLEG LSKDLFIEHI GAEEGFGENI EIPVEAGQKP QKRRFPEEHA MDSKHRKLVP
TSRTSLNYLD LPTGHIQIFT TLPQGLWQIS GAGTGLSSVL IYHGEMPQVN QVLPSSSLSI
PSLPESPDRP GSTSPFTPSA ADLPSMPEPA LTSRVNETED TSPSPCQEGP ESSIKLPKWP
EAVERFQHSL QDKYKALPQS PRGPLVAVEL VRARLERGSN KSQERELATP DWTERQLAHG
GLAEVLQVVS DCRRPGETQV VAVLGKAGQG KSHWARTVSH TWACGQLLQY DFVFYVPCHC
LDRPGDTYHL RDLLCPPSLQ PLAMDDEVLD YIVRQPDRVL LILDAFEELE AQDGLLHGPC
GSLSPEPCSL RGLLAGIFQR KLLRGCTLLL TARPRGRLAQ SLSKADAIFE VPSFSTKQAK
TYMRHYFENS GTAGNQDKAL GLLEGQPLLC SYSHSPVVCR AVCQLSKALL EQGTEAQLPC
TLTGLYVSLL GPAAQNSPPG ALVELAKLAW ELGRRHQSTL QETRFSSVEV KTWAVTQGLM
QQTLETTEAQ LAFSSFLLQC FLGAVWLAQC NEIKDKELPQ YLALTPRKKR PYDNWLEGVP
RFLAGLVFQP RAHCLGALVE PAVAAVADRK QKVLTRYLKR LKLGTLRAGR LLELLHCAHE
TQQPGIWEHV AHQLPGHLSF LGTRLTPPDV YVLGRALETA SQDFSLDLRQ TGVEPSGLGN
LVGLSCVTSF RASLSDTMAL WESLQQQGEA QLLQAAEEKF TIEPFKAKSP KDVEDLDRLV
QTQRLRNPSE DAAKDLPAIR DLKKLEFALG PILGPQAFPT LAKILPAFSS LQHLDLDSLS
ENKIGDKGVS KLSATFPQLK ALETLNLSQN NITDVGACKL AEALPALAKS LLRLSLYNNC
ICDKGAKSLA QVLPDMVSLR VMDVQFNKFT AAGAQQLASS LQKCPQVETL AMWTPTIPFG
VQEHLQQLDA RISLR
