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UniProtKB - P33076 (C2TA_HUMAN)

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Protein

MHC class II transactivator

Gene

CIITA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Essential for transcriptional activity of the HLA class II promoter; activation is via the proximal promoter. No DNA binding of in vitro translated CIITA was detected. May act in a coactivator-like fashion through protein-protein interactions by contacting factors binding to the proximal MHC class II promoter, to elements of the transcription machinery, or both. Alternatively it may activate HLA class II transcription by modifying proteins that bind to the MHC class II promoter. Also mediates enhanced MHC class I transcription; the promoter element requirements for CIITA-mediated transcription are distinct from those of constitutive MHC class I transcription, and CIITA can functionally replace TAF1 at these genes. Exhibits intrinsic GTP-stimulated acetyltransferase activity. Exhibits serine/threonine protein kinase activity: can phosphorylate the TFIID component TAF7, the RAP74 subunit of the general transcription factor TFIIF, histone H2B at 'Ser-37' and other histones (in vitro).4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi420 – 427GTP8

GO - Molecular functioni

  • activating transcription factor binding Source: BHF-UCL
  • ATP binding Source: UniProtKB-KW
  • GTP binding Source: UniProtKB-KW
  • kinase activity Source: UniProtKB-KW
  • protein-containing complex binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • transcription coactivator activity Source: ProtInc
  • transcription regulatory region DNA binding Source: BHF-UCL
  • transferase activity, transferring acyl groups Source: UniProtKB-KW
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • immune response Source: ProtInc
  • interferon-gamma-mediated signaling pathway Source: Reactome
  • negative regulation of collagen biosynthetic process Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: BHF-UCL
  • negative regulation of transcription by RNA polymerase II Source: BHF-UCL
  • positive regulation of MHC class I biosynthetic process Source: BHF-UCL
  • positive regulation of MHC class II biosynthetic process Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription by RNA polymerase II Source: BHF-UCL
  • response to antibiotic Source: MGI
  • response to interferon-gamma Source: BHF-UCL
  • transcription, DNA-templated Source: UniProtKB-KW
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionActivator, Acyltransferase, Kinase, Transferase
Biological processTranscription, Transcription regulation
LigandATP-binding, GTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-877300 Interferon gamma signaling
SIGNORiP33076

Names & Taxonomyi

Protein namesi
Recommended name:
MHC class II transactivator (EC:2.3.1.-, EC:2.7.11.1)
Short name:
CIITA
Gene namesi
Name:CIITA
Synonyms:MHC2TA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000179583.17
HGNCiHGNC:7067 CIITA
MIMi600005 gene
neXtProtiNX_P33076

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Bare lymphocyte syndrome 2 (BLS2)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA severe combined immunodeficiency disease with early onset. It is characterized by a profound defect in constitutive and interferon-gamma induced MHC II expression, absence of cellular and humoral T-cell response to antigen challenge, hypogammaglobulinemia and impaired antibody production. The consequence include extreme susceptibility to viral, bacterial and fungal infections.
See also OMIM:209920
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_005127120K → IE in BLS2. 1
Natural variantiVAR_015551469L → P in BLS2; mild immunodeficiency; has residual MHC class II trans activation activity. 1 Publication1
Natural variantiVAR_005129940 – 963Missing in BLS2. 1 PublicationAdd BLAST24
Natural variantiVAR_015553962F → S in BLS2. 1 Publication1
Natural variantiVAR_015554964 – 991Missing in BLS2. Add BLAST28
Natural variantiVAR_0155551027Missing in BLS2. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi420 – 421Missing : Strongly reduces GTP-binding and abolishes transactivation at MHC promoters. 1 Publication2
Mutagenesisi561D → A: Strongly reduces GTP-binding and abolishes transactivation at MHC promoters. 1 Publication1

Keywords - Diseasei

Disease mutation, SCID

Organism-specific databases

DisGeNETi4261
MalaCardsiCIITA
MIMi209920 phenotype
OpenTargetsiENSG00000179583
Orphaneti572 Immunodeficiency by defective expression of HLA class 2
PharmGKBiPA30795

Polymorphism and mutation databases

BioMutaiCIITA
DMDMi317373472

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000892411 – 1130MHC class II transactivatorAdd BLAST1130

Post-translational modificationi

Autophosphorylated, affecting interaction with TAF7.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP33076
PaxDbiP33076
PeptideAtlasiP33076
PRIDEiP33076
ProteomicsDBi54897

PTM databases

iPTMnetiP33076
PhosphoSitePlusiP33076

Expressioni

Gene expression databases

BgeeiENSG00000179583
CleanExiHS_CIITA
ExpressionAtlasiP33076 baseline and differential

Organism-specific databases

HPAiCAB016084

Interactioni

Subunit structurei

Interacts with ZXDA and ZXDC. Interacts with PML (isoform PML-2).3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • activating transcription factor binding Source: BHF-UCL
  • protein C-terminus binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi110416, 28 interactors
ELMiP33076
IntActiP33076, 3 interactors
STRINGi9606.ENSP00000316328

Structurei

3D structure databases

ProteinModelPortaliP33076
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini414 – 724NACHTPROSITE-ProRule annotationAdd BLAST311
Repeati985 – 1008LRR 1Add BLAST24
Repeati1016 – 1037LRR 2Add BLAST22
Repeati1045 – 1066LRR 3Add BLAST22
Repeati1073 – 1093LRR 4Add BLAST21

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni94 – 132Required for acetyltransferase activityAdd BLAST39

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi52 – 137Asp/Glu-rich (acidic)Add BLAST86

Domaini

The acetyltransferase domain is necessary for activation of both class I and class II transcription.
The GTP-binding motif doesn't confer GTPase activity but promotes nuclear localization.

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG4308 Eukaryota
ENOG410ZBX3 LUCA
GeneTreeiENSGT00860000133673
HOGENOMiHOG000107439
HOVERGENiHBG000174
InParanoidiP33076
KOiK08060
PhylomeDBiP33076
TreeFamiTF352118

Family and domain databases

Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
IPR008095 MHC_II_transact
IPR007111 NACHT_NTPase
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF13516 LRR_6, 3 hits
PF05729 NACHT, 1 hit
PRINTSiPR01719 MHCIIACTVATR
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 4 hits
PS50837 NACHT, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P33076-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRCLAPRPAG SYLSEPQGSS QCATMELGPL EGGYLELLNS DADPLCLYHF 
        60         70         80         90        100
YDQMDLAGEE EIELYSEPDT DTINCDQFSR LLCDMEGDEE TREAYANIAE 
       110        120        130        140        150
LDQYVFQDSQ LEGLSKDIFK HIGPDEVIGE SMEMPAEVGQ KSQKRPFPEE 
       160        170        180        190        200
LPADLKHWKP AEPPTVVTGS LLVRPVSDCS TLPCLPLPAL FNQEPASGQM 
       210        220        230        240        250
RLEKTDQIPM PFSSSSLSCL NLPEGPIQFV PTISTLPHGL WQISEAGTGV 
       260        270        280        290        300
SSIFIYHGEV PQASQVPPPS GFTVHGLPTS PDRPGSTSPF APSATDLPSM 
       310        320        330        340        350
PEPALTSRAN MTEHKTSPTQ CPAAGEVSNK LPKWPEPVEQ FYRSLQDTYG 
       360        370        380        390        400
AEPAGPDGIL VEVDLVQARL ERSSSKSLER ELATPDWAER QLAQGGLAEV 
       410        420        430        440        450
LLAAKEHRRP RETRVIAVLG KAGQGKSYWA GAVSRAWACG RLPQYDFVFS 
       460        470        480        490        500
VPCHCLNRPG DAYGLQDLLF SLGPQPLVAA DEVFSHILKR PDRVLLILDG 
       510        520        530        540        550
FEELEAQDGF LHSTCGPAPA EPCSLRGLLA GLFQKKLLRG CTLLLTARPR 
       560        570        580        590        600
GRLVQSLSKA DALFELSGFS MEQAQAYVMR YFESSGMTEH QDRALTLLRD 
       610        620        630        640        650
RPLLLSHSHS PTLCRAVCQL SEALLELGED AKLPSTLTGL YVGLLGRAAL 
       660        670        680        690        700
DSPPGALAEL AKLAWELGRR HQSTLQEDQF PSADVRTWAM AKGLVQHPPR 
       710        720        730        740        750
AAESELAFPS FLLQCFLGAL WLALSGEIKD KELPQYLALT PRKKRPYDNW 
       760        770        780        790        800
LEGVPRFLAG LIFQPPARCL GALLGPSAAA SVDRKQKVLA RYLKRLQPGT 
       810        820        830        840        850
LRARQLLELL HCAHEAEEAG IWQHVVQELP GRLSFLGTRL TPPDAHVLGK 
       860        870        880        890        900
ALEAAGQDFS LDLRSTGICP SGLGSLVGLS CVTRFRAALS DTVALWESLQ 
       910        920        930        940        950
QHGETKLLQA AEEKFTIEPF KAKSLKDVED LGKLVQTQRT RSSSEDTAGE 
       960        970        980        990       1000
LPAVRDLKKL EFALGPVSGP QAFPKLVRIL TAFSSLQHLD LDALSENKIG 
      1010       1020       1030       1040       1050
DEGVSQLSAT FPQLKSLETL NLSQNNITDL GAYKLAEALP SLAASLLRLS 
      1060       1070       1080       1090       1100
LYNNCICDVG AESLARVLPD MVSLRVMDVQ YNKFTAAGAQ QLAASLRRCP 
      1110       1120       1130
HVETLAMWTP TIPFSVQEHL QQQDSRISLR
Length:1,130
Mass (Da):123,514
Last modified:January 11, 2011 - v3
Checksum:i7A61CAA4F3FFECE0
GO
Isoform 2 (identifier: P33076-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     161-210: AEPPTVVTGSLLVRPVSDCSTLPCLPLPALFNQEPASGQMRLEKTDQIPM → V
     887-930: AALSDTVALW...KAKSLKDVED → WGEGLGRDIL...RVGQNGFSPF
     931-1128: Missing.

Show »
Length:883
Mass (Da):96,429
Checksum:iC2D59921C3D5F6C5
GO
Isoform 3 (identifier: P33076-3) [UniParc]FASTAAdd to basket
Also known as: hCIITA'

The sequence of this isoform differs from the canonical sequence as follows:
     161-210: AEPPTVVTGSLLVRPVSDCSTLPCLPLPALFNQEPASGQMRLEKTDQIPM → V
     336-350: EPVEQFYRSLQDTYG → GLAWSPCLGLRPSLH
     351-885: Missing.

Note: Exhibits dominant-negative suppression of MHC class II gene expression.
Show »
Length:546
Mass (Da):59,641
Checksum:i95471F528074C11A
GO
Isoform 4 (identifier: P33076-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     887-930: AALSDTVALW...KAKSLKDVED → WGEGLGRDIL...RVGQNGFSPF
     931-1128: Missing.

Show »
Length:932
Mass (Da):101,661
Checksum:i1C9D9F9BF43DD142
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1020 – 1021LN → RS in ABK41930 (PubMed:12859996).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02927045L → V. Corresponds to variant dbSNP:rs2229317EnsemblClinVar.1
Natural variantiVAR_005127120K → IE in BLS2. 1
Natural variantiVAR_047907174R → G4 PublicationsCorresponds to variant dbSNP:rs8046121Ensembl.1
Natural variantiVAR_015551469L → P in BLS2; mild immunodeficiency; has residual MHC class II trans activation activity. 1 Publication1
Natural variantiVAR_005128500G → A3 PublicationsCorresponds to variant dbSNP:rs4774EnsemblClinVar.1
Natural variantiVAR_015552658A → G. Corresponds to variant dbSNP:rs2229319EnsemblClinVar.1
Natural variantiVAR_060104781S → L. Corresponds to variant dbSNP:rs13330686EnsemblClinVar.1
Natural variantiVAR_057711782V → A. Corresponds to variant dbSNP:rs13336804EnsemblClinVar.1
Natural variantiVAR_047908900Q → R4 PublicationsCorresponds to variant dbSNP:rs7197779EnsemblClinVar.1
Natural variantiVAR_005129940 – 963Missing in BLS2. 1 PublicationAdd BLAST24
Natural variantiVAR_015553962F → S in BLS2. 1 Publication1
Natural variantiVAR_015554964 – 991Missing in BLS2. Add BLAST28
Natural variantiVAR_0155551027Missing in BLS2. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_055099161 – 210AEPPT…DQIPM → V in isoform 2 and isoform 3. 2 PublicationsAdd BLAST50
Alternative sequenceiVSP_055100336 – 350EPVEQ…QDTYG → GLAWSPCLGLRPSLH in isoform 3. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_055101351 – 885Missing in isoform 3. 1 PublicationAdd BLAST535
Alternative sequenceiVSP_055102887 – 930AALSD…KDVED → WGEGLGRDILVLGINCGLGA KPSALWGPFSMQSSRVGQNG FSPF in isoform 2 and isoform 4. 2 PublicationsAdd BLAST44
Alternative sequenceiVSP_055103931 – 1128Missing in isoform 2 and isoform 4. 2 PublicationsAdd BLAST198

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X74301 mRNA Translation: CAA52354.1
U18259 mRNA Translation: AAA88861.1
U18288 mRNA Translation: AAA88862.1
AY084054 mRNA Translation: AAM15723.1
AF410154 mRNA Translation: AAL04118.1
EF064747 Genomic DNA Translation: ABK41930.1
AC133065 Genomic DNA No translation available.
CH471112 Genomic DNA Translation: EAW85169.1
CH471112 Genomic DNA Translation: EAW85172.1
CH471112 Genomic DNA Translation: EAW85173.1
CCDSiCCDS10544.1 [P33076-1]
CCDS66943.1 [P33076-3]
PIRiA48843
RefSeqiNP_000237.2, NM_000246.3
NP_001273332.1, NM_001286403.1 [P33076-3]
UniGeneiHs.592051
Hs.701991

Genome annotation databases

EnsembliENST00000381835; ENSP00000371257; ENSG00000179583 [P33076-3]
GeneIDi4261
KEGGihsa:4261
UCSCiuc002dak.5 human [P33076-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiC2TA_HUMAN
AccessioniPrimary (citable) accession number: P33076
Secondary accession number(s): A0N0N9
, D3DUG0, E9PFE0, Q29675, Q8SNB8, Q96KL4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: January 11, 2011
Last modified: July 18, 2018
This is version 179 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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