Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol CIITA contributors: mct - updated : 07-03-2016
HGNC name class II, major histocompatibility complex, transactivator
HGNC id 7067
RNA
TRANSCRIPTS type messenger
text
  • primarily regulated at the transcriptional level and is expressed from three main promoters with myeloid, lymphoid and interferon (IFNG1)-treated non-hematopoietic cells using promoters pI, pIII and pIV, respectively (PMID: 25101797)
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    20 initiation site 4657 - 1131 dendritic cells 2002 11983150
  • MHC2TA-P1
  • promoter P1
  • 20 initiation site 4654 - 1130 - 2002 11983150
  • MHC2TA-P2
  • promoter P2
  • 18 initiation site 2902 - 546 B cells 2016 26871568
  • MHC2TA-P3
  • promoter P3
  • the extreme N-terminal end induces both rapid degradation and transactivation, and is responsible for efficient recruitment to the HLA-DRA promoter and increased interaction with components of the transcription machinery
  • - initiation site - - 121 - 2002 11983150
  • promoter P4
  • IFNG1 inducible CIITA promoter IV (CIITA pIV) during activation, and characterized by a decrease in trimethylation of histone H3 lysine 27 (H3K27me3), catalyzed by the histone methyltransferase(EZH2)
  • novel roles of YY1 and JARID2 in the epigenetic regulation of the CIITA pIV by recruitment of PRC2
  • - splicing - - - . in DC is upregulated upon lipopolysaccharides (LPS) induction . localizes to mitochondria 2011 21203976
  • dendritic cells-expressed caspase inhibitory isoform of CIITA
  • interacts with caspases and inhibits its activity in Dendritic cells (DC)
  • is a key molecule that regulates caspases activity and NO synthesis in DC
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   predominantly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte
    Skeletonosteoclast Homo sapiensFetal
    cell lineage
    cell lines
    fluid/secretion lymph
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES acid
    STRUCTURE
    motifs/domains
  • N terminal acidic transcription activation domain
  • a proline/serine/threonine-rich (P/S/T) region
  • a consensus GTP-binding motif
  • a leucine-rich region and four leucine and charged residue-rich domains (LCD)
  • one NACHT domain
  • HOMOLOGY
    interspecies homolog to murine C2ta
    Homologene
    FAMILY NACHT protein family
    CATEGORY immunity/defense , regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,PML
    basic FUNCTION
  • important regulator of both MHC class I and class II transcription
  • stabilizing the binding of RFX-CREB-NF-Y complex
  • transcriptional coactivator involved in inflammatory responses and apoptosis
  • CIITA chromatin in T-cells expressing CIITA display similar histone acetylation and methylation characteristics associated with an open chromatin structure
  • transcriptional co-activator that regulates IFNG1-activated transcription of MHC class I and class II genes
  • TAF1 and CIITA both possess intrinsic acetyltransferase (AT) activity that is required for transcription initiation
  • is a master transcriptional co-activator believed to be exclusively dedicated for antigen presentation
  • plays a novel, unexpected function in skeletal homeostasis, independent of MHC Class II expression and T cells, by exerting a selective and intrinsic control of osteoclast differentiation and bone resorption
  • CIITA expression is likely mediated in hematopoietic cells by common elements with promoter accessibility having a part in promoter choice 7)
  • coordinates constitutive and IFNG-induced expression of MHC class II genes
  • is the master regulator of MHC class II gene expression and is a short-lived protein
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding
    RNA binding
    small molecule
    protein
  • interacting with ZXDC
  • TAF7 binds to CIITA and inhibits its AT (acetyltransferase) activity, thereby repressing activated transcription
  • TAF7 interacts with and regulates the enzymatic activities of other transcription factors, including CDK9, GTF2H1, and CIITA, ensuring an orderly progression in transcription initiation
  • PML is required for efficient IFNG1-induced MHC II gene transcription through regulation of the class II transactivator (CIITA), and mediates this function through protection of CIITA from proteasomal degradation
  • SEMA3A signaling in ECs is linked with increased CIITA levels and higher HLA-DR expression, resulting in CD4+ T-cell activation
  • ADORA2B signaling represses CIITA transcription in VSMCs by manipulating the interaction between STAT1 and the epigenetic machinery
  • IFNG1 responsiveness of CIITA requires SMARCA4, the ATPase engine of the chromatin remodeling SWI/SNF complex (also called BAF)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) BLS2A
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    by epigenetic mechanisms that prevent the recruitment of transactivating factors in rhabdomyosarcoma cells
    tumoral     --low  
    in diffuse large B-cell lymphoma (DLBCL)
    Susceptibility
  • to rheumatoid arthritis, multiple sclerosis, myocardial infarction
  • to autoimmune Addison disease (AAD)
  • Variant & Polymorphism other
  • polymorphism 168A>G associated with susceptibility to rheumatoid arthritis, multiple sclerosis, myocardial infarction
  • association of the polymorphism with genetic risk for AAD that appears to be independent from the well-known association with the polymorphism of HLA class II genes
  • polymorphisms significantly associated with Addison disease
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS