CIITA
Domain
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.
Function
Essential for transcriptional activity of the HLA class II promoter; activation is via the proximal promoter (PubMed:16600381, PubMed:17493635, PubMed:7749984, PubMed:8402893). Does not bind DNA (PubMed:16600381, PubMed:17493635, PubMed:7749984, PubMed:8402893). 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 PubMed:8402893, PubMed:7749984, (PubMed:16600381, PubMed:17493635). Alternatively it may activate HLA class II transcription by modifying proteins that bind to the MHC class II promoter (PubMed:16600381, PubMed:17493635, PubMed:7749984, PubMed:8402893). 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. Activates CD74 transcription (PubMed:32855215). Exhibits intrinsic GTP-stimulated acetyltransferase activity (PubMed:11172716). 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) (PubMed:24036077). Has antiviral activity against Ebola virus and coronaviruses, including SARS-CoV-2 (PubMed:32855215). Induces resistance by up-regulation of the p41 isoform of CD74, which blocks cathepsin-mediated cleavage of viral glycoproteins, thereby preventing viral fusion (PubMed:32855215).
Isoform 3
Exhibits dominant-negative suppression of MHC class II gene expression.
Involvement in disease
MHC class II deficiency 1
MHC2D1
An autosomal recessive immunologic disorder characterized by the loss of expression of MHC class II antigens on antigen-presenting cells. Affected individuals present in early infancy with severe recurrent bacterial, viral, fungal and parasitic infections, usually affecting the gastrointestinal and respiratory tracts.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Autophosphorylated, affecting interaction with TAF7.
Cellular localization
- Nucleus
- Nucleus
- PML body
- Recruited to PML body by PML.
Alternative names
MHC2TA, CIITA, MHC class II transactivator