CIITA

This gene encodes a protein with an acidic transcriptional activation domain, 4 LRRs (leucine-rich repeats) and a GTP binding domain. The protein is located in the nucleus and acts as a positive regulator of class II major histocompatibility complex gene transcription, and is referred to as the "master control factor" for the expression of these genes. The protein also binds GTP and uses GTP binding to facilitate its own transport into the nucleus. Once in the nucleus it does not bind DNA but rather uses an intrinsic acetyltransferase (AT) activity to act in a coactivator-like fashion. Mutations in this gene have been associated with bare lymphocyte syndrome type II (also known as hereditary MHC class II deficiency or HLA class II-deficient combined immunodeficiency), increased susceptibility to rheumatoid arthritis, multiple sclerosis, and possibly myocardial infarction. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

Class II Major Histocompatibility Complex Transactivator

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. Activates CD74 transcription (PubMed:32855215).

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). Has antiviral activity against Ebola virus and coronaviruses, including SARS-CoV-2. 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).

Immune response Source: ProtInc
Inflammatory response Source: GO_Central
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
Negative regulation of viral entry into host cell Source: UniProtKB
Positive regulation of MHC class I biosynthetic process Source: BHF-UCL
Positive regulation of MHC class II biosynthetic process Source: GO_Central
Positive regulation of transcription, DNA-templated Source: BHF-UCL
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Response to antibiotic Source: MGI
Response to interferon-gamma Source: UniProtKB

Nucleus; PML body. Recruited to PML body by PML.

Bare lymphocyte syndrome 2 (BLS2):
A 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.

Autophosphorylated, affecting interaction with TAF7.