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 (By similarity). Activates CD74 transcription (By similarity) (PubMed:32855215). Exhibits intrinsic GTP-stimulated acetyltransferase activity. Exhibits serine/threonine protein kinase activity: phosphorylates the TFIID component TAF7, the RAP74 subunit of the general transcription factor TFIIF, histone H2B at 'Ser-37' and other histones (By similarity). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Interacts with ZXDA and ZXDC. Interacts with PML (isoform PML-2). Interacts with TAF7; interaction inhibits CIITA acetyltransferase activity, thereby repressing transcription. Recruited to PML body by PML. Isoform 1 is expressed at very high levels in dendritic cells, at very low levels in spleen and thymus and is not detected in other tissues. Isoform 2 is detected at high levels in spleen and tonsil as well as in a number of B-lymphocyte cell lines, and at very low levels in dendritic cells. By IFNG and LPS. 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. Autophosphorylated, affecting interaction with TAF7.