RFX5 is part of the regulatory factor X (RFX), a heterotrimeric DNA binding complex that binds to the X boxes of all MHC-II promoters. RFX5 is essential for the binding activity and function of the RFX complex []. It contains an N-terminal DNA binding domain (DBD) and a C-terminal domain that mediates cooperative binding between the RFX complex and NF-Y, a transcription factor binding to the Y box sequence of MHC-II promoters [].Mutations in the RFX5 gene cause Bare lymphocyte syndrome 2 (BLS2), a severe combined immunodeficiency disease with early onset [].
This superfamily represents the C-terminal domain ofRFXAP (regulatory factor X-associated protein) that binds to RFXANK [, ], the ankyrin-repeat regulatory factor X protein. RFXAP is part of the RFX complex, mutants of either RFXAP or RFXANK protein fail to bind to each other. RFX5 binds only to the RFXANK-RFXAP scaffold and not to either protein alone, and neither the scaffold nor RFX5 alone can bind DNA. The binding of the RFXANK-RFXAP scaffold to RFX5 leads to a conformational change in the latter that exposes the DNA-binding domain of RFX5. The DNA-binding domain of RFX5 anchors the RFX complex to MHC class II X and S promoter boxes [].
This C-terminal domain of Regulatory factor X-associated protein (RFXAP) binds to RFXANK [, ], the ankyrin-repeat regulatory factor X protein. RFXAP is part of the RFX complex, mutants of either RFXAP or RFXANK protein fail to bind to each other. RFX5 binds only to the RFXANK-RFXAP scaffold and not to either protein alone, and neither the scaffold nor RFX5 alone can bind DNA. The binding of the RFXANK-RFXAP scaffold to RFX5 leads to a conformational change in the latter that exposes the DNA-binding domain of RFX5. The DNA-binding domain of RFX5 anchors the RFX complex to MHC class II X and S promoter boxes [].
This entry represents the N-terminal domain of regulatory factor X (RFX)-5, which is part of the human RFX complex. The RFX complex (consists of RFX5, RFXAP and RFXB) is involved in the regulation of the expression of the major histocompatibility complex class II (MHCII) gene products essential for the initiation and regulation of the mammalian immune response. The N-terminal domain of RFX5 is responsible for homodimerization of RFX5 which promotes folding of the C-terminal domain of RFXAP. The folding of RFXAP results in the formation of a potential binding site for RFXB to bind to the MHCII promoter [].
Transcription of all the members of MHCII family of genes is controlled by a set of conserved transcription factors and promoter elements. One of these class II transactivators is the DNA-binding RFX complex, which consists of subunits RFX5 and its accessory proteins RFXAP and RFXANK [].This entry represents the C-terminal domain of RFX5. The C-terminal domain mediates cooperative binding between the RFX complex and NF-Y, a transcription factor binding to the Y box sequence of MHC-II promoters [].
This entry includes Rfx1 from budding yeasts, Sak1 from fission yeasts and RFX1-8 from humans []. They are transcription factors that contain a RFX DNA binding domain and a conserved C-terminal region [].Mutations in the RFX5 gene cause Bare lymphocyte syndrome 2 (BLS2), a severe combined immunodeficiency disease with early onset []. Mutations in the RFX6 gene cause Mitchell-Riley syndrome (MTCHRS), a disorder characterized by neonatal diabetes, hypoplastic or annular pancreas, duodenal and jejunal atresia, and absent gallbladder [, ].
