RFX5 explained

DNA-binding protein RFX5 is a protein that in humans is encoded by the RFX5 gene.^{[1] [2]}

Function

A lack of MHC-II expression results in a severe immunodeficiency syndrome called MHC-II deficiency, or the bare lymphocyte syndrome (BLS; MIM 209920). At least 4 complementation groups have been identified in B-cell lines established from patients with BLS. The molecular defects in complementation groups B, C, and D all lead to a deficiency in RFX, a nuclear protein complex that binds to the Xbox of MHC-II promoters. The lack of RFX binding activity in complementation group C results from mutations in the RFX5 gene encoding the 75-kD subunit of RFX (Steimle et al., 1995). RFX5 is the fifth member of the growing family of DNA-binding proteins sharing a novel and highly characteristic DNA-binding domain called the RFX motif. Multiple alternatively spliced transcript variants have been found but the full-length natures of only two have been determined.

Interactions

RFX5 has been shown to interact with CIITA.^{[3] [4]}

Further reading

• Reith W, Mach B . The bare lymphocyte syndrome and the regulation of MHC expression . Annual Review of Immunology . 19 . 331–73 . 2001 . 11244040 . 10.1146/annurev.immunol.19.1.331 .
• Steimle V, Durand B, Barras E, Zufferey M, Hadam MR, Mach B, Reith W . A novel DNA-binding regulatory factor is mutated in primary MHC class II deficiency (bare lymphocyte syndrome) . Genes & Development . 9 . 9 . 1021–32 . May 1995 . 7744245 . 10.1101/gad.9.9.1021 . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Durand B, Sperisen P, Emery P, Barras E, Zufferey M, Mach B, Reith W . RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency . The EMBO Journal . 16 . 5 . 1045–55 . Mar 1997 . 9118943 . 1169704 . 10.1093/emboj/16.5.1045 .
• Scholl T, Mahanta SK, Strominger JL . Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5 . Proceedings of the National Academy of Sciences of the United States of America . 94 . 12 . 6330–4 . Jun 1997 . 9177217 . 21049 . 10.1073/pnas.94.12.6330 . 1997PNAS...94.6330S . free .
• Moreno CS, Rogers EM, Brown JA, Boss JM . Regulatory factor X, a bare lymphocyte syndrome transcription factor, is a multimeric phosphoprotein complex . Journal of Immunology . 158 . 12 . 5841–8 . Jun 1997 . 10.4049/jimmunol.158.12.5841 . 9190936 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Masternak K, Barras E, Zufferey M, Conrad B, Corthals G, Aebersold R, Sanchez JC, Hochstrasser DF, Mach B, Reith W . A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients . Nature Genetics . 20 . 3 . 273–7 . Nov 1998 . 9806546 . 10.1038/3081 . 23780606 .
• Nagarajan UM, Louis-Plence P, DeSandro A, Nilsen R, Bushey A, Boss JM . RFX-B is the gene responsible for the most common cause of the bare lymphocyte syndrome, an MHC class II immunodeficiency . Immunity . 10 . 2 . 153–62 . Feb 1999 . 10072068 . 10.1016/S1074-7613(00)80016-3 . free .
• Peijnenburg A, Van Eggermond MC, Van den Berg R, Sanal O, Vossen JM, Van den Elsen PJ . Molecular analysis of an MHC class II deficiency patient reveals a novel mutation in the RFX5 gene . Immunogenetics . 49 . 4 . 338–45 . Apr 1999 . 10079298 . 10.1007/s002510050501 . 23271370 .
• Villard J, Peretti M, Masternak K, Barras E, Caretti G, Mantovani R, Reith W . A functionally essential domain of RFX5 mediates activation of major histocompatibility complex class II promoters by promoting cooperative binding between RFX and NF-Y . Molecular and Cellular Biology . 20 . 10 . 3364–76 . May 2000 . 10779326 . 85629 . 10.1128/MCB.20.10.3364-3376.2000 .
• Nekrep N, Jabrane-Ferrat N, Peterlin BM . Mutations in the bare lymphocyte syndrome define critical steps in the assembly of the regulatory factor X complex . Molecular and Cellular Biology . 20 . 12 . 4455–61 . Jun 2000 . 10825209 . 85813 . 10.1128/MCB.20.12.4455-4461.2000 .
• Sengupta PK, Fargo J, Smith BD . The RFX family interacts at the collagen (COL1A2) start site and represses transcription . The Journal of Biological Chemistry . 277 . 28 . 24926–37 . Jul 2002 . 11986307 . 10.1074/jbc.M111712200 . free .
• Nekrep N, Jabrane-Ferrat N, Wolf HM, Eibl MM, Geyer M, Peterlin BM . Mutation in a winged-helix DNA-binding motif causes atypical bare lymphocyte syndrome . Nature Immunology . 3 . 11 . 1075–81 . Nov 2002 . 12368908 . 10.1038/ni840 . 7241082 .
• Xu Y, Wang L, Buttice G, Sengupta PK, Smith BD . Interferon gamma repression of collagen (COL1A2) transcription is mediated by the RFX5 complex . The Journal of Biological Chemistry . 278 . 49 . 49134–44 . Dec 2003 . 12968017 . 10.1074/jbc.M309003200 . free .
• Nagarajan UM, Long AB, Harreman MT, Corbett AH, Boss JM . A hierarchy of nuclear localization signals governs the import of the regulatory factor X complex subunits and MHC class II expression . Journal of Immunology . 173 . 1 . 410–9 . Jul 2004 . 15210800 . 10.4049/jimmunol.173.1.410 . free .
• Hjerrild M, Stensballe A, Rasmussen TE, Kofoed CB, Blom N, Sicheritz-Ponten T, Larsen MR, Brunak S, Jensen ON, Gammeltoft S . Identification of phosphorylation sites in protein kinase A substrates using artificial neural networks and mass spectrometry . Journal of Proteome Research . 3 . 3 . 426–33 . 2004 . 15253423 . 10.1021/pr0341033 .

Notes and References

1. Villard J, Reith W, Barras E, Gos A, Morris MA, Antonarakis SE, Van den Elsen PJ, Mach B . Analysis of mutations and chromosomal localisation of the gene encoding RFX5, a novel transcription factor affected in major histocompatibility complex class II deficiency . Human Mutation . 10 . 6 . 430–5 . January 1998 . 9401005 . 10.1002/(SICI)1098-1004(1997)10:6<430::AID-HUMU3>3.0.CO;2-H . 41660134 .
2. Web site: Entrez Gene: RFX5 regulatory factor X, 5 (influences HLA class II expression).
3. Hake SB, Masternak K, Kammerbauer C, Janzen C, Reith W, Steimle V . CIITA leucine-rich repeats control nuclear localization, in vivo recruitment to the major histocompatibility complex (MHC) class II enhanceosome, and MHC class II gene transactivation . Molecular and Cellular Biology . 20 . 20 . 7716–25 . Oct 2000 . 11003667 . 86349 . 10.1128/MCB.20.20.7716-7725.2000 .
4. Scholl T, Mahanta SK, Strominger JL . Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5 . Proceedings of the National Academy of Sciences of the United States of America . 94 . 12 . 6330–4 . Jun 1997 . 9177217 . 21049 . 10.1073/pnas.94.12.6330 . 1997PNAS...94.6330S . free .