RFXANK explained

DNA-binding protein RFXANK is a protein that in humans is encoded by the RFXANK gene.^{[1] [2] [3]}

Function

Major histocompatibility (MHC) class II molecules are transmembrane proteins that have a central role in development and control of the immune system. The protein encoded by this gene, along with regulatory factor X-associated protein and regulatory factor-5, forms a complex that binds to the X box motif of certain MHC class II gene promoters and activates their transcription. Once bound to the promoter, this complex associates with the non-DNA-binding factor MHC class II transactivator, which controls the cell type specificity and inducibility of MHC class II gene expression. This protein contains ankyrin repeats involved in protein-protein interactions. Mutations in this gene have been linked to bare lymphocyte syndrome type II, complementation group B. Two transcript variants encoding different isoforms have been described for this gene, with only one isoform showing activation activity.^[3]

Interactions

RFXANK has been shown to interact with RFXAP^{[4] [5]} and CIITA.^{[4] [6]}

Further reading

• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . Sep 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Lin JH, Makris A, McMahon C, Bear SE, Patriotis C, Prasad VR, Brent R, Golemis EA, Tsichlis PN . The ankyrin repeat-containing adaptor protein Tvl-1 is a novel substrate and regulator of Raf-1 . The Journal of Biological Chemistry . 274 . 21 . 14706–15 . May 1999 . 10329666 . 10.1074/jbc.274.21.14706 . free . 20.500.12613/9172 . free .
• Nagarajan UM, Peijnenburg A, Gobin SJ, Boss JM, van den elsen PJ . Novel mutations within the RFX-B gene and partial rescue of MHC and related genes through exogenous class II transactivator in RFX-B-deficient cells . Journal of Immunology . 164 . 7 . 3666–74 . Apr 2000 . 10725724 . 10.4049/jimmunol.164.7.3666 . free .
• Wiszniewski W, Fondaneche MC, Lambert N, Masternak K, Picard C, Notarangelo L, Schwartz K, Bal J, Reith W, Alcaide C, de Saint Basile G, Fischer A, Lisowska-Grospierre B . Founder effect for a 26-bp deletion in the RFXANK gene in North African major histocompatibility complex class II-deficient patients belonging to complementation group B . Immunogenetics . 51 . 4–5 . 261–7 . Apr 2000 . 10803838 . 10.1007/s002510050619 . 630411 .
• 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 .
• Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z . Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells . Genome Research . 10 . 10 . 1546–60 . Oct 2000 . 11042152 . 310934 . 10.1101/gr.140200 .
• Nekrep N, Geyer M, Jabrane-Ferrat N, Peterlin BM . Analysis of ankyrin repeats reveals how a single point mutation in RFXANK results in bare lymphocyte syndrome . Molecular and Cellular Biology . 21 . 16 . 5566–76 . Aug 2001 . 11463838 . 87278 . 10.1128/MCB.21.16.5566-5576.2001 .
• Dimberg J, Hugander A, Häll-Karlsson BM, Sirsjö A . RFX-B, a MHC class II transcription factor, suppressed in human colorectal adenocarcinomas . International Journal of Molecular Medicine . 9 . 3 . 213–6 . Mar 2002 . 11836625 . 10.3892/ijmm.9.3.213 .
• Wiszniewski W, Fondaneche MC, Louise-Plence P, Prochnicka-Chalufour A, Selz F, Picard C, Le Deist F, Eliaou JF, Fischer A, Lisowska-Grospierre B . Novel mutations in the RFXANK gene: RFX complex containing in-vitro-generated RFXANK mutant binds the promoter without transactivating MHC II . Immunogenetics . 54 . 11 . 747–55 . Feb 2003 . 12618906 . 10.1007/s00251-002-0521-1 . 32423001 .
• Wang AH, Grégoire S, Zika E, Xiao L, Li CS, Li H, Wright KL, Ting JP, Yang XJ . Identification of the ankyrin repeat proteins ANKRA and RFXANK as novel partners of class IIa histone deacetylases . The Journal of Biological Chemistry . 280 . 32 . 29117–27 . Aug 2005 . 15964851 . 10.1074/jbc.M500295200 . free .
• Krawczyk M, Masternak K, Zufferey M, Barras E, Reith W . New functions of the major histocompatibility complex class II-specific transcription factor RFXANK revealed by a high-resolution mutagenesis study . Molecular and Cellular Biology . 25 . 19 . 8607–18 . Oct 2005 . 16166641 . 1265745 . 10.1128/MCB.25.19.8607-8618.2005 .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .

Notes and References

1. 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 .
2. 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 .
3. Web site: Entrez Gene: RFXANK regulatory factor X-associated ankyrin-containing protein.
4. Nekrep N, Geyer M, Jabrane-Ferrat N, Peterlin BM . Analysis of ankyrin repeats reveals how a single point mutation in RFXANK results in bare lymphocyte syndrome . Molecular and Cellular Biology . 21 . 16 . 5566–76 . Aug 2001 . 11463838 . 87278 . 10.1128/MCB.21.16.5566-5576.2001 .
5. 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 .
6. 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 .