title: Evolutionary conservation and characterization of the bare lymphocyte syndrome transcription factor RFX-B and its paralogue ANKRA2.
abstract: The extraordinary homology between major histocompatibility complex class II (MHC II) proteins across species from human to bony fish suggests that transcription factors that regulate these proteins might be conserved as well. Deficiencies in four proteins that regulate MHC II genes in humans (RFX-B, RFX5, RFXAP, and CIITA) cause an inherited immunodeficiency disorder known as the bare lymphocyte syndrome (BLS). To understand the structure and mechanism of function of the BLS transcription factors, we analyzed the evolutionary history of RFX-B, the factor deficient in the majority of patients with BLS. Sequence comparison and analysis of the RFX-B proteins showed that RFX-B and a closely related protein, ANKRA2, are present in humans to bony fish and that specific domains are highly conserved. In addition to sequence conservation, functional conservation exists, as mouse and Xenopus RFX-B orthologues, but not the paralogous protein ANKRA2, were able to complement the MHC II deficiency in a BLS-patient-derived cell line deficient in RFX-B. The remarkable conservation of the RFX-B lineage attests to the conservation of the regulation mechanism for this gene system and its importance to precisely regulate MHC class II molecules in both the developing and active immune response.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322, USA.
authors.forename: Alyssa Bushey
authors.initials: AB
authors.lastname: Long
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Boss
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D004268:DNA-Binding Proteins; D019143:Evolution, Molecular; D017930:Genes, Reporter; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010802:Phylogeny; D016415:Sequence Alignment; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: C419548:ANKRA2 protein, human; D017487:Ankyrins; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; C117892:RFXANK protein, human; D014157:Transcription Factors