LIG_NBox_RRM_1

Far upstream element (FUSE) Binding Proteins (FBPs) comprise an ancient family of single stranded DNA binding proteins which have different functions in gene regulation. They are originally identified as factors responsible for binding the AT-rich single-stranded DNA (ssDNA) sequence upstream of the P1 promoter of c-Myc (P01106) known as FUSE DNA (Duncan,1994). During the initiation of transcription FUSE starts to melt because of the torsional stress and is recognized by the FUSE binding protein (FBP) (Q96AE4). FBP is a stimulator of transcription factor TFIIH and thereby increases the transcription of c-Myc. The KH domains (PF00013) of FBP recognize the melted FUSE. On later stage an FBP-interacting repressor (FIR) (Q9UHX1) is recruited to the FBP-FUSE complex. It binds to both the FBP and FUSE, which is fully melted due to high level of DNA super-coiling. Upon binding to FBP-FUSE complex, FIR interacts with TFIIH reducing FBP mediated transcription and dissolution of the complex which brings the gene transcription to basal levels (Zhang,2013).
A similar system of regulation of gene transcription is also observed in drosophila protein (d-myc) (Mitchell,2010). Among the FBPs, the FBP1 (Q96AE4) and FBP2 (Q92945) contain a specific region known as N-box, which mediates the recruitment of FIR through its RRM1 (PF00076)-RRM2 (PF04059) tandem domains (Cukier,2010). FIR recognizes the hydrophobic surface of the α helix formed by the N-box, while the hydrophilic surface does not seem to mediate the interaction. The KH domains (PF00013) present in the FBP proteins are also essential to recruit and retain FIR (Chung,2006). Apart from the regulation of gene transcription, FBPs take part in RNA binding, RNA trafficking, RNA editing, mRNA stabilization and degradation. The misregulation of the FBP-FIR-TFIIH is associated with many diseases. A splice isoform of FIR in human colorectal cancer tissue not only lacked the c-Myc suppressor action but also prevented the normal FIR from its function (Matsushita,2006). A defect in the operation of FBP-FIR-TFIIH is seen in patients with xeroderma pigmentosum B (XPB) (Liu,2006).