Computational Modeling of Human SETBP1 Protein
Fig 1: Proposed model for SETBP1 epigenetic network [Piazza et al. (2018)]
A region named SKI homologous region (figure 2) is present in the protein that shows significant homology to human SKI protein. Within this region lies a degron motif that is targeted by SCF-βTrCP1 E3 ubiquitin ligase during ubiquitination. Interestingly, most of the mutations related to SGS and malignancies overlap and cluster in a mutational hotspot in the degron (figure 3).
Fig 2: Schematic representation of SETBP1 [modified from Piazza et al. (2012)].
Fig 3: Mutations found in SGS and in hematologic malignancies. The residues of the canonical degron are highlighted with arrows [Acuna-Hidalgo et al. (2017)].
Fig 4: A model generated by I-TASSER.