?
N-terminal domain of transcription factor Specificity Protein (SP) 8 Specificity Proteins (SPs) are transcription factors that are involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. SP8 is crucial for limb outgrowth and neuropore closure. It is expressed during embryogenesis in the forming apical ectodermal ridge, restricted regions of the central nervous system, and tail bud. SP8 and SP9 are two closely related transcription factors that mediate FGF10 signaling, which in turn regulates FGF8 expression which is essential for normal limb development. Both SP8 and SP9 have been found in vertebrates, but only SP8 is present in invertebrates. SP8 belongs to a family of proteins, called the SP/Kruppel or Krueppel-like Factor (KLF) family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. SP factors preferentially bind GC boxes, while KLFs bind CACCC boxes. Another characteristic hallmark of SP factors is the presence of the Buttonhead (BTD) box CXCPXC, just N-terminal to the zinc fingers. The function of the BTD box is unknown, but it is thought to play an important physiological role. Another feature of most SP factors is the presence of a conserved amino acid stretch, the so-called SP box, located close to the N-terminus. SP factors may be separated into three groups based on their domain architecture and the similarity of their N-terminal transactivation domains: SP1-4, SP5, and SP6-9. The transactivation domains between the three groups are not homologous to one another. This model represents the N-terminal domain of SP8. |
Lu S et al.(2020). "CDD/SPARCLE: the conserved domain database in 2020.",