The Superfamily of SCAN Domain Containing Zinc Finger Transcription Factors

Abstract

The SCAN domain is a highly conserved 84 residue motif that is found near the N-terminus of a subfamily of C2H2 zinc finger proteins. The SCAN domain, which is also known as the leucine rich region (LeR), functions as a protein interaction domain, mediating self-association or selective association with other proteins. Bioinformatic approaches were used to identify 71 SCAN domains in the human genome and to define the structures of the members in the human SCAN domain family. In addition to a single SCAN domain, the members of the family can have a variable number of zinc fingers (2–22), a KRAB domain, as well as a novel N-terminal motif. The genes encoding SCAN domains are clustered, often in tandem arrays, in both the human and mouse genomes and are capable of generating isoforms that may affect the function of family members. Twenty-three members of the mouse SCAN family appear to be orthologous with human family members, and human-specific cluster expansions were observed. Although the function of most of the family members is unknown, an overview of selected members of this group of transcription factors suggests that the SCAN domain family is involved in the regulation of growth factor gene expression, genes involved in lipid metabolism, as well as other genes involved in cell survival and differentiation. Analysis of the SCAN domain family using phylogenetic and comparative genomics approaches reveals that the SCAN family is vertebrate -specific. Remarkably, the SCAN domains in lower vertebrates are not associated with C2H2 zinc finger genes, but are contained in large retrovirus-like polyproteins. Collectively, these studies define a large family of transcriptional regulators that have rapidly expanded during recent evolution.