title: Gypsy and the birth of the SCAN domain.
abstract: SCAN is a protein domain frequently found at the N termini of proteins encoded by mammalian tandem zinc finger (ZF) genes, whose structure is known to be similar to that of retroviral gag capsid domains and whose multimerization has been proposed as a model for retroviral assembly. We report that the SCAN domain is derived from the C-terminal portion of the gag capsid (CA) protein from the Gmr1-like family of Gypsy/Ty3-like retrotransposons. On the basis of sequence alignments and phylogenetic distributions, we show that the ancestral host SCAN domain (ESCAN for extended SCAN) was exapted from a full-length CA gene from a Gmr1-like retrotransposon at or near the root of the tetrapod animal branch. A truncated variant of ESCAN that corresponds to the annotated SCAN domain arose shortly thereafter and appears to be the only form extant in mammals. The Anolis lizard has a large number of tandem ZF genes with N-terminal ESCAN or SCAN domains. We predict DNA binding sites for all Anolis ESCAN-ZF and SCAN-ZF proteins and demonstrate several highly significant matches to Anolis Gmr1-like sequences, suggesting that at least some of these proteins target retroelements. SCAN is known to mediate protein dimerization, and the CA protein multimerizes to form the core retroviral and retrotransposon capsid structure. We speculate that the SCAN domain originally functioned to target host ZF proteins to retroelement capsids.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Ryan O
authors.initials: RO
authors.lastname: Emerson
authors.forename: James H
authors.initials: JH
authors.lastname: Thomas
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D008322:Mammals; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics; D018626:Retroelements; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D036022:Capsid Proteins; D011994:Recombinant Proteins; D018626:Retroelements; D014157:Transcription Factors; C110987:mdg4 protein (gypsy)