The SCAN/KRAB cellular integrases (C-INTs) are two intron-exon structured host gene paralogs of the eutherian genomes, which split into two variants (formally called ZNF452/SCAND3 (of approximately 1,300 residues) and KRBA2 (460-500 residues) according to the Genbank nomenclature (Benson et al. 2010). ZNF452/SCAND3 shows at its N-terminus, a dimerization SCAN domain involved in transcriptional regulation of growth factors and genes involved in metabolism, cell survival and differentiation (Sander et al. 2003; Collins & Sander 2010), as well as a hATd dimerization domain similar to that of the TR activator superfamily (Rubin et al. 2001) at its C-terminus. In turn, the KRBA2 variant lacks the hATd domain and substitutes the SCAN domain by a module called Krüppel-associated box (KRAB) domain (Bellefroid et al. 1991; Lander et al. 2001; Venter et al. 2001), a gene expression repressor motif involved in maintenance of the nucleolus, cell differentiation, cell proliferation, apoptosis, and neoplastic transformation (Bellefroid et al. 1991; Lander et al. 2001; Venter et al. 2001). For simplicity´s sake the figure below shows the genomic structure of each variant without introns.


While the original notion in the origin of SCAN/KRAB C-INTs is that they might me related to the Integrases (INTs) of LTR retroelements or with the transposases (TRs) coded by the Maverick/Polinton transposons (Gao & Voytas 2005; Feschotte & Pritham 2005; Pritham et al. 2007), recent research has revealed that SCAN/KRAB C-INTs unequivocally evolve from the domestication of a GINGER2 transposon, which probably was horizontally transferred from insects to the eutherians after to the methaterian-eutherian (Llorens et al. submitted).

There are three complementary classifications for SCAN/KRAB C-INTs. Based on sequence these enzymes can be classified as DDE TRs and INTs. Based on INT-like structural potential similarities, SCAN/KRAB C-INTs are members of the Retroviral Integrase Superfamily (Nowotny 2009) of nucleic acid-processing enzymes involved in; a) selfish evolution; b) replication and repair of DNA; c) recombination and gene fusion; d) RNA-mediated gene silencing; and e) oncogenesis. Based on the presence of additional SCAN/KRAB domains these enzymes can be classified as chimeric members of the SCAN superfamily of zinc finger transcription factors (Sander et al. 2003; Collins & Sander 2010).

Welcome to the Gypsy Database (GyDB) an open editable database about the evolutionary relationship of viruses, mobile genetic elements (MGEs) and the genomic repeats where we invite all authors to contribute with their knowledge to improve and expand the topics.
Cite this project:

Llorens, C., Futami, R., Covelli, L., Dominguez-Escriba, L., Viu, J.M., Tamarit, D., Aguilar-Rodriguez, J. Vicente-Ripolles, M., Fuster, G., Bernet, G.P., Maumus, F., Munoz-Pomer, A., Sempere, J.M., LaTorre, A., Moya, A. (2011) The Gypsy Database (GyDB) of Mobile Genetic Elements: Release 2.0 Nucleic Acids Research (NARESE) 39 (suppl 1): D70-D74 doi: 10.1093/nar/gkq1061

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