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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 ([[literature:100814|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 ([[literature:100815|Sander ''et al''. 2003]]; [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A31264| Collins & Sander 2010]), as well as a ''hATd'' dimerization domain similar to that of the TR activator superfamily ([[literature:100817|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 ([[literature:100816|Bellefroid ''et al''. 1991]]; [[literature:33562 |Lander ''et al''. 2001]]; [[literature:79836|Venter ''et al''. 2001]]), a gene expression repressor motif involved in maintenance of the nucleolus, cell differentiation, cell proliferation, apoptosis, and neoplastic transformation ([[literature:100816|Bellefroid et al. 1991]]; [[literature:33562 |Lander et al. 2001]]; [[literature:79836|Venter ''et al''. 2001]]). For simplicity´s sake the figure below shows the genomic structure of each variant without introns.

<center>[[File:SCAN_KRAB.jpg]]</center>

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 ([[literature:24379|Gao & Voytas 2005]]; [[literature:100810|Feschotte & Pritham 2005]]; [[literature:61077|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 ([[literature:|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 ([[literature:100803|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 ([[literature:100815|Sander ''et al''. 2003]]; [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A31264| Collins & Sander 2010]).

SCAN/KRAB - Revision history

imported>GydbAdmin at 10:48, 4 November 2011