Identification and characterization of LASP2 gene in silico.

LASP1 (also known as MLN50) gene, located centromeric to the PPP1R1B-ERBB2-GRB7 locus on human chromosome 17q12, is amplified and over-expressed in breast cancer. Here, we identified and characterized a novel LASP1-related gene, LASP2, by using bioinformatics. Nucleotide sequence of human LASP2 cDNA was determined in silico by assembling EST BF699808 and 5'-truncated FLJ39221 cDNA. Nucleotide sequence of mouse Lasp2 cDNA was derived from 1200007O21Rik cDNA. Human LASP2 (270 aa) showed 97.4% and 63.7% total-amino-acid identity with mouse Lasp2 and human LASP1, respectively. LASP2 and LASP1 were the LASP family proteins consisting of LIM domain, Nebulin repeat, and SH3 domain. LASP2 and NEBL mRNAs were transcribed from the LASP2/NEBL gene on human chromosome 10p12 due to alternative splicing. LASP2 mRNA consists of exons 1a-4a, 24, 27, and 28 of the LASP2/NEBL gene, while NEBL mRNA consists of exons 1-28. Exon 1a-4a of the LASP2/NEBL gene were more homologous to exon 1-4 of the LASP1 gene on human chromosome 17q12, while exon 1-28 of the LASP2/NEBL gene were more homologous to exons of NEB gene on human chromosome 2q23. Some part of the LASP2/ NEBL-TEM7L-ARL8-CACNB2 locus on 10p12 was paralogous to the LASP1-TEM7-CACNB1 locus on 17q12, while the other part of the LASP2/NEBL-TEM7L-ARL8-CACNB2 locus was paralogous to the NEB-ARL5-CACNB4 locus on 2q23. These facts indicate that the LASP2/NEBL-TEM7L-ARL8-CACNB2 is a chimeric locus, which might be generated through the homologous recombination between the ancestral lasp2-tem7l-cacnb2 locus and the ancestral nebl-arl8 locus. Therefore, gene fusion during evolution is one of the mechanisms to generate alternative splicing.