Drosophila Crumbs (Crb) - Stardust (Sdt) - Discs lost (Dlt) complex plays a pivotal role in the establishment and the maintenance of epithelial polarity. CRB1 and CRB3 are human homologs of Drosophila Crb, MPP1-MPP7 are human homologs of Drosophila Sdt, INADL/PATJ and MPDZ/MUPP1 are human homologs of Drosophila Dlt. Here, we identified and characterized a novel Crumbs family gene, Crumbs homolog 2 (CRB2), by using bioinformatics. CRB2 isoform 1 was assembled by adding nucleotide position 1-3353 of FLJ16786 cDNA (AK123000) to the 5'-end of 5'-truncated FLJ38464 cDNA (NM_173689.1), while that of CRB2 isoform 2 was derived from FLJ16786 cDNA. CRB2 isoform 1, consisting of exon 1-13, encoded a 1285-aa transmembrane protein. CRB2 isoform 2, consisting of exon 1-10 and intron 10, encoded a 1176-aa secreted protein. CRB2 gene was found to encode transmembrane protein as well as secreted protein due to alternative splicing. CRB2 isoform 1, showing 24.4% total amino-acid identity with CRB1, was type I transmembrane protein with 14 extracellular EGF-like domains, 3 extracellular Laminin G-like domains and the Crb cytoplasmic tail (CCT) domain. CCT domain, functioning as the binding site for PDZ domain of Sdt homologs, was conserved among human CRB1, CRB2, CRB3, mouse Crb1, Crb3, Drosophila Crb, and C. elegans crb. Comparative genomics revealed that CRB2-KIAA1608-LHX2-NEK6 locus at human chromosome 9q33.3 and CRB1-MGC27044-LHX9-NEK7 locus at human chromosome 1q31.3 were paralogous regions within the human genome. This is the first report on identification and characterization of the CRB2 gene.

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