Identification and characterization of DISP3 gene in silico

Lipid-modified soluble proteins Hedgehog (SHH, DHH and IHH) and WNT (WNT1, WNT2, WNT2B, WNT3, etc.) share distantly related mechanisms for ligand modification as well as for signaling through seven-transmembrane protein with Frizzled domain. Hedgehog and WNT signaling pathways network together during embryogenesis and carcinogenesis. Dispatched 1 (DISP1) and Dispatched 2 (DISP2) are human homologs for Drosophila Dispatched implicated in the release of lipid-anchored Hedgehog from producing cells. Here, we identified and characterized Dispatched 3 (DISP3) gene by using bioinformatics. DISP3 complete coding sequence was determined by assembling BU170953 EST and KIAA1337 uncharacterized cDNA. DISP3 gene at human chromosome 1p36.22 was linked to D1S2667 microsatellite maker and TERE1 gene, whose locus is associated with prostate cancer, bladder cancer, and liver cancer. DISP3 mRNA was expressed in human embryonic stem (ES) cells, brain, testis, lung carcinoid, neuroblastoma, retinoblastoma and brain tumor. DISPH1 domain with five transmembrane regions (codon 452-637 of DISP3) and DISPH2 domain with four transmembrane regions (codon 1116-1319 of DISP3) were identified as novel domains conserved between DISP3 (1392 aa) and DISP1. The region around DISPH1 and DISPH2 domains of DISP3 protein was the Patched homologous region conserved among Patched family members and DISP family members. Because DISP3 and DISP1 are multi-span transmembrane proteins with the Patched homologous region, DISP3 is predicted to be implicated in the release of lipid-anchored secreted proteins. This is the first report on identification and characterization of the DISP3 gene.