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.