Human and mouse homologues of the Drosophila melanogaster tweety (tty) gene: A novel gene family encoding predicted transmembrane proteins

We have cloned cDNA for TTYH1, a human homologue of the Drosophila melanoga ster tweety (tty) gene. The 450-residue predicted protein shows 27% amino a cid sequence identity (51% similarity) to the Drosophila protein, which con tains an additional C-terminal repetitive region. A second Drosophila homol ogue exhibits 42% identity (65% similarity) to the tty protein. Mouse (Ttyh 1), macaque, and Caenorhabditis elegans homologues were also identified, an d the complete coding sequence for the mouse gene was determined. The mouse protein is 91% identical to the human protein. Hydrophobicity analysis of the tty-related proteins indicates that they represent a new family of memb rane proteins with five potential membrane-spanning regions. The yeast FTR1 and FTH1 iron transporter proteins and the mammalian neurotensin receptors 1 and 2 have a similar hydrophobicity profile, although there is no detect able sequence homology to the tty-related proteins, This suggests that the tweety-related proteins could be involved in transport of iron or other div alent cations or alternatively that they may be membrane-bound receptors, T TYH1 was mapped to chromosome 19q13.4 by FISH and by radiation hybrid mappi ng using the Stanford G3 panel. (C) 2000 Academic Press.