Molecular characterization of a novel tubby gene family member, TULP3, in mouse and humans

Tubby and related proteins are derived from a small family of novel genes. The carboxytermini of this family are highly conserved across a number of s pecies including humans, mice, Caenorhabditis elegans, Arabidopsis, rice, a nd maize. Splicing defects in both tub and another member of the gene famil y, TULP1 (tubby-like protein 1), lead to phenotypes of retinal degeneration in mice and humans, respectively. We describe here the isolation of the hu man and mouse homologs of a new family member, TULP3. The cDNAs code for pr oteins of 442 and 460 amino acids, respectively. The level of identity betw een the human TULP3 and the mouse homolog is 69%, lower than that observed for the homologs of the other family members (96% for human and mouse TUB), and is higher at the amino-and carboxytermini than in the central region o f the protein. Phylogenetically, TULP3 is the family member most closely re lated to TUB. Also, like TUB, it has a wider pattern of tissue expression t han either TULP1 or TULP2. TULP3 is detected at high levels in human RNA fr om testis, ovaries, thyroid, and spinal chord. Tulp3 is also highly express ed in mouse RNA from eyes and adipose depots, tissues not tested in the hum an Northern analysis. We also report that TULP3 maps to human chromosome 12 p13. The murine homolog, Tulp3, maps to the telomere of mouse chromosome 6. (C) 1998 Academic Press.