IDENTIFICATION AND CHARACTERIZATION OF THE HUMAN ORTHOLOG OF RAT STXBP1, A PROTEIN IMPLICATED IN VESICLE TRAFFICKING AND NEUROTRANSMITTER RELEASE

In a screen designed to identify genes expressed preferentially in ret ina, me identified a cDNA encoding the human ortholog of rat STXBP1 (n -Sec1, Munc-18-1, rbSec1), a protein implicated in vesicle trafficking and neurotransmitter release. This protein also has similarity to Dro sophila Rop (64% aa identity) and Caenorhabditis elegans UNC-18 (58% a a identity). The major human cDNA encodes a protein of 594 amino acids which has 100% amino acid identity with its rat and murine counterpar ts. Additionally, there is an alternative splice form in humans, arisi ng from the inclusion of an additional exon, which encodes a protein o f 603 amino acids and is also 100% identical to the corresponding rat isoform. We found expression of the shorter cDNA in all tissues and ce ll lines we examined with highest levels in retina and cerebellum. By RT-PCR analysis, we found expression of the longer cDNA in neural tiss ues only. We mapped the structural gene to 9q34.1, a region without ob vious candidate phenotypes. However, due to its evolutionary conservat ion and abundant expression in retina and brain, STXBP1 should be cons idered a candidate gene for retinal and/ or neural disorders mapping t o 9q34.1. (C) 1998 Academic Press.