Exon‐Intron Structure, Analysis of Promoter Region, and Chromosomal Localization of the Human Type 1 σ Receptor Gene

Abstract

a receptor is a protein that interacts with a variety of psychotomimetic drugs including cocaine and amphetamines and is believed to play an important role in the cellular functions of various tissues associated with the endocrine, immune, and nervous systems. Here we report on the structure and organization of the human gene coding for this receptor. The gene is -~7kbp long and contains four exons, interrupted by three introns. Exon 3 is the shortest (93 bp), and exon 4 is the longest (1,132 bp). Among the introns, intron 3 is the longest ('-~1250 bp). Exon 2 codes for the single transmembrane domain present in the receptor. 5' rapid amplification of cDNA end reactions with mRNA from the JAR human trophoblast cell line have identified 56 bp upstream of the translation start codon as the initiation site for transcription. This transcription start site has been confirmed by RNase protection analysis. Structural analysis of the 5' flanking region has revealed that the gene is TATAless. This region, however, contains a CCAATC box in the reverse complement and several GO boxes that are recognition sites for SP1. There are also consensus sequences for the liver-specific transcription factor nuclear factor-i IL, for a variety of cytokine responsive factors, and for the xenobiotic responsive factor called the arylhydrocarbon receptor. Southern blot analysis of the genomic DNA from Chinese hamster-human and mouse-human hybrid cell lines and fluorescent in situ hybridization with human metaphase chromosome spreads have shown that the gene is located on human chromosome 9, band p13, a region known to be associated with different psychiatric disorders.

Crucial Interactions Between Selective Serotonin Uptake Inhibitors and Sigma-1 Receptor in Heart Failure

“…The murine sigma-1 receptor gene (approximately 7 kb) is made up of 4 exons and 3 introns and is TATAless, containing CCAATC and GC boxes immediately upstream of the transcription start site (12). Southern blot analysis of genomic DNA indicates that the gene is located on human chromosome 9, band p13, a region associated with different psychiatric disorders (14).…”

The Sigma1 Protein as a Target for the Non-genomic Effects of Neuro(active)steroids: Molecular, Physiological, and Behavioral Aspects

“…In addition, anionic amino acid residues were identified, D126 and E172, that also appeared critical for ligand binding (63). The promoter region sequence of the σ 1 receptor contains several consensus sequences for the liver-specific transcription factors nuclear factor (NF)-1 / L, activator protein (AP)-1, AP-2, IL-6RE, NF-GMa, NF-GMb, NF-κB, steroid response element, GATA-1, Zeste, and for the xenobiotic responsive factor called the arylhydrocarbon receptor (61,64).…”

Sigma Receptors and Cancer

“…Among the introns, intron 3 is the longest (ϳ1250 bp). Exon 2 codes for the single transmembrane domain present in the receptor (15). In humans, the gene for the 1 receptor is located on chromosome 9p13, a region associated with psychiatric disorders (15).…”