The alpha and beta forms of Neurexins 1 - 3 are transmembrane neuronal glycoproteins which are transcribed from each of three NRXN genes that utilize alternate promoters. Like other Neurexins, the extracellular domain (ECD) of Neurexin 3 alpha contains six LNS domains interspersed with three EGF-like domains, while that of Neurexin 3 beta contains only the sixth LNS domain and no EGF-like domains (1 - 3). Mature human Neurexin 3 beta is a 70 kDa glycosylated protein with a 528 amino acid (aa) ECD and a 56 aa cytoplasmic domain that contains a motif for binding PDZ scaffolding proteins (3 - 5). Within comparable regions of the ECD, human Neurexin 3 beta shares 99% aa sequence identity with mouse and rat Neurexin 3 beta . It shares 65% aa sequence identity with comparable regions of the ECD of human Neurexin 1 beta and 2 beta . Alternative splicing of human Neurexin 3 beta generates multiple isoforms. There are potentially soluble and secreted variants and some which contain a fibronectin type III-like domain (4, 6). Neurexin 3 beta is widely expressed in the brain where it binds the postsynaptic Neuroligins 1, 2, and 3 (6 - 9). Neurexin 3 beta may also be expressed in non-nervous tissues with a potentially cardiac-specific isoform (10). Human Neurexin 3 beta polymorphisms which affect the splicing pattern are associated with susceptibility to alcohol dependence (6). The Neurexin 3 beta genetic locus has been linked to opioid and nicotine addiction, and Neurexin 3 beta gene expression is upregulated after short term exposure of mice to cocaine (11 - 13).
| Uniprot | Human |
| Product By Gene ID | 9369 |
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