This is the N-terminal domain of Caenorhabditis elegans NRF-6 (Nose Resistant to Fluoxetine-4) and NDG-4 (resistant to nordihydroguaiaretic acid-4) proteins; the domain is also present in several other worm and fly proteins. NRF-6 and NDG-4 are multipass transmembrane proteins which may act together in a complex to function to transport fluoxetine across the hypodermal barrier to the inside of the animal, where it can then act on neuromuscular targets to induce muscle contraction.The complex may more generally play a role in regulation of membrane transport in C. elegans [ (PUBMED:10488330) ].
Family alignment:
There are 3235 NRF domains in 3202 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing NRF domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with NRF domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing NRF domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
Fluoxetine-resistant mutants in C. elegans define a novel family oftransmembrane proteins.
Mol Cell. 1999; 4: 143-52
Display abstract
Fluoxetine (Prozac) is an antidepressant that is thought to act byblocking presynaptic reuptake of the neurotransmitter serotonin. Despitewidespread clinical use of fluoxetine, direct evidence for this mechanismhas been difficult to obtain in vivo. We have determined that fluoxetinehas an additional neuromuscular effect on C. elegans that is distinct frominhibition of serotonin reuptake. By screening for mutants resistant tothis effect, we have identified seven genes. We report that two of thesegenes are homologous to each other and define a novel gene family thatencodes over a dozen multipass transmembrane proteins. Our findings mayhave clinical implications for the mechanism of action of fluoxetine.
Links (links to other resources describing this domain)
