{PDOC00533} {PS00610; NA_NEUROTRAN_SYMP_1} {PS00754; NA_NEUROTRAN_SYMP_2} {PS50267; NA_NEUROTRAN_SYMP_3} {BEGIN} ******************************************************************* * Sodium:neurotransmitter symporter family signatures and profile * ******************************************************************* After their release by synapses the action of a number of neurotransmitters is terminated by their high affinity sodium-dependent reuptake into presynaptic terminals by specific transport proteins [1 to 4]. These proteins are the target of psychomotor stimulants such as amphetamines or cocaine. All these proteins belong to a family, known [5] as the sodium:neurotransmitter symporter family (SNF), that also include some transporters that function outside the brain and carry related molecules. The SNF family is currently known to consist of transporters for: - Betaine (also transports GABA). - Choline. - Creatine. - Dopamine. - GABA (four different forms of GABA transporters have been characterized). - Glycine (two forms). - Noradrenaline. - Proline. - Serotonin (5HT). - Taurine. - Mammalian orphan transporter NTT4. - Caenorhabditis elegans hypothetical transporter T23G5.5. - Haemophilus hypothetical proteins HI0736 and HI1690. - Methanococcus jannaschii hypothetical MJ1319. These transporters are glycoproteins of about 600 to 700 amino-acid residues. The two bacterial proteins are smaller (457 to 508 residues). These proteins seem to contain 12 transmembrane domains and both termini are predicted to be located in the cytoplasm. As signature patterns for these proteins we have selected two highly conserved regions. The first region spans the C-terminal part of the first transmembrane domain, a short extracellular loop, and the N-terminal part of the second transmembrane domain. The second region is located in the largest extracellular loop between the third and fourth transmembrane domains; this region contains two conserved cysteines that could be involved in disulfide bonds. We also developed a profile for this family of proteins. -Consensus pattern: W-[RK]-F-[GPA]-[YF]-x(4)-[NYHS]-G-G-[GCA]-x-[FY] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Consensus pattern: [YF]-[LIVMFY]-x(2)-[SC]-[LIVMFY]-[STQV]-x(2)-[LVI]-P-W- x(2)-C-x(3,4)-[NWDS]-[GSTERHAK] [The C may be involved in a disulfide bond] -Sequences known to belong to this class detected by the pattern: ALL, except for the bacterial and archaebacterial proteins which are divergent in this region. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: December 2004 / Patterns and text revised. [ 1] Snyder S.H. "Neuroscience. Vehicles of inactivation." Nature 354:187-187(1991). PubMed=1683684; DOI=10.1038/354187a0 [ 2] Schloss P., Mayser W., Betz H. "Neurotransmitter transporters. A novel family of integral plasma membrane proteins." FEBS Lett. 307:76-80(1992). PubMed=1353462 [ 3] Attwell D., Bouvier M. "Cloners quick on the uptake." Curr. Biol. 2:541-543(1992). PubMed=15336049 [ 4] Uhl G.R. "Neurotransmitter transporters (plus): a promising new gene family." Trends Neurosci. 15:265-268(1992). PubMed=1381123 [ 5] Reizer J., Reizer A., Saier M.H. Jr. "A functional superfamily of sodium/solute symporters." Biochim. Biophys. Acta 1197:133-166(1994). PubMed=8031825 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}