******************************************************* * Sodium:neurotransmitter symporter family signatures * ******************************************************* 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. - Noradrenaline. - Proline. - Serotonin (5HT). - Taurine. - Rat orphan transporter NTT4. - Caenorhabditis elegans hypothetical transporter T23G5.5. All these transporters are glycoproteins of about 600 to 700 amino acid residues which seem to contain 12 transmembrane domains. Apparently both termini are cytoplasmically located. 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. -Consensus pattern: W-R-F-P-Y-x-[CA]-x(2)-N-G-G-G-x-[FY] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in SWISS-PROT: NONE. -Consensus pattern: Y-[LIVMFY]-x(2)-[SC]-[LIVMFY]-[STQ]-x(2)-L-P-W-x(2)-C- x(4)-N-[GST] [The C could be involved in a disulfide bond] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in SWISS-PROT: NONE. -Last update: June 1994 / Patterns and text revised. [ 1] Snyder S.H. Nature 354:187-187(1991). [ 2] Schloss P., Mayser W., Betz H. FEBS Lett. 307:76-80(1992). [ 3] Attwell D., Bouvier M. Curr. Biol. 2:541-543(1992). [ 4] Uhl G.R. Trends Neurosci. 15:265-268(1992). [ 5] Reizer J., Reizer A., Saier M.H. Jr. Submitted(1993).