PROSITE documentation PDOC00533

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 [1,2,3,4]. 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:

• βine (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.