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Solute carrier 6 family, neurotransmitter transporters; solute-binding domain This family represents the solute-binding domain of SLC6 proteins (also called the sodium- and chloride-dependent neurotransmitter transporter family or Na+/Cl--dependent transporter family). These use sodium and chloride electrochemical gradients to catalyze the thermodynamically uphill movement of a variety of substrates, and include neurotransmitter transporters (NTTs). The latter are Na+/Cl--dependent plasma membrane transporters for the monoamine neurotransmitters serotonin (5-hydroxytryptamine), dopamine, and norepinephrine, and the amino acid neurotransmitters GABA and glycine. NTTs are widely expressed in the mammalian brain, and are involved in regulating neurotransmitter signaling and homeostasis, through facilitating the uptake of released neurotransmitters from the extracellular space into neurons and glial cells. NTTs are the target of a range of therapeutic drugs for the treatment of psychiatric diseases, such as major depression, anxiety disorders, attention deficit hyperactivity disorder and epilepsy. In addition, they are the primary targets of cocaine, amphetamines and other psychostimulants. This family also includes Drosophila Blot which is expressed primarily in epithelial tissues of ectodermal origin and in the nervous system of the embryo and larvae, but in addition found in the developing oocyte and the freshly laid egg. A lack or reduction of Blot function during oogenesis results in early arrest of embryonic development. 12 transmembrane helices (TMs) appears to be common for eukaryotic and some prokaryotic and archaeal SLC6s, (a core inverted topology repeat, TM1-5 and TM6-10, plus TMs11-12; TMs numbered to conform to the SLC6 Aquifex aeolicus LeuT), although a majority of bacterial, and some archaeal SLC6s lack TM12, for example the functional Fusobacterium nucleatum tyrosine transporter Tyt1. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",