Solute carrier families 5 and 6-like; solute binding domain; This superfamily includes the solute-binding domain of SLC5 proteins (also called the sodium/glucose cotransporters or solute sodium symporters), SLC6 proteins (also called the sodium- and chloride-dependent neurotransmitter transporters or Na+/Cl--dependent transporters), and nucleobase-cation-symport-1 (NCS1) transporters. SLC5s co-transport Na+ with sugars, amino acids, inorganic ions or vitamins. SLC6s include Na+/Cl--dependent plasma membrane transporters for the monoamine neurotransmitters serotonin, dopamine, and norepinephrine, and the amino acid neurotransmitters GABA and glycine. NCS1s are essential components of salvage pathways for nucleobases and related metabolites; their known substrates include allantoin, uracil, thiamine, and nicotinamide riboside. Members of this superfamily are important in human physiology and disease. They contain a functional core of 10 transmembrane helices (TMs): an inverted structural repeat, TMs1-5 and TMs6-10; TMs numbered to conform to the SLC6 Aquifex aeolicus LeuT.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119628565  15 PFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHCNNSWNSPNCSDAHPGDSSGDSSGLNDTFGTTPAAE 94
Cdd:cd11514   77 PIFKGVGFTVILISLYVGFFYNVIIAWALFYLFSSFTGELPWIHCNNSWNSPNCSDAHPGDSSGDSSGLNDTYKTTPAAE 156

                 ....
gi 119628565  95 YFER 98
Cdd:cd11514  157 YFER 160

Na(+)- and Cl(-)-dependent dopamine transporter 1; solute-binding domain; DAT1 (also called DAT), is a plasma membrane transport protein that functions at the dopaminergic synapses to transport dopamine from the extracellular space back into the presynaptic nerve terminal. Human DAT1 is encoded by the SLC6A3 gene, and is expressed in the brain. DAT1 may play a role in diseases or disorders related to dopaminergic neurons, including attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, Parkinson's disease, alcoholism, drug abuse, schizophrenia, extraversion, and risky behavior. This subgroup belongs to the solute carrier 6 (SLC6) transporter family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119628565  15 PFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHCNNSWNSPNCSDAHPGDSSGDSSGLNDTFGTTPAAE 94
Cdd:cd11514   77 PIFKGVGFTVILISLYVGFFYNVIIAWALFYLFSSFTGELPWIHCNNSWNSPNCSDAHPGDSSGDSSGLNDTYKTTPAAE 156

                 ....
gi 119628565  95 YFER 98
Cdd:cd11514  157 YFER 160

Na+-dependent transporter, SNF family [General function prediction only];

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 119628565  20 VGFTVILISLYVGFFYNVIIAWALHYLFSSFTTEL 54
Cdd:COG0733   89 IGWLGVLGAFLILSYYSVVAGWVLAYLFKSLTGAF 123

Na(+)- and Cl(-)-dependent dopamine transporter 1; solute-binding domain; DAT1 (also called DAT), is a plasma membrane transport protein that functions at the dopaminergic synapses to transport dopamine from the extracellular space back into the presynaptic nerve terminal. Human DAT1 is encoded by the SLC6A3 gene, and is expressed in the brain. DAT1 may play a role in diseases or disorders related to dopaminergic neurons, including attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, Parkinson's disease, alcoholism, drug abuse, schizophrenia, extraversion, and risky behavior. This subgroup belongs to the solute carrier 6 (SLC6) transporter family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119628565  15 PFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHCNNSWNSPNCSDAHPGDSSGDSSGLNDTFGTTPAAE 94
Cdd:cd11514   77 PIFKGVGFTVILISLYVGFFYNVIIAWALFYLFSSFTGELPWIHCNNSWNSPNCSDAHPGDSSGDSSGLNDTYKTTPAAE 156

                 ....
gi 119628565  95 YFER 98
Cdd:cd11514  157 YFER 160

Sodium:neurotransmitter symporter family; These are twelve xTM-containing region transporters.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119628565   14 SPFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHCNNSWNSPNCSDAHpgdssGDSSGLNDTFGTTPAA 93
Cdd:pfam00209  77 CPLFKGIGYASMVIAFYIGIYYNVIIAWALYYLFSSFTTELPWASCNNSWNTPNCTEFF-----SANNTTNSLNKTSPVE 151

                          90
                  ....*....|....*.
gi 119628565   94 EYFER-TLRLSRHFGE 108
Cdd:pfam00209 152 EFWERkVLKLSDGIED 167

uncharacterized subgroup of the SERT-like Na(+)- and Cl(-)-dependent monoamine transporter subfamily; solute binding domain; SERT-like Na(+)- and Cl(-)-dependent monoamine transporters, transport monoamine neurotransmitters from synaptic spaces into presynaptic neurons. Members include: the norepinephrine transporter NET, the serotonin transporter SERT , and the dopamine transporter DAT1. These latter may play a role in diseases or disorders including depression, anxiety disorders, and attention-deficit hyperactivity disorder, and in the control of human behavior and emotional states. They belongs to the solute carrier 6 (SLC6) transporter family. Members of this subgroup are uncharacterized.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119628565   7 TCVGSMAsPFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHCNNSWNSPNCSDAHPG------------ 74
Cdd:cd11556   71 TSWGRLC-PLFKGIGYAVVLIAFYVDFFYNVIIAWSLYYFFASFTFNLPWTSCNNSWNTPNCREFHWSedgtvpcrsanq 149

                         90       100
                 ....*....|....*....|....
gi 119628565  75 DSSGDSSGLNDTFGTTPAAEYFER 98
Cdd:cd11556  150 SFSAENQSAQSENFTSAASEYFER 173

Na(+)- and Cl(-)-dependent serotonin transporter SERT; solute-binding domain; SERT (also called 5-HTT), is a transmembrane transporter that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. The antiport of a K+ ion is believed to follow the transport of serotonin and promote the reorientation of SERT for another transport cycle. Human SERT is encoded by the SLC6A4 gene. SERT is expressed in brain, peripheral nervous system, placenta, epithelium, and platelets. SERT may play a role in diseases or disorders including anxiety, depression, autism, gastrointestinal disorders, premature ejaculation, and obesity. It may also have a role in social cognition. This subgroup belongs to the solute carrier 6 (SLC6) transporter family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119628565  15 PFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHCNNSWNSPNCSDAHPGDssgDSSGLNDTfgTTPAAE 94
Cdd:cd11513   78 PIFKGIGYAICIIALYVASYYNTIIAWALYYLYSSFTDELPWTSCNNSWNTGNCTNYFAKD---NITWTLHS--TSPAEE 152

                 ....
gi 119628565  95 YFER 98
Cdd:cd11513  153 FYTR 156

Na(+)- and Cl(-)-dependent taurine transporter; solute-binding domain; TauT is a Na(+)- and Cl(-)-dependent, high-affinity, low-capacity transporter of taurine and beta-alanine. Human TauT is encoded by the SLC6A6 gene. TauT is expressed in brain, retina, liver, kidney, heart, spleen, and pancreas. It may play a part in the supply of taurine to the intestinal epithelium and in the between-meal-capture of taurine. It may also participate in re-absorbing taurine that has been deconjugated from bile acids in the distal lumen. Functional TauT protects kidney cells from nephrotoxicity caused by the chemotherapeutic agent cisplatin; cisplatin down-regulates TauT in a p53-dependent manner. In mice, TauT has been shown to be important for the maintenance of skeletal muscle function and total exercise capacity. TauT-/- mice develop additional clinically important diseases, some of which are characterized by apoptosis, including vision loss, olfactory dysfunction, and chronic liver disease. This subgroup belongs to the solute carrier 6 (SLC6) transporter family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119628565  15 PFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHCNNSWNSPNCSDAHPGDSSGDSSGLNDTFGTTPAAE 94
Cdd:cd11510   78 PIFTGIGYASIVIVSLLNIYYIVILAWALYYLFQSFQSELPWAHCNQKWNTPCCVEDTLRKNKTLWASINATNFTSPVTE 157

                 ....
gi 119628565  95 YFER 98
Cdd:cd11510  158 FWER 161

Na(+)- and Cl(-)-dependent glycine transporter GlyT1; solute-binding domain; GlyT1 is a membrane-bound transporter that re-uptakes glycine from the synaptic cleft. Human GlyT1 is encoded by the SLC6A9 gene. GlyT1 is expressed in brain, pancreas, uterus, stomach, spleen, liver, and retina. GlyT1 may play a role in schizophrenia. This subgroup belongs to the solute carrier 6 (SLC6) transporter family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119628565  14 SPFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHCNNSWNSPNCSDAHPGDSSGDSS------------ 81
Cdd:cd11498   92 SPMFKGVGYGMMVVSTYIGIYYNVVICIAFYYFFMSMTRVLPWTYCNNPWNTPDCAGVLSTNRSNATFanmsavvsnlte 171

                         90       100
                 ....*....|....*....|....*....
gi 119628565  82 GLNDTFG-TTPAAEYFER-TLRLSRHFGE 108
Cdd:cd11498  172 LLNRTLKrTSPSEEYWRRyVLNISDDIGN 200

Na(+)- and Cl(-)-dependent GABA transporter 1; solute-binding domain; GAT1 transports gamma-aminobutyric acid (GABA). GABA is the main inhibitory neurotransmitter within the mammalian CNS. Human GAT1 is encoded by the SLC6A1 gene. GAT1 is expressed in brain and peripheral nervous system. The antiepileptic drug, Tiagabine, inhibits GAT1. This subgroup belongs to the solute carrier 6 (SLC6) transporter family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119628565  14 SPFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHCNNSWNSPNCSDAHpgdssgdsSGLNDTFGTTPAA 93
Cdd:cd11506  118 APMFKGVGLAAAVLSFWLNIYYIVIIAWAIYYLYNSFTTTLPWKSCDNPWNTDRCFSNY--------SMANTTNMTSAVV 189

                 ....*..
gi 119628565  94 EYFERTL 100
Cdd:cd11506  190 EFWERNM 196

Na(+)- and Cl(-)-dependent creatine transporter 1; solute-binding domain; CT1 (also called CRTR, CRT) transports creatine. Human CT1 is encoded by the SLC6A8 gene. CT1 is ubiquitously expressed, with highest levels found in skeletal muscle and kidney. Creatine is absorbed from food or synthesized from arginine and plays an important role in energy metabolism. Deficiency in human CT1 leads to X-linked cerebral creatine transporter deficiency. In males, this disorder is characterized by language and speech delays, autistic-like behavior, seizures in about 50% of cases, and can also involve midfacial hypoplasia, and short stature. In females, it is characterized by mild cognitive impairment with behavior and learning problems. This subgroup belongs to the solute carrier 6 (SLC6) transporter family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119628565  14 SPFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHCNNSWNSPNCSDAHPGDSSGDSSGLNDTFGT---- 89
Cdd:cd11509   76 APLFKGLGYASMVIVFFCNTYYIMVLAWGFYYLVKSFTNTLPWATCGNPWNTPNCTEIFRHADCNNGASSAGSLANltcd 155

                         90       100
                 ....*....|....*....|....*.
gi 119628565  90 ------TPAAEYFER-TLRLSRHFGE 108
Cdd:cd11509  156 elanrrSPVIEFWERkVLRLSGGLEE 181

Na(+)- and Cl(-)-dependent GABA transporter 3; solute-binding domain; This family includes human GAT3 (hGAT3) a high-affinity transporter of gamma-aminobutyric acid (GABA). GABA is the main inhibitory neurotransmitter within the mammalian CNS. hGAT3 is encoded by the SLC6A11 gene, and is similar to mouse GAT4, and rat GAT3/GATB. GAT3 is expressed primarily in the glia of the brain, and is a potential drug target for antiepileptic drugs. This subgroup belongs to the solute carrier 6 (SLC6) transporter family

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119628565  15 PFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHCNNSWNSPNCSDAHPGDSSgDSSGLNDTFGTTPAAE 94
Cdd:cd11508   79 PLFEGIGYATQVIEAHLNVYYIIILAWAIFYLFNCFTTELPWATCGHEWNTENCVEFQKLNSS-NCSHVSLQNATSPVME 157

                         90
                 ....*....|.
gi 119628565  95 YFE-RTLRLSR 104
Cdd:cd11508  158 FWErRVLAISD 168

Na(+)-dependent neutral amino acids transporter, B0AT1; solute-binding domain; B0AT1 (also called HND) transports neutral amino acids. Human B0AT1 is encoded by the SLC6A19 gene. B0AT1 is expressed primarily in the kidney and intestine; it requires collectrin for expression in the kidney, and angiotensin-converting enzyme 2 for expression in the intestine. Interaction with these two proteins implicates B0AT1 in more complex processes such as glomerular structure, exocytosis, and blood pressure control. The autosomal recessive disorder, Hartnup disorder, is caused by mutations in B0AT1. This subgroup belongs to the solute carrier 6 (SLC6) transporter family.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 119628565   6 STCVGSMASPFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHC----NNSWNSPNCSDAHPGD 75
Cdd:cd11516   69 SVGVWSTIHPTLKGVGIASMCVSFLVSLYYNTIIAWVMWYFFNSFQEPLPWSQCplneNRTGYIPECAKSSPVD 142

Na(+)-dependent neurotransmitter transporter 4, and related proteins; solute-binding domain; This subgroup includes the solute-binding domain of NTT4 (also called XT1) and SBAT1 (also called B0AT2, v7-3, NTT7-3); both these proteins can transport neutral amino acids. Human SBAT1 is encoded by the SLC6A15 gene, a susceptibility gene for major depression. SBAT1 is expressed in brain, and may have a role in transporting neurotransmitter precursors into neurons. Human NTT4 is encoded by the SLC6A17 gene. NTT4 is specifically expressed in the nervous system, in synaptic vesicles of glutamatergic and GABAergic neurons, and may play an important role in synaptic transmission. This subgroup belongs to the solute carrier 6 (SLC6) transporter family.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 119628565  14 SPFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHC 59
Cdd:cd11515   77 SPRLGGIGFASCVVCLFVALYYNVIIGWSLFYFSQSFQQPLPWDQC 122

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.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 119628565  12 MASPFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSF 50
Cdd:cd10324   74 RIAPLFKGVGYAQVLVSFLVAIYYNVIIAWTLYYLFASF 112

glycine transporter, B0AT3; solute-binding domain; B0AT3 (also called Xtrp2, XT2) transports glycine. Human B0AT3 is encoded by the SLC6A18 gene. B0AT3 is expressed in the kidney. Mutations in the SLC6A18 gene may contribute to the autosomal recessive disorder iminoglycinuria and its related disorder hyperglycinuria. SLC6A18 or its neighboring genes are associated with increased susceptibility to myocardial infarction. This subgroup belongs to the solute carrier 6 (SLC6) transporter family.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 119628565  14 SPFPLGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHC 59
Cdd:cd11517   78 SPYLGGVGLGCVTVSFLVSLYYNTILAWVLWYFLNSFQHPLPWSSC 123

Na+-dependent transporter, SNF family [General function prediction only];

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 119628565  20 VGFTVILISLYVGFFYNVIIAWALHYLFSSFTTEL 54
Cdd:COG0733   89 IGWLGVLGAFLILSYYSVVAGWVLAYLFKSLTGAF 123