Sodium-dependent serotonin transporter
Details
- Name
- Sodium-dependent serotonin transporter
- Kind
- protein
- Synonyms
- 5HT transporter
- 5HTT
- HTT
- SERT
- Solute carrier family 6 member 4
- Gene Name
- SLC6A4
- UniProtKB Entry
- P31645Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0001494|Sodium-dependent serotonin transporter METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTR HSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLP YTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIM AWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIH RSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGA TLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQD ALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPAS TFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVT LTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRIC WVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIIT PGTFKERIIKSITPETPTEIPCGDIRLNAV
- Number of residues
- 630
- Molecular Weight
- 70324.165
- Theoretical pI
- 6.17
- GO Classification
- Functionsactin filament binding / cocaine binding / monoamine transmembrane transporter activity / serotoninProcessesbrain morphogenesis / cellular response to cGMP / cellular response to retinoic acid / circadian rhythm / memory / monoamine transport / negative regulation of cerebellar granule cell precursor proliferation / negative regulation of neuron differentiation / negative regulation of organ growth / negative regulation of synaptic transmission, dopaminergic / positive regulation of cell cycle / positive regulation of gene expression / response to estradiol / response to hypoxia / response to nutrient / response to toxic substance / serotonin uptake / social behavior / sperm ejaculation / vasoconstrictionComponentsendomembrane system / endosome membrane / membrane raft / neuron projection / plasma membrane
- General Function
- Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the plasma membrane from the extracellular compartment to the cytosol thus limiting serotonin intercellular signaling (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Essential for serotonin homeostasis in the central nervous system. In the developing somatosensory cortex, acts in glutamatergic neurons to control serotonin uptake and its trophic functions accounting for proper spatial organization of cortical neurons and elaboration of sensory circuits. In the mature cortex, acts primarily in brainstem raphe neurons to mediate serotonin uptake from the synaptic cleft back into the pre-synaptic terminal thus terminating serotonin signaling at the synapse (By similarity). Modulates mucosal serotonin levels in the gastrointestinal tract through uptake and clearance of serotonin in enterocytes. Required for enteric neurogenesis and gastrointestinal reflexes (By similarity). Regulates blood serotonin levels by ensuring rapid high affinity uptake of serotonin from plasma to platelets, where it is further stored in dense granules via vesicular monoamine transporters and then released upon stimulation (PubMed:17506858, PubMed:18317590). Mechanistically, the transport cycle starts with an outward-open conformation having Na1(+) and Cl(-) sites occupied. The binding of a second extracellular Na2(+) ion and serotonin substrate leads to structural changes to outward-occluded to inward-occluded to inward-open, where the Na2(+) ion and serotonin are released into the cytosol. Binding of intracellular K(+) ion induces conformational transitions to inward-occluded to outward-open and completes the cycle by releasing K(+) possibly together with a proton bound to Asp-98 into the extracellular compartment. Na1(+) and Cl(-) ions remain bound throughout the transport cycle (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Additionally, displays serotonin-induced channel-like conductance for monovalent cations, mainly Na(+) ions. The channel activity is uncoupled from the transport cycle and may contribute to the membrane resting potential or excitability (By similarity)
- Specific Function
- actin filament binding
- Pfam Domain Function
- Signal Regions
- Not Available
- Transmembrane Regions
- 88-112 116-135 161-186 253-271 278-297 325-347 361-380 422-443 464-483 495-516 539-558 575-595
- Cellular Location
- Cell membrane
- Gene sequence
>lcl|BSEQ0021275|Sodium-dependent serotonin transporter (SLC6A4) ATGGAGACGACGCCCTTGAATTCTCAGAAGCAGCTATCAGCGTGTGAAGATGGAGAAGAT TGTCAGGAAAACGGAGTTCTACAGAAGGTTGTTCCCACCCCAGGGGACAAAGTGGAGTCC GGGCAAATATCCAATGGGTACTCAGCAGTTCCAAGTCCTGGTGCGGGAGATGACACACGG CACTCTATCCCAGCGACCACCACCACCCTAGTGGCTGAGCTTCATCAAGGGGAACGGGAG ACCTGGGGCAAGAAGGTGGATTTCCTTCTCTCAGTGATTGGCTATGCTGTGGACCTGGGC AATGTCTGGCGCTTCCCCTACATATGTTACCAGAATGGAGGGGGGGCATTCCTCCTCCCC TACACCATCATGGCCATTTTTGGGGGAATCCCGCTCTTTTACATGGAGCTCGCACTGGGA CAGTACCACCGAAATGGATGCATTTCAATATGGAGGAAAATCTGCCCGATTTTCAAAGGG ATTGGTTATGCCATCTGCATCATTGCCTTTTACATTGCTTCCTACTACAACACCATCATG GCCTGGGCGCTATACTACCTCATCTCCTCCTTCACGGACCAGCTGCCCTGGACCAGCTGC AAGAACTCCTGGAACACTGGCAACTGCACCAATTACTTCTCCGAGGACAACATCACCTGG ACCCTCCATTCCACGTCCCCTGCTGAAGAATTTTACACGCGCCACGTCCTGCAGATCCAC CGGTCTAAGGGGCTCCAGGACCTGGGGGGCATCAGCTGGCAGCTGGCCCTCTGCATCATG CTGATCTTCACTGTTATCTACTTCAGCATCTGGAAAGGCGTCAAGACCTCTGGCAAGGTG GTGTGGGTGACAGCCACCTTCCCTTATATCATCCTTTCTGTCCTGCTGGTGAGGGGTGCC ACCCTCCCTGGAGCCTGGAGGGGTGTTCTCTTCTACTTGAAACCCAATTGGCAGAAACTC CTGGAGACAGGGGTGTGGATAGATGCAGCCGCTCAGATCTTCTTCTCTCTTGGTCCGGGC TTTGGGGTCCTGCTGGCTTTTGCTAGCTACAACAAGTTCAACAACAACTGCTACCAAGAT GCCCTGGTGACCAGCGTGGTGAACTGCATGACGAGCTTCGTTTCGGGATTTGTCATCTTC ACAGTGCTCGGTTACATGGCTGAGATGAGGAATGAAGATGTGTCTGAGGTGGCCAAAGAC GCAGGTCCCAGCCTCCTCTTCATCACGTATGCAGAAGCGATAGCCAACATGCCAGCGTCC ACTTTCTTTGCCATCATCTTCTTTCTGATGTTAATCACGCTGGGCTTGGACAGCACGTTT GCAGGCTTGGAGGGGGTGATCACGGCTGTGCTGGATGAGTTCCCACACGTCTGGGCCAAG CGCCGGGAGCGGTTCGTGCTCGCCGTGGTCATCACCTGCTTCTTTGGATCCCTGGTCACC CTGACTTTTGGAGGGGCCTACGTGGTGAAGCTGCTGGAGGAGTATGCCACGGGGCCCGCA GTGCTCACTGTCGCGCTGATCGAAGCAGTCGCTGTGTCTTGGTTCTATGGCATCACTCAG TTCTGCAGGGACGTGAAGGAAATGCTCGGCTTCAGCCCGGGGTGGTTCTGGAGGATCTGC TGGGTGGCCATCAGCCCTCTGTTTCTCCTGTTCATCATTTGCAGTTTTCTGATGAGCCCG CCACAACTACGACTTTTCCAATATAATTATCCTTACTGGAGTATCATCTTGGGTTACTGC ATAGGAACCTCATCTTTCATTTGCATCCCCACATATATAGCTTATCGGTTGATCATCACT CCAGGGACATTTAAAGAGCGTATTATTAAAAGTATTACCCCAGAAACACCAACAGAAATT CCTTGTGGGGACATCCGCTTGAATGCTGTGTAA
- Chromosome Location
- 17
- Locus
- 17q11.2
- External Identifiers
Resource Link UniProtKB ID P31645 UniProtKB Entry Name SC6A4_HUMAN GenBank Protein ID 36433 GenBank Gene ID X70697 GeneCard ID SLC6A4 GenAtlas ID SLC6A4 HGNC ID HGNC:11050 PDB ID(s) 5I6X, 5I6Z, 5I71, 5I73, 5I74, 5I75, 6AWN, 6AWO, 6AWP, 6AWQ, 6DZV, 6DZW, 6DZY, 6DZZ, 6VRH, 6VRK, 6VRL, 6W2B, 6W2C, 7LI6, 7LI7, 7LI8, 7LI9, 7LIA, 7LWD, 7MGW, 7TXT KEGG ID hsa:6532 IUPHAR/Guide To Pharmacology ID 928 NCBI Gene ID 6532 - General References
- Lesch KP, Wolozin BL, Estler HC, Murphy DL, Riederer P: Isolation of a cDNA encoding the human brain serotonin transporter. J Neural Transm Gen Sect. 1993;91(1):67-72. [Article]
- Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS, Ganapathy V, Blakely RD: Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2542-6. [Article]
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- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
- Carneiro AM, Blakely RD: Serotonin-, protein kinase C-, and Hic-5-associated redistribution of the platelet serotonin transporter. J Biol Chem. 2006 Aug 25;281(34):24769-80. Epub 2006 Jun 27. [Article]
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- Ahmed BA, Jeffus BC, Bukhari SI, Harney JT, Unal R, Lupashin VV, van der Sluijs P, Kilic F: Serotonin transamidates Rab4 and facilitates its binding to the C terminus of serotonin transporter. J Biol Chem. 2008 Apr 4;283(14):9388-98. doi: 10.1074/jbc.M706367200. Epub 2008 Jan 28. [Article]
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Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Fluvoxamine approved, investigational yes target inhibitor Details Citalopram approved yes target inhibitor Details Venlafaxine approved yes target inhibitor Details Amitriptyline approved yes target inhibitor Details Fluoxetine approved, vet_approved yes target inhibitor Details Duloxetine approved yes target inhibitor Details Nortriptyline approved yes target inhibitor Details Amoxapine approved yes target inhibitor Details Paroxetine approved, investigational yes target inhibitor Details Trimipramine approved yes target inhibitor Details Sertraline approved yes target inhibitorbinderdownregulator Details Sibutramine approved, illicit, investigational, withdrawn yes target inhibitor Details Doxepin approved, investigational yes target inhibitor Details Escitalopram approved yes target inhibitor Details Dexfenfluramine approved, illicit, investigational, withdrawn yes target inhibitor Details Clomipramine approved, investigational, vet_approved yes target inhibitor Details Protriptyline approved yes target inhibitor Details Imipramine approved yes target inhibitor Details Dextromethorphan approved unknown target inhibitor Details Trazodone approved, investigational yes target inhibitor Details Minaprine approved unknown target inhibitor Details Cocaine approved, illicit yes target inhibitor Details Nefazodone approved, withdrawn yes target inhibitor Details Desipramine approved, investigational yes target inhibitor Details Midomafetamine experimental, illicit, investigational yes target negative modulator Details Zimelidine approved, withdrawn yes target inhibitor Details Amineptine illicit, withdrawn unknown target Details MMDA experimental, illicit yes target negative modulator Details Phentermine approved, illicit yes target inhibitor Details Bicifadine investigational yes target modulator Details Milnacipran approved, investigational yes target inhibitor Details OPC-14523 investigational unknown target Details CRx-119 investigational unknown target Details Tramadol approved, investigational yes target inhibitor Details Dasotraline investigational yes target inhibitor Details Tesofensine investigational unknown target Details Amitifadine investigational yes target inhibitor Details Mianserin approved, investigational unknown target inhibitor Details Atomoxetine approved unknown target binder Details Verapamil approved unknown target unknown Details Mazindol approved, investigational yes target inhibitor Details Chlorpheniramine approved unknown target inhibitor Details Fenfluramine approved, illicit, investigational, withdrawn yes target substrateinhibitor Details Tegaserod approved, investigational, withdrawn unknown transporter substrateinhibitor Details Desvenlafaxine approved, investigational yes target inhibitor Details Dexmethylphenidate approved, investigational unknown target inhibitor Details Pseudoephedrine approved yes target inhibitor Details 4-Methoxyamphetamine experimental, illicit yes target inhibitor Details Metamfetamine approved, illicit, withdrawn yes target negative modulator Details Ephedra sinica root nutraceutical yes target negative modulator Details Midomafetamine experimental, illicit, investigational unknown transporter Details Tapentadol approved no target inhibitor Details Levomilnacipran approved, investigational yes target inhibitor Details Loxapine approved unknown target binder Details Amphetamine approved, illicit, investigational unknown target binder Details Dopamine approved unknown target inhibitor Details Meperidine approved unknown target binder Details Butriptyline approved, withdrawn yes target antagonistinhibitor Details Vortioxetine approved, investigational yes target inhibitor Details Dosulepin approved yes target inhibitor Details Serotonin investigational, nutraceutical unknown target Details Nisoxetine experimental yes target inhibitor Details Nomifensine approved, withdrawn unknown target Details Etoperidone withdrawn no transporter inhibitor Details Lorpiprazole approved yes target antagonist Details Zotepine approved, investigational, withdrawn yes target antagonist Details Benzatropine approved no target inhibitor Details Vilazodone approved yes target inhibitor Details Mirtazapine approved unknown transporter substrateinhibitor Details Cyclobenzaprine approved unknown target inhibitor Details Aripiprazole approved, investigational unknown target modulator Details Lumateperone approved, investigational yes target inhibitor Details Pseudoephedrine approved unknown transporter inhibitor Details Procaine approved, investigational, vet_approved unknown transporter inhibitor Details Tenamfetamine experimental, illicit yes target inhibitor Details Seproxetine investigational yes target inhibitor Details Lubazodone experimental yes target inhibitor Details NS-2359 investigational yes target inhibitor Details Ampreloxetine investigational yes target modulator Details Brasofensine investigational yes target modulator Details Litoxetine investigational yes target modulator Details Deudextromethorphan investigational yes target modulator Details Bupropion approved yes target inhibitor Details Diethylpropion approved, illicit yes target inhibitor Details Tianeptine investigational yes target inhibitor Details Acetaminophen approved yes target inhibitor Details Chlorphentermine illicit, withdrawn yes target modulator Details