Sodium-dependent serotonin transporter

Details

Name
Sodium-dependent serotonin transporter
Synonyms
  • 5HT transporter
  • 5HTT
  • HTT
  • SERT
  • Solute carrier family 6 member 4
Gene Name
SLC6A4
Organism
Humans
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
Functions
actin filament binding / cocaine binding / monoamine transmembrane transporter activity / Rab GTPase binding / serotonin / serotonin transmembrane transporter activity
Processes
brain 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 / protein homooligomerization / protein oligomerization / response to drug / response to estradiol / response to hypoxia / response to nutrient / response to toxic substance / serotonin transport / serotonin uptake / social behavior / sperm ejaculation / synaptic transmission / thalamus development / vasoconstriction
Components
cytosol / endomembrane system / endosome membrane / integral component of plasma membrane / membrane raft / neuron projection / plasma membrane
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Pfam Domain Function
Transmembrane Regions
88-108 116-135 160-180 253-271 280-297 333-350 362-383 417-436 464-482 498-518 539-558 577-595
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
17q11.1-q12
External Identifiers
ResourceLink
UniProtKB IDP31645
UniProtKB Entry NameSC6A4_HUMAN
GenBank Protein ID36433
GenBank Gene IDX70697
GenAtlas IDSLC6A4
HGNC IDHGNC:11050
General References
  1. 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. [PubMed:8452685]
  2. 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. [PubMed:7681602]
  3. Lesch KP, Wolozin BL, Murphy DL, Reiderer P: Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem. 1993 Jun;60(6):2319-22. [PubMed:7684072]
  4. Iceta R, Mesonero JE, Aramayona JJ, Alcalde AI: Molecular characterization and intracellular regulation of the human serotonin transporter in Caco-2 cells. J Physiol Pharmacol. 2006 Mar;57(1):119-30. [PubMed:16601320]
  5. 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. [PubMed:15489334]
  6. 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. [PubMed:14702039]
  7. 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. [PubMed:16803896]
  8. Muller HK, Wiborg O, Haase J: Subcellular redistribution of the serotonin transporter by secretory carrier membrane protein 2. J Biol Chem. 2006 Sep 29;281(39):28901-9. Epub 2006 Jul 26. [PubMed:16870614]
  9. Brenner B, Harney JT, Ahmed BA, Jeffus BC, Unal R, Mehta JL, Kilic F: Plasma serotonin levels and the platelet serotonin transporter. J Neurochem. 2007 Jul;102(1):206-15. Epub 2007 May 15. [PubMed:17506858]
  10. Zhang YW, Gesmonde J, Ramamoorthy S, Rudnick G: Serotonin transporter phosphorylation by cGMP-dependent protein kinase is altered by a mutation associated with obsessive compulsive disorder. J Neurosci. 2007 Oct 3;27(40):10878-86. [PubMed:17913921]
  11. 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. [PubMed:18227069]
  12. Ahmed BA, Bukhari IA, Jeffus BC, Harney JT, Thyparambil S, Ziu E, Fraer M, Rusch NJ, Zimniak P, Lupashin V, Tang D, Kilic F: The cellular distribution of serotonin transporter is impeded on serotonin-altered vimentin network. PLoS One. 2009;4(3):e4730. doi: 10.1371/journal.pone.0004730. Epub 2009 Mar 9. [PubMed:19270731]
  13. Annamalai B, Mannangatti P, Arapulisamy O, Shippenberg TS, Jayanthi LD, Ramamoorthy S: Tyrosine phosphorylation of the human serotonin transporter: a role in the transporter stability and function. Mol Pharmacol. 2012 Jan;81(1):73-85. doi: 10.1124/mol.111.073171. Epub 2011 Oct 12. [PubMed:21992875]
  14. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed:10391209]
  15. Ozaki N, Goldman D, Kaye WH, Plotnicov K, Greenberg BD, Lappalainen J, Rudnick G, Murphy DL: Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. Mol Psychiatry. 2003 Nov;8(11):933-6. [PubMed:14593431]
  16. Kilic F, Murphy DL, Rudnick G: A human serotonin transporter mutation causes constitutive activation of transport activity. Mol Pharmacol. 2003 Aug;64(2):440-6. [PubMed:12869649]
  17. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R: Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003 Jul 18;301(5631):386-9. [PubMed:12869766]
  18. Feinn R, Nellissery M, Kranzler HR: Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence. Am J Med Genet B Neuropsychiatr Genet. 2005 Feb 5;133B(1):79-84. [PubMed:15635638]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00176Fluvoxamineapproved, investigationalyesinhibitorDetails
DB00215CitalopramapprovedyesinhibitorDetails
DB00285VenlafaxineapprovedyesinhibitorDetails
DB00321AmitriptylineapprovedyesinhibitorDetails
DB00472Fluoxetineapproved, vet_approvedyesinhibitorDetails
DB00476DuloxetineapprovedyesinhibitorDetails
DB00540NortriptylineapprovedyesinhibitorDetails
DB00543AmoxapineapprovedyesinhibitorDetails
DB00715Paroxetineapproved, investigationalyesinhibitorDetails
DB00726TrimipramineapprovedyesinhibitorDetails
DB01104SertralineapprovedyesinhibitorDetails
DB01105Sibutramineapproved, illicit, investigational, withdrawnyesinhibitorDetails
DB01142Doxepinapproved, investigationalyesinhibitorDetails
DB01175EscitalopramapprovedyesinhibitorDetails
DB01191Dexfenfluramineapproved, illicit, investigational, withdrawnyesinhibitorDetails
DB01242Clomipramineapproved, investigational, vet_approvedyesinhibitorDetails
DB00344ProtriptylineapprovedyesinhibitorDetails
DB00458ImipramineapprovedyesinhibitorDetails
DB00514DextromethorphanapprovedunknowninhibitorDetails
DB00656Trazodoneapproved, investigationalyesinhibitorDetails
DB00805MinaprineapprovedunknowninhibitorDetails
DB00907Cocaineapproved, illicityesinhibitorDetails
DB01149Nefazodoneapproved, withdrawnyesinhibitorDetails
DB01151Desipramineapproved, investigationalyesinhibitorDetails
DB01454Midomafetamineexperimental, illicit, investigationalyesnegative modulatorDetails
DB04832Zimelidineapproved, withdrawnunknownDetails
DB04836Amineptineillicit, withdrawnunknownDetails
DB01442MMDAexperimental, illicityesnegative modulatorDetails
DB00191Phentermineapproved, illicityesinhibitorDetails
DB04889BicifadineinvestigationalunknownDetails
DB04896Milnacipranapproved, investigationalyesinhibitorDetails
DB05422OPC-14523investigationalunknownDetails
DB05688CRx-119investigationalunknownDetails
DB00193Tramadolapproved, investigationalyesinhibitorDetails
DB12305DasotralineinvestigationalunknownDetails
DB06156TesofensineinvestigationalunknownDetails
DB05964AmitifadineinvestigationalunknownDetails
DB06148Mianserinapproved, investigationalunknowninhibitorDetails
DB00289AtomoxetineapprovedunknownbinderDetails
DB00661Verapamilapprovedunknownother/unknownDetails
DB00579Mazindolapproved, investigationalyesinhibitorDetails
DB01114ChlorpheniramineapprovedunknowninhibitorDetails
DB00574Fenfluramineapproved, illicit, investigational, withdrawnyesinhibitorDetails
DB01079Tegaserodapproved, investigational, withdrawnunknownsubstrateinhibitorDetails
DB06700Desvenlafaxineapproved, investigationalyesinhibitorDetails
DB06701Dexmethylphenidateapproved, investigationalunknowninhibitorDetails
DB00852PseudoephedrineapprovedyesinhibitorDetails
DB014724-Methoxyamphetamineexperimental, illicityesinhibitorDetails
DB01577Metamfetamineapproved, illicityesnegative modulatorDetails
DB01363Ephedra sinica rootnutraceuticalyesnegative modulatorDetails
DB01454Midomafetamineexperimental, illicit, investigationalunknownDetails
DB06204TapentadolapprovedunknowninhibitorDetails
DB08918Levomilnacipranapproved, investigationalyesinhibitorDetails
DB00408LoxapineapprovedunknownbinderDetails
DB00182Amphetamineapproved, illicit, investigationalunknownbinderDetails
DB00988DopamineapprovedunknowninhibitorDetails
DB00454MeperidineapprovedunknownbindingDetails
DB09016ButriptylineapprovedyesantagonistinhibitorDetails
DB09068Vortioxetineapproved, investigationalyesinhibitorDetails
DB09167DosulepinapprovedyesinhibitorDetails
DB08839Serotonininvestigational, nutraceuticalunknownDetails
DB09186NisoxetineexperimentalunknownDetails
DB04821Nomifensineapproved, withdrawnunknownDetails
DB09194EtoperidonewithdrawnyesinhibitorDetails
DB09195LorpiprazoleapprovedyesantagonistDetails
DB09225Zotepineapproved, investigational, withdrawnyesantagonistDetails
DB00245BenzatropineapprovednoinhibitorDetails
DB06684VilazodoneapprovedyesinhibitorDetails
DB00370MirtazapineapprovedunknownsubstrateinhibitorDetails
DB00924CyclobenzaprineapprovedunknowninhibitorDetails
DB01238Aripiprazoleapproved, investigationalunknownmodulatorDetails