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Identification
HMDB Protein ID HMDBP02165
Secondary Accession Numbers
  • 7649
  • HMDBP03539
Name Sodium-dependent serotonin transporter
Synonyms
  1. 5HT transporter
  2. 5HTT
  3. Solute carrier family 6 member 4
Gene Name SLC6A4
Protein Type Transporter
Biological Properties
General Function Involved in neurotransmitter: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.
Pathways
  • 3-Methylthiofentanyl Action Pathway
  • Alfentanil Action Pathway
  • Alvimopan Action Pathway
  • Anileridine Action Pathway
  • Benzocaine Action Pathway
  • Bupivacaine Action Pathway
  • Buprenorphine Action Pathway
  • Carfentanil Action Pathway
  • Chloroprocaine Action Pathway
  • Citalopram Action Pathway
  • Citalopram Metabolism Pathway
  • Cocaine Action Pathway
  • Codeine Action Pathway
  • Desipramine Action Pathway
  • Desipramine Metabolism Pathway
  • Dezocine Action Pathway
  • Dibucaine Action Pathway
  • Dihydromorphine Action Pathway
  • Dimethylthiambutene Action Pathway
  • Diphenoxylate Action Pathway
  • Escitalopram Action Pathway
  • Ethylmorphine Action Pathway
  • Fentanyl Action Pathway
  • Fluoxetine Action Pathway
  • Fluoxetine Metabolism Pathway
  • Heroin Action Pathway
  • Hydrocodone Action Pathway
  • Hydromorphone Action Pathway
  • Imipramine Action Pathway
  • Imipramine Metabolism Pathway
  • Ketobemidone Action Pathway
  • Levallorphan Action Pathway
  • Levobupivacaine Action Pathway
  • Levomethadyl Acetate Action Action Pathway
  • Levorphanol Action Pathway
  • Lidocaine (Local Anaesthetic) Action Pathway
  • Mepivacaine Action Pathway
  • Methadone Action Pathway
  • Methadyl Acetate Action Pathway
  • Morphine Action Pathway
  • Nalbuphine Action Pathway
  • Naloxone Action Pathway
  • Naltrexone Action Pathway
  • Nicotine Action Pathway
  • Oxybuprocaine Action Pathway
  • Oxycodone Action Pathway
  • Oxymorphone Action Pathway
  • Pentazocine Action Pathway
  • Prilocaine Action Pathway
  • Procaine Action Pathway
  • Proparacaine Action Pathway
  • Propoxyphene Action Pathway
  • Remifentanil Action Pathway
  • Ropivacaine Action Pathway
  • Serotonergic synapse
  • Sufentanil Action Pathway
  • Tramadol Action Action Pathway
  • Venlafaxine Metabolism Pathway
Reactions Not Available
GO Classification
Biological Process
positive regulation of cell cycle
negative regulation of synaptic transmission, dopaminergic
negative regulation of organ growth
thalamus development
response to drug
response to nutrient
social behavior
memory
protein oligomerization
protein homooligomerization
brain morphogenesis
negative regulation of cerebellar granule cell precursor proliferation
serotonin uptake
sperm ejaculation
vasoconstriction
cellular response to retinoic acid
cellular response to cGMP
response to toxin
positive regulation of gene expression
response to estradiol stimulus
response to hypoxia
negative regulation of neuron differentiation
circadian rhythm
Cellular Component
cytosol
membrane raft
endomembrane system
endosome membrane
integral to plasma membrane
Component
integral to plasma membrane
membrane
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
neurotransmitter transporter activity
neurotransmitter:sodium symporter activity
serotonin:sodium symporter activity
transmembrane transporter activity
transporter activity
Molecular Function
actin filament binding
cocaine binding
serotonin transmembrane transporter activity
serotonin:sodium symporter activity
Process
establishment of localization
transport
neurotransmitter transport
Cellular Location
  1. Cell membrane
  2. Endomembrane system
  3. Endosome membrane
  4. Multi-pass membrane protein
  5. Multi-pass membrane protein
  6. Multi-pass membrane protein
Gene Properties
Chromosome Location 17
Locus 17q11.2
SNPs SLC6A4
Gene Sequence
>1893 bp
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
CCAGGGACATTTAAAGAGCGTATTATTAAAAGTATTACCCCGGAGACACCAACAGAAATT
CCTTGTGGGGACATCCGCTTGAATGCTGTGTAA
Protein Properties
Number of Residues 630
Molecular Weight 70324.165
Theoretical pI 6.246
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Sodium-dependent serotonin transporter
METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTR
HSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLP
YTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIM
AWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIH
RSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGA
TLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQD
ALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPAS
TFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVT
LTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRIC
WVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIIT
PGTFKERIIKSITPETPTEIPCGDIRLNAV
GenBank ID Protein 36433
UniProtKB/Swiss-Prot ID P31645
UniProtKB/Swiss-Prot Entry Name SC6A4_HUMAN
PDB IDs Not Available
GenBank Gene ID X70697
GeneCard ID SLC6A4
GenAtlas ID SLC6A4
HGNC ID HGNC:11050
References
General References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  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. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]