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UniProtKB/Swiss-Prot entry P31645


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name SC6A4_HUMAN
Primary accession number P31645
Secondary accession numbers None
Integrated into Swiss-Prot on July 1, 1993
Sequence was last modified on July 1, 1993 (Sequence version 1)
Annotations were last modified on    November 25, 2008 (Entry version 88)
Name and origin of the protein
Protein name Sodium-dependent serotonin transporter
Synonyms 5HT transporter
5HTT
Solute carrier family 6 member 4
Gene name
Name: SLC6A4
Synonyms: HTT, SERT
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Brain;
DOI=10.1007/BF01244919; PubMed=8452685 [NCBI, ExPASy, EBI, Israel, Japan]
Lesch K.P., Wolozin B.L., Estler H.C., Murphy D.L., Riederer P.;
"Isolation of a cDNA encoding the human brain serotonin transporter.";
J. Neural Transm. 91:67-73(1993).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=7681602 [NCBI, ExPASy, EBI, Israel, Japan]
Ramamoorthy S., Bauman A.L., Moore K.R., Han H., Yang-Feng T., Chang A.S., Ganapathy V., Blakely R.D.;
"Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization.";
Proc. Natl. Acad. Sci. U.S.A. 90:2542-2546(1993).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Platelet;
PubMed=7684072 [NCBI, ExPASy, EBI, Israel, Japan]
Lesch K.P., Wolozin B.L., Murphy D.L., Reiderer P.;
"Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter.";
J. Neurochem. 60:2319-2322(1993).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-114.
TISSUE=Placenta;
Bradley C.C., Blakely R.D.;
Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
[6]
INTERACTION WITH TGFB1I1.
DOI=10.1074/jbc.M603877200; PubMed=16803896 [NCBI, ExPASy, EBI, Israel, Japan]
Carneiro A.M.D., Blakely R.D.;
"Serotonin-, protein kinase C-, and Hic-5-associated redistribution of the platelet serotonin transporter.";
J. Biol. Chem. 281:24769-24780(2006).
[7]
VARIANTS ALA-56 AND ASN-605.
DOI=10.1038/10290; PubMed=10391209 [NCBI, ExPASy, EBI, Israel, Japan]
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.;
"Characterization of single-nucleotide polymorphisms in coding regions of human genes.";
Nat. Genet. 22:231-238(1999).
[8]
ERRATUM.
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.;
Nat. Genet. 23:373-373(1999).
[9]
VARIANT VAL-425.
DOI=10.1038/sj.mp.4001365; PubMed=14593431 [NCBI, ExPASy, EBI, Israel, Japan]
Ozaki N., Goldman D., Kaye W.H., Plotnicov K., Greenberg B.D., Lappalainen J., Rudnick G., Murphy D.L.;
"Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype.";
Mol. Psychiatry 8:933-936(2003).
[10]
CHARACTERIZATION OF VARIANT VAL-425.
DOI=10.1124/mol.64.2.440; PubMed=12869649 [NCBI, ExPASy, EBI, Israel, Japan]
Kilic F., Murphy D.L., Rudnick G.;
"A human serotonin transporter mutation causes constitutive activation of transport activity.";
Mol. Pharmacol. 64:440-446(2003).
[11]
POLYMORPHISM IN THE PROMOTER REGION.
DOI=10.1126/science.1083968; PubMed=12869766 [NCBI, ExPASy, EBI, Israel, Japan]
Caspi A., Sugden K., Moffitt T.E., Taylor A., Craig I.W., 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 301:386-389(2003).
[12]
INVOLVEMENT IN SUSCEPTIBILITY TO ALCOHOLISM.
DOI=10.1002/ajmg.b.30132; PubMed=15635638 [NCBI, ExPASy, EBI, Israel, Japan]
Feinn R., Nellissery M., Kranzler H.R.;
"Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence.";
Am. J. Med. Genet. B Neuropsychiatr. Genet. 133:79-84(2005).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X70697; CAA50029.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L05568; AAA35492.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC069484; AAH69484.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U79746; AAB93475.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A47398; A47398.
RefSeq NP_001036.1; -.
UniGene Hs.591192
3D structure databases
ModBase P31645.
PTM databases
PhosphoSite P31645; -.
Organism-specific databases
H-InvDB HIX0039143; -.
HGNC HGNC:11050; SLC6A4.
GenAtlas SLC6A4.
HPA CAB000074; -.
MIM 103780; phenotype. [NCBI / EBI]
164230; phenotype. [NCBI / EBI]
182138; gene. [NCBI / EBI]
PharmGKB PA312; -.
GeneCards P31645.
Gene expression databases
ArrayExpress P31645; -.
CleanEx HS_HTT; -.
HS_SLC6A4; -.
GermOnline ENSG00000108576; Homo sapiens.
Ontologies
GO
GO:0005887; Cellular component: integral to plasma membrane (traceable author statement from ProtInc).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0015222; Molecular function: serotonin transmembrane transporter activity (traceable author statement from ProtInc).
GO:0005335; Molecular function: serotonin:sodium symporter activity (inferred from electronic annotation from InterPro).
GO:0015844; Biological process: monoamine transport (inferred from direct assay from MGI).
GO:0001504; Biological process: neurotransmitter uptake (traceable author statement from ProtInc).
GO:0006837; Biological process: serotonin transport (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR000175; Na/ntran_symport.
IPR013086; Na/ntran_symport_serotonin_N.
Graphical view of domain structure.
PANTHER PTHR11616; Na/ntran_symport; 1.
Pfam PF03491; 5HT_transporter; 1.
PF00209; SNF; 1.
Pfam graphical view of domain structure.
PRINTS PR01203; 5HTTRANSPORT.
PR00176; NANEUSMPORT.
ProDom PD000448; Na/ntran_symport; 1.
[Domain structure / List of seq. sharing at least 1 domain]
PROSITE PS00610; NA_NEUROTRAN_SYMP_1; 1.
PS00754; NA_NEUROTRAN_SYMP_2; 1.
PS50267; NA_NEUROTRAN_SYMP_3; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P31645.
ProtoNet P31645.
Genome annotation databases
Ensembl ENSG00000108576; Homo sapiens. [Contig view]
GeneID 6532; -.
KEGG hsa:6532; -.
Phylogenomic databases
HOGENOM P31645; -.
HOVERGEN P31645; -.
Other
DrugBank DB04836; Amineptine.
DB00321; Amitriptyline.
DB00543; Amoxapine.
DB00215; Citalopram.
DB01242; Clomipramine.
DB00907; Cocaine.
DB01151; Desipramine.
DB01191; Dexfenfluramine.
DB00514; Dextromethorphan.
DB01142; Doxepin.
DB00476; Duloxetine.
DB01175; Escitalopram.
DB00472; Fluoxetine.
DB00176; Fluvoxamine.
DB00458; Imipramine.
DB00422; Methylphenidate.
DB04896; Milnacipran.
DB00805; Minaprine.
DB01149; Nefazodone.
DB00540; Nortriptyline.
DB00715; Paroxetine.
DB00191; Phentermine.
DB00344; Protriptyline.
DB01104; Sertraline.
DB01105; Sibutramine.
DB01079; Tegaserod.
DB00193; Tramadol.
DB00656; Trazodone.
DB00726; Trimipramine.
DB00285; Venlafaxine.
DB04832; Zimelidine.
NextBio 25415; -.
SOURCE SLC6A4; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Glycoprotein; Membrane; Neurotransmitter transport; Polymorphism; Symport; Transmembrane; Transport.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   630  630     Sodium-dependent serotonin transporter. PRO_0000214757
TOPO_DOM   1    87  87     Cytoplasmic (Potential). 
TRANSMEM   88   108  21     1 (Potential). 
TRANSMEM   116   135  20     2 (Potential). 
TRANSMEM   160   180  21     3 (Potential). 
TOPO_DOM   181   252  72     Extracellular (Potential). 
TRANSMEM   253   271  19     4 (Potential). 
TRANSMEM   280   297  18     5 (Potential). 
TRANSMEM   333   350  18     6 (Potential). 
TRANSMEM   362   383  22     7 (Potential). 
TRANSMEM   417   436  20     8 (Potential). 
TRANSMEM   464   482  19     9 (Potential). 
TRANSMEM   498   518  21     10 (Potential). 
TRANSMEM   539   558  20     11 (Potential). 
TRANSMEM   577   595  19     12 (Potential). 
TOPO_DOM   596   630  35     Cytoplasmic (Potential). 
CARBOHYD   208   208        N-linked (GlcNAc...) (Potential). 
CARBOHYD   217   217        N-linked (GlcNAc...) (Potential). 
VARIANT   56    56  1     G -> A (in dbSNP:rs6355 [NCBI]). VAR_014181 
VARIANT   201   201  1     K -> N (in dbSNP:rs2228673 [NCBI]). VAR_029158 
VARIANT   425   425  1     I -> L (in dbSNP:rs28914832 [NCBI]). VAR_036788 
VARIANT   425   425  1     I -> V (polymorphism linked with susceptibility to obsessive-compulsive disorder; increased serotonin transport capacity). VAR_026751 
VARIANT   465   465  1     F -> L (in dbSNP:rs28914833 [NCBI]). VAR_036789 
VARIANT   550   550  1     L -> V (in dbSNP:rs28914834 [NCBI]). VAR_036790 
VARIANT   605   605  1     K -> N (in dbSNP:rs6352 [NCBI]). VAR_014182 
Sequence information
Length: 630 AA [This is the length of the unprocessed precursor] Molecular weight: 70325 Da [This is the MW of the unprocessed precursor] CRC64: 0EB535B0A579BDA2 [This is a checksum on the sequence]
        10         20         30         40         50         60 
METTPLNSQK QLSACEDGED CQENGVLQKV VPTPGDKVES GQISNGYSAV PSPGAGDDTR 

        70         80         90        100        110        120 
HSIPATTTTL VAELHQGERE TWGKKVDFLL SVIGYAVDLG NVWRFPYICY QNGGGAFLLP 

       130        140        150        160        170        180 
YTIMAIFGGI PLFYMELALG QYHRNGCISI WRKICPIFKG IGYAICIIAF YIASYYNTIM 

       190        200        210        220        230        240 
AWALYYLISS FTDQLPWTSC KNSWNTGNCT NYFSEDNITW TLHSTSPAEE FYTRHVLQIH 

       250        260        270        280        290        300 
RSKGLQDLGG ISWQLALCIM LIFTVIYFSI WKGVKTSGKV VWVTATFPYI ILSVLLVRGA 

       310        320        330        340        350        360 
TLPGAWRGVL FYLKPNWQKL LETGVWIDAA AQIFFSLGPG FGVLLAFASY NKFNNNCYQD 

       370        380        390        400        410        420 
ALVTSVVNCM TSFVSGFVIF TVLGYMAEMR NEDVSEVAKD AGPSLLFITY AEAIANMPAS 

       430        440        450        460        470        480 
TFFAIIFFLM LITLGLDSTF AGLEGVITAV LDEFPHVWAK RRERFVLAVV ITCFFGSLVT 

       490        500        510        520        530        540 
LTFGGAYVVK LLEEYATGPA VLTVALIEAV AVSWFYGITQ FCRDVKEMLG FSPGWFWRIC 

       550        560        570        580        590        600 
WVAISPLFLL FIICSFLMSP PQLRLFQYNY PYWSIILGYC IGTSSFICIP TYIAYRLIIT 

       610        620        630 
PGTFKERIIK SITPETPTEI PCGDIRLNAV 

P31645 in FASTA format

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