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P31645

- SC6A4_HUMAN

UniProt

P31645 - SC6A4_HUMAN

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Protein

Sodium-dependent serotonin transporter

Gene

SLC6A4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

  1. actin filament binding Source: UniProtKB
  2. cocaine binding Source: Ensembl
  3. monoamine transmembrane transporter activity Source: MGI
  4. Rab GTPase binding Source: UniProtKB
  5. serotonin:sodium symporter activity Source: UniProtKB
  6. serotonin transmembrane transporter activity Source: UniProtKB

GO - Biological processi

  1. brain morphogenesis Source: BHF-UCL
  2. cellular response to cGMP Source: Ensembl
  3. cellular response to retinoic acid Source: Ensembl
  4. circadian rhythm Source: Ensembl
  5. memory Source: Ensembl
  6. monoamine transport Source: MGI
  7. negative regulation of cerebellar granule cell precursor proliferation Source: Ensembl
  8. negative regulation of neuron differentiation Source: Ensembl
  9. negative regulation of organ growth Source: BHF-UCL
  10. negative regulation of synaptic transmission, dopaminergic Source: Ensembl
  11. positive regulation of cell cycle Source: Ensembl
  12. positive regulation of gene expression Source: Ensembl
  13. protein homooligomerization Source: Ensembl
  14. protein oligomerization Source: UniProtKB
  15. response to drug Source: Ensembl
  16. response to estradiol Source: Ensembl
  17. response to hypoxia Source: Ensembl
  18. response to nutrient Source: Ensembl
  19. response to toxic substance Source: UniProtKB
  20. serotonin transport Source: UniProtKB
  21. serotonin uptake Source: UniProtKB
  22. social behavior Source: BHF-UCL
  23. sperm ejaculation Source: Ensembl
  24. thalamus development Source: UniProtKB
  25. vasoconstriction Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Neurotransmitter transport, Symport, Transport

Protein family/group databases

TCDBi2.A.22.1.1. the neurotransmitter:sodium symporter (nss) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium-dependent serotonin transporter
Alternative name(s):
5HT transporter
Short name:
5HTT
Solute carrier family 6 member 4
Gene namesi
Name:SLC6A4
Synonyms:HTT, SERT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:11050. SLC6A4.

Subcellular locationi

Cell membrane; Multi-pass membrane protein. Endomembrane system; Multi-pass membrane protein. Endosome membrane; Multi-pass membrane protein
Note: Translocates from intracellular locations to the plasma membrane. Density of transporter molecules on the plasma membrane is itself regulated by serotonin.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8787CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei88 – 10821Helical; Name=1Sequence AnalysisAdd
BLAST
Transmembranei116 – 13520Helical; Name=2Sequence AnalysisAdd
BLAST
Transmembranei160 – 18021Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini181 – 25272ExtracellularSequence AnalysisAdd
BLAST
Transmembranei253 – 27119Helical; Name=4Sequence AnalysisAdd
BLAST
Transmembranei280 – 29718Helical; Name=5Sequence AnalysisAdd
BLAST
Transmembranei333 – 35018Helical; Name=6Sequence AnalysisAdd
BLAST
Transmembranei362 – 38322Helical; Name=7Sequence AnalysisAdd
BLAST
Transmembranei417 – 43620Helical; Name=8Sequence AnalysisAdd
BLAST
Transmembranei464 – 48219Helical; Name=9Sequence AnalysisAdd
BLAST
Transmembranei498 – 51821Helical; Name=10Sequence AnalysisAdd
BLAST
Transmembranei539 – 55820Helical; Name=11Sequence AnalysisAdd
BLAST
Transmembranei577 – 59519Helical; Name=12Sequence AnalysisAdd
BLAST
Topological domaini596 – 63035CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cytosol Source: UniProtKB
  2. endomembrane system Source: UniProtKB
  3. endosome Source: UniProtKB-KW
  4. integral component of plasma membrane Source: UniProtKB
  5. membrane raft Source: UniProtKB
  6. neuron projection Source: Ensembl
  7. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi611 – 6111S → A: Loss of 10 % of serotonin uptake activity. Loss of 5 % of serotonin uptake activity; when associated with A-613 and A-616. 1 Publication
Mutagenesisi611 – 6111S → D: Loss of 61 % of serotonin uptake activity. Loss of 95 % of serotonin uptake activity and lack of association between VIM and the plasma membrane; when associated with D-613 and D-616. 1 Publication
Mutagenesisi613 – 6131T → A: Loss of 26 % of serotonin uptake activity. Loss of 5 % of serotonin uptake activity; when associated with A-611 and A-616. 1 Publication
Mutagenesisi613 – 6131T → D: Loss of 26 % of serotonin uptake activity. Loss of 95 % of serotonin uptake activity and lack of association between VIM and the plasma membrane; when associated with D-611 and D-616. 1 Publication
Mutagenesisi616 – 6161T → A: No change. Loss of 5 % of serotonin uptake activity; when associated with A-611 and A-613. 1 Publication
Mutagenesisi616 – 6161T → D: No change. Loss of 95 % of serotonin uptake activity and lack of association between VIM and the plasma membrane; when associated with D-611 and D-613. 1 Publication

Organism-specific databases

MIMi103780. phenotype.
164230. phenotype.
PharmGKBiPA312.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 630630Sodium-dependent serotonin transporterPRO_0000214757Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei47 – 471Phosphotyrosine1 Publication
Modified residuei142 – 1421Phosphotyrosine1 Publication
Glycosylationi208 – 2081N-linked (GlcNAc...)Sequence Analysis
Glycosylationi217 – 2171N-linked (GlcNAc...)Sequence Analysis
Modified residuei276 – 2761Phosphothreonine; by PKG1 Publication
Modified residuei611 – 6111Phosphoserine1 Publication
Modified residuei613 – 6131Phosphothreonine1 Publication
Modified residuei616 – 6161Phosphothreonine1 Publication

Post-translational modificationi

Glycosylated; modification with sialylated N-glycans is a requirement for transporters to associate with each other and to function as homooligomeric forms.By similarity
Phosphorylation at Thr-276 increases 5-HT uptake and is required for cGMP-mediated SERT regulation. Phosphorylation upon PKC stimulation modifies the SERT distribution and density in the membrane, and diminishes the uptake capacity.3 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP31645.
PRIDEiP31645.

PTM databases

PhosphoSiteiP31645.

Expressioni

Tissue specificityi

Expressed in platelets (at protein level).1 Publication

Inductioni

Down-regulated when plasma serotonin is elevated.2 Publications

Gene expression databases

BgeeiP31645.
CleanExiHS_HTT.
HS_SLC6A4.
ExpressionAtlasiP31645. baseline and differential.
GenevestigatoriP31645.

Interactioni

Subunit structurei

Monomer or homooligomer (By similarity). Interacts with TGFB1I1. Interacts (via sialylated form) with MYH9. Interacts with SEC23A, SEC24C and INADL. Interacts with NOS1; the interaction may diminish the cell surface localization of SERT in the brain and, correspondingly, reduce serotonin reuptake. Interacts with filamentous actin and STX1A (By similarity). Interacts (via C-terminus) with VIM. Interacts (via C-terminus) with SCAMP2; the interaction is direct and retains transporter molecules intracellularly. Interacts with RAB4 (GTP-bound form); the interaction retains transporter molecules intracellularly.By similarity4 Publications

Protein-protein interaction databases

BioGridi112423. 5 interactions.
IntActiP31645. 2 interactions.
MINTiMINT-577123.
STRINGi9606.ENSP00000261707.

Structurei

3D structure databases

ProteinModelPortaliP31645.
SMRiP31645. Positions 78-614.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni611 – 63020Required for serotonin uptake activityAdd
BLAST
Regioni616 – 6249Interaction with RAB4A

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0733.
GeneTreeiENSGT00760000118857.
HOGENOMiHOG000116406.
HOVERGENiHBG071421.
InParanoidiP31645.
KOiK05037.
OMAiTSCKNSW.
OrthoDBiEOG793B71.
PhylomeDBiP31645.
TreeFamiTF343812.

Family and domain databases

InterProiIPR000175. Na/ntran_symport.
IPR013086. Na/ntran_symport_serotonin_N.
[Graphical view]
PANTHERiPTHR11616. PTHR11616. 1 hit.
PfamiPF03491. 5HT_transporter. 1 hit.
PF00209. SNF. 1 hit.
[Graphical view]
PRINTSiPR01203. 5HTTRANSPORT.
PR00176. NANEUSMPORT.
PROSITEiPS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P31645-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
METTPLNSQK QLSACEDGED CQENGVLQKV VPTPGDKVES GQISNGYSAV
60 70 80 90 100
PSPGAGDDTR HSIPATTTTL VAELHQGERE TWGKKVDFLL SVIGYAVDLG
110 120 130 140 150
NVWRFPYICY QNGGGAFLLP YTIMAIFGGI PLFYMELALG QYHRNGCISI
160 170 180 190 200
WRKICPIFKG IGYAICIIAF YIASYYNTIM AWALYYLISS FTDQLPWTSC
210 220 230 240 250
KNSWNTGNCT NYFSEDNITW TLHSTSPAEE FYTRHVLQIH RSKGLQDLGG
260 270 280 290 300
ISWQLALCIM LIFTVIYFSI WKGVKTSGKV VWVTATFPYI ILSVLLVRGA
310 320 330 340 350
TLPGAWRGVL FYLKPNWQKL LETGVWIDAA AQIFFSLGPG FGVLLAFASY
360 370 380 390 400
NKFNNNCYQD ALVTSVVNCM TSFVSGFVIF TVLGYMAEMR NEDVSEVAKD
410 420 430 440 450
AGPSLLFITY AEAIANMPAS TFFAIIFFLM LITLGLDSTF AGLEGVITAV
460 470 480 490 500
LDEFPHVWAK RRERFVLAVV ITCFFGSLVT LTFGGAYVVK LLEEYATGPA
510 520 530 540 550
VLTVALIEAV AVSWFYGITQ FCRDVKEMLG FSPGWFWRIC WVAISPLFLL
560 570 580 590 600
FIICSFLMSP PQLRLFQYNY PYWSIILGYC IGTSSFICIP TYIAYRLIIT
610 620 630
PGTFKERIIK SITPETPTEI PCGDIRLNAV
Length:630
Mass (Da):70,325
Last modified:July 1, 1993 - v1
Checksum:i0EB535B0A579BDA2
GO
Isoform 2 (identifier: P31645-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MSQSRRVNPDDRELGGDLQIQAPRDQLGSLADGHQCHLLTSRM

Show »
Length:672
Mass (Da):74,979
Checksum:i142F04437BA1DE39
GO

Polymorphismi

A polymorphism in the promoter region (5-HTT gene-linked polymorphic region, 5-HTTLPR) is located approximately 1 kb upstream of the transcription initiation site and is composed of 16 repeat elements. The polymorphism consists of a 44-bp insertion or deletion involving repeat elements 6 to 8. The short allele is associated with lower transcriptional efficiency of the promoter compared with the long allele. Over half of the Caucasian population has a short allele. Individuals with one or two copies of the short allele exhibit more depressive symptoms, diagnosable depression and suicidality in relation to stressful life events than individuals homozygous for the long allele.
The polymorphism Val-425 seems to be linked to a susceptibility to obsessive-compulsive disorder (OCD) [MIMi:164230].
Genetic variations in SLC6A4 determine the genetic susceptibility to alcoholism [MIMi:103780].

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti56 – 561G → A.1 Publication
Corresponds to variant rs6355 [ dbSNP | Ensembl ].
VAR_014181
Natural varianti201 – 2011K → N.
Corresponds to variant rs2228673 [ dbSNP | Ensembl ].
VAR_029158
Natural varianti425 – 4251I → L.
Corresponds to variant rs28914832 [ dbSNP | Ensembl ].
VAR_036788
Natural varianti425 – 4251I → V Polymorphism linked with susceptibility to obsessive-compulsive disorder; increased serotonin transport capacity. 2 Publications
VAR_026751
Natural varianti465 – 4651F → L.
Corresponds to variant rs28914833 [ dbSNP | Ensembl ].
VAR_036789
Natural varianti550 – 5501L → V.
Corresponds to variant rs28914834 [ dbSNP | Ensembl ].
VAR_036790
Natural varianti605 – 6051K → N.1 Publication
Corresponds to variant rs6352 [ dbSNP | Ensembl ].
VAR_014182

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MSQSRRVNPDDRELGGDLQI QAPRDQLGSLADGHQCHLLT SRM in isoform 2. 1 PublicationVSP_046553

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X70697 mRNA. Translation: CAA50029.1.
L05568 mRNA. Translation: AAA35492.1.
AY902473 mRNA. Translation: AAW80933.1.
EU099989 Genomic DNA. Translation: ABV02581.1.
BC069484 mRNA. Translation: AAH69484.1.
U79746 Genomic DNA. Translation: AAB93475.1.
AK308014 mRNA. No translation available.
CCDSiCCDS11256.1. [P31645-1]
PIRiA47398.
RefSeqiNP_001036.1. NM_001045.5. [P31645-1]
UniGeneiHs.134662.
Hs.29792.

Genome annotation databases

EnsembliENST00000261707; ENSP00000261707; ENSG00000108576. [P31645-1]
ENST00000401766; ENSP00000385822; ENSG00000108576. [P31645-1]
GeneIDi6532.
KEGGihsa:6532.
UCSCiuc002hey.5. human. [P31645-1]

Polymorphism databases

DMDMi400630.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

Serotonin transporter entry

Protein Spotlight

Love, love, love... -Issue 123 of November 2010

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X70697 mRNA. Translation: CAA50029.1 .
L05568 mRNA. Translation: AAA35492.1 .
AY902473 mRNA. Translation: AAW80933.1 .
EU099989 Genomic DNA. Translation: ABV02581.1 .
BC069484 mRNA. Translation: AAH69484.1 .
U79746 Genomic DNA. Translation: AAB93475.1 .
AK308014 mRNA. No translation available.
CCDSi CCDS11256.1. [P31645-1 ]
PIRi A47398.
RefSeqi NP_001036.1. NM_001045.5. [P31645-1 ]
UniGenei Hs.134662.
Hs.29792.

3D structure databases

ProteinModelPortali P31645.
SMRi P31645. Positions 78-614.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112423. 5 interactions.
IntActi P31645. 2 interactions.
MINTi MINT-577123.
STRINGi 9606.ENSP00000261707.

Chemistry

BindingDBi P31645.
ChEMBLi CHEMBL2111346.
DrugBanki DB00321. Amitriptyline.
DB00543. Amoxapine.
DB00182. Amphetamine.
DB00289. Atomoxetine.
DB01114. Chlorphenamine.
DB00215. Citalopram.
DB01242. Clomipramine.
DB00907. Cocaine.
DB01151. Desipramine.
DB06700. Desvenlafaxine.
DB01191. Dexfenfluramine.
DB06701. Dexmethylphenidate.
DB00514. Dextromethorphan.
DB00988. Dopamine.
DB01142. Doxepin.
DB00476. Duloxetine.
DB01363. Ephedra.
DB01175. Escitalopram.
DB00472. Fluoxetine.
DB00176. Fluvoxamine.
DB00458. Imipramine.
DB08918. Levomilnacipran.
DB00408. Loxapine.
DB00579. Mazindol.
DB01577. Methamphetamine.
DB00422. Methylphenidate.
DB06148. Mianserin.
DB04896. Milnacipran.
DB00805. Minaprine.
DB00370. Mirtazapine.
DB01149. Nefazodone.
DB00540. Nortriptyline.
DB00715. Paroxetine.
DB00454. Pethidine.
DB00191. Phentermine.
DB00344. Protriptyline.
DB00852. Pseudoephedrine.
DB01104. Sertraline.
DB01105. Sibutramine.
DB06204. Tapentadol.
DB00193. Tramadol.
DB00656. Trazodone.
DB00726. Trimipramine.
DB00285. Venlafaxine.
DB00661. Verapamil.
DB06684. Vilazodone.
GuidetoPHARMACOLOGYi 928.

Protein family/group databases

TCDBi 2.A.22.1.1. the neurotransmitter:sodium symporter (nss) family.

PTM databases

PhosphoSitei P31645.

Polymorphism databases

DMDMi 400630.

Proteomic databases

PaxDbi P31645.
PRIDEi P31645.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000261707 ; ENSP00000261707 ; ENSG00000108576 . [P31645-1 ]
ENST00000401766 ; ENSP00000385822 ; ENSG00000108576 . [P31645-1 ]
GeneIDi 6532.
KEGGi hsa:6532.
UCSCi uc002hey.5. human. [P31645-1 ]

Organism-specific databases

CTDi 6532.
GeneCardsi GC17M028521.
HGNCi HGNC:11050. SLC6A4.
MIMi 103780. phenotype.
164230. phenotype.
182138. gene.
neXtProti NX_P31645.
PharmGKBi PA312.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0733.
GeneTreei ENSGT00760000118857.
HOGENOMi HOG000116406.
HOVERGENi HBG071421.
InParanoidi P31645.
KOi K05037.
OMAi TSCKNSW.
OrthoDBi EOG793B71.
PhylomeDBi P31645.
TreeFami TF343812.

Miscellaneous databases

GeneWikii Serotonin_transporter.
GenomeRNAii 6532.
NextBioi 25415.
PROi P31645.
SOURCEi Search...

Gene expression databases

Bgeei P31645.
CleanExi HS_HTT.
HS_SLC6A4.
ExpressionAtlasi P31645. baseline and differential.
Genevestigatori P31645.

Family and domain databases

InterProi IPR000175. Na/ntran_symport.
IPR013086. Na/ntran_symport_serotonin_N.
[Graphical view ]
PANTHERi PTHR11616. PTHR11616. 1 hit.
Pfami PF03491. 5HT_transporter. 1 hit.
PF00209. SNF. 1 hit.
[Graphical view ]
PRINTSi PR01203. 5HTTRANSPORT.
PR00176. NANEUSMPORT.
PROSITEi PS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation of a cDNA encoding the human brain serotonin transporter."
    Lesch K.P., Wolozin B.L., Estler H.C., Murphy D.L., Riederer P.
    J. Neural Transm. 91:67-73(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Brain.
  2. "Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization."
    Ramamoorthy S., Bauman A.L., Moore K.R., Han H., Yang-Feng T., Chang A.S., Ganapathy V., Blakely R.D.
    Proc. Natl. Acad. Sci. U.S.A. 90:2542-2546(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter."
    Lesch K.P., Wolozin B.L., Murphy D.L., Reiderer P.
    J. Neurochem. 60:2319-2322(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Platelet.
  4. "Molecular characterization and intracellular regulation of the human serotonin transporter in Caco-2 cells."
    Iceta R., Mesonero J.E., Aramayona J.J., Alcalde A.I.
    J. Physiol. Pharmacol. 57:119-130(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  5. NIEHS SNPs program
    Submitted (AUG-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  7. Bradley C.C., Blakely R.D.
    Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-114.
    Tissue: Placenta.
  8. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    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 T.-O., 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.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-317 (ISOFORM 2).
    Tissue: Lung.
  9. "Serotonin-, protein kinase C-, and Hic-5-associated redistribution of the platelet serotonin transporter."
    Carneiro A.M.D., Blakely R.D.
    J. Biol. Chem. 281:24769-24780(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TGFB1I1.
  10. "Subcellular redistribution of the serotonin transporter by secretory carrier membrane protein 2."
    Mueller H.K., Wiborg O., Haase J.
    J. Biol. Chem. 281:28901-28909(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SCAMP2, SUBCELLULAR LOCATION.
  11. "Plasma serotonin levels and the platelet serotonin transporter."
    Brenner B., Harney J.T., Ahmed B.A., Jeffus B.C., Unal R., Mehta J.L., Kilic F.
    J. Neurochem. 102:206-215(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  12. "Serotonin transporter phosphorylation by cGMP-dependent protein kinase is altered by a mutation associated with obsessive compulsive disorder."
    Zhang Y.W., Gesmonde J., Ramamoorthy S., Rudnick G.
    J. Neurosci. 27:10878-10886(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-276, VARIANT VAL-425.
  13. "Serotonin transamidates Rab4 and facilitates its binding to the C terminus of serotonin transporter."
    Ahmed B.A., Jeffus B.C., Bukhari S.I., Harney J.T., Unal R., Lupashin V.V., van der Sluijs P., Kilic F.
    J. Biol. Chem. 283:9388-9398(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH RAB4, SUBCELLULAR LOCATION, INDUCTION BY SEROTONIN.
  14. "The cellular distribution of serotonin transporter is impeded on serotonin-altered vimentin network."
    Ahmed B.A., Bukhari I.A., Jeffus B.C., Harney J.T., Thyparambil S., Ziu E., Fraer M., Rusch N.J., Zimniak P., Lupashin V., Tang D., Kilic F.
    PLoS ONE 4:E4730-E4730(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH VIM, SUBCELLULAR LOCATION, INDUCTION BY SEROTONIN, MUTAGENESIS OF SER-611; THR-613 AND THR-616, PHOSPHORYLATION AT SER-611; THR-613 AND THR-616.
  15. "Tyrosine phosphorylation of the human serotonin transporter: a role in the transporter stability and function."
    Annamalai B., Mannangatti P., Arapulisamy O., Shippenberg T.S., Jayanthi L.D., Ramamoorthy S.
    Mol. Pharmacol. 81:73-85(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-47 AND TYR-142.
  16. Cited for: VARIANTS ALA-56 AND ASN-605.
  17. "Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype."
    Ozaki N., Goldman D., Kaye W.H., Plotnicov K., Greenberg B.D., Lappalainen J., Rudnick G., Murphy D.L.
    Mol. Psychiatry 8:933-936(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT VAL-425.
  18. "A human serotonin transporter mutation causes constitutive activation of transport activity."
    Kilic F., Murphy D.L., Rudnick G.
    Mol. Pharmacol. 64:440-446(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANT VAL-425.
  19. "Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene."
    Caspi A., Sugden K., Moffitt T.E., Taylor A., Craig I.W., Harrington H., McClay J., Mill J., Martin J., Braithwaite A., Poulton R.
    Science 301:386-389(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: POLYMORPHISM IN THE PROMOTER REGION.
  20. "Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence."
    Feinn R., Nellissery M., Kranzler H.R.
    Am. J. Med. Genet. B Neuropsychiatr. Genet. 133:79-84(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ALCOHOLISM.

Entry informationi

Entry nameiSC6A4_HUMAN
AccessioniPrimary (citable) accession number: P31645
Secondary accession number(s): Q5EE02
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: October 29, 2014
This is version 148 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

This protein is the target of psychomotor stimulants such as amphetamines or cocaine.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3