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UniProtKB - P31645 (SC6A4_HUMAN)

Entry version 197 (22 Apr 2020)
Sequence version 1 (01 Jul 1993)
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Protein

Sodium-dependent serotonin transporter

Gene

SLC6A4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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.4 Publications

Miscellaneous

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi94Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi96Sodium 2; via carbonyl oxygen1 Publication1
Metal bindingi97Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi101Sodium 21 Publication1
Metal bindingi336Sodium 21 Publication1
Metal bindingi368Sodium 21 Publication1
Metal bindingi434Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi437Sodium 1By similarity1
Metal bindingi438Sodium 1By similarity1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processNeurotransmitter transport, Symport, Transport
LigandMetal-binding, Sodium

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-380615 Serotonin clearance from the synaptic cleft

SIGNOR Signaling Network Open Resource

More...SIGNORi		P31645

Protein family/group databases

Transport Classification Database

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

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Sodium-dependent serotonin transporter
Short name:
SERTBy similarity
Alternative name(s):
5HT transporter
Short name:
5HTT
Solute carrier family 6 member 4
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:SLC6A4
Synonyms:HTT, SERT
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 17

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:11050 SLC6A4

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		182138 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P31645

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini1 – 87CytoplasmicCuratedAdd BLAST87
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei88 – 112Helical; Name=11 PublicationAdd BLAST25
Topological domaini113 – 115ExtracellularCurated3
Transmembranei116 – 135Helical; Name=21 PublicationAdd BLAST20
Topological domaini136 – 160CytoplasmicCuratedAdd BLAST25
Transmembranei161 – 186Helical; Name=31 PublicationAdd BLAST26
Topological domaini187 – 252ExtracellularCuratedAdd BLAST66
Transmembranei253 – 271Helical; Name=41 PublicationAdd BLAST19
Topological domaini272 – 277CytoplasmicCurated6
Transmembranei278 – 297Helical; Name=51 PublicationAdd BLAST20
Topological domaini298 – 324ExtracellularCuratedAdd BLAST27
Transmembranei325 – 347Helical; Name=61 PublicationAdd BLAST23
Topological domaini348 – 360CytoplasmicCuratedAdd BLAST13
Transmembranei361 – 380Helical; Name=71 PublicationAdd BLAST20
Topological domaini381 – 421ExtracellularCuratedAdd BLAST41
Transmembranei422 – 443Helical; Name=81 PublicationAdd BLAST22
Topological domaini444 – 463CytoplasmicCuratedAdd BLAST20
Transmembranei464 – 483Helical; Name=91 PublicationAdd BLAST20
Topological domaini484 – 494ExtracellularCuratedAdd BLAST11
Transmembranei495 – 516Helical; Name=101 PublicationAdd BLAST22
Topological domaini517 – 538CytoplasmicCuratedAdd BLAST22
Transmembranei539 – 558Helical; Name=111 PublicationAdd BLAST20
Topological domaini559 – 574ExtracellularCuratedAdd BLAST16
Transmembranei575 – 595Helical; Name=121 PublicationAdd BLAST21
Topological domaini596 – 630CytoplasmicCuratedAdd BLAST35

Keywords - Cellular componenti

Cell junction, Cell membrane, Endosome, Membrane, Synapse

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi611S → A: Loss of 10 % of serotonin uptake activity. Loss of 5 % of serotonin uptake activity; when associated with A-613 and A-616. 1 Publication1
Mutagenesisi611S → 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 Publication1
Mutagenesisi613T → A: Loss of 26 % of serotonin uptake activity. Loss of 5 % of serotonin uptake activity; when associated with A-611 and A-616. 1 Publication1
Mutagenesisi613T → 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 Publication1
Mutagenesisi616T → A: No change. Loss of 5 % of serotonin uptake activity; when associated with A-611 and A-613. 1 Publication1
Mutagenesisi616T → 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 Publication1

Organism-specific databases

DisGeNET

More...DisGeNETi		6532

MalaCards human disease database

More...MalaCardsi		SLC6A4
MIMi103780 phenotype
164230 phenotype
607834 phenotype

Open Targets

More...OpenTargetsi		ENSG00000108576

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA312

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P31645 Tclin

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL228

Drug and drug target database

More...DrugBanki		DB01472 4-Methoxyamphetamine
DB04836 Amineptine
DB05964 Amitifadine
DB00321 Amitriptyline
DB00543 Amoxapine
DB00182 Amphetamine
DB01238 Aripiprazole
DB00289 Atomoxetine
DB00245 Benzatropine
DB04889 Bicifadine
DB09016 Butriptyline
DB01114 Chlorpheniramine
DB00215 Citalopram
DB01242 Clomipramine
DB00907 Cocaine
DB05688 CRx-119
DB00924 Cyclobenzaprine
DB12305 Dasotraline
DB01151 Desipramine
DB06700 Desvenlafaxine
DB01191 Dexfenfluramine
DB06701 Dexmethylphenidate
DB00514 Dextromethorphan
DB00988 Dopamine
DB09167 Dosulepin
DB01142 Doxepin
DB00476 Duloxetine
DB01363 Ephedra sinica root
DB01175 Escitalopram
DB09194 Etoperidone
DB00574 Fenfluramine
DB00472 Fluoxetine
DB00176 Fluvoxamine
DB00458 Imipramine
DB08918 Levomilnacipran
DB09195 Lorpiprazole
DB00408 Loxapine
DB06077 Lumateperone
DB00579 Mazindol
DB00454 Meperidine
DB01577 Metamfetamine
DB06148 Mianserin
DB01454 Midomafetamine
DB04896 Milnacipran
DB00805 Minaprine
DB00370 Mirtazapine
DB01442 MMDA
DB01149 Nefazodone
DB09186 Nisoxetine
DB04821 Nomifensine
DB00540 Nortriptyline
DB05422 OPC-14523
DB00715 Paroxetine
DB00191 Phentermine
DB00344 Protriptyline
DB00852 Pseudoephedrine
DB08839 Serotonin
DB01104 Sertraline
DB01105 Sibutramine
DB06204 Tapentadol
DB01079 Tegaserod
DB06156 Tesofensine
DB00193 Tramadol
DB00656 Trazodone
DB00726 Trimipramine
DB00285 Venlafaxine
DB00661 Verapamil
DB06684 Vilazodone
DB09068 Vortioxetine
DB04832 Zimelidine
DB09225 Zotepine

DrugCentral

More...DrugCentrali		P31645

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		928

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		SLC6A4

Domain mapping of disease mutations (DMDM)

More...DMDMi		400630

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00002147571 – 630Sodium-dependent serotonin transporterAdd BLAST630

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei47Phosphotyrosine1 Publication1
Modified residuei142Phosphotyrosine1 Publication1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi200 ↔ 209Combined sources
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi208N-linked (GlcNAc...) asparagineSequence analysis1 Publication1
Glycosylationi217N-linked (GlcNAc...) asparagineSequence analysis1 Publication1
Modified residuei276Phosphothreonine; by PKG1 Publication1
Modified residuei611Phosphoserine1 Publication1
Modified residuei613Phosphothreonine1 Publication1
Modified residuei616Phosphothreonine1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P31645

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P31645

PeptideAtlas

More...PeptideAtlasi		P31645

PRoteomics IDEntifications database

More...PRIDEi		P31645

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		54798 [P31645-1]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P31645

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P31645

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in platelets (at protein level).1 Publication

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Down-regulated when plasma serotonin is elevated.2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000108576 Expressed in upper lobe of lung and 104 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P31645 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P31645 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000108576 Tissue enhanced (intestine, lung)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer or homooligomer (By similarity).

Interacts with TGFB1I1 (PubMed:16803896).

Interacts (via sialylated form) with MYH9.

Interacts with SEC23A, SEC24C and PATJ.

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 (PubMed:19270731).

Interacts (via C-terminus) with SCAMP2; the interaction is direct and retains transporter molecules intracellularly (PubMed:16870614).

Interacts with RAB4 (GTP-bound form); the interaction retains transporter molecules intracellularly (PubMed:18227069).

Interacts with ITGAV:ITGB3 (By similarity).

By similarity4 Publications

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...BioGridi		112423, 11 interactors

Protein interaction database and analysis system

More...IntActi		P31645, 2 interactors

Molecular INTeraction database

More...MINTi		P31645

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000261707

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P31645

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P31645 protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1630
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P31645

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni611 – 630Required for serotonin uptake activity1 PublicationAdd BLAST20
Regioni616 – 624Interaction with RAB4A9

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A4 subfamily. [View classification]Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG3659 Eukaryota
COG0733 LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00940000157855

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P31645

KEGG Orthology (KO)

More...KOi		K05037

Identification of Orthologs from Complete Genome Data

More...OMAi		STTVWID

Database for complete collections of gene phylogenies

More...PhylomeDBi		P31645

TreeFam database of animal gene trees

More...TreeFami		TF343812

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR000175 Na/ntran_symport
IPR013086 Na/ntran_symport_serotonin_N
IPR037272 SNS_sf

The PANTHER Classification System

More...PANTHERi		PTHR11616 PTHR11616, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF03491 5HT_transport_N, 1 hit
PF00209 SNF, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR01203 5HTTRANSPORT
PR00176 NANEUSMPORT

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF161070 SSF161070, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS00610 NA_NEUROTRAN_SYMP_1, 1 hit
PS00754 NA_NEUROTRAN_SYMP_2, 1 hit
PS50267 NA_NEUROTRAN_SYMP_3, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3KPR9J3KPR9_HUMAN
Transporter
SLC6A4
618Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
J3QKP3J3QKP3_HUMAN
Sodium-dependent serotonin transpor...
SLC6A4
72Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the 'Sequence' section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement%5Fin%5Fdisease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>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.1 Publication
The 5-HTTLPR polymorphism may influence susceptibility to anxiety [MIMi:607834].1 Publication
The polymorphism Val-425 seems to be linked to a susceptibility to obsessive-compulsive disorder (OCD) [MIMi:164230].3 Publications
Genetic variations in SLC6A4 determine the genetic susceptibility to alcoholism [MIMi:103780].1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_01418156G → A1 PublicationCorresponds to variant dbSNP:rs6355Ensembl.1
Natural variantiVAR_029158201K → N. Corresponds to variant dbSNP:rs2228673Ensembl.1
Natural variantiVAR_036788425I → L. Corresponds to variant dbSNP:rs28914832EnsemblClinVar.1
Natural variantiVAR_026751425I → V Polymorphism linked with susceptibility to obsessive-compulsive disorder; increased serotonin transport capacity. 3 PublicationsCorresponds to variant dbSNP:rs28914832EnsemblClinVar.1
Natural variantiVAR_036789465F → L. Corresponds to variant dbSNP:rs28914833Ensembl.1
Natural variantiVAR_036790550L → V. Corresponds to variant dbSNP:rs28914834Ensembl.1
Natural variantiVAR_014182605K → N1 PublicationCorresponds to variant dbSNP:rs6352EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0465531M → MSQSRRVNPDDRELGGDLQI QAPRDQLGSLADGHQCHLLT SRM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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.

The Consensus CDS (CCDS) project

More...CCDSi		CCDS11256.1 [P31645-1]

Protein sequence database of the Protein Information Resource

More...PIRi		A47398

NCBI Reference Sequences

More...RefSeqi		NP_001036.1, NM_001045.5 [P31645-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000261707; ENSP00000261707; ENSG00000108576 [P31645-1]
ENST00000401766; ENSP00000385822; ENSG00000108576 [P31645-1]
ENST00000650711; ENSP00000498537; ENSG00000108576 [P31645-1]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		6532

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:6532

UCSC genome browser

More...UCSCi		uc002hey.6 human [P31645-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>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.
CCDSiCCDS11256.1 [P31645-1]
PIRiA47398
RefSeqiNP_001036.1, NM_001045.5 [P31645-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5I6XX-ray3.14A76-618[»]
5I6ZX-ray4.53A76-618[»]
5I71X-ray3.15A76-618[»]
5I73X-ray3.24A76-618[»]
5I74X-ray3.40A76-618[»]
5I75X-ray3.49A76-618[»]
6AWNX-ray3.62A76-618[»]
6AWOX-ray3.53A76-618[»]
6AWPX-ray3.80A76-618[»]
6AWQX-ray4.05A76-618[»]
6DZVelectron microscopy4.20A79-615[»]
6DZWelectron microscopy4.30A79-615[»]
6DZYelectron microscopy4.10A79-615[»]
6DZZelectron microscopy3.60A78-617[»]
SMRiP31645
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi112423, 11 interactors
IntActiP31645, 2 interactors
MINTiP31645
STRINGi9606.ENSP00000261707

Chemistry databases

BindingDBiP31645
ChEMBLiCHEMBL228
DrugBankiDB01472 4-Methoxyamphetamine
DB04836 Amineptine
DB05964 Amitifadine
DB00321 Amitriptyline
DB00543 Amoxapine
DB00182 Amphetamine
DB01238 Aripiprazole
DB00289 Atomoxetine
DB00245 Benzatropine
DB04889 Bicifadine
DB09016 Butriptyline
DB01114 Chlorpheniramine
DB00215 Citalopram
DB01242 Clomipramine
DB00907 Cocaine
DB05688 CRx-119
DB00924 Cyclobenzaprine
DB12305 Dasotraline
DB01151 Desipramine
DB06700 Desvenlafaxine
DB01191 Dexfenfluramine
DB06701 Dexmethylphenidate
DB00514 Dextromethorphan
DB00988 Dopamine
DB09167 Dosulepin
DB01142 Doxepin
DB00476 Duloxetine
DB01363 Ephedra sinica root
DB01175 Escitalopram
DB09194 Etoperidone
DB00574 Fenfluramine
DB00472 Fluoxetine
DB00176 Fluvoxamine
DB00458 Imipramine
DB08918 Levomilnacipran
DB09195 Lorpiprazole
DB00408 Loxapine
DB06077 Lumateperone
DB00579 Mazindol
DB00454 Meperidine
DB01577 Metamfetamine
DB06148 Mianserin
DB01454 Midomafetamine
DB04896 Milnacipran
DB00805 Minaprine
DB00370 Mirtazapine
DB01442 MMDA
DB01149 Nefazodone
DB09186 Nisoxetine
DB04821 Nomifensine
DB00540 Nortriptyline
DB05422 OPC-14523
DB00715 Paroxetine
DB00191 Phentermine
DB00344 Protriptyline
DB00852 Pseudoephedrine
DB08839 Serotonin
DB01104 Sertraline
DB01105 Sibutramine
DB06204 Tapentadol
DB01079 Tegaserod
DB06156 Tesofensine
DB00193 Tramadol
DB00656 Trazodone
DB00726 Trimipramine
DB00285 Venlafaxine
DB00661 Verapamil
DB06684 Vilazodone
DB09068 Vortioxetine
DB04832 Zimelidine
DB09225 Zotepine
DrugCentraliP31645
GuidetoPHARMACOLOGYi928

Protein family/group databases

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

PTM databases

iPTMnetiP31645
PhosphoSitePlusiP31645

Polymorphism and mutation databases

BioMutaiSLC6A4
DMDMi400630

Proteomic databases

MassIVEiP31645
PaxDbiP31645
PeptideAtlasiP31645
PRIDEiP31645
ProteomicsDBi54798 [P31645-1]

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		P31645

Antibodypedia a portal for validated antibodies

More...Antibodypediai		26840 320 antibodies

Genome annotation databases

EnsembliENST00000261707; ENSP00000261707; ENSG00000108576 [P31645-1]
ENST00000401766; ENSP00000385822; ENSG00000108576 [P31645-1]
ENST00000650711; ENSP00000498537; ENSG00000108576 [P31645-1]
GeneIDi6532
KEGGihsa:6532
UCSCiuc002hey.6 human [P31645-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		6532
DisGeNETi6532

GeneCards: human genes, protein and diseases

More...GeneCardsi		SLC6A4
HGNCiHGNC:11050 SLC6A4
HPAiENSG00000108576 Tissue enhanced (intestine, lung)
MalaCardsiSLC6A4
MIMi103780 phenotype
164230 phenotype
182138 gene
607834 phenotype
neXtProtiNX_P31645
OpenTargetsiENSG00000108576
PharmGKBiPA312

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG3659 Eukaryota
COG0733 LUCA
GeneTreeiENSGT00940000157855
InParanoidiP31645
KOiK05037
OMAiSTTVWID
PhylomeDBiP31645
TreeFamiTF343812

Enzyme and pathway databases

ReactomeiR-HSA-380615 Serotonin clearance from the synaptic cleft
SIGNORiP31645

Miscellaneous databases

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		Serotonin_transporter

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		6532
PharosiP31645 Tclin

Protein Ontology

More...PROi		PR:P31645
RNActiP31645 protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000108576 Expressed in upper lobe of lung and 104 other tissues
ExpressionAtlasiP31645 baseline and differential
GenevisibleiP31645 HS

Family and domain databases

InterProiView protein in InterPro
IPR000175 Na/ntran_symport
IPR013086 Na/ntran_symport_serotonin_N
IPR037272 SNS_sf
PANTHERiPTHR11616 PTHR11616, 1 hit
PfamiView protein in Pfam
PF03491 5HT_transport_N, 1 hit
PF00209 SNF, 1 hit
PRINTSiPR01203 5HTTRANSPORT
PR00176 NANEUSMPORT
SUPFAMiSSF161070 SSF161070, 1 hit
PROSITEiView protein in PROSITE
PS00610 NA_NEUROTRAN_SYMP_1, 1 hit
PS00754 NA_NEUROTRAN_SYMP_2, 1 hit
PS50267 NA_NEUROTRAN_SYMP_3, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiSC6A4_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P31645
Secondary accession number(s): Q5EE02
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: April 22, 2020
This is version 197 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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