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SLC6A3 solute carrier family 6 member 3 [ Homo sapiens (human) ]

Gene ID: 6531, updated on 3-Nov-2018

Summary

Official Symbol
SLC6A3provided by HGNC
Official Full Name
solute carrier family 6 member 3provided by HGNC
Primary source
HGNC:HGNC:11049
See related
Ensembl:ENSG00000142319 MIM:126455; Vega:OTTHUMG00000131016
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
DAT; DAT1; PKDYS; PKDYS1
Summary
This gene encodes a dopamine transporter which is a member of the sodium- and chloride-dependent neurotransmitter transporter family. The 3' UTR of this gene contains a 40 bp tandem repeat, referred to as a variable number tandem repeat or VNTR, which can be present in 3 to 11 copies. Variation in the number of repeats is associated with idiopathic epilepsy, attention-deficit hyperactivity disorder, dependence on alcohol and cocaine, susceptibility to Parkinson disease and protection against nicotine dependence.[provided by RefSeq, Nov 2009]
Expression
Low expression observed in reference dataset See more
Orthologs

Genomic context

See SLC6A3 in Genome Data Viewer
Location:
5p15.33
Exon count:
15
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 5 NC_000005.10 (1392790..1445428, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (1392905..1445543, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene CLPTM1 like Neighboring gene long intergenic non-protein coding RNA 1511 Neighboring gene lysophosphatidylcholine acyltransferase 1 Neighboring gene microRNA 6075 Neighboring gene uncharacterized LOC107986397

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 and HIV-1 Tat decrease dopamine uptake into striatal synaptosomes by decreasing the V(max) of the dopamine transporter (DAT); 17beta-Estradiol prevents the oxidative stress and loss of DAT function associated with gp120/Tat neurotoxicity PubMed
Nef nef HIV-1 Nef-mediated downregulation of HLA (MHCI) may be affected by/inhibited by SLC6A3 as demonstrated by siRNA genome-wide screen [in HeLa cells) PubMed
Tat tat HIV-1 Tat inhibits SLC6A3 (hDAT) and dopamine uptake PubMed
tat A three-dimensional structural model for HIV-1 Tat binding with human dopamine transporter is developed by computational modeling and molecular dynamics simulations PubMed
tat Mutation of either Tyr88 (Y88F) or Lys92 (K92M) in human dopamine transporter (hDAT) attenuates HIV-1 Tat-induced inhibition of hDAT function in cells PubMed
tat Co-immunoprecipitation analysis indicates that HIV-1 Tat directly binds to human dopamine transporter (hDAT). The hDAT Y470H mutant attenuates Tat-induced reduction of hDAT function PubMed
tat HIV-1 Tat allosterically modulates DAT activity in HEK293 cells PubMed
tat HIV-1 Tat increases plasma membrane (PM) dopamine transporter (DAT) activity and calpain protease activity at the PM PubMed
tat HIV-1 gp120 and HIV-1 Tat decrease dopamine uptake into striatal synaptosomes by decreasing the V(max) of the dopamine transporter (DAT); 17beta-Estradiol prevents the oxidative stress and loss of DAT function associated with gp120/Tat neurotoxicity PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Alcoholism, organism-specific biosystem (from KEGG)
    Alcoholism, organism-specific biosystemAlcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the reward...
  • Alcoholism, conserved biosystem (from KEGG)
    Alcoholism, conserved biosystemAlcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the reward...
  • Alpha-synuclein signaling, organism-specific biosystem (from Pathway Interaction Database)
    Alpha-synuclein signaling, organism-specific biosystem
    Alpha-synuclein signaling
  • Amphetamine addiction, organism-specific biosystem (from KEGG)
    Amphetamine addiction, organism-specific biosystemAmphetamine is a psychostimulant drug that exerts persistent addictive effects. Most addictive drugs increase extracellular concentrations of dopamine (DA) in nucleus accumbens (NAc) and medial prefr...
  • Amphetamine addiction, conserved biosystem (from KEGG)
    Amphetamine addiction, conserved biosystemAmphetamine is a psychostimulant drug that exerts persistent addictive effects. Most addictive drugs increase extracellular concentrations of dopamine (DA) in nucleus accumbens (NAc) and medial prefr...
  • Cocaine addiction, organism-specific biosystem (from KEGG)
    Cocaine addiction, organism-specific biosystemDrug addiction is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behavior persists despite serious negative consequences.There is strong evidence that the dopaminergic...
  • Cocaine addiction, conserved biosystem (from KEGG)
    Cocaine addiction, conserved biosystemDrug addiction is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behavior persists despite serious negative consequences.There is strong evidence that the dopaminergic...
  • Dopamine clearance from the synaptic cleft, organism-specific biosystem (from REACTOME)
    Dopamine clearance from the synaptic cleft, organism-specific biosystemThe human gene SLC6A3 encodes the sodium-dependent dopamine transporter, DAT which mediates the re-uptake of dopamine from the synaptic cleft (Vandenbergh DJ et al, 2000). Dopamine can then be degrad...
  • Dopaminergic Neurogenesis, organism-specific biosystem (from WikiPathways)
    Dopaminergic Neurogenesis, organism-specific biosystemConverted to human from mouse: http://www.wikipathways.org/index.php/Pathway:WP1498
  • Dopaminergic synapse, organism-specific biosystem (from KEGG)
    Dopaminergic synapse, organism-specific biosystemDopamine (DA) is an important and prototypical slow neurotransmitter in the mammalian brain, where it controls a variety of functions including locomotor activity, motivation and reward, learning an...
  • Dopaminergic synapse, conserved biosystem (from KEGG)
    Dopaminergic synapse, conserved biosystemDopamine (DA) is an important and prototypical slow neurotransmitter in the mammalian brain, where it controls a variety of functions including locomotor activity, motivation and reward, learning an...
  • Monoamine Transport, organism-specific biosystem (from WikiPathways)
    Monoamine Transport, organism-specific biosystem
    Monoamine Transport
  • NRF2 pathway, organism-specific biosystem (from WikiPathways)
    NRF2 pathway, organism-specific biosystemNRF2 is part of a group of transcription factors called nuclear receptors. It is activated under oxidative stress conditions and subsequently activates several antioxidative genes and proteins.
  • Na+/Cl- dependent neurotransmitter transporters, organism-specific biosystem (from REACTOME)
    Na+/Cl- dependent neurotransmitter transporters, organism-specific biosystemThe SLC6 gene family encodes proteins that mediate neurotransmitter uptake thus terminating a synaptic signal. The proteins mediate transport of GABA (gamma-aminobutyric acid), norepinephrine, dopami...
  • Neuronal System, organism-specific biosystem (from REACTOME)
    Neuronal System, organism-specific biosystemThe human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication a...
  • Neurotransmitter Clearance In The Synaptic Cleft, organism-specific biosystem (from REACTOME)
    Neurotransmitter Clearance In The Synaptic Cleft, organism-specific biosystemNeurotransmitter released in the synaptic cleft binds to specific receptors on the post-synaptic cell and the excess of the neurotransmitter is cleared to prevent over activation of the post-synapti...
  • Parkinson's disease, organism-specific biosystem (from KEGG)
    Parkinson's disease, organism-specific biosystemParkinson's disease (PD) is a progressive neurodegenerative movement disorder that results primarily from the death of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Mutations...
  • Parkinsons Disease Pathway, organism-specific biosystem (from WikiPathways)
    Parkinsons Disease Pathway, organism-specific biosystemMost people with Parkinson's disease have idiopathic Parkinson's disease (having no specific known cause). A small proportion of cases, however, can be attributed to known genetic factors. Mutations ...
  • SLC-mediated transmembrane transport, organism-specific biosystem (from REACTOME)
    SLC-mediated transmembrane transport, organism-specific biosystemProteins with transporting functions can be roughly classified into 3 categories: ATP-powered pumps, ion channels, and transporters. Pumps utilize the energy released by ATP hydrolysis to power the m...
  • Transmembrane transport of small molecules, organism-specific biosystem (from REACTOME)
    Transmembrane transport of small molecules, organism-specific biosystem
    Transmembrane transport of small molecules
  • Transmission across Chemical Synapses, organism-specific biosystem (from REACTOME)
    Transmission across Chemical Synapses, organism-specific biosystemChemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron,...
  • Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds, organism-specific biosystem (from REACTOME)
    Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds, organism-specific biosystemHexoses like glucose, galactose and fructose serve as basic fuel molecules for eukaryotic cells. Indeed, glucose is the main energy source for mammalian cells. These sugars are unable to diffuse acro...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
dopamine binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
dopamine:sodium symporter activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
dopamine:sodium symporter activity IDA
Inferred from Direct Assay
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
monoamine transmembrane transporter activity IDA
Inferred from Direct Assay
more info
PubMed 
monoamine transmembrane transporter activity TAS
Traceable Author Statement
more info
 
neurotransmitter:sodium symporter activity IEA
Inferred from Electronic Annotation
more info
 
protease binding IEA
Inferred from Electronic Annotation
more info
 
protein N-terminus binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein phosphatase 2A binding IEA
Inferred from Electronic Annotation
more info
 
protein-containing complex binding IEA
Inferred from Electronic Annotation
more info
 
signaling receptor binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
adenohypophysis development IEA
Inferred from Electronic Annotation
more info
 
aging IEA
Inferred from Electronic Annotation
more info
 
dopamine biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
dopamine catabolic process IEA
Inferred from Electronic Annotation
more info
 
dopamine transport IDA
Inferred from Direct Assay
more info
PubMed 
dopamine uptake IDA
Inferred from Direct Assay
more info
PubMed 
lactation IEA
Inferred from Electronic Annotation
more info
 
locomotory behavior IEA
Inferred from Electronic Annotation
more info
 
monoamine transport IDA
Inferred from Direct Assay
more info
PubMed 
neurotransmitter biosynthetic process TAS
Traceable Author Statement
more info
 
neurotransmitter uptake IEA
Inferred from Electronic Annotation
more info
 
positive regulation of multicellular organism growth IEA
Inferred from Electronic Annotation
more info
 
prepulse inhibition IEA
Inferred from Electronic Annotation
more info
 
regulation of dopamine metabolic process IEA
Inferred from Electronic Annotation
more info
 
response to cAMP IEA
Inferred from Electronic Annotation
more info
 
response to cocaine IEA
Inferred from Electronic Annotation
more info
 
response to ethanol IEA
Inferred from Electronic Annotation
more info
 
response to iron ion IEA
Inferred from Electronic Annotation
more info
 
response to nicotine IEA
Inferred from Electronic Annotation
more info
 
sensory perception of smell IEA
Inferred from Electronic Annotation
more info
 
transmembrane transport IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
axon IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
axon IDA
Inferred from Direct Assay
more info
PubMed 
cell surface IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm TAS
Traceable Author Statement
more info
PubMed 
dopaminergic synapse IEA
Inferred from Electronic Annotation
more info
 
flotillin complex IDA
Inferred from Direct Assay
more info
PubMed 
integral component of membrane TAS
Traceable Author Statement
more info
PubMed 
integral component of postsynaptic membrane IEA
Inferred from Electronic Annotation
more info
 
integral component of presynaptic membrane IEA
Inferred from Electronic Annotation
more info
 
membrane raft IDA
Inferred from Direct Assay
more info
PubMed 
neuron projection IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
neuron projection IDA
Inferred from Direct Assay
more info
PubMed 
neuronal cell body IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
sodium-dependent dopamine transporter
Names
DA transporter
dopamine transporter 1
solute carrier family 6 (neurotransmitter transporter), member 3
solute carrier family 6 (neurotransmitter transporter, dopamine), member 3

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_015885.1 RefSeqGene

    Range
    5001..57639
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001044.4NP_001035.1  sodium-dependent dopamine transporter

    See identical proteins and their annotated locations for NP_001035.1

    Status: REVIEWED

    Source sequence(s)
    AC026748, AI586989, EF174603
    Consensus CDS
    CCDS3863.1
    UniProtKB/Swiss-Prot
    Q01959
    Related
    ENSP00000270349.9, OTTHUMP00000161635, ENST00000270349.11, OTTHUMT00000253650
    Conserved Domains (1) summary
    cd11514
    Location:60614
    SLC6sbd_DAT1; Na(+)- and Cl(-)-dependent dopamine transporter 1; solute-binding domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p12 Primary Assembly

    Range
    1392790..1445428 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p12 ALT_REF_LOCI_1

Genomic

  1. NT_187547.1 Reference GRCh38.p12 ALT_REF_LOCI_1

    Range
    64345..121219
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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