Gene Report

Basic Information

Approved Symbol	SLC6A3
Approved Name	solute carrier family 6 (neurotransmitter transporter, dopamine), member 3
Previous Symbol	DAT1
Symbol Alias	DAT
Name Alias	dopamine transporter
Location	5p15.3
Position	chr5:1392905-1445543 (-)
External Links	Entrez Gene: 6531 Ensembl: ENSG00000142319 UCSC: uc003jck.3 HGNC ID: 11049
No. of Studies (Positive/Negative)	3(2/1)
Type	Literature-origin; SNP mapped; Protein mapped

Positive relationships between SLC6A3 and MDD (count: 0)

Positive relationships between SLC6A3 and other components at different levels (count: 2)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Relation Description
Name in Literature	Related Components
dopamine transporter (DAT1)		Basal ganglia(basal ganglia)	brain morphology and function	Dillon, 2010	normal people	Results revealed that TREK1 and DAT/COMT genotypes were inde...... Results revealed that TREK1 and DAT/COMT genotypes were independently related to basal ganglia responses to gains. More...
DAT		Executive functions(executive dysfunction)	cognition and behavior	Lavretsky, 2008	patients only	Subjects with DAT VNTR 10/10 genotype had greater cognitive ...... Subjects with DAT VNTR 10/10 genotype had greater cognitive executive dysfunction at baseline compared to others. More...

Positive relationship network of SLC6A3 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between SLC6A3 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
dopamine transporter gene (DAT1)	Huang, 2011	patients and normal controls		Several association tendencies were found between DAT1 and m...... Several association tendencies were found between DAT1 and major depression More...

Negative relationships between SLC6A3 and other components at different levels (count: 0)

SLC6A3 related SNPs in MK4MDD (count: 1)

#rs	Location	Annotation	No. of Studies (Positive/Negative)
rs40184	chr5:1395077(Forward)	intron_variant	2(1/1)

SLC6A3 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Sodium-dependent dopamine transporter	Q01959	6(6/0)	Literature-origin

SLC6A3 related GO terms (count: 39)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0007268	synaptic transmission	biological process	TAS

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0047485	protein N-terminus binding	molecular function	IEA
GO:0035094	response to nicotine	biological process	IEA
GO:0043025	neuronal cell body	cellular component	IDA[12958153]
GO:0007608	sensory perception of smell	biological process	IEA
GO:0007626	locomotory behavior	biological process	IEA
GO:0042136	neurotransmitter biosynthetic process	biological process	TAS
GO:0042420	dopamine catabolic process	biological process	IEA
GO:0042416	dopamine biosynthetic process	biological process	IEA
GO:0055085	transmembrane transport	biological process	TAS
GO:0030424	axon	cellular component	IDA[12958153]
GO:0007568	aging	biological process	IEA
GO:0015844	monoamine transport	biological process	IDA[16024787]
GO:0015872	dopamine transport	biological process	IEA
GO:0006810	transport	biological process	TAS[8628395]
GO:0005887	integral to plasma membrane	cellular component	IEA
GO:0005515	protein binding	molecular function	IPI[12958153]
GO:0005330	dopamine:sodium symporter activity	molecular function	IEA
GO:0051591	response to cAMP	biological process	IEA
GO:0045471	response to ethanol	biological process	IEA
GO:0021984	adenohypophysis development	biological process	IEA
GO:0042493	response to drug	biological process	IEA
GO:0008504	monoamine transmembrane transporter activity	molecular function	IDA[16024787]
GO:0008144	drug binding	molecular function	IEA
GO:0005329	dopamine transmembrane transporter activity	molecular function	TAS[10823899]
GO:0040018	positive regulation of multicellular organism growth	biological process	IEA
GO:0060134	prepulse inhibition	biological process	IEA
GO:0032403	protein complex binding	molecular function	IEA
GO:0016021	integral to membrane	cellular component	TAS[8628395]
GO:0008219	cell death	biological process	IEA
GO:0002020	protease binding	molecular function	IEA
GO:0007595	lactation	biological process	IEA
GO:0042220	response to cocaine	biological process	IEA
GO:0010039	response to iron ion	biological process	IEA
GO:0042053	regulation of dopamine metabolic process	biological process	IEA
GO:0035240	dopamine binding	molecular function	IEA
GO:0005102	receptor binding	molecular function	IEA
GO:0005886	plasma membrane	cellular component	IDA[12958153]; TAS
GO:0005737	cytoplasm	cellular component	TAS[10823899]

SLC6A3 related KEGG pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa05012	parkinsons disease	Parkinson's disease	Parkinson's disease (PD) is a progressive neurodegenerative ...... Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that results primarily from the death of dopaminergic neurons in the substantia nigra. Mutations in alpha-synuclein, UCHL1 (a ubiquitin carboxy-terminal hydrolase L1), parkin, DJ1 (a parkin-associated protein involved with oxidative stress), and PINK1 (a putative serine threonine kinase) are known to cause early-onset PD. Mutations or altered expression of these proteins contributes to PD pathogenesis through common mechanisms that result in proteasome dysfunction, mitochondrial impairment, and oxidative stress. Point mutations in alpha-synuclein and the recently described Iowan functional duplication of alpha-synuclein lead to excessive intracellular accumulation and protofibril formation. Decrease in the amount of soluble alpha-synuclein tends to increase free cytoplasmic dopamine and the formation of reactive oxygen species (ROS). Indeed, formation of protofibrils or aggregates and Lewy bodies (LBs) diminishes the availability of the physiological forms of alpha-synuclein, favoring an increase in TH (tyrosine hydroxylase) and DAT (dopamine transporter), but diminishes vesicles formation and neuronal plasticity. Modification of parkin and UCHL1 are associated with the ubiquitin-proteasome system pathway and may increase proteotoxic stress. Mutations in parkin, DJ1, and PINK1 may alter mitochondiral activity, potentially impairing proteasomal function. Environmental toxins such as N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rotenone can cause mitochondrial dysfunction and oxidative stress. More...

SLC6A3 related BioCarta pathways (count: 0)

SLC6A3 related Reactome pathways (count: 6)

ID	Name	Description
Gene mapped Reactome pathways
REACT_19305	glucose and_other_sugar_slc_transporters	Hexoses like glucose, galactose and fructose serve as basic ...... Hexoses 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 across cellular membranes, and require transporter proteins for entry into and exit out of cells. Four gene families encode hexose transporter proteins. SLC2 family contains 14 genes and encode facilitative glucose transporters. SLC5 family contains 12 genes and encode Na+/glucose symporters. SLC37 family contains 4 members and encode sugar-phosphate/phosphate exchangers. SLC45 family has 4 members and encode putative sugar/H+ symporters. More...
REACT_15518	transmembrane transport_of_small_molecules
REACT_19118	slc mediated_transmembrane_transport	Proteins with transporting functions can be roughly classifi...... Proteins 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 movement of the substrates across the membrane, against their electrochemical gradient. Channels at the open state can transfer the substrates. At least 20-25% amino-acid sequence identity is shared by members belonging to the same SLC family. No homology is shared between different SLC families. While the HUGO nomenclature system by definition only includes human genes, the nomenclature system has been informally extended to include rodent species through the use of lower cases letters (e.g., Slc1a1 denotes the rodent ortholog of the human SLC1A1 gene). And it's worthwhile to mention that pumps, channels and aquporins are not included in SLC superfamily. More...
REACT_20506	na cl_dependent_neurotransmitter_transporters	The SLC6 gene family encodes proteins that mediate neurotran...... The SLC6 gene family encodes proteins that mediate neurotransmitter uptake thus terminating a synaptic signal. The proteins mediate transport of GABA. More...
REACT_13477	transmission across_chemical_synapses	Chemical synapses are specialized junctions that are used fo...... Chemical 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, muscle cell or glad cell. The pre and the post-synaptic cell are separated by a gap of 20nm called the synaptic cleft. The signals pass in a unidirection from pre-synaptic to post-synaptic. The pre-synaptic neuron communicates via the release of neurotransmitter which bind the receptors on the post-synaptic cell. More...
REACT_20679	amine compound_slc_transporters	Five SLC gene families encode proteins that mediate transpor...... Five SLC gene families encode proteins that mediate transport of amines. More...

SLC6A3 related interactors from protein-protein interaction data in HPRD (count: 7)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
SLC6A3	SNCA	No	in vivo;yeast 2-hybrid	12672538 , 11292651
SLC6A3	STX1A	Yes	in vitro;in vivo;yeast 2-hybrid	15202772
SLC6A3	GNB2L1	No	in vitro;in vivo;yeast 2-hybrid	15202772
SLC6A3	DRD2	Yes	in vitro;in vivo	17380124
SLC6A3	PICK1	No	in vivo;yeast 2-hybrid	11343649
SLC6A3	TGFB1I1	No	in vitro;in vivo;yeast 2-hybrid	12177201
SLC6A3	SLC6A3	Yes	yeast 2-hybrid	15202772

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped Reactome pathways