Excitatory amino acid transporter 3

SLC1A1

Identifiers

SLC1A1, EAAC1, EAAT3, SCZD18, DCBXA, solute carrier family 1 member 1

External IDs

OMIM: 133550 MGI: 105083 HomoloGene: 20881 GeneCards: SLC1A1

Gene location (Human)

Chr.	Chromosome 9 (human)^[1]

Band	9p24.2	Start	4,490,468 bp^[1]
Band	9p24.2	End	4,587,469 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 19 (mouse)^[2]

Band	19\|19 C1	Start	28,812,449 bp^[2]
Band	19\|19 C1	End	28,891,360 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

corpus epididymis

jejunal mucosa

kidney tubule

pancreatic ductal cell

duodenum

lower lobe of lung

postcentral gyrus

endothelial cell

superior frontal gyrus

caput epididymis

Top expressed in

retinal pigment epithelium

subiculum

lateral geniculate nucleus

kidney

medial geniculate nucleus

Region I of hippocampus proper

proximal tubule

medial dorsal nucleus

anterior horn of spinal cord

hippocampus proper

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	cysteine transmembrane transporter activity protein binding symporter activity L-glutamate transmembrane transporter activity glutamate binding amino acid transmembrane transporter activity high-affinity glutamate transmembrane transporter activity chloride transmembrane transporter activity glutamate:sodium symporter activity metal ion binding
Cellular component	integral component of membrane membrane plasma membrane apical plasma membrane extracellular exosome integral component of plasma membrane early endosome membrane recycling endosome membrane
Biological process	chemical synaptic transmission D-aspartate import across plasma membrane ion transport positive regulation of heart rate glutamate secretion cysteine transport protein homooligomerization L-glutamate import L-glutamate transmembrane transport cysteine transmembrane transport L-aspartate import across plasma membrane chloride transmembrane transport L-glutamate import across plasma membrane amino acid transport transport
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


6505


20510

Ensembl


ENSG00000106688


ENSMUSG00000024935

UniProt


P43005


P51906

RefSeq (mRNA)


NM_004170


NM_009199

RefSeq (protein)


NP_004161


NP_033225

Location (UCSC)

Chr 9: 4.49 – 4.59 Mb

Chr 19: 28.81 – 28.89 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Excitatory amino acid transporter 3 (EAAT3), is a protein that in humans is encoded by the SLC1A1 gene.^[5]^[6]

YouTube Encyclopedic

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Transcription

Tissue distribution

EAAT3 is expressed on the plasma membrane of neurons, specifically on the dendrites and axon terminals.^[7]

Function

Excitatory amino acid transporter 3 is a member of the high-affinity glutamate transporters which plays an essential role in transporting glutamate across plasma membranes in neurons. In the brain, excitatory amino acid transporters are crucial in terminating the postsynaptic action of the neurotransmitter glutamate, and in maintaining extracellular glutamate concentrations below neurotoxic levels. EAAT3 also transports aspartate, and mutations in this gene are thought to cause dicarboxylic aminoaciduria, also known as glutamate-aspartate transport defect.^[6] EAAT3 is also the major route of neuronal cysteine uptake. Cysteine is a component of the major antioxidant glutathione, and mice lacking EAAT3 exhibit reduced levels of glutathione in neurons, increased oxidative stress, and age-dependent loss of neurons, especially neurons of the substantia nigra. A meta-analysis identified a small but significant association between a polymorphism of the gene SLC1A1 and Obsessive-Compulsive Disorder.^[8]

Interactions

SLC1A1 has been shown to interact with ARL6IP5.^[9]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000106688 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000024935 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Smith CP, Weremowicz S, Kanai Y, Stelzner M, Morton CC, Hediger MA (March 1994). "Assignment of the gene coding for the human high-affinity glutamate transporter EAAC1 to 9p24: potential role in dicarboxylic aminoaciduria and neurodegenerative disorders". Genomics. 20 (2): 335–6. doi:10.1006/geno.1994.1183. PMID 8020993.
^ ^a ^b "Entrez Gene: SLC1A1 solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1".
^ Underhill SM, Wheeler DS, Li M, Watts SD, Ingram SL, Amara SG (July 2014). "Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons". Neuron. 83 (2): 404–416. doi:10.1016/j.neuron.2014.05.043. PMC 4159050. PMID 25033183. In general, EAATs 1 and 2 are found predominantly in astrocytes, EAAT3 in neurons, EAAT4 in Purkinje cells, and EAAT5 expression is restricted to the retina (Danbolt, 2001). The dependence of EAAT3 internalization on the DAT also suggests that the two transporters might be internalized together. We found that EAAT3 and DAT are expressed in the same cells, as well as in axons and dendrites. However, the subcellular co-localization of the two neurotransmitter transporters remains to be established definitively by high resolution electron microscopy.
^ Stewart SE, Mayerfeld C, Arnold PD, Crane JR, O'Dushlaine C, Fagerness JA, et al. (June 2013). "Meta-analysis of association between obsessive-compulsive disorder and the 3' region of neuronal glutamate transporter gene SLC1A1" (PDF). American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 162B (4): 367–79. doi:10.1002/ajmg.b.32137. hdl:2027.42/98412. PMID 23606572. S2CID 20929721.
^ Lin CI, Orlov I, Ruggiero AM, Dykes-Hoberg M, Lee A, Jackson M, Rothstein JD (March 2001). "Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18". Nature. 410 (6824): 84–8. Bibcode:2001Natur.410...84L. doi:10.1038/35065084. PMID 11242046. S2CID 4622513.

Nieoullon A, Canolle B, Masmejean F, Guillet B, Pisano P, Lortet S (August 2006). "The neuronal excitatory amino acid transporter EAAC1/EAAT3: does it represent a major actor at the brain excitatory synapse?". Journal of Neurochemistry. 98 (4): 1007–18. doi:10.1111/j.1471-4159.2006.03978.x. PMID 16800850. S2CID 22532007.
Arriza JL, Fairman WA, Wadiche JI, Murdoch GH, Kavanaugh MP, Amara SG (September 1994). "Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex". The Journal of Neuroscience. 14 (9): 5559–69. doi:10.1523/jneurosci.14-09-05559.1994. PMC 6577102. PMID 7521911.
Shashidharan P, Huntley GW, Meyer T, Morrison JH, Plaitakis A (October 1994). "Neuron-specific human glutamate transporter: molecular cloning, characterization and expression in human brain". Brain Research. 662 (1–2): 245–50. doi:10.1016/0006-8993(94)90819-2. PMID 7859077. S2CID 35811464.
Kanai Y, Stelzner M, Nussberger S, Khawaja S, Hebert SC, Smith CP, Hediger MA (August 1994). "The neuronal and epithelial human high affinity glutamate transporter. Insights into structure and mechanism of transport". The Journal of Biological Chemistry. 269 (32): 20599–606. doi:10.1016/S0021-9258(17)32035-5. PMID 7914198.
Zerangue N, Kavanaugh MP (June 1996). "Interaction of L-cysteine with a human excitatory amino acid transporter". The Journal of Physiology. 493 (Pt 2): 419–23. doi:10.1113/jphysiol.1996.sp021393. PMC 1158927. PMID 8782106.
Bar-Peled O, Ben-Hur H, Biegon A, Groner Y, Dewhurst S, Furuta A, Rothstein JD (December 1997). "Distribution of glutamate transporter subtypes during human brain development". Journal of Neurochemistry. 69 (6): 2571–80. doi:10.1046/j.1471-4159.1997.69062571.x. PMID 9375691. S2CID 34227788.
He Y, Janssen WG, Rothstein JD, Morrison JH (March 2000). "Differential synaptic localization of the glutamate transporter EAAC1 and glutamate receptor subunit GluR2 in the rat hippocampus". The Journal of Comparative Neurology. 418 (3): 255–69. doi:10.1002/(SICI)1096-9861(20000313)418:3<255::AID-CNE2>3.0.CO;2-6. PMID 10701825. S2CID 23608989.
Lin CI, Orlov I, Ruggiero AM, Dykes-Hoberg M, Lee A, Jackson M, Rothstein JD (March 2001). "Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18". Nature. 410 (6824): 84–8. Bibcode:2001Natur.410...84L. doi:10.1038/35065084. PMID 11242046. S2CID 4622513.
Veenstra-VanderWeele J, Kim SJ, Gonen D, Hanna GL, Leventhal BL, Cook EH (March 2001). "Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder". Molecular Psychiatry. 6 (2): 160–7. doi:10.1038/sj.mp.4000806. PMID 11317217. S2CID 13969870.
Borre L, Kavanaugh MP, Kanner BI (April 2002). "Dynamic equilibrium between coupled and uncoupled modes of a neuronal glutamate transporter". The Journal of Biological Chemistry. 277 (16): 13501–7. doi:10.1074/jbc.M110861200. PMID 11823462.
González MI, Bannerman PG, Robinson MB (July 2003). "Phorbol myristate acetate-dependent interaction of protein kinase Calpha and the neuronal glutamate transporter EAAC1". The Journal of Neuroscience. 23 (13): 5589–93. doi:10.1523/jneurosci.23-13-05589.2003. PMC 6741220. PMID 12843260.
Noorlander CW, de Graan PN, Nikkels PG, Schrama LH, Visser GH (July 2004). "Distribution of glutamate transporters in the human placenta". Placenta. 25 (6): 489–95. doi:10.1016/j.placenta.2003.10.018. PMID 15135231.
Koch HP, Larsson HP (February 2005). "Small-scale molecular motions accomplish glutamate uptake in human glutamate transporters". The Journal of Neuroscience. 25 (7): 1730–6. doi:10.1523/JNEUROSCI.4138-04.2005. PMC 6725926. PMID 15716409.
Vallejo-Illarramendi A, Domercq M, Pérez-Cerdá F, Ravid R, Matute C (January 2006). "Increased expression and function of glutamate transporters in multiple sclerosis". Neurobiology of Disease. 21 (1): 154–64. doi:10.1016/j.nbd.2005.06.017. PMID 16061389. S2CID 17817187.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Rainesalo S, Keränen T, Saransaari P, Honkaniemi J (November 2005). "GABA and glutamate transporters are expressed in human platelets". Brain Research. Molecular Brain Research. 141 (2): 161–5. doi:10.1016/j.molbrainres.2005.08.013. PMID 16198020.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Amphetamine

Main articles
and
pharmaceuticals

Amphetamine	Adzenys ER Adzenys XR-ODT Dyanavel XR Evekeo Evekeo ODT Mixed amphetamine salts Adderall Adderall XR Mydayis
Levoamphetamine	N/A
Dextroamphetamine	Dexedrine ProCentra Zenzedi
Lisdexamfetamine	Vyvanse

Neuropharmacology

Biomolecular targets	TAAR1 (full agonist) CART (mRNA inducer) 5-HT1A receptor (low affinity ligand) MAO (weak competitive inhibitor) Carbonic anhydrases hCA4, hCA5A, hCA5B, hCA7, hCA12, hCA13, and hCA14 (enzyme activator)
Inhibited transporters	DAT NET SERT VMAT1 VMAT2 EAAT3 SLC22A3 SLC22A5

Active metabolites

Category

Membrane proteins, carrier proteins: membrane transport proteins solute carrier (TC 2A)

By group

SLC1–10

(1):	high affinity glutamate and neutral amino-acid transporter SLC1A1 2 3 4 5 6 7
(2):	facilitative GLUT transporter SLC2A1 2 3 4 5 6 7 8 9 10 11 12 13 14
(3):	heavy subunits of heterodimeric amino-acid transporters SLC3A1 2
(4):	bicarbonate transporter SLC4A1 2 3 4 5 6 7 8 9 10 11
(5):	sodium glucose cotransporter SLC5A1 2 3 4 5 6 7 8 9 10 11 12
(6):	sodium- and chloride- dependent sodium:neurotransmitter symporters SLC6A1 SLC6A2 SLC6A3 SLC6A4 SLC6A5 SLC6A6 SLC6A7 SLC6A8 SLC6A9 SLC6A10 SLC6A11 SLC6A12 SLC6A13 SLC6A14 SLC6A15 SLC6A16 SLC6A17 SLC6A18 SLC6A19 SLC6A20
(7):	cationic amino-acid transporter/glycoprotein-associated SLC7A1 SLC7A2 SLC7A3 SLC7A4 glycoprotein-associated/light or catalytic subunits of heterodimeric amino-acid transporters SLC7A5 SLC7A6 SLC7A7 SLC7A8 SLC7A9 SLC7A10 SLC7A11 SLC7A13 SLC7A14
(8):	Na⁺/Ca²⁺ exchanger SLC8A1 SLC8A2 SLC8A3
(9):	Na⁺/H⁺ exchanger SLC9A1 SLC9A2 SLC9A3 SLC9A4 SLC9A5 SLC9A6 SLC9A7 SLC9A8 SLC9A9 SLC9A10 SLC9A11
(10):	sodium bile salt cotransport SLC10A1 SLC10A2 SLC10A3 SLC10A4 SLC10A5 SLC10A6 SLC10A7 10A1 10A2 10A3 10A7

SLC11–20

(11):	proton coupled metal ion transporter SLC11A1 SLC11A2 11A3
(12):	electroneutral cation-Cl cotransporter SLC12A1 SLC12A2 SLC12A3 SLC12A4 SLC12A5 SLC12A6 SLC12A7 SLC12A8 SLC12A9
(13):	human Na<sup>+</sup>-sulfate/carboxylate cotransporter SLC13A1 SLC13A2 SLC13A3 SLC13A4 SLC13A5
(14):	urea transporter SLC14A1 SLC14A2
(15):	proton oligopeptide cotransporter SLC15A1 SLC15A2 SLC15A3 SLC15A4
(16):	monocarboxylate transporter SLC16A1 SLC16A2 SLC16A3 SLC16A4 SLC16A5 SLC16A6 SLC16A7 SLC16A8 SLC16A9 SLC16A10 SLC16A11 SLC16A12 SLC16A13 SLC16A14
(17):	Vesicular glutamate transporter 1 SLC17A1 SLC17A2 SLC17A3 SLC17A4 SLC17A5 SLC17A6 SLC17A7 SLC17A8 SLC17A9
(18):	vesicular monoamine transporter SLC18A1 SLC18A2 SLC18A3
(19):	folate/thiamine transporter SLC19A1 SLC19A2 SLC19A3
(20):	type III Na⁺-phosphate cotransporter SLC20A1 SLC20A2

SLC21–30

(21):	Organic anion-transporting polypeptide SLCO1A2 SLCO1B1 SLCO1B3 SLCO1B4 SLCO1C1 SLCO2A1 SLCO2B1 SLCO3A1 SLCO4A1 SLCO4C1 SLCO5A1(SLCO6A1)
(22):	organic cation/anion/zwitterion transporter SLC22A1 SLC22A2 SLC22A3 SLC22A4 SLC22A5 SLC22A6 SLC22A7 SLC22A8 SLC22A9 SLC22A10 SLC22A11 SLC22A12 SLC22A13 SLC22A14 SLC22A15 SLC22A16 SLC22A17 SLC22A18 SLC22A19 SLC22A20
(23):	Na+-dependent ascorbic acid transporter SLC23A1 SLC23A2 SLC23A3 SLC23A4
(24):	Na⁺/(Ca²⁺-K⁺) exchanger SLC24A1 SLC24A2 SLC24A3 SLC24A4 SLC24A5 SLC24A6
(25):	mitochondrial carrier SLC25A1 SLC25A2 SLC25A3 SLC25A4 SLC25A5 SLC25A6 SLC25A7 SLC25A8 SLC25A9 SLC25A10 SLC25A11 SLC25A12 SLC25A13 SLC25A14 SLC25A15 SLC25A16 SLC25A17 SLC25A18 SLC25A19 SLC25A20 SLC25A21 SLC25A22 SLC25A23 SLC25A24 SLC25A25 SLC25A26 SLC25A27 SLC25A28 SLC25A29 SLC25A30 SLC25A31 SLC25A32 SLC25A33 SLC25A34 SLC25A35 SLC25A36 SLC25A37 SLC25A38 SLC25A39 SLC25A40 SLC25A41 SLC25A42 SLC25A43 SLC25A44 SLC25A45 SLC25A46
(26):	multifunctional anion exchanger SLC26A1 SLC26A2 SLC26A3 SLC26A4 SLC26A5 SLC26A6 SLC26A7 SLC26A8 SLC26A9 SLC26A10 SLC26A11
(27):	fatty acid transport proteins SLC27A1 SLC27A2 SLC27A3 SLC27A4 SLC27A5 SLC27A6
(28):	Na<sup>+</sup>-coupled nucleoside transport (SLC28A1 SLC28A2 SLC28A3
(29):	facilitative nucleoside transporter SLC29A1 SLC29A2 SLC29A3 SLC29A4
(30):	zinc efflux SLC30A1 SLC30A2 SLC30A3 SLC30A4 SLC30A5 SLC30A6 SLC30A7 SLC30A8 SLC30A9 SLC30A10

SLC31–40

(31):	copper transporter SLC31A1
(32):	Vesicular glutamate transporter 1 SLC32A1
(33):	Acetyl-CoA transporter SLC33A1
(34):	type II Na<sup>+</sup>-phosphate cotransporter SLC34A1 SLC34A2 SLC34A3
(35):	nucleoside-sugar transporter SLC35A1 SLC35A2 SLC35A3 SLC35A4 SLC35A5 SLC35B1 SLC35B2 SLC35B3 SLC35B4 SLC35C1 SLC35C2 SLC35D1 SLC35D2 SLC35D3 SLC35E1 SLC35E2 SLC35E3 SLC35E4
(36):	proton-coupled amino-acid transporter SLC36A1 SLC36A2 SLC36A3 SLC36A436A2
(37):	sugar-phosphate/phosphate exchanger SLC37A1 SLC37A2 SLC37A3 SLC37A4
(38):	System A & N, sodium-coupled neutral amino-acid transporter SLC38A1 SLC38A2 SLC38A3 SLC38A4 SLC38A5 SLC38A6 SLC38A10
(39):	metal ion transporter SLC39A1 SLC39A2 SLC39A3 SLC39A4 SLC39A5 SLC39A6 SLC39A7 SLC39A8 SLC39A9 SLC39A10 SLC39A11 SLC39A12 SLC39A13 SLC39A14
(40):	basolateral iron transporter SLC40A1

SLC41–48

(41):	Magnesium transporter E SLC41A1 SLC41A2 SLC41A3
(42):	Ammonia transporter RhAG RhBG RhCG
(43):	Na<sup>+</sup>-independent, system-L like amino-acid transporter SLC43A1 SLC43A2 SLC43A3
(44):	Choline-like transporter SLC44A1 SLC44A2 SLC44A3 SLC44A4 SLC44A5
(45):	Putative sugar transporter SLC45A1 SLC45A2 SLC54A3 SLC45A4
(46):	Folate transporter SLC46A1 SLC46A2
(47):	multidrug and toxin extrusion SLC47A1 SLC47A2
(48):	Heme transporter

SLCO1–4
O1A2 O1B1 O1B3 O2B1 O431 O4A1

Ion pumps

Symporter, Cotransporter	Na⁺/K⁺,Cl⁻ Na⁺/P_i3 Na⁺/Cl⁻ Na⁺/glucose Na⁺/I⁻ Cl⁻/K⁺ 4 5
Antiporter (exchanger)	Na⁺/H⁺ Na⁺/Ca²⁺ Na⁺/(Ca²⁺-K⁺) - Cl⁻/HCO⁻ ₃ (Band 3) Cl⁻-formate Cl⁻-oxalate

see also solute carrier disorders

Glutamate metabolism and transport modulators

Transporter

EAATs

Amphetamine
Aspartic acid (aspartate)
cis-ACBD
DHKA
Glutamic acid (glutamate)
HIP-A
HIP-B
Kainic acid
L-(-)-threo-3-Hydroxyaspartic acid
L-αAA
L-CCG-III ((2S,3S,4R)-CCG)
L-Serine-O-sulphate (SOS)
L-trans-2,4-PDC
MPDC
Maslinic acid
SYM-2081
TBOA
TFB-TBOA
Theanine
threo-3-Methylglutamic acid
UCPH-101
WAY-213,613

vGluTs

4-Methylene-L-glutamate
6-(4'-Phenylstyryl)-QDC
6-Biphenyl-4-yl-QDC
7-CKA
Acid red 114
Amido black 10B (naphthol blue black)
Bafilomycin A1
Benzopurpurin 4B
Bumetamide
Chicago sky blue 6B
Aspartic acid (aspartate)
DIDS
Direct blue 71
Erythro-4-methyl-L-glutamic acid
Evans blue
Furosemide
Glutamic acid (glutamate)
Kynurenic acid
Nigericin
NPPB (N144)
Ponceau SS
Reactive blue 2
Rose bengal
SITS
trans-ACDP
Trypan blue
Valinomycin
Xanthurenic acid

Enzyme

GAH	BPTES CB-839 DON
AST	2-Amino-3-butenoic acid AAOA AMB β-<span style="font-size:85%;">DL</span>-Methylene-aspartate Hydrazinosuccinate
ALT	β-Chloro-<span style="font-size:85%;">L</span>-alanine L-Cycloserine Propargylglycine
GDH	AAOA Bithionol Chloroquine EGCG GTP GW5074 Hexachlorophene Hydroxylamine Palmitoyl-CoA Pyridoxal phosphate
GS	2-Aminoadipic acid JFD01307SC Methionine sulfoximine Phosphinothricin (glufosinate)
GAD	3-Mercaptopropionic acid AAOA L-Allylglycine Semicarbazide

See also: Receptor/signaling modulators • Ionotropic glutamate receptor modulators • Metabotropic glutamate receptor modulators • GABA metabolism and transport modulators

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