GABA transporter 1

Solute carrier family 6 (neurotransmitter transporter), member 1

Identifiers

SLC6A1 ; GABATHG; GABATR; GAT1; MAE

External IDs

OMIM: 137165 MGI: 95627 HomoloGene: 2290 ChEMBL: 1903 GeneCards: SLC6A1 Gene

Gene ontology
Molecular function	• neurotransmitter:sodium symporter activity • gamma-aminobutyric acid:sodium symporter activity
Cellular component	• plasma membrane • integral component of plasma membrane • cell surface • membrane • integral component of membrane • axon • neuron projection
Biological process	• transport • neurotransmitter transport • synaptic transmission • neurotransmitter secretion • learning • response to toxic substance • response to sucrose • response to lead ion • positive regulation of gamma-aminobutyric acid secretion • response to purine-containing compound • gamma-aminobutyric acid transport • negative regulation of synaptic transmission, GABAergic • response to estradiol • response to cocaine • protein homooligomerization • response to calcium ion • gamma-aminobutyric acid import • transmembrane transport • activation of mitophagy in response to mitochondrial depolarization
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 3:
10.99 – 11.04 Mb

Chr 6:
114.28 – 114.32 Mb

PubMed search

GABA transporter 1 (GAT1) also known as sodium- and chloride-dependent GABA transporter 1 is a protein that in humans is encoded by the SLC6A1 gene.^[1]^[2]

Function

GAT1 a gamma-aminobutyric acid (GABA) transporter, which removes GABA from the synaptic cleft.^[3]

Interactions

SLC6A1 has been shown to interact with STX1A.^[4]^[5]^[6]

References

↑ Huang F, Shi LJ, Heng HH, Fei J, Guo LH (February 1996). "Assignment of the human GABA transporter gene (GABATHG) locus to chromosome 3p24-p25". Genomics 29 (1): 302–4. doi:10.1006/geno.1995.1253. PMID 8530094.
↑ "Entrez Gene: SLC6A1 solute carrier family 6 (neurotransmitter transporter, GABA), member 1".
↑ Hirunsatit R, George ED, Lipska BK, Elwafi HM, Sander L, Yrigollen CM, Gelernter J, Grigorenko EL, Lappalainen J, Mane S, Nairn AC, Kleinman JE, Simen AA (January 2009). "Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity". Pharmacogenet. Genomics 19 (1): 53–65. doi:10.1097/FPC.0b013e328318b21a. PMC 2791799. PMID 19077666.
↑ Beckman ML, Bernstein EM, Quick MW (August 1998). "Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A". J. Neurosci. 18 (16): 6103–12. PMID 9698305.
↑ Quick MW (April 2002). "Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner". Proc. Natl. Acad. Sci. U.S.A. 99 (8): 5686–91. doi:10.1073/pnas.082712899. PMC 122832. PMID 11960023.
↑ Deken SL, Beckman ML, Boos L, Quick MW (October 2000). "Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A". Nat. Neurosci. 3 (10): 998–1003. doi:10.1038/79939. PMID 11017172.

Nelson H, Mandiyan S, Nelson N (1990). "Cloning of the human brain GABA transporter.". FEBS Lett. 269 (1): 181–4. doi:10.1016/0014-5793(90)81149-I. PMID 2387399.
Bennett ER, Kanner BI (1997). "The membrane topology of GAT-1, a (Na+ + Cl-)-coupled gamma-aminobutyric acid transporter from rat brain.". J. Biol. Chem. 272 (2): 1203–10. doi:10.1074/jbc.272.2.1203. PMID 8995422.
Bismuth Y, Kavanaugh MP, Kanner BI (1997). "Tyrosine 140 of the gamma-aminobutyric acid transporter GAT-1 plays a critical role in neurotransmitter recognition.". J. Biol. Chem. 272 (26): 16096–102. doi:10.1074/jbc.272.26.16096. PMID 9195904.
DeFelipe J, González-Albo MC (1998). "Chandelier cell axons are immunoreactive for GAT-1 in the human neocortex.". NeuroReport 9 (3): 467–70. doi:10.1097/00001756-199802160-00020. PMID 9512391.
Conti F, Melone M, De Biasi S, Minelli A, Brecha NC, Ducati A (1998). "Neuronal and glial localization of GAT-1, a high-affinity gamma-aminobutyric acid plasma membrane transporter, in human cerebral cortex: with a note on its distribution in monkey cortex.". J. Comp. Neurol. 396 (1): 51–63. doi:10.1002/(SICI)1096-9861(19980622)396:1<51::AID-CNE5>3.0.CO;2-H. PMID 9623887.
Beckman ML, Bernstein EM, Quick MW (1998). "Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A.". J. Neurosci. 18 (16): 6103–12. PMID 9698305.
Augood SJ, Waldvogel HJ, Münkle MC, Faull RL, Emson PC (1999). "Localization of calcium-binding proteins and GABA transporter (GAT-1) messenger RNA in the human subthalamic nucleus.". Neuroscience 88 (2): 521–34. doi:10.1016/S0306-4522(98)00226-7. PMID 10197772.
Ong WY, Yeo TT, Balcar VJ, Garey LJ (2000). "A light and electron microscopic study of GAT-1-positive cells in the cerebral cortex of man and monkey.". J. Neurocytol. 27 (10): 719–30. doi:10.1023/A:1006946717065. PMID 10640187.
Deken SL, Beckman ML, Boos L, Quick MW (2000). "Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A.". Nat. Neurosci. 3 (10): 998–1003. doi:10.1038/79939. PMID 11017172.
Whitworth TL, Quick MW (2001). "Substrate-induced regulation of gamma-aminobutyric acid transporter trafficking requires tyrosine phosphorylation.". J. Biol. Chem. 276 (46): 42932–7. doi:10.1074/jbc.M107638200. PMID 11555659.
Hachiya Y, Takashima S (2002). "Development of GABAergic neurons and their transporter in human temporal cortex.". Pediatr. Neurol. 25 (5): 390–6. doi:10.1016/S0887-8994(01)00348-4. PMID 11744314.
Quick MW (2002). "Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner.". Proc. Natl. Acad. Sci. U.S.A. 99 (8): 5686–91. doi:10.1073/pnas.082712899. PMC 122832. PMID 11960023.
Kanner BI (2003). "Transmembrane domain I of the gamma-aminobutyric acid transporter GAT-1 plays a crucial role in the transition between cation leak and transport modes.". J. Biol. Chem. 278 (6): 3705–12. doi:10.1074/jbc.M210525200. PMID 12446715.
Zomot E, Kanner BI (2003). "The interaction of the gamma-aminobutyric acid transporter GAT-1 with the neurotransmitter is selectively impaired by sulfhydryl modification of a conformationally sensitive cysteine residue engineered into extracellular loop IV.". J. Biol. Chem. 278 (44): 42950–8. doi:10.1074/jbc.M209307200. PMID 12925537.
Zhou Y, Bennett ER, Kanner BI (2004). "The aqueous accessibility in the external half of transmembrane domain I of the GABA transporter GAT-1 Is modulated by its ligands.". J. Biol. Chem. 279 (14): 13800–8. doi:10.1074/jbc.M311579200. PMID 14744863.
Hu JH, Ma YH, Jiang J, Yang N, Duan SH, Jiang ZH, Mei ZT, Fei J, Guo LH (2004). "Cognitive impairment in mice over-expressing gamma-aminobutyric acid transporter 1 (GAT1).". NeuroReport 15 (1): 9–12. doi:10.1097/00001756-200401190-00003. PMID 15106822.
Korkhov VM, Farhan H, Freissmuth M, Sitte HH (2005). "Oligomerization of the {gamma}-aminobutyric acid transporter-1 is driven by an interplay of polar and hydrophobic interactions in transmembrane helix II.". J. Biol. Chem. 279 (53): 55728–36. doi:10.1074/jbc.M409449200. PMID 15496410.

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

GABAergics

Receptor
(ligands)

GABA_A

Agonists	(+)-Catechin Bamaluzole Barbiturates (e.g., phenobarbital) BL-1020 DAVA Dihydromuscimol GABA Gabamide GABOB Gaboxadol (THIP) Homotaurine (tramiprosate, 3-APS) Ibotenic acid iso-THAZ iso-THIP Isoguvacine Isomuscimol Isonipecotic acid Kojic amine Lignans (e.g., honokiol) Monastrol Muscimol Neuroactive steroids (e.g., allopregnanolone) Org 20599 Phenibut Picamilon P4S Progabide Propofol Quisqualamine SL-75102 TACA TAMP Terpenoids (e.g., borneol) Thiomuscimol Tolgabide ZAPA

PAMs	(abridged; see here for a full list): α-EMTBL Alcohols (e.g., ethanol) Avermectins (e.g., ivermectin) Barbiturates (e.g., phenobarbital) Benzodiazepines (e.g., diazepam) Bromide compounds (e.g., potassium bromide) Carbamates (e.g., meprobamate) Carbamazepine Chloralose Chlormezanone Clomethiazole Dihydroergolines (e.g., ergoloid (dihydroergotoxine)) Etazepine Etifoxine Fenamates (e.g., mefenamic acid) Flavonoids (e.g., apigenin, hispidulin) Fluoxetine Flupirtine Imidazoles (e.g., etomidate) Kava constituents (e.g., kavain) Lanthanum Loreclezole Monastrol Neuroactive steroids (e.g., allopregnanolone, cholesterol) Niacin Nicotinamide (niacinamide) Nonbenzodiazepines (e.g., β-carbolines (e.g., abecarnil), cyclopyrrolones (e.g., zopiclone), imidazopyridines (e.g., zolpidem), pyrazolopyrimidines (e.g., zaleplon)) Norfluoxetine Petrichloral Phenols (e.g., propofol) Phenytoin Piperidinediones (e.g., glutethimide) Propanidid Pyrazolopyridines (e.g., etazolate) Quinazolinones (e.g., methaqualone) Retigabine (ezogabine) ROD-188 Skullcap constituents (e.g., baicalin) Stiripentol Sulfonylalkanes (e.g., sulfonmethane (sulfonal)) Topiramate Valerian constituents (e.g., valerenic acid) Volatiles/gases (e.g., chloral hydrate, chloroform, diethyl ether, paraldehyde, sevoflurane)

Antagonists	Bicuculline Coriamyrtin Dihydrosecurinine Gabazine (SR-95531) Hydrastine Hyenachin (mellitoxin) PHP-501 Pitrazepin Securinine Sinomenine SR-42641 SR-95103 Thiocolchicoside Tutin

NAMs	1,3M1B 3M2B 17-Phenylandrostenol α5IA (LS-193,268) β-CCB β-CCE β-CCM β-CCP β-EMGBL Amiloride Anisatin β-Lactams (e.g., penicillins, cephalosporins, carbapenems) Basmisanil Bemegride Bilobalide CHEB Cicutoxin Cloflubicyne Cyclothiazide DHEA DHEA-S Dieldrin (+)-DMBB DMCM DMPC EBOB Etbicyphat FG-7142 (ZK-31906) Fiproles (e.g., fipronil) Flavonoids (e.g., amentoflavone, oroxylin A) Flumazenil Fluoroquinolones (e.g., ciprofloxacin) Flurothyl Furosemide Iomazenil (¹²³I) Isoallopregnanolone Isopregnanolone (sepranolone) L-655,708 Laudanosine Leptazol Lindane MaxiPost Morphine Morphine-3-glucuronide MRK-016 Naloxone Naltrexone Nicardipine Non-steroidal antiandrogens (e.g., apalutamide, bicalutamide, enzalutamide, flutamide, nilutamide) Oenanthotoxin Pentetrazol (metrazol) Phenylsilatrane Picrotoxin (i.e., picrotin and picrotoxinin) Pregnenolone sulfate Propybicyphat PWZ-029 Radequinil Ro 15-4513 Ro 19-4603 RO4882224 RO4938581 Sarmazenil SCS Suritozole TB-21007 TBOB TBPS TCS-1105 Terbequinil TETS Thujone U-93631 Zinc ZK-93426

GABA_A-ρ

Agonists	BL-1020 CACA CAMP Homohypotaurine GABA GABOB Ibotenic acid Isoguvacine Muscimol N⁴-Chloroacetylcytosine arabinoside Picamilon Progabide TACA TAMP Thiomuscimol Tolgabide

PAMs	Allopregnanolone Alphaxolone ATHDOC Lanthanides

Antagonists	(S)-2-MeGABA (S)-4-ACPBPA (S)-4-ACPCA 2-MeTACA 3-APMPA 4-ACPAM 4-GBA cis-3-ACPBPA CGP-36742 (SGS-742) DAVA Gabazine (SR-95531) Gaboxadol (THIP) I4AA Isonipecotic acid Loreclezole P4MPA P4S SKF-97541 SR-95318 SR-95813 TPMPA trans-3-ACPBPA ZAPA

NAMs	5α-Dihydroprogesterone Bilobalide Loreclezole Picrotoxin (picrotin, picrotoxinin) Pregnanolone ROD-188 THDOC Zinc

GABA_B

Agonists	1,4-Butanediol Aceburic acid Arbaclofen Arbaclofen placarbil Baclofen BL-1020 GABA Gabamide GABOB GBL GHB GHBAL GHV GVL Isovaline Lesogaberan Phenibut Picamilon Progabide Sodium oxybate SKF-97,541 SL 75102 Tolgabide

Antagonists	2-Hydroxysaclofen CGP-35348 CGP-46381 CGP-52432 CGP-54626 CGP-55845 CGP-64213 DAVA Homotaurine (tramiprosate, 3-APS) Phaclofen Saclofen SCH-50911 SKF-97541

NAMs	Compound 14

PAMs	ADX-71441 BHF-177 BHFF BSPP CGP-7930 CGP-13501 GS-39783 rac-BHFF

Transporter
(blockers)

GAT	4-Aminovaleric acid β-Alanine Arecaidine CI-966 DABA Deramciclane (EGIS-3886, EGYT-3886) EF-1502 Gabaculine Guvacine Ibotenic acid Muscimol Nipecotic acid NNC 05-2090 NO-711 Riluzole SKF-89976A SNAP-5114 TACA Tiagabine

VIAAT	β-Alanine Bafilomycin A1 Chicago sky blue 6B Evans blue GABA Glycine N-Butyric acid Nigericin Nipecotic acid Valinomycin Vigabatrin

Enzyme
(inhibitors)

GAD	3-Mercaptopropionic acid AAOA L-Allylglycine Semicarbazide

GABA-T	3-Hydrazinopropionic acid γ-Acetylenic-GABA AOAA EOS Gabaculine Isoniazid L-Cycloserine Phenelzine PEH Rosmarinic acid (lemon balm) Sodium valproate Valnoctamide Valproate pivoxil Valproate semisodium (divalproex sodium) Valproic acid Valpromide Vigabatrin

Others

Precursors	1,4-Butanediol GHB GHBAL Glutamate Glutamine

Analogues	Pregabalin 4-Methylpregabalin Atagabalin Gabapentin Gabapentin enacarbil Imagabalin Mirogabalin PD-200,347 PD-217,014 PD-299,685 Phenibut

Others	Vitamin B₆ GABA-T activators: 3-Methyl-GABA

See also: GHBergics • Glutamatergics • Glycinergics

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+-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+-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+-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+-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+,l- Na/Pi3 Na+/Cl- Na/glucose Na+/I- Cl-/K+ 4 5

Antiporter (exchanger)	Na+/H+ Na+/Ca2+ Na+/(Ca2+-K+) - Cl-/HCO3- (Band 3) Cl-formate exchanger Cl-oxalate exchanger

see also solute carrier disorders

Membrane transport protein: neurotransmitter transporters (TC 2.A.1.2)

Vesicular	Vesicular monoamine VMAT1 VMAT2 Vesicular acetylcholine Vesicular glutamate Vesicular GABA

Other	Monoamine DAT NET SERT PMAT Excitatory amino-acid transporter GABA transporter

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GABA transporter 1

Function

Interactions

See also

References

Further reading