GABA transporter 1

Solute carrier family 6 (neurotransmitter transporter, GABA), member 1

Identifiers

SLC6A1; GABATHG; GABATR; GAT1

External IDs

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

Gene Ontology
Molecular function	• neurotransmitter:sodium symporter activity • gamma-aminobutyric acid:sodium symporter activity • symporter activity
Cellular component	• membrane fraction • plasma membrane • integral to plasma membrane • integral to membrane • synaptosome • axon
Biological process	• transport • synaptic transmission • neurotransmitter secretion • learning • response to toxin • response to sucrose stimulus • response to organic nitrogen • response to lead ion • response to purine-containing compound • negative regulation of synaptic transmission, GABAergic • response to estradiol stimulus • response to cocaine • protein homooligomerization • response to calcium ion • gamma-aminobutyric acid import • transmembrane transport
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 3:
11.03 – 11.08 Mb

Chr 6:
114.23 – 114.27 Mb

PubMed search

[1]

[2]

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

1 Function
2 Interactions
3 See also
4 References
5 Further reading

Function

GAT-1 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 (Feb 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". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6529.
^ 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. PMID 19077666.
^ Beckman, M L; Bernstein E M, Quick M W (Aug. 1998). "Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A". J. Neurosci. (UNITED STATES) 18 (16): 6103–12. ISSN 0270-6474. PMID 9698305.
^ Quick, Michael W (Apr. 2002). "Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (8): 5686–91. doi:10.1073/pnas.082712899. ISSN 0027-8424. PMC 122832. PMID 11960023. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=122832.
^ Deken, S L; Beckman M L, Boos L, Quick M W (Oct. 2000). "Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A". Nat. Neurosci. (UNITED STATES) 3 (10): 998–1003. doi:10.1038/79939. ISSN 1097-6256. 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, et al. (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, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=122832.
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.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
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.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
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, et al. (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: Main site: Bamaluzole • Gaboxadol • Ibotenic acid • Isoguvacine • Isonipecotic acid • Muscimol (Amanita Muscaria) • Progabide • SL 75102 • Thiomuscimol • Tolgabide; Positive allosteric modulators: Barbiturates • Benzodiazepines • Carbamates • Chlormezanone • Clomethiazole • Ethanol (Alcohol) • Etomidate • Kavalactones (Kava) • Loreclezole • Metomidate • Neuroactive steroids • Nonbenzodiazepines (β-Carbolines, Cyclopyrrolones, Imidazopyridines, Pyrazolopyrimidines, etc.) • Phenols • Piperidinediones • Propanidid • Pyrazolopyridines • Quinazolinones • ROD-188 • Skullcap • Stiripentol • Valerenic acid (Valerian) * See Template:GABAAergics for a full list of GABA_A positive allosteric modulators. Antagonists: Main site: Bicuculline • Gabazine • Pitrazepin • Quisqualamine; Negative allosteric modulators: α5IA • Bilobalide • Cicutoxin • Cyclothiazide • DMCM • Flumazenil • Flurothyl • Furosemide • L-655,708 • Oenanthotoxin • Penicillin • Pentylenetetrazol • Picrotoxin • PWZ-029 • Ro15-4513 • Sarmazenil • Suritozole • Thujone (Absinthe) • Thiocolchicoside • ZK-93426

GABA_B	Agonists: Main site: 1,4-Butanediol • Baclofen • GBL • GHB • GHV • GVL • Lesogaberan • Phenibut • Progabide • SKF-97,541 • Tolgabide; Positive allosteric modulators: BHF-177 • BHFF • BSPP • CGP-7930 • GS-39783 Antagonists: Main site: CGP-35348 • Phaclofen • Saclofen • SCH-50911

GABA_C	Agonists: Main site: CACA • CAMP • GABOB • N(4)-chloroacetylcytosine arabinoside • Progabide • Tolgabide Antagonists: Main site: Bilobalide • TPMPA

Reuptake
inhibitors

Plasmalemmal

GAT inhibitors	CI-966 • Deramciclane • EF-1502 • Gabaculine • Guvacine • Nipecotic acid • NNC 05-2090 • SKF-89976A • SNAP-5114 • Tiagabine

Enzyme
inhibitors

Anabolism

GAD inhibitors	Allylglycine

Catabolism

GABA-T inhibitors	3-Hydrazinopropionic acid • Aminooxyacetic acid • Gabaculine • Isoniazid • Phenelzine • Phenylethylidenehydrazine • Sodium valproate • Valnoctamide • Valproate pivoxil • Valproate semisodium (Divalproex sodium) • Valproic acid • Valpromide • Vigabatrin

Others

Precursors	Glutamate • Glutamine

Cofactors	Vitamin B6 (pyridoxine, pyridoxamine, pyridoxal phosphate)

Others	Gabapentin • L-Theanine • Picamilon • Pregabalin

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, 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 (SLC17A1, SLC17A2, SLC17A3, SLC17A4, SLC17A5, SLC17A6, SLC17A7, SLC17A8, SLC17A9)

(18) vesicular amine 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 (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 inhibitory amino-acid transporter (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, SLC36A4)36A2 ·

(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) MgtE-like magnesium transporter (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+/2Cl- - 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
B memb: cead, trns (1A, 1C, 1F, 2A, 3A1, 3A2-3, 3D), othr

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

Vesicular

Vesicular monoamine (VMAT1, VMAT2) - Vesicular acetylcholine

Other

Glutamate - Monoamine (DAT, NET, SERT, PMAT)

M: PNS

anat(h/r/t/c/b/l/s/a)/phys(r)/devp/prot/nttr/nttm/ntrp

noco/auto/cong/tumr, sysi/epon, injr

proc, drug(N1B)

GABA transporter 1

Contents

Function

Interactions

See also

References

Further reading