VIAAT_RAT
ID VIAAT_RAT Reviewed; 525 AA.
AC O35458;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Vesicular inhibitory amino acid transporter;
DE AltName: Full=GABA and glycine transporter;
DE AltName: Full=Solute carrier family 32 member 1;
DE AltName: Full=Vesicular GABA transporter {ECO:0000303|PubMed:9349821};
DE Short=rGVAT;
DE AltName: Full=rat UNC-47 homolog {ECO:0000303|PubMed:9349821};
DE Short=RUNC-47 {ECO:0000303|PubMed:9349821};
GN Name=Slc32a1 {ECO:0000312|RGD:621402}; Synonyms=Vgat, Viaat;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, FUNCTION, TRANSPORTER
RP ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=Sprague-Dawley;
RX PubMed=9349821; DOI=10.1038/39908;
RA McIntire S.L., Reimer R.J., Schuske K., Edwards R.H., Jorgensen E.M.;
RT "Identification and characterization of the vesicular GABA transporter.";
RL Nature 389:870-876(1997).
RN [2]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9822734; DOI=10.1523/jneurosci.18-23-09733.1998;
RA Chaudhry F.A., Reimer R.J., Bellocchio E.E., Danbolt N.C., Osen K.K.,
RA Edwards R.H., Storm-Mathisen J.;
RT "The vesicular GABA transporter, VGAT, localizes to synaptic vesicles in
RT sets of glycinergic as well as GABAergic neurons.";
RL J. Neurosci. 18:9733-9750(1998).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=10036231; DOI=10.1242/jcs.112.6.811;
RA Dumoulin A., Rostaing P., Bedet C., Levi S., Isambert M.F., Henry J.P.,
RA Triller A., Gasnier B.;
RT "Presence of the vesicular inhibitory amino acid transporter in GABAergic
RT and glycinergic synaptic terminal boutons.";
RL J. Cell Sci. 112:811-823(1999).
RN [4]
RP CHARACTERIZATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=12031963; DOI=10.2337/diabetes.51.6.1763;
RA Chessler S.D., Simonson W.T., Sweet I.R., Hammerle L.P.;
RT "Expression of the vesicular inhibitory amino acid transporter in
RT pancreatic islet cells: distribution of the transporter within rat
RT islets.";
RL Diabetes 51:1763-1771(2002).
RN [5]
RP TOPOLOGY.
RX PubMed=19052203; DOI=10.1523/jneurosci.3887-08.2008;
RA Martens H., Weston M.C., Boulland J.L., Groenborg M., Grosche J., Kacza J.,
RA Hoffmann A., Matteoli M., Takamori S., Harkany T., Chaudhry F.A.,
RA Rosenmund C., Erck C., Jahn R., Haertig W.;
RT "Unique luminal localization of VGAT-C terminus allows for selective
RT labeling of active cortical GABAergic synapses.";
RL J. Neurosci. 28:13125-13131(2008).
RN [6]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, CAUTION, AND MUTAGENESIS OF
RP GLU-213.
RX PubMed=19843525; DOI=10.1074/jbc.m109.062414;
RA Juge N., Muroyama A., Hiasa M., Omote H., Moriyama Y.;
RT "Vesicular inhibitory amino acid transporter is a Cl-/gamma-aminobutyrate
RT Co-transporter.";
RL J. Biol. Chem. 284:35073-35078(2009).
RN [7]
RP FUNCTION, CAUTION, MUTAGENESIS OF GLU-213 AND LYS-351, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND TRANSPORTER ACTIVITY.
RX PubMed=23919636; DOI=10.1111/jnc.12393;
RA Juge N., Omote H., Moriyama Y.;
RT "Vesicular GABA transporter (VGAT) transports beta-alanine.";
RL J. Neurochem. 127:482-486(2013).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Antiporter that exchanges vesicular protons for cytosolic 4-
CC aminobutanoate or to a lesser extend glycine, thus allowing their
CC secretion from nerve terminals (By similarity) (PubMed:9349821). The
CC transport is equally dependent on the chemical and electrical
CC components of the proton gradient (PubMed:9349821). May also transport
CC beta-alanine (PubMed:23919636). Acidification of GABAergic synaptic
CC vesicles is a prerequisite for 4-aminobutanoate uptake (By similarity).
CC {ECO:0000250|UniProtKB:O35633, ECO:0000269|PubMed:23919636,
CC ECO:0000269|PubMed:9349821}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-alanine(out) + n H(+)(in) = beta-alanine(in) + n
CC H(+)(out); Xref=Rhea:RHEA:70987, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57966; Evidence={ECO:0000305|PubMed:23919636};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-aminobutanoate(out) + n H(+)(in) = 4-aminobutanoate(in) + n
CC H(+)(out); Xref=Rhea:RHEA:70979, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:59888; Evidence={ECO:0000269|PubMed:9349821};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycine(out) + n H(+)(in) = glycine(in) + n H(+)(out);
CC Xref=Rhea:RHEA:70983, ChEBI:CHEBI:15378, ChEBI:CHEBI:57305;
CC Evidence={ECO:0000250|UniProtKB:O35633};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5 mM for 4-aminobutanoate {ECO:0000269|PubMed:9349821};
CC KM=3.5 mM for beta-alanine {ECO:0000269|PubMed:23919636};
CC KM=0.8 mM for 4-aminobutanoate {ECO:0000269|PubMed:19843525};
CC KM=2.1 mM for chloride {ECO:0000269|PubMed:19843525};
CC KM=2.3 mM for chloride (for 4-aminobutanoate uptake)
CC {ECO:0000269|PubMed:19843525};
CC Vmax=38 nmol/min/mg enzyme toward beta-alanine
CC {ECO:0000269|PubMed:23919636};
CC Vmax=41 nmol/min/mg enzyme toward 4-aminobutanoate
CC {ECO:0000269|PubMed:19843525};
CC Vmax=90.6 nmol/min/mg enzyme toward chloride
CC {ECO:0000269|PubMed:19843525};
CC Vmax=7.4 nmol/min/mg enzyme toward chloride (for 4-aminobutanoate
CC uptake) {ECO:0000269|PubMed:19843525};
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000269|PubMed:10036231,
CC ECO:0000269|PubMed:9822734}; Multi-pass membrane protein {ECO:0000255}.
CC Presynapse {ECO:0000269|PubMed:10036231}. Note=Presents in glycine-,
CC GABA- or GABA- and glycine-containing boutons.
CC {ECO:0000269|PubMed:10036231}.
CC -!- TISSUE SPECIFICITY: Brain (PubMed:9822734, PubMed:9349821). Expressed
CC at high levels within the neocortex, hippocampus, cerebellum, striatum,
CC septal nuclei and the reticular nucleus of the thalamus
CC (PubMed:9349821). Also expressed in islets where it is more abundant in
CC the peripheral/mantle region (PubMed:12031963). Highly expressed in the
CC nerve endings of GABA neurons in the brain and spinal cord but also in
CC glycinergic nerve endings (PubMed:9822734). Expressed in glycine-,
CC GABA- or GABA- and glycine-containing boutons (PubMed:10036231,
CC PubMed:9822734). {ECO:0000269|PubMed:10036231,
CC ECO:0000269|PubMed:12031963, ECO:0000269|PubMed:9349821,
CC ECO:0000269|PubMed:9822734}.
CC -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC {ECO:0000305}.
CC -!- CAUTION: Juge et al. shows that SLC32A1 is a symporter of both 4-
CC aminobutanoate or glycine or beta-alanine with Cl(-) that operates
CC according an electrical gradient without the need for a chemical
CC gradient (PubMed:19843525, PubMed:23919636). However Farsi et al. and
CC Egashira et al. confirm that SLC32A1 is an antiporter that exchanges
CC vesicular protons for cytosolic 4-aminobutanoate or glycine and exclude
CC any coupling with chloride (By similarity).
CC {ECO:0000250|UniProtKB:O35633, ECO:0000269|PubMed:19843525,
CC ECO:0000269|PubMed:23919636}.
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DR EMBL; AF030253; AAB82950.1; -; mRNA.
DR RefSeq; NP_113970.1; NM_031782.1.
DR RefSeq; XP_006235503.1; XM_006235441.3.
DR AlphaFoldDB; O35458; -.
DR SMR; O35458; -.
DR BioGRID; 249777; 2.
DR IntAct; O35458; 2.
DR MINT; O35458; -.
DR STRING; 10116.ENSRNOP00000020720; -.
DR GlyGen; O35458; 1 site.
DR SwissPalm; O35458; -.
DR PaxDb; O35458; -.
DR PRIDE; O35458; -.
DR ABCD; O35458; 2 sequenced antibodies.
DR Ensembl; ENSRNOT00000020720; ENSRNOP00000020720; ENSRNOG00000015393.
DR GeneID; 83612; -.
DR KEGG; rno:83612; -.
DR UCSC; RGD:621402; rat.
DR CTD; 140679; -.
DR RGD; 621402; Slc32a1.
DR eggNOG; KOG4303; Eukaryota.
DR GeneTree; ENSGT00490000043380; -.
DR HOGENOM; CLU_036432_0_0_1; -.
DR InParanoid; O35458; -.
DR OMA; KTFFQDG; -.
DR OrthoDB; 570025at2759; -.
DR PhylomeDB; O35458; -.
DR TreeFam; TF312818; -.
DR Reactome; R-RNO-425393; Transport of inorganic cations/anions and amino acids/oligopeptides.
DR Reactome; R-RNO-888590; GABA synthesis, release, reuptake and degradation.
DR PRO; PR:O35458; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000015393; Expressed in cerebellum and 2 other tissues.
DR Genevisible; O35458; RN.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0051286; C:cell tip; ISO:RGD.
DR GO; GO:0044316; C:cone cell pedicle; ISO:RGD.
DR GO; GO:0030425; C:dendrite; ISO:RGD.
DR GO; GO:0044292; C:dendrite terminus; ISO:RGD.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0060077; C:inhibitory synapse; IDA:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; TAS:RGD.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IDA:SynGO.
DR GO; GO:0043229; C:intracellular organelle; IDA:RGD.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; ISO:RGD.
DR GO; GO:0044306; C:neuron projection terminus; ISO:RGD.
DR GO; GO:0098793; C:presynapse; IDA:UniProtKB.
DR GO; GO:0048786; C:presynaptic active zone; ISO:RGD.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0008021; C:synaptic vesicle; IDA:UniProtKB.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015185; F:gamma-aminobutyric acid transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0015495; F:gamma-aminobutyric acid:proton symporter activity; ISO:RGD.
DR GO; GO:0015187; F:glycine transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0003333; P:amino acid transmembrane transport; IBA:GO_Central.
DR GO; GO:0051939; P:gamma-aminobutyric acid import; IMP:UniProtKB.
DR GO; GO:0015812; P:gamma-aminobutyric acid transport; IDA:BHF-UCL.
DR GO; GO:0015816; P:glycine transport; IMP:UniProtKB.
DR GO; GO:0021766; P:hippocampus development; IEP:RGD.
DR GO; GO:0098700; P:neurotransmitter loading into synaptic vesicle; IDA:SynGO.
DR GO; GO:0006836; P:neurotransmitter transport; TAS:RGD.
DR InterPro; IPR013057; AA_transpt_TM.
DR Pfam; PF01490; Aa_trans; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasmic vesicle; Membrane; Neurotransmitter transport;
KW Nitration; Reference proteome; Synapse; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..525
FT /note="Vesicular inhibitory amino acid transporter"
FT /id="PRO_0000093823"
FT TOPO_DOM 1..132
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:19052203"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 154..204
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000305|PubMed:19052203"
FT TRANSMEM 205..225
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 226..265
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:19052203"
FT TRANSMEM 266..286
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 287..305
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000305|PubMed:19052203"
FT TRANSMEM 306..326
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 327..341
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:19052203"
FT TRANSMEM 342..362
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 363..383
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000305|PubMed:19052203"
FT TRANSMEM 384..404
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 405..438
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:19052203"
FT TRANSMEM 439..459
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 460..461
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000305|PubMed:19052203"
FT TRANSMEM 462..482
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 483..489
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:19052203"
FT TRANSMEM 490..510
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 511..525
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000305|PubMed:19052203"
FT MOD_RES 186
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O35633"
FT MUTAGEN 213
FT /note="E->A: Loss of GABA and glycine transport activity.
FT Loss of potential gradient-induced Cl(-) uptake. Loss of
FT beta-alanine transport activity."
FT /evidence="ECO:0000269|PubMed:19843525,
FT ECO:0000269|PubMed:23919636"
FT MUTAGEN 351
FT /note="K->A: Retains around 80% of the beta-alanine
FT transport activity."
FT /evidence="ECO:0000269|PubMed:23919636"
SQ SEQUENCE 525 AA; 57407 MW; 33C5E8D31B7BD510 CRC64;
MATLLRSKLT NVATSVSNKS QAKVSGMFAR MGFQAATDEE AVGFAHCDDL DFEHRQGLQM
DILKSEGEPC GDEGAEPPVE GDIHYQRGGA PLPPSGSKDQ AVGAGGEFGG HDKPKITAWE
AGWNVTNAIQ GMFVLGLPYA ILHGGYLGLF LIIFAAVVCC YTGKILIACL YEENEDGEVV
RVRDSYVAIA NACCAPRFPT LGGRVVNVAQ IIELVMTCIL YVVVSGNLMY NSFPGLPVSQ
KSWSIIATAV LLPCAFLKNL KAVSKFSLLC TLAHFVINIL VIAYCLSRAR DWAWEKVKFY
IDVKKFPISI GIIVFSYTSQ IFLPSLEGNM QQPSEFHCMM NWTHIAACVL KGLFALVAYL
TWADETKEVI TDNLPGSIRA VVNIFLVAKA LLSYPLPFFA AVEVLEKSLF QEGSRAFFPA
CYGGDGRLKS WGLTLRCALV VFTLLMAIYV PHFALLMGLT GSLTGAGLCF LLPSLFHLRL
LWRKLLWHQV FFDVAIFVIG GICSVSGFVH SLEGLIEAYR TNAED
