VIAAT_MOUSE
ID VIAAT_MOUSE Reviewed; 525 AA.
AC O35633;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2003, sequence version 3.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Vesicular inhibitory amino acid transporter {ECO:0000303|PubMed:12115694};
DE AltName: Full=Solute carrier family 32 member 1;
DE AltName: Full=Vesicular GABA and glycine transporter {ECO:0000303|PubMed:12573541};
DE AltName: Full=Vesicular GABA transporter;
DE Short=mVGAT;
DE Short=mVIAAT;
GN Name=Slc32a1 {ECO:0000312|MGI:MGI:1194488}; Synonyms=Vgat, Viaat;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND TRANSPORTER ACTIVITY.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=9395291; DOI=10.1016/s0014-5793(97)01279-9;
RA Sagne C., El Mestikawy S., Isambert M.-F., Hamon M., Henry J.-P.,
RA Giros B.P., Gasnier B.;
RT "Cloning of a functional vesicular GABA and glycine transporter by
RT screening of genome databases.";
RL FEBS Lett. 417:177-183(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
RX PubMed=12573541; DOI=10.1016/s0169-328x(02)00648-4;
RA Ebihara S., Obata K., Yanagawa Y.;
RT "Mouse vesicular GABA transporter gene: genomic organization,
RT transcriptional regulation and chromosomal localization.";
RL Brain Res. Mol. Brain Res. 110:126-139(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
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 [5]
RP TISSUE SPECIFICITY.
RX PubMed=12115694; DOI=10.1002/cne.10272;
RA Jellali A., Stussi-Garaud C., Gasnier B., Rendon A., Sahel J.-A.,
RA Dreyfus H., Picaud S.;
RT "Cellular localization of the vesicular inhibitory amino acid transporter
RT in the mouse and human retina.";
RL J. Comp. Neurol. 449:76-87(2002).
RN [6]
RP NITRATION [LARGE SCALE ANALYSIS] AT TYR-186, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16800626; DOI=10.1021/bi060474w;
RA Sacksteder C.A., Qian W.-J., Knyushko T.V., Wang H., Chin M.H., Lacan G.,
RA Melega W.P., Camp D.G. II, Smith R.D., Smith D.J., Squier T.C.,
RA Bigelow D.J.;
RT "Endogenously nitrated proteins in mouse brain: links to neurodegenerative
RT disease.";
RL Biochemistry 45:8009-8022(2006).
RN [7]
RP FUNCTION, TRANSPORTER ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=16701208; DOI=10.1016/j.neuron.2006.04.016;
RA Wojcik S.M., Katsurabayashi S., Guillemin I., Friauf E., Rosenmund C.,
RA Brose N., Rhee J.S.;
RT "A shared vesicular carrier allows synaptic corelease of GABA and
RT glycine.";
RL Neuron 50:575-587(2006).
RN [8]
RP SUBCELLULAR LOCATION.
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP FUNCTION, AND TRANSPORTER ACTIVITY.
RX PubMed=27601664; DOI=10.1073/pnas.1604527113;
RA Egashira Y., Takase M., Watanabe S., Ishida J., Fukamizu A., Kaneko R.,
RA Yanagawa Y., Takamori S.;
RT "Unique pH dynamics in GABAergic synaptic vesicles illuminates the
RT mechanism and kinetics of GABA loading.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:10702-10707(2016).
RN [11]
RP FUNCTION, TRANSPORTER ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=26912364; DOI=10.1126/science.aad8142;
RA Farsi Z., Preobraschenski J., van den Bogaart G., Riedel D., Jahn R.,
RA Woehler A.;
RT "Single-vesicle imaging reveals different transport mechanisms between
RT glutamatergic and GABAergic vesicles.";
RL Science 351:981-984(2016).
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 (PubMed:9395291, PubMed:26912364,
CC PubMed:27601664, PubMed:16701208). The transport is equally dependent
CC on the chemical and electrical components of the proton gradient
CC (PubMed:9395291, PubMed:27601664). May also transport beta-alanine (By
CC similarity). Acidification of GABAergic synaptic vesicles is a
CC prerequisite for 4-aminobutanoate uptake (PubMed:27601664).
CC {ECO:0000250|UniProtKB:O35458, ECO:0000269|PubMed:16701208,
CC ECO:0000269|PubMed:26912364, ECO:0000269|PubMed:27601664,
CC ECO:0000269|PubMed:9395291}.
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:16701208,
CC ECO:0000269|PubMed:26912364, ECO:0000269|PubMed:27601664,
CC ECO:0000305|PubMed:9395291};
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:0000269|PubMed:16701208, ECO:0000269|PubMed:26912364,
CC ECO:0000305|PubMed:9395291};
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:0000250|UniProtKB:O35458};
CC -!- ACTIVITY REGULATION: Chloride ions activate 4-aminobutanoate/H(+)
CC transport. {ECO:0000269|PubMed:26912364}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:O35458}; Multi-pass membrane protein
CC {ECO:0000255}. Presynapse {ECO:0000269|PubMed:19052203}. Note=Presents
CC in glycine-, GABA- or GABA- and glycine-containing boutons.
CC {ECO:0000250|UniProtKB:O35458}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=b;
CC IsoId=O35633-1; Sequence=Displayed;
CC Name=2; Synonyms=a;
CC IsoId=O35633-2; Sequence=VSP_007063;
CC -!- TISSUE SPECIFICITY: Brain and retina. Localized in horizontal cell tips
CC at both rod and cone terminals. {ECO:0000269|PubMed:12115694}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice exhibit embryonic lethality and a
CC cleft palate and omphalocele. {ECO:0000269|PubMed:16701208}.
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 (By similarity). However Farsi et al. and Egashira et al.
CC confirm that SLC32A1 is an antiporter that exchanges vesicular protons
CC for cytosolic 4-aminobutanoate or glycine and exclude any coupling with
CC chloride (PubMed:27601664, PubMed:26912364).
CC {ECO:0000250|UniProtKB:O35458, ECO:0000269|PubMed:26912364,
CC ECO:0000269|PubMed:27601664}.
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DR EMBL; AB080232; BAC44888.1; -; Genomic_DNA.
DR EMBL; AB080232; BAC44889.1; -; Genomic_DNA.
DR EMBL; AJ001598; CAA04864.1; -; mRNA.
DR EMBL; BC052020; AAH52020.1; -; mRNA.
DR CCDS; CCDS38309.1; -. [O35633-1]
DR RefSeq; NP_033534.2; NM_009508.2. [O35633-1]
DR AlphaFoldDB; O35633; -.
DR SMR; O35633; -.
DR BioGRID; 204520; 2.
DR IntAct; O35633; 1.
DR STRING; 10090.ENSMUSP00000036299; -.
DR TCDB; 2.A.18.5.3; the amino acid/auxin permease (aaap) family.
DR GlyGen; O35633; 1 site.
DR iPTMnet; O35633; -.
DR PhosphoSitePlus; O35633; -.
DR SwissPalm; O35633; -.
DR MaxQB; O35633; -.
DR PaxDb; O35633; -.
DR PeptideAtlas; O35633; -.
DR PRIDE; O35633; -.
DR ProteomicsDB; 297883; -. [O35633-1]
DR ProteomicsDB; 297884; -. [O35633-2]
DR ABCD; O35633; 2 sequenced antibodies.
DR Antibodypedia; 26904; 280 antibodies from 28 providers.
DR DNASU; 22348; -.
DR Ensembl; ENSMUST00000045738; ENSMUSP00000036299; ENSMUSG00000037771. [O35633-1]
DR GeneID; 22348; -.
DR KEGG; mmu:22348; -.
DR UCSC; uc008nqk.1; mouse. [O35633-1]
DR UCSC; uc029uhu.1; mouse. [O35633-2]
DR CTD; 140679; -.
DR MGI; MGI:1194488; Slc32a1.
DR VEuPathDB; HostDB:ENSMUSG00000037771; -.
DR eggNOG; KOG4303; Eukaryota.
DR GeneTree; ENSGT00490000043380; -.
DR HOGENOM; CLU_036432_0_0_1; -.
DR InParanoid; O35633; -.
DR OMA; KTFFQDG; -.
DR PhylomeDB; O35633; -.
DR TreeFam; TF312818; -.
DR Reactome; R-MMU-425393; Transport of inorganic cations/anions and amino acids/oligopeptides.
DR Reactome; R-MMU-888590; GABA synthesis, release, reuptake and degradation.
DR BioGRID-ORCS; 22348; 1 hit in 71 CRISPR screens.
DR PRO; PR:O35633; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; O35633; protein.
DR Bgee; ENSMUSG00000037771; Expressed in dorsal tegmental nucleus and 102 other tissues.
DR ExpressionAtlas; O35633; baseline and differential.
DR Genevisible; O35633; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0051286; C:cell tip; IDA:MGI.
DR GO; GO:0044316; C:cone cell pedicle; IDA:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0044292; C:dendrite terminus; IDA:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:MGI.
DR GO; GO:0060077; C:inhibitory synapse; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IC:MGI.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; ISO:MGI.
DR GO; GO:0043229; C:intracellular organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0044306; C:neuron projection terminus; IDA:MGI.
DR GO; GO:0048786; C:presynaptic active zone; IDA:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0008021; C:synaptic vesicle; ISS: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; IDA:UniProtKB.
DR GO; GO:0015495; F:gamma-aminobutyric acid:proton symporter activity; IDA:MGI.
DR GO; GO:0015187; F:glycine transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0003333; P:amino acid transmembrane transport; IBA:GO_Central.
DR GO; GO:0051939; P:gamma-aminobutyric acid import; IDA:UniProtKB.
DR GO; GO:0015812; P:gamma-aminobutyric acid transport; ISO:MGI.
DR GO; GO:0015816; P:glycine transport; IDA:UniProtKB.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0098700; P:neurotransmitter loading into synaptic vesicle; ISO:MGI.
DR InterPro; IPR013057; AA_transpt_TM.
DR Pfam; PF01490; Aa_trans; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Cytoplasmic vesicle; Membrane;
KW Neurotransmitter transport; Nitration; Reference proteome; Synapse;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..525
FT /note="Vesicular inhibitory amino acid transporter"
FT /id="PRO_0000093822"
FT TOPO_DOM 1..132
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35458"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 154..204
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000250|UniProtKB:O35458"
FT TRANSMEM 205..225
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 226..265
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35458"
FT TRANSMEM 266..286
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 287..305
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000250|UniProtKB:O35458"
FT TRANSMEM 306..326
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 327..341
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35458"
FT TRANSMEM 342..362
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 363..383
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000250|UniProtKB:O35458"
FT TRANSMEM 384..404
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 405..438
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35458"
FT TRANSMEM 439..459
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 460..461
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000250|UniProtKB:O35458"
FT TRANSMEM 462..482
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 483..489
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35458"
FT TRANSMEM 490..510
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 511..525
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000250|UniProtKB:O35458"
FT MOD_RES 186
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0007744|PubMed:16800626"
FT VAR_SEQ 515..525
FT /note="LIEAYRTNAED -> KFAGLET (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9395291"
FT /id="VSP_007063"
FT CONFLICT 432
FT /note="G -> E (in Ref. 1; CAA04864)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 525 AA; 57381 MW; EBD63E01A4B54C07 CRC64;
MATLLRSKLT NVATSVSNKS QAKVSGMFAR MGFQAATDEE AVGFAHCDDL DFEHRQGLQM
DILKSEGEPC GDEGAEAPVE 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 VVNLFLVAKA LLSYPLPFFA AVEVLEKSLF QEGSRAFFPA
CYGGDGRLKS WGLTLRCALV VFTLLMAIYV PHFALLMGLT GSLTGAGLCF LLPSLFHLRL
LWRKLLWHQV FFDVAIFVIG GICSVSGFVH SLEGLIEAYR TNAED
