VIAAT_HUMAN
ID VIAAT_HUMAN Reviewed; 525 AA.
AC Q9H598; Q8N489;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Vesicular inhibitory amino acid transporter {ECO:0000303|PubMed:12031963};
DE AltName: Full=GABA and glycine transporter;
DE AltName: Full=Solute carrier family 32 member 1;
DE AltName: Full=Vesicular GABA transporter;
DE Short=hVIAAT;
GN Name=SLC32A1 {ECO:0000312|HGNC:HGNC:11018}; Synonyms=VGAT, VIAAT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [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).
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. The transport is equally dependent on
CC the chemical and electrical components of the proton gradient (By
CC similarity). May also transport beta-alanine (By similarity).
CC Acidification of GABAergic synaptic vesicles is a prerequisite for 4-
CC aminobutanoate uptake (By similarity). {ECO:0000250|UniProtKB:O35458,
CC ECO:0000250|UniProtKB:O35633}.
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:0000250|UniProtKB:O35633};
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 -!- 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 -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:O35458}; Multi-pass membrane protein
CC {ECO:0000255}. Presynapse {ECO:0000250|UniProtKB:O35633}. Note=Presents
CC in glycine-, GABA- or GABA- and glycine-containing boutons.
CC {ECO:0000250|UniProtKB:O35458}.
CC -!- TISSUE SPECIFICITY: Retina. Expressed throughout the horizontal cells
CC or more specifically at the terminals. {ECO:0000269|PubMed:12115694}.
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 (By similarity). {ECO:0000250|UniProtKB:O35458,
CC ECO:0000250|UniProtKB:O35633}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH36458.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY044836; AAK98782.1; -; mRNA.
DR EMBL; AK055051; BAB70846.1; -; mRNA.
DR EMBL; AL133519; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036458; AAH36458.2; ALT_INIT; mRNA.
DR EMBL; BC053582; AAH53582.1; -; mRNA.
DR CCDS; CCDS13307.1; -.
DR RefSeq; NP_542119.1; NM_080552.2.
DR AlphaFoldDB; Q9H598; -.
DR SMR; Q9H598; -.
DR BioGRID; 126644; 7.
DR IntAct; Q9H598; 6.
DR MINT; Q9H598; -.
DR STRING; 9606.ENSP00000217420; -.
DR DrugBank; DB00145; Glycine.
DR GuidetoPHARMACOLOGY; 1133; -.
DR TCDB; 2.A.18.5.4; the amino acid/auxin permease (aaap) family.
DR GlyGen; Q9H598; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H598; -.
DR PhosphoSitePlus; Q9H598; -.
DR BioMuta; SLC32A1; -.
DR DMDM; 29428257; -.
DR MassIVE; Q9H598; -.
DR PaxDb; Q9H598; -.
DR PeptideAtlas; Q9H598; -.
DR PRIDE; Q9H598; -.
DR ProteomicsDB; 80902; -.
DR Antibodypedia; 26904; 280 antibodies from 28 providers.
DR DNASU; 140679; -.
DR Ensembl; ENST00000217420.2; ENSP00000217420.1; ENSG00000101438.4.
DR GeneID; 140679; -.
DR KEGG; hsa:140679; -.
DR MANE-Select; ENST00000217420.2; ENSP00000217420.1; NM_080552.3; NP_542119.1.
DR UCSC; uc002xjc.3; human.
DR CTD; 140679; -.
DR DisGeNET; 140679; -.
DR GeneCards; SLC32A1; -.
DR HGNC; HGNC:11018; SLC32A1.
DR HPA; ENSG00000101438; Tissue enriched (brain).
DR MIM; 616440; gene.
DR neXtProt; NX_Q9H598; -.
DR OpenTargets; ENSG00000101438; -.
DR PharmGKB; PA401; -.
DR VEuPathDB; HostDB:ENSG00000101438; -.
DR eggNOG; KOG4303; Eukaryota.
DR GeneTree; ENSGT00490000043380; -.
DR HOGENOM; CLU_036432_0_0_1; -.
DR InParanoid; Q9H598; -.
DR OMA; KTFFQDG; -.
DR OrthoDB; 570025at2759; -.
DR PhylomeDB; Q9H598; -.
DR TreeFam; TF312818; -.
DR PathwayCommons; Q9H598; -.
DR Reactome; R-HSA-425393; Transport of inorganic cations/anions and amino acids/oligopeptides.
DR Reactome; R-HSA-888590; GABA synthesis, release, reuptake and degradation.
DR SignaLink; Q9H598; -.
DR BioGRID-ORCS; 140679; 15 hits in 1068 CRISPR screens.
DR GeneWiki; SLC32A1; -.
DR GenomeRNAi; 140679; -.
DR Pharos; Q9H598; Tchem.
DR PRO; PR:Q9H598; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9H598; protein.
DR Bgee; ENSG00000101438; Expressed in nucleus accumbens and 56 other tissues.
DR Genevisible; Q9H598; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0051286; C:cell tip; IEA:Ensembl.
DR GO; GO:0061202; C:clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane; TAS:Reactome.
DR GO; GO:0044316; C:cone cell pedicle; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0044292; C:dendrite terminus; IBA:GO_Central.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0060077; C:inhibitory synapse; IEA:Ensembl.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IBA:GO_Central.
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:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098793; C:presynapse; ISS:UniProtKB.
DR GO; GO:0048786; C:presynaptic active zone; IEA:Ensembl.
DR GO; GO:0008021; C:synaptic vesicle; ISS:UniProtKB.
DR GO; GO:0030672; C:synaptic vesicle membrane; TAS:Reactome.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015185; F:gamma-aminobutyric acid transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015495; F:gamma-aminobutyric acid:proton symporter activity; IBA:GO_Central.
DR GO; GO:0015187; F:glycine transmembrane transporter activity; ISS: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; ISS:UniProtKB.
DR GO; GO:0015812; P:gamma-aminobutyric acid transport; ISS:UniProtKB.
DR GO; GO:0015816; P:glycine transport; ISS:UniProtKB.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0098700; P:neurotransmitter loading into synaptic vesicle; IBA:GO_Central.
DR GO; GO:0007269; P:neurotransmitter secretion; TAS:Reactome.
DR InterPro; IPR013057; AA_transpt_TM.
DR Pfam; PF01490; Aa_trans; 1.
PE 2: Evidence at transcript 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_0000093820"
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 REGION 83..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 186
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O35633"
FT VARIANT 423
FT /note="S -> G (in dbSNP:rs34517228)"
FT /id="VAR_048121"
FT CONFLICT 261
FT /note="K -> R (in Ref. 4; AAH36458)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 525 AA; 57415 MW; C3C4B0786B8DE745 CRC64;
MATLLRSKLS NVATSVSNKS QAKMSGMFAR MGFQAATDEE AVGFAHCDDL DFEHRQGLQM
DILKAEGEPC GDEGAEAPVE GDIHYQRGSG APLPPSGSKD QVGGGGEFGG 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
CYSGDGRLKS WGLTLRCALV VFTLLMAIYV PHFALLMGLT GSLTGAGLCF LLPSLFHLRL
LWRKLLWHQV FFDVAIFVIG GICSVSGFVH SLEGLIEAYR TNAED
