VGL2A_DANRE
ID VGL2A_DANRE Reviewed; 584 AA.
AC Q5W8I8; B3DGT1; Q8AW47;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Vesicular glutamate transporter 2.1 {ECO:0000305};
DE AltName: Full=Protein blumenkohl;
DE AltName: Full=Solute carrier family 17 member 6-B;
DE AltName: Full=Vesicular glutamate transporter 2-A;
GN Name=slc17a6b; Synonyms=blu, slc17a6, vglut2.1, vglut2a;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=15515020; DOI=10.1002/cne.20278;
RA Higashijima S., Mandel G., Fetcho J.R.;
RT "Distribution of prospective glutamatergic, glycinergic, and GABAergic
RT neurons in embryonic and larval zebrafish.";
RL J. Comp. Neurol. 480:1-18(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17196531; DOI=10.1016/j.neuron.2006.12.013;
RA Smear M.C., Tao H.W., Staub W., Orger M.B., Gosse N.J., Liu Y.,
RA Takahashi K., Poo M.-M., Baier H.;
RT "Vesicular glutamate transport at a central synapse limits the acuity of
RT visual perception in zebrafish.";
RL Neuron 53:65-77(2007).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=17941721; DOI=10.1371/journal.pbio.0050277;
RA Yokogawa T., Marin W., Faraco J., Pezeron G., Appelbaum L., Zhang J.,
RA Rosa F., Mourrain P., Mignot E.;
RT "Characterization of sleep in zebrafish and insomnia in hypocretin receptor
RT mutants.";
RL PLoS Biol. 5:E277-E277(2007).
CC -!- FUNCTION: Multifunctional transporter that transports L-glutamate as
CC well as multiple ions such as chloride, proton, potassium, sodium and
CC phosphate. At the synaptic vesicle membrane, mainly functions as a
CC uniporter which transports preferentially L-glutamate but also,
CC phosphate from the cytoplasm into synaptic vesicles at presynaptic
CC nerve terminals of excitatory neural cells. The L-glutamate or
CC phosphate uniporter activity is electrogenic and is driven by the
CC proton electrochemical gradient, mainly by the electrical gradient
CC established by the vacuolar H(+)-ATPase across the synaptic vesicle
CC membrane. In addition, functions as a chloride channel that allows a
CC chloride permeation through the synaptic vesicle membrane therefore
CC affects the proton electrochemical gradient and promotes synaptic
CC vesicles acidification. Moreover, functions as a vesicular K(+)/H(+)
CC antiport allowing to maintain the electrical gradient and to decrease
CC chemical gradient and therefore sustain vesicular L-glutamate uptake.
CC The vesicular H(+)/H(+) antiport activity is electroneutral. At the
CC plasma membrane, following exocytosis, functions as a symporter of
CC Na(+) and phosphate from the extracellular space to the cytoplasm
CC allowing synaptic phosphate homeostasis regulation. The symporter
CC activity is driven by an inside negative membrane potential and is
CC electrogenic (By similarity). Also involved in the regulation of
CC retinal hyaloid vessel regression during postnatal development (By
CC similarity). May also play a role in the endocrine L-glutamatergic
CC system of other tissues such as pineal gland and pancreas (By
CC similarity). Required for glutamate release by retinotectal synapses
CC and visual acuity (PubMed:17196531). {ECO:0000250|UniProtKB:Q8BLE7,
CC ECO:0000250|UniProtKB:Q9JI12, ECO:0000269|PubMed:17196531}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-glutamate(out) = L-glutamate(in); Xref=Rhea:RHEA:66336,
CC ChEBI:CHEBI:29985; Evidence={ECO:0000250|UniProtKB:Q9JI12};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 Na(+)(out) + phosphate(out) = 3 Na(+)(in) + phosphate(in);
CC Xref=Rhea:RHEA:71255, ChEBI:CHEBI:29101, ChEBI:CHEBI:43474;
CC Evidence={ECO:0000250|UniProtKB:Q9JI12};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=phosphate(in) = phosphate(out); Xref=Rhea:RHEA:32823,
CC ChEBI:CHEBI:43474; Evidence={ECO:0000250|UniProtKB:Q9JI12};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(out) + K(+)(in) = H(+)(in) + K(+)(out);
CC Xref=Rhea:RHEA:29467, ChEBI:CHEBI:15378, ChEBI:CHEBI:29103;
CC Evidence={ECO:0000250|UniProtKB:Q9JI12};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC ChEBI:CHEBI:17996; Evidence={ECO:0000250|UniProtKB:Q9JI12};
CC -!- ACTIVITY REGULATION: Chloride channel activity is allosterically
CC activated by lumenal H(+) and Cl(-) leading to synaptic vesicles
CC acidification. The L-glutamate transport activity is allosterically
CC activated by lumenal H(+) and Cl(-). The allosteric requirement for
CC H(+) efficiently prevents non-vesicular efflux across the plasma
CC membrane. The L-glutamate uniporter activity exhibits a biphasic
CC dependence on chloride concentration. {ECO:0000250|UniProtKB:Q9JI12}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000250}. Membrane {ECO:0000305}; Multi-pass
CC membrane protein {ECO:0000305}. Synapse, synaptosome {ECO:0000250}.
CC Cell membrane {ECO:0000250|UniProtKB:Q8BLE7}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in spinal cord and retinal ganglion
CC cells. {ECO:0000269|PubMed:15515020, ECO:0000269|PubMed:17196531,
CC ECO:0000269|PubMed:17941721}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Sodium/anion
CC cotransporter family. VGLUT subfamily. {ECO:0000305}.
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DR EMBL; AB183386; BAD67437.1; -; mRNA.
DR EMBL; AL627170; CAD52142.1; -; Genomic_DNA.
DR EMBL; BC162508; AAI62508.1; -; mRNA.
DR RefSeq; NP_001122293.1; NM_001128821.1.
DR AlphaFoldDB; Q5W8I8; -.
DR SMR; Q5W8I8; -.
DR STRING; 7955.ENSDARP00000090645; -.
DR PaxDb; Q5W8I8; -.
DR Ensembl; ENSDART00000099872; ENSDARP00000090645; ENSDARG00000041150.
DR GeneID; 100149756; -.
DR KEGG; dre:100149756; -.
DR CTD; 100149756; -.
DR ZFIN; ZDB-GENE-030616-554; slc17a6b.
DR eggNOG; KOG2532; Eukaryota.
DR GeneTree; ENSGT00940000155891; -.
DR HOGENOM; CLU_001265_5_0_1; -.
DR InParanoid; Q5W8I8; -.
DR OMA; YNEQSQM; -.
DR OrthoDB; 497052at2759; -.
DR PhylomeDB; Q5W8I8; -.
DR TreeFam; TF313535; -.
DR Reactome; R-DRE-428643; Organic anion transporters.
DR PRO; PR:Q5W8I8; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 7.
DR Bgee; ENSDARG00000041150; Expressed in habenula and 25 other tissues.
DR ExpressionAtlas; Q5W8I8; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0060076; C:excitatory synapse; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; ISS:UniProtKB.
DR GO; GO:0030672; C:synaptic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0005254; F:chloride channel activity; ISS:UniProtKB.
DR GO; GO:0005313; F:L-glutamate transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0022810; F:membrane potential driven uniporter activity; ISS:UniProtKB.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015386; F:potassium:proton antiporter activity; ISS:UniProtKB.
DR GO; GO:0005436; F:sodium:phosphate symporter activity; ISS:UniProtKB.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0006820; P:anion transport; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; IMP:ZFIN.
DR GO; GO:0051938; P:L-glutamate import; ISS:UniProtKB.
DR GO; GO:0015813; P:L-glutamate transmembrane transport; ISS:UniProtKB.
DR GO; GO:0098700; P:neurotransmitter loading into synaptic vesicle; IBA:GO_Central.
DR GO; GO:0055062; P:phosphate ion homeostasis; ISS:UniProtKB.
DR GO; GO:0050803; P:regulation of synapse structure or activity; IBA:GO_Central.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0044341; P:sodium-dependent phosphate transport; ISS:UniProtKB.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; IMP:CACAO.
DR Gene3D; 1.20.1250.20; -; 2.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 2: Evidence at transcript level;
KW Antiport; Cell membrane; Chloride; Chloride channel; Cytoplasmic vesicle;
KW Glycoprotein; Ion channel; Ion transport; Membrane;
KW Neurotransmitter transport; Phosphate transport; Reference proteome;
KW Sensory transduction; Sodium; Sodium transport; Symport; Synapse;
KW Synaptosome; Transmembrane; Transmembrane helix; Transport; Vision.
FT CHAIN 1..584
FT /note="Vesicular glutamate transporter 2.1"
FT /id="PRO_0000318172"
FT TOPO_DOM 1..70
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 71..91
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 92..124
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 125..145
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 146..148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..169
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 170..177
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 199..216
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 217..237
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 238..244
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..310
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 311..331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 332..349
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 350..370
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 371..386
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 387..407
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 408..409
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 410..430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 431..445
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 446..466
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 467..477
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 478..498
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 499..584
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 55
FT /note="K -> R (in Ref. 1; BAD67437)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="L -> S (in Ref. 1; BAD67437)"
FT /evidence="ECO:0000305"
FT CONFLICT 445
FT /note="L -> H (in Ref. 1; BAD67437)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 584 AA; 64122 MW; 91C140D929EB85DB CRC64;
METPREPAGF SKEGLKQLAG KTLGHVYRVI EKRQKPGENI ELTEDGRPAQ INERKAPLCD
CTCFGLPRRY IIAIMSGLGF CISFGIRCNL GVAIVSMVNN STIHLNGKII IKEKAKFNWD
PETVGLIHGS FFWGYIVTQI PGGYISSRLA ANRVFGAAIL LTSTLNMFIP SAARGHYGCV
IFVRILQGLV EGVTYPACHG IWSKWAPPLE RSRLATTSFC GSYAGAVIAM PLAGILVQYT
GWSSVFYVYG CFGIFWYMFW ILVSYESPAE HPTITAEERC YIEESIGESA KLLGPADKFK
TPWRKFFTSM PVYAIIVANF CRSWTFYLLL ISQPAYFEEV FGFEISKVGM LSALPHLVMT
IIVPIGGQLA DHLRSKNILS TTTVRKIMNC GGFGMEATLL LIVGYSHSKG VAISFLVLAV
GFSGFAISGF NVNHLDIAPR YASILMGISN GVGTLSGMVC PLIVGAMTKH KTREEWQYVF
LIASLVHYGG VIFYGIFASG EKQPWADPEL TSDEKCGFID EDELAEETGD ITQSYGALGA
PAKSYGATTQ LNGGWAEGWD KREEYVQDGV EEGGYGYRQG GNYS
