VGLU3_DANRE
ID VGLU3_DANRE Reviewed; 590 AA.
AC Q1L8X9;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Vesicular glutamate transporter 3 {ECO:0000250|UniProtKB:Q8NDX2};
DE Short=VGluT3 {ECO:0000250|UniProtKB:Q8NDX2};
DE AltName: Full=Solute carrier family 17 member 8;
GN Name=slc17a8 {ECO:0000250|UniProtKB:Q8NDX2}; Synonyms=vglut3;
GN ORFNames=si:ch211-264e16.4;
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 [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).
CC -!- FUNCTION: Multifunctional transporter that transports L-glutamate as
CC well as multiple ions such as chloride, sodium and phosphate. At the
CC synaptic vesicle membrane, mainly functions as an uniporter that
CC mediates the uptake of L-glutamate into synaptic vesicles at
CC presynaptic nerve terminals of excitatory neural cells. The L-glutamate
CC uniporter activity is electrogenic and is driven by the proton
CC electrochemical gradient, mainly by the electrical gradient established
CC by the vacuolar H(+)-ATPase across the synaptic vesicle membrane (By
CC similarity). In addition, functions as a chloride channel that allows a
CC chloride permeation through the synaptic vesicle membrane that affects
CC the proton electrochemical gradient and promotes synaptic vesicles
CC acidification (By similarity). At the plasma membrane, following
CC exocytosis, functions as a symporter of Na(+) and phosphate from the
CC extracellular space to the cytoplasm allowing synaptic phosphate
CC homeostasis regulation. The symporter activity is electrogenic (By
CC similarity). Moreover, operates synergistically with SLC18A3/VACHT
CC under a constant H(+) gradient, thereby allowing striatal vesicular
CC acetylcholine uptake (By similarity). {ECO:0000250|UniProtKB:Q7TSF2,
CC ECO:0000250|UniProtKB:Q8NDX2}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-glutamate(out) = L-glutamate(in); Xref=Rhea:RHEA:66336,
CC ChEBI:CHEBI:29985; Evidence={ECO:0000250|UniProtKB:Q8NDX2};
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:Q8NDX2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC ChEBI:CHEBI:17996; Evidence={ECO:0000250|UniProtKB:Q7TSF2};
CC -!- ACTIVITY REGULATION: The L-glutamate uniporter activity exhibits a
CC biphasic dependence on chloride concentration. Chloride channel
CC activity is allosterically activated by lumenal H(+) and Cl(-) leading
CC to synaptic vesicles acidification. The glutamate transport activity is
CC allosterically activated by lumenal H(+) and Cl(-), preventing non-
CC vesicular L-glutamate release. {ECO:0000250|UniProtKB:Q7TSF2}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000250|UniProtKB:Q7TSF2}. Cell membrane
CC {ECO:0000250|UniProtKB:Q8NDX2}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8NDX2}. Synapse, synaptosome
CC {ECO:0000250|UniProtKB:Q7TSF2}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Sodium/anion
CC cotransporter family. VGLUT subfamily. {ECO:0000305}.
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DR EMBL; CR536616; CAK04857.2; -; Genomic_DNA.
DR RefSeq; NP_001076304.1; NM_001082835.1.
DR AlphaFoldDB; Q1L8X9; -.
DR SMR; Q1L8X9; -.
DR STRING; 7955.ENSDARP00000074903; -.
DR PaxDb; Q1L8X9; -.
DR Ensembl; ENSDART00000080454; ENSDARP00000074903; ENSDARG00000057728.
DR GeneID; 563467; -.
DR KEGG; dre:563467; -.
DR CTD; 246213; -.
DR ZFIN; ZDB-GENE-060503-416; slc17a8.
DR eggNOG; KOG2532; Eukaryota.
DR GeneTree; ENSGT00940000158187; -.
DR HOGENOM; CLU_001265_5_0_1; -.
DR InParanoid; Q1L8X9; -.
DR OMA; ACMAYLP; -.
DR OrthoDB; 497052at2759; -.
DR PhylomeDB; Q1L8X9; -.
DR TreeFam; TF313535; -.
DR Reactome; R-DRE-428643; Organic anion transporters.
DR PRO; PR:Q1L8X9; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 18.
DR Bgee; ENSDARG00000057728; Expressed in ovary and 2 other tissues.
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; IEA:UniProtKB-KW.
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:0005326; F:neurotransmitter transmembrane transporter activity; IBA:GO_Central.
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:0050957; P:equilibrioception; 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:0051951; P:positive regulation of glutamate uptake involved in transmission of nerve impulse; ISS:UniProtKB.
DR GO; GO:0051631; P:regulation of acetylcholine uptake; ISS:UniProtKB.
DR GO; GO:0050803; P:regulation of synapse structure or activity; IMP:ZFIN.
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:0060005; P:vestibular reflex; IMP:ZFIN.
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 3: Inferred from homology;
KW Cell membrane; Chloride; Chloride channel; Cytoplasmic vesicle;
KW Glycoprotein; Ion channel; Ion transport; Membrane;
KW Neurotransmitter transport; Phosphate transport; Reference proteome;
KW Sodium; Sodium transport; Symport; Synapse; Synaptosome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..590
FT /note="Vesicular glutamate transporter 3"
FT /id="PRO_0000331617"
FT TOPO_DOM 1..76
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 98..130
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 131..151
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 152..153
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 154..174
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 175..182
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 183..203
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 204..221
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..242
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 243..249
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 271..315
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 316..336
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 337..354
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 355..375
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 376..391
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 392..412
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 413..414
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 415..435
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 436..448
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 449..469
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 470..482
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 483..503
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 504..587
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 526..590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 536..556
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 565..581
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 590 AA; 64815 MW; 48C304B4714DC227 CRC64;
MPLGGFAGLK EKLNPGKEEL KNNVGDSLGN LQKKIDGSNV TEEDNIELTE DGRPVAAPKR
SPPLLDCGCF GLPKRYIIAM LSGLGFCISF GIRCNLGVAI VEMVNNNTVY INGTAVMQPA
QFNWDPETVG LIHGSFFWGY IVTQIPGGFI SNKLAANRVF GAAIFLTSVL NMFIPSAARV
HYGCVMFVRI LQGLVEGVTY PACHGMWSKW APPLERSRLA TTSFCGSYAG AVIAMPLAGI
LVQYVGWPSV FYIYGVFGII WYIFWILLAY NSPAVHPTIS EEERNYIETS IGEGANLMSS
TEKFKTPWRE FFTSMPVYAI IVANFCRSWT FYLLLISQPA YFEEVFGFPI SKVGILSAVP
HMVMTIIVPI GGQLADFLRS RKILSTTTVR KIMNCGGFGM EATLLLVVGF SHTRAVAISF
LILAVGFSGF AISGFNVNHL DIAPRYASIL MGISNGVGTL SGMVCPLIVG ALTKHKTRLE
WQHVFVIASM VHYTGVIFYA IFASGEKQDW ADPENTSDEK CGIIGEDELA DETEPSSDSG
LATRQKTYGT TDNSSGRKQG WKKKRGVTMQ AEDDHESNHY ENGEYQTQYQ
