VGL2B_DANRE
ID VGL2B_DANRE Reviewed; 587 AA.
AC Q5W8I7;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Vesicular glutamate transporter 2.2 {ECO:0000305};
DE AltName: Full=Solute carrier family 17 member 6-A;
DE AltName: Full=Vesicular glutamate transporter 2-B;
GN Name=slc17a6a; Synonyms=slc17a6l, vglut2.2, vglut2b;
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 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). {ECO:0000250|UniProtKB:Q8BLE7,
CC ECO:0000250|UniProtKB:Q9JI12}.
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 chord.
CC {ECO:0000269|PubMed:15515020, 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; AB183387; BAD67438.1; -; mRNA.
DR RefSeq; NP_001009982.1; NM_001009982.1.
DR AlphaFoldDB; Q5W8I7; -.
DR SMR; Q5W8I7; -.
DR STRING; 7955.ENSDARP00000011755; -.
DR PaxDb; Q5W8I7; -.
DR GeneID; 494492; -.
DR KEGG; dre:494492; -.
DR CTD; 494492; -.
DR ZFIN; ZDB-GENE-050105-4; slc17a6a.
DR eggNOG; KOG2532; Eukaryota.
DR InParanoid; Q5W8I7; -.
DR OrthoDB; 497052at2759; -.
DR PhylomeDB; Q5W8I7; -.
DR PRO; PR:Q5W8I7; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
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: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:0044341; P:sodium-dependent phosphate transport; ISS:UniProtKB.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IBA:GO_Central.
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 Sodium; Sodium transport; Symport; Synapse; Synaptosome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..587
FT /note="Vesicular glutamate transporter 2.2"
FT /id="PRO_0000318173"
FT TOPO_DOM 1..71
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 72..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 93..125
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 126..146
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 147..149
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..170
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 171..180
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..203
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 204..217
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..238
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 239..245
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 246..266
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 267..311
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 312..332
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 333..350
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 351..371
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 372..387
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 388..408
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 409..410
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 411..431
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 432..444
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 445..465
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 466..479
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 480..500
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 501..587
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 471
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 587 AA; 64461 MW; 8667A3A50A7882B8 CRC64;
MDTVKERVLA PGKEKMRNLA GKTLGHMHRV MERKQKTGEV IELTEDGRPM HMPEKKAPLV
DCTCFGLPRR YIIAIMSGLG FCISFGIRCN LGVAIVDMVN NSTIHKGGKI IIKGKAKFNW
DPETVGMIHG SFFWGYTVTQ IPGGYISSRL AANRVFGAAI LLTSTLNMFI PSAARVHYGC
VMFVRILQGL VEGVTYPACH GIWSKWAPPL ERSRLATTSF CGSYAGAVVA MPLAGILVQY
SGWSSVFYIY GSFGIVWYMF WILVSYESPA DHPTITDEER TYIEESIGES AKLLGAMEKY
KTPWRKFFTS MPVYAIIVAN FCRSWTFYLL LISQPAYFEE VFGFEISKVG MVSALPHLVM
TIIVPIGGQL ADYLRSKNIL TTTTVRKIMN CGGFGMEATL LLVVGFSHSK GVAISFLVLA
VGFSGFAISG FNVNHLDIAP RYASILMGIS NGVGTLSGMV CPLIVGAMTK NKTREEWQNV
FLIASLVHYG GVIFYGIFAS GEKQPWADPE ETSDEKCGFI DEDELAEETG DITLSHAPFG
AQGALGAPAK TYGATTQLNG GWAKGWEKTE EFIQEDAERT YTGDGYS
