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Protein

Excitatory amino acid transporter 4

Gene

SLC1A6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:7791878). Functions as a symporter that transports one amino acid molecule together with two or three Na+ ions and one proton, in parallel with the counter-transport of one K+ ion. Mediates Cl- flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na+ symport (By similarity). Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate (Probable).By similarityCurated1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi419Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi421Sodium 2; via carbonyl oxygenBy similarity1
Metal bindingi423Sodium 1By similarity1
Binding sitei427AspartateBy similarity1
Binding sitei501AspartateBy similarity1
Metal bindingi508Sodium 1; via carbonyl oxygenBy similarity1
Binding sitei508AspartateBy similarity1
Metal bindingi512Sodium 1By similarity1

GO - Molecular functioni

GO - Biological processi

  • aspartate transport Source: ProtInc
  • chemical synaptic transmission Source: ProtInc
  • glutamate secretion Source: Reactome
  • ion transport Source: Reactome
  • L-glutamate import across plasma membrane Source: UniProtKB
  • L-glutamate transport Source: ProtInc
  • regulation of membrane potential Source: Ensembl

Keywordsi

Biological processAmino-acid transport, Symport, Transport
LigandChloride, Metal-binding, Potassium, Sodium

Enzyme and pathway databases

ReactomeiR-HSA-210500. Glutamate Neurotransmitter Release Cycle.
R-HSA-425393. Transport of inorganic cations/anions and amino acids/oligopeptides.

Protein family/group databases

TCDBi2.A.23.2.8. the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Excitatory amino acid transporter 4
Alternative name(s):
Sodium-dependent glutamate/aspartate transporter
Solute carrier family 1 member 6
Gene namesi
Name:SLC1A6
Synonyms:EAAT4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105143.12.
HGNCiHGNC:10944. SLC1A6.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 55CytoplasmicSequence analysisAdd BLAST55
Transmembranei56 – 76HelicalSequence analysisAdd BLAST21
Transmembranei99 – 119HelicalSequence analysisAdd BLAST21
Transmembranei133 – 153HelicalSequence analysisAdd BLAST21
Transmembranei262 – 285Helical; Name=4By similarityAdd BLAST24
Transmembranei295 – 322Helical; Name=5By similarityAdd BLAST28
Transmembranei344 – 365Helical; Name=6By similarityAdd BLAST22
Intramembranei371 – 401Discontinuously helicalBy similarityAdd BLAST31
Transmembranei411 – 437Helical; Name=7By similarityAdd BLAST27
Intramembranei451 – 484Discontinuously helicalBy similarityAdd BLAST34
Transmembranei498 – 519Helical; Name=8By similarityAdd BLAST22

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi6511.
OpenTargetsiENSG00000105143.
PharmGKBiPA35831.

Chemistry databases

DrugBankiDB00142. L-Glutamic Acid.
GuidetoPHARMACOLOGYi871.

Polymorphism and mutation databases

DMDMi1352333.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002020701 – 564Excitatory amino acid transporter 4Add BLAST564

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2PhosphoserineBy similarity1
Glycosylationi216N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi232N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi239N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP48664.
PaxDbiP48664.
PeptideAtlasiP48664.
PRIDEiP48664.

PTM databases

iPTMnetiP48664.
PhosphoSitePlusiP48664.

Expressioni

Tissue specificityi

Brain. Expressed densely and selectively in cell bodies of Purkinje cells.

Gene expression databases

BgeeiENSG00000105143.
CleanExiHS_SLC1A6.
ExpressionAtlasiP48664. baseline and differential.
GenevisibleiP48664. HS.

Organism-specific databases

HPAiHPA041505.
HPA044066.

Interactioni

Subunit structurei

Homotrimer.Curated

Protein-protein interaction databases

BioGridi112402. 1 interactor.
IntActiP48664. 1 interactor.
STRINGi9606.ENSP00000221742.

Structurei

3D structure databases

ProteinModelPortaliP48664.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni388 – 390Aspartate bindingBy similarity3
Regioni468 – 472Aspartate bindingBy similarity5

Domaini

Contains eight transmembrane regions plus two helical hairpins that dip into the membrane. These helical hairpin structures play an important role in the transport process. The first enters the membrane from the cytoplasmic side, the second one from the extracellular side. During the transport cycle, the regions involved in amino acid transport, and especially the helical hairpins, move vertically by about 15-18 Angstroms, alternating between exposure to the aqueous phase and reinsertion in the lipid bilayer. In contrast, the regions involved in trimerization do not move.By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3787. Eukaryota.
COG1301. LUCA.
GeneTreeiENSGT00760000119117.
HOGENOMiHOG000208776.
HOVERGENiHBG000080.
InParanoidiP48664.
KOiK05617.
OMAiEKAWWIS.
OrthoDBiEOG091G0UCE.
PhylomeDBiP48664.
TreeFamiTF315206.

Family and domain databases

Gene3Di1.10.3860.10. 1 hit.
InterProiView protein in InterPro
IPR036458. Na-dicarbo_symporter_sf.
IPR001991. Na-dicarboxylate_symporter.
IPR018107. Na-dicarboxylate_symporter_CS.
PfamiView protein in Pfam
PF00375. SDF. 1 hit.
PRINTSiPR00173. EDTRNSPORT.
SUPFAMiSSF118215. SSF118215. 2 hits.
PROSITEiView protein in PROSITE
PS00713. NA_DICARBOXYL_SYMP_1. 1 hit.
PS00714. NA_DICARBOXYL_SYMP_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P48664-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSSHGNSLFL RESGQRLGRV GWLQRLQESL QQRALRTRLR LQTMTLEHVL
60 70 80 90 100
RFLRRNAFIL LTVSAVVIGV SLAFALRPYQ LTYRQIKYFS FPGELLMRML
110 120 130 140 150
QMLVLPLIVS SLVTGMASLD NKATGRMGMR AAVYYMVTTI IAVFIGILMV
160 170 180 190 200
TIIHPGKGSK EGLHREGRIE TIPTADAFMD LIRNMFPPNL VEACFKQFKT
210 220 230 240 250
QYSTRVVTRT MVRTENGSEP GASMPPPFSV ENGTSFLENV TRALGTLQEM
260 270 280 290 300
LSFEETVPVP GSANGINALG LVVFSVAFGL VIGGMKHKGR VLRDFFDSLN
310 320 330 340 350
EAIMRLVGII IWYAPVGILF LIAGKILEME DMAVLGGQLG MYTLTVIVGL
360 370 380 390 400
FLHAGIVLPL IYFLVTHRNP FPFIGGMLQA LITAMGTSSS SATLPITFRC
410 420 430 440 450
LEEGLGVDRR ITRFVLPVGA TVNMDGTALY EALAAIFIAQ VNNYELNLGQ
460 470 480 490 500
ITTISITATA ASVGAAGIPQ AGLVTMVIVL TSVGLPTEDI TLIIAVDWFL
510 520 530 540 550
DRLRTMTNVL GDSIGAAVIE HLSQRELELQ EAELTLPSLG KPYKSLMAQE
560
KGASRGRGGN ESAM
Length:564
Mass (Da):61,565
Last modified:February 1, 1996 - v1
Checksum:iBB6700D6EAEC2B20
GO
Isoform 2 (identifier: P48664-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     313-564: Missing.

Show »
Length:312
Mass (Da):34,846
Checksum:i0C06E0DEC9A864C6
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_055130313 – 564Missing in isoform 2. 1 PublicationAdd BLAST252

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U18244 mRNA. Translation: AAA75314.1.
AC004659 Genomic DNA. Translation: AAC15754.1.
AC104528 Genomic DNA. No translation available.
BC028721 mRNA. Translation: AAH28721.1.
BC040604 mRNA. Translation: AAH40604.1.
CCDSiCCDS12321.1. [P48664-1]
CCDS62578.1. [P48664-2]
PIRiS58398.
RefSeqiNP_001259016.1. NM_001272087.1. [P48664-2]
NP_001259017.1. NM_001272088.1. [P48664-2]
NP_005062.1. NM_005071.2. [P48664-1]
XP_006722905.1. XM_006722842.1. [P48664-1]
XP_006722907.1. XM_006722844.1. [P48664-1]
XP_016882641.1. XM_017027152.1. [P48664-1]
UniGeneiHs.515217.
Hs.733178.

Genome annotation databases

EnsembliENST00000221742; ENSP00000221742; ENSG00000105143. [P48664-1]
ENST00000544886; ENSP00000446175; ENSG00000105143. [P48664-2]
ENST00000598504; ENSP00000471781; ENSG00000105143. [P48664-2]
GeneIDi6511.
KEGGihsa:6511.
UCSCiuc002naa.3. human. [P48664-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiEAA4_HUMAN
AccessioniPrimary (citable) accession number: P48664
Secondary accession number(s): Q8N753
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: October 25, 2017
This is version 148 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families