P43004 (EAA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Excitatory amino acid transporter 2

Alternative name(s):
Glutamate/aspartate transporter II
Sodium-dependent glutamate/aspartate transporter 2
Solute carrier family 1 member 2

Gene names

Name:	SLC1A2
Synonyms:	EAAT2, GLT1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	574 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport by cotransporting sodium.
Subunit structure	Homotrimer. Interacts with AJUBA By similarity. Ref.9
Subcellular location	Membrane; Multi-pass membrane protein.
Post-translational modification	Glycosylated. Palmitoylation at Cys-38 is not required for correct subcellular localization, but is important for glutamate uptake activity By similarity.
Sequence similarities	Belongs to the sodium:dicarboxylate (SDF) symporter (TC 2.A.23) family. SLC1A2 subfamily. [View classification]

Ontologies

Keywords
Biological process	Symport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	D-aspartate import Inferred from direct assay Ref.1. Source: UniProtKB L-glutamate import Inferred from direct assay Ref.1. Source: UniProtKB adult behavior Inferred from electronic annotation. Source: Compara cellular response to extracellular stimulus Inferred from electronic annotation. Source: Compara multicellular organism growth Inferred from electronic annotation. Source: Compara multicellular organismal aging Inferred from electronic annotation. Source: Compara positive regulation of glucose import Inferred from electronic annotation. Source: Compara response to amino acid stimulus Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to wounding Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement Ref.1. Source: ProtInc telencephalon development Inferred from electronic annotation. Source: Compara visual behavior Inferred from electronic annotation. Source: Compara
Cellular_component	axolemma Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	L-glutamate transmembrane transporter activity Traceable author statement Ref.1. Source: ProtInc glutamate:sodium symporter activity Inferred from electronic annotation. Source: Compara sodium:dicarboxylate symporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P43004-1)

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.

Isoform 2 (identifier: P43004-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 574	574	Excitatory amino acid transporter 2		PRO_0000202061
Regions
	Topological domain	1 – 44	44	Cytoplasmic Potential
	Transmembrane	45 – 64	20	Helical; Potential
	Transmembrane	88 – 108	21	Helical; Potential
	Transmembrane	121 – 142	22	Helical; Potential
	Topological domain	143 – 239	97	Extracellular Potential
	Transmembrane	240 – 259	20	Helical; Potential
	Transmembrane	280 – 301	22	Helical; Potential
	Transmembrane	317 – 339	23	Helical; Potential
	Transmembrane	406 – 430	25	Helical; Potential
	Transmembrane	437 – 459	23	Helical; Potential
Amino acid modifications
	Modified residue	494	1	Phosphotyrosine By similarity
	Modified residue	539	1	Phosphotyrosine By similarity
	Modified residue	564	1	Phosphoserine By similarity
	Lipidation	38	1	S-palmitoyl cysteine By similarity
	Glycosylation	206	1	N-linked (GlcNAc...) Potential
	Glycosylation	216	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 9	9	Missing in isoform 2.		VSP_037152
Experimental info
	Sequence conflict	19	1	H → P in AAA50429. Ref.1
	Sequence conflict	27	1	E → G in CAA83532. Ref.3
	Sequence conflict	50	1	T → Q in AAA18900. Ref.2
	Sequence conflict	58	1	A → S in AAA18900. Ref.2
	Sequence conflict	141	1	A → G in CAA83532. Ref.3
	Sequence conflict	155	1	P → A in CAA83532. Ref.3
	Sequence conflict	211	1	V → E in AAA50429. Ref.1
	Sequence conflict	253 – 255	3	GIA → AIP in CAA83532. Ref.3
	Sequence conflict	263 – 289	27	AKLMV…MWYSP → GQADGGFLQHFERDCNEVSD HDHVVLS in CAA83532. Ref.3
	Sequence conflict	347	1	F → L in AAA50429. Ref.1
	Sequence conflict	539	1	Y → F in CAA83532. Ref.3
	Sequence conflict	556	1	A → G in CAA83532. Ref.3
	Sequence conflict	563 – 565	3	CSV → RVL in CAA83532. Ref.3
	Sequence conflict	570	1	W → G in CAA83532. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: C8104E6727979435	FASTA	574	62,104
	10 20 30 40 50 60 MASTEGANNM PKQVEVRMHD SHLGSEEPKH RHLGLRLCDK LGKNLLLTLT VFGVILGAVC 70 80 90 100 110 120 GGLLRLASPI HPDVVMLIAF PGDILMRMLK MLILPLIISS LITGLSGLDA KASGRLGTRA 130 140 150 160 170 180 MVYYMSTTII AAVLGVILVL AIHPGNPKLK KQLGPGKKND EVSSLDAFLD LIRNLFPENL 190 200 210 220 230 240 VQACFQQIQT VTKKVLVAPP PDEEANATSA VVSLLNETVT EVPEETKMVI KKGLEFKDGM 250 260 270 280 290 300 NVLGLIGFFI AFGIAMGKMG DQAKLMVDFF NILNEIVMKL VIMIMWYSPL GIACLICGKI 310 320 330 340 350 360 IAIKDLEVVA RQLGMYMVTV IIGLIIHGGI FLPLIYFVVT RKNPFSFFAG IFQAWITALG 370 380 390 400 410 420 TASSAGTLPV TFRCLEENLG IDKRVTRFVL PVGATINMDG TALYEAVAAI FIAQMNGVVL 430 440 450 460 470 480 DGGQIVTVSL TATLASVGAA SIPSAGLVTM LLILTAVGLP TEDISLLVAV DWLLDRMRTS 490 500 510 520 530 540 VNVVGDSFGA GIVYHLSKSE LDTIDSQHRV HEDIEMTKTQ SIYDDMKNHR ESNSNQCVYA 550 560 570 AHNSVIVDEC KVTLAANGKS ADCSVEEEPW KREK
	Isoform 2 [UniParc]. Checksum: A7286207F550252F	FASTA	565	61,228
	10 20 30 40 50 60 MPKQVEVRMH DSHLGSEEPK HRHLGLRLCD KLGKNLLLTL TVFGVILGAV CGGLLRLASP 70 80 90 100 110 120 IHPDVVMLIA FPGDILMRML KMLILPLIIS SLITGLSGLD AKASGRLGTR AMVYYMSTTI 130 140 150 160 170 180 IAAVLGVILV LAIHPGNPKL KKQLGPGKKN DEVSSLDAFL DLIRNLFPEN LVQACFQQIQ 190 200 210 220 230 240 TVTKKVLVAP PPDEEANATS AVVSLLNETV TEVPEETKMV IKKGLEFKDG MNVLGLIGFF 250 260 270 280 290 300 IAFGIAMGKM GDQAKLMVDF FNILNEIVMK LVIMIMWYSP LGIACLICGK IIAIKDLEVV 310 320 330 340 350 360 ARQLGMYMVT VIIGLIIHGG IFLPLIYFVV TRKNPFSFFA GIFQAWITAL GTASSAGTLP 370 380 390 400 410 420 VTFRCLEENL GIDKRVTRFV LPVGATINMD GTALYEAVAA IFIAQMNGVV LDGGQIVTVS 430 440 450 460 470 480 LTATLASVGA ASIPSAGLVT MLLILTAVGL PTEDISLLVA VDWLLDRMRT SVNVVGDSFG 490 500 510 520 530 540 AGIVYHLSKS ELDTIDSQHR VHEDIEMTKT QSIYDDMKNH RESNSNQCVY AAHNSVIVDE 550 560 CKVTLAANGK SADCSVEEEP WKREK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex." Arriza J.L., Fairman W.A., Wendy A., Wadiche J.I., Murdoch G.H., Kavanaugh M.P., Amara S.G. J. Neurosci. 14:5559-5569(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain cortex.
[2]	"Molecular cloning of human brain glutamate/aspartate transporter II." Shashidharan P., Wittenberg I., Plaitakis A. Biochim. Biophys. Acta 1191:393-396(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Brain.
[3]	"Cloning and characterization of a glutamate transporter cDNA from human brain and pancreas." Manfras B.J., Rudert W.A., Trucco M., Boehm B.O. Biochim. Biophys. Acta 1195:185-188(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Pancreas.
[4]	"DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters." Shimamoto K., Lebrun B., Yasuda-Kamatani Y., Sakaitani M., Shigeri Y., Yumoto N., Nakajima T. Mol. Pharmacol. 53:195-201(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[5]	"Cloning and characterization of the 3'-untranslated region of the human excitatory amino acid transporter 2 transcript." Kim S.Y., Chao W., Choi S.Y., Volsky D.J. J. Neurochem. 86:1458-1467(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[9]	"A trimeric quaternary structure is conserved in bacterial and human glutamate transporters." Gendreau S., Voswinkel S., Torres-Salazar D., Lang N., Heidtmann H., Detro-Dassen S., Schmalzing G., Hidalgo P., Fahlke C. J. Biol. Chem. 279:39505-39512(2004) [PubMed] [Europe PMC] [Abstract] Cited for: QUATERNARY STRUCTURE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U03505 mRNA. Translation: AAA50429.1. U01824 mRNA. Translation: AAA18900.1. Z32517 mRNA. Translation: CAA83532.1. D85884 mRNA. Translation: BAA28706.1. AY066021 mRNA. Translation: AAL57716.1. AL133330, AC090625 Genomic DNA. Translation: CAM28291.1. CH471064 Genomic DNA. Translation: EAW68143.1. BC132768 mRNA. Translation: AAI32769.1.
IPI	IPI00300020. IPI00794423.
PIR	I37426. I38432.
RefSeq	NP_001182657.1. NM_001195728.2. NP_001239581.1. NM_001252652.1. NP_004162.2. NM_004171.3.
UniGene	Hs.502338.
3D structure databases
ProteinModelPortal	P43004.
ModBase	Search...
Protein-protein interaction databases
IntAct	P43004. 1 interaction.
STRING	9606.ENSP00000278379.
PTM databases
PhosphoSite	P43004.
Polymorphism databases
DMDM	3041668.
Proteomic databases
PaxDb	P43004.
PRIDE	P43004.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000278379; ENSP00000278379; ENSG00000110436. ENST00000395750; ENSP00000379099; ENSG00000110436. ENST00000395753; ENSP00000379102; ENSG00000110436.
GeneID	6506.
KEGG	hsa:6506.
UCSC	uc001mwd.3. human.
Organism-specific databases
CTD	6506.
GeneCards	GC11M035272.
HGNC	HGNC:10940. SLC1A2.
HPA	CAB002574. HPA009172.
MIM	600300. gene.
neXtProt	NX_P43004.
PharmGKB	PA35827.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1301.
HOVERGEN	HBG000080.
InParanoid	P43004.
KO	K05613.
OMA	VMVIAFP.
OrthoDB	EOG4P8FHT.
PhylomeDB	P43004.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System. REACT_15518. Transmembrane transport of small molecules. REACT_19419. Amino acid and oligopeptide SLC transporters.
Gene expression databases
ArrayExpress	P43004.
Bgee	P43004.
CleanEx	HS_SLC1A2.
Genevestigator	P43004.
GermOnline	ENSG00000110436. Homo sapiens.
Family and domain databases
InterPro	IPR001991. Na-dicarboxylate_symporter. IPR018107. Na-dicarboxylate_symporter_CS. [Graphical view]
PANTHER	PTHR11958. PTHR11958. 1 hit.
Pfam	PF00375. SDF. 1 hit. [Graphical view]
PRINTS	PR00173. EDTRNSPORT.
PROSITE	PS00713. NA_DICARBOXYL_SYMP_1. 1 hit. PS00714. NA_DICARBOXYL_SYMP_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P43004.
ChEMBL	CHEMBL4973.
ChiTaRS	SLC1A2. human.
DrugBank	DB00142. L-Glutamic Acid.
GenomeRNAi	6506.
NextBio	25297.
PMAP-CutDB	P43004.
SOURCE	Search...

Entry information

Entry name

EAA2_HUMAN

Accession

Primary (citable) accession number: P43004
Secondary accession number(s): Q14417, Q541G6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	July 15, 1998
Last modified:	May 1, 2013
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.