P48058 (GRIA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutamate receptor 4
Short name=GluR-4
Short name=GluR4

Alternative name(s):
AMPA-selective glutamate receptor 4
GluR-D
Glutamate receptor ionotropic, AMPA 4
Short name=GluA4

Gene names

Name:	GRIA4
Synonyms:	GLUR4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	902 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist.In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate. Ref.3
Subunit structure	Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. Interacts with EPB41L1 via its C-terminus By similarity. Found in a complex with GRIA1, GRIA2, GRIA3, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5 and PRKCG By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein. Cell projection › dendrite. Note: Interaction with CNIH2, CNIH3 and PRKCG promotes cell surface expression By similarity.
Post-translational modification	Palmitoylated. Depalmitoylated upon glutamate stimulation. Cys-611 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-837 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis By similarity. Phosphorylated at Ser-862 by PRKCG; phoshporylation increases plasma membrane-associated GRI4 expression By similarity.
Miscellaneous	The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds AMPA (quisqualate) > glutamate > kainate.
Sequence similarities	Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIA4 subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell junction Cell membrane Cell projection Membrane Postsynaptic cell membrane Synapse
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Ionic channel Ligand-gated ion channel Receptor
PTM	Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	glutamate signaling pathway Traceable author statement. Source: ProtInc synaptic transmission Traceable author statement. Source: Reactome
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW endocytic vesicle membrane Traceable author statement. Source: Reactome postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity Inferred from direct assay Ref.3. Source: UniProtKB extracellular-glutamate-gated ion channel activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 902	882	Glutamate receptor 4		PRO_0000011538
Regions
	Topological domain	21 – 544	524	Extracellular Potential
	Transmembrane	545 – 565	21	Helical; Potential
	Topological domain	566 – 625	60	Cytoplasmic Potential
	Transmembrane	626 – 646	21	Helical; Potential
	Topological domain	647 – 813	167	Extracellular Potential
	Transmembrane	814 – 834	21	Helical; Potential
	Topological domain	835 – 902	68	Cytoplasmic Potential
	Region	500 – 502	3	Glutamate binding By similarity
	Region	676 – 677	2	Glutamate binding By similarity
Sites
	Binding site	507	1	Glutamate By similarity
	Binding site	727	1	Glutamate By similarity
Amino acid modifications
	Modified residue	862	1	Phosphoserine; by PKC/PRKCG By similarity
	Lipidation	611	1	S-palmitoyl cysteine By similarity
	Lipidation	837	1	S-palmitoyl cysteine By similarity
	Glycosylation	56	1	N-linked (GlcNAc...) Potential
	Glycosylation	258	1	N-linked (GlcNAc...) Potential
	Glycosylation	371	1	N-linked (GlcNAc...) Potential
	Glycosylation	407	1	N-linked (GlcNAc...) Potential
	Glycosylation	414	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	54	1	S → A in AAA95962. Ref.1
	Sequence conflict	273	1	I → T in AAA95962. Ref.1
	Sequence conflict	327 – 328	2	NA → KS in AAA95962. Ref.1
	Sequence conflict	732 – 733	2	EY → DN in AAA95962. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P48058 [UniParc]. Last modified December 16, 2008. Version 2. Checksum: 7793AEF0AB829FC5	FASTA	902	100,871
	10 20 30 40 50 60 MRIISRQIVL LFSGFWGLAM GAFPSSVQIG GLFIRNTDQE YTAFRLAIFL HNTSPNASEA 70 80 90 100 110 120 PFNLVPHVDN IETANSFAVT NAFCSQYSRG VFAIFGLYDK RSVHTLTSFC SALHISLITP 130 140 150 160 170 180 SFPTEGESQF VLQLRPSLRG ALLSLLDHYE WNCFVFLYDT DRGYSILQAI MEKAGQNGWH 190 200 210 220 230 240 VSAICVENFN DVSYRQLLEE LDRRQEKKFV IDCEIERLQN ILEQIVSVGK HVKGYHYIIA 250 260 270 280 290 300 NLGFKDISLE RFIHGGANVT GFQLVDFNTP MVIKLMDRWK KLDQREYPGS ETPPKYTSAL 310 320 330 340 350 360 TYDGVLVMAE TFRSLRRQKI DISRRGNAGD CLANPAAPWG QGIDMERTLK QVRIQGLTGN 370 380 390 400 410 420 VQFDHYGRRV NYTMDVFELK STGPRKVGYW NDMDKLVLIQ DVPTLGNDTA AIENRTVVVT 430 440 450 460 470 480 TIMESPYVMY KKNHEMFEGN DKYEGYCVDL ASEIAKHIGI KYKIAIVPDG KYGARDADTK 490 500 510 520 530 540 IWNGMVGELV YGKAEIAIAP LTITLVREEV IDFSKPFMSL GISIMIKKPQ KSKPGVFSFL 550 560 570 580 590 600 DPLAYEIWMC IVFAYIGVSV VLFLVSRFSP YEWHTEEPED GKEGPSDQPP NEFGIFNSLW 610 620 630 640 650 660 FSLGAFMQQG CDISPRSLSG RIVGGVWWFF TLIIISSYTA NLAAFLTVER MVSPIESAED 670 680 690 700 710 720 LAKQTEIAYG TLDSGSTKEF FRRSKIAVYE KMWTYMRSAE PSVFTRTTAE GVARVRKSKG 730 740 750 760 770 780 KFAFLLESTM NEYIEQRKPC DTMKVGGNLD SKGYGVATPK GSSLRTPVNL AVLKLSEAGV 790 800 810 820 830 840 LDKLKNKWWY DKGECGPKDS GSKDKTSALS LSNVAGVFYI LVGGLGLAML VALIEFCYKS 850 860 870 880 890 900 RAEAKRMKLT FSEAIRNKAR LSITGSVGEN GRVLTPDCPK AVHTGTAIRQ SSGLAVIASD LP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression and pharmacological characterization of a human glutamate receptor: hGluR4." Fletcher E.J., Nutt S.L., Hoo K.H., Elliott C.E., Korczak B., McWhinnie E.A., Kamboj R.K. Recept. Channels 3:21-31(1995) [PubMed: 8589990] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"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: 16554811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins." Kato A.S., Gill M.B., Ho M.T., Yu H., Tu Y., Siuda E.R., Wang H., Qian Y.W., Nisenbaum E.S., Tomita S., Bredt D.S. Neuron 68:1082-1096(2010) [PubMed: 21172611] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U16129 mRNA. Translation: AAA95962.1. AP000641 Genomic DNA. No translation available. AP000673 Genomic DNA. No translation available. AP000813 Genomic DNA. No translation available. AP001561 Genomic DNA. No translation available.
IPI	IPI00007632.
RefSeq	NP_000820.3. NM_000829.3.
UniGene	Hs.503743.
3D structure databases
ProteinModelPortal	P48058.
SMR	P48058. Positions 25-839.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-95403.
STRING	P48058.
PTM databases
PhosphoSite	P48058.
Polymorphism databases
DMDM	218512059.
Proteomic databases
PRIDE	P48058.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000282499; ENSP00000282499; ENSG00000152578.
GeneID	2893.
KEGG	hsa:2893.
Organism-specific databases
CTD	2893.
GeneCards	GC11P105514.
H-InvDB	HIX0026176.
HGNC	HGNC:4574. GRIA4.
MIM	138246. gene.
neXtProt	NX_P48058.
PharmGKB	PA28969.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11728.
HOGENOM	HBG381523.
HOVERGEN	HBG051839.
InParanoid	P48058.
OMA	KAVHTGT.
OrthoDB	EOG4DBTD0.
PhylomeDB	P48058.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	P48058.
Bgee	P48058.
CleanEx	HS_GRIA4.
Genevestigator	P48058.
Family and domain databases
InterPro	IPR001828. ANF_lig-bd_rcpt. IPR019594. Glu_rcpt_Glu/Gly-bd. IPR001320. Iontro_glu_rcpt. IPR001508. NMDA_rcpt. [Graphical view]
KO	K05200.
Pfam	PF01094. ANF_receptor. 1 hit. PF00060. Lig_chan. 1 hit. PF10613. Lig_chan-Glu_bd. 1 hit. [Graphical view]
PRINTS	PR00177. NMDARECEPTOR.
SMART	SM00918. Lig_chan-Glu_bd. 1 hit. SM00079. PBPe. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00142. L-Glutamic Acid.
SOURCE	Search...

Entry information

Entry name

GRIA4_HUMAN

Accession

Primary (citable) accession number: P48058

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	December 16, 2008
Last modified:	January 25, 2012
This is version 107 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.