P31424 (GRM5_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Metabotropic glutamate receptor 5
Short name=mGluR5

Gene names

Name:	Grm5
Synonyms:	Gprc1e, Mglur5

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1203 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for glutamate. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current.
Subunit structure	The PPXXF motif binds HOMER1, HOMER2 and HOMER3. Interacts with RYR1, RYR2, ITPR1, SHANK1 and SHANK3 By similarity. Interacts with SIAH1 and GRASP. Interacts with NCDN. Ref.3 Ref.4 Ref.5 Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Widely distributed in neuronal cells of the central nervous system.
Miscellaneous	Activated by quisqualate > glutamate > ibotenate > trans-1- aminocyclopentyl-1,3-dicarboxylate.
Sequence similarities	Belongs to the G-protein coupled receptor 3 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of MAPKKK activity Inferred from direct assay PubMed 15758184. Source: UniProtKB desensitization of G-protein coupled receptor protein signaling pathway Inferred from direct assay PubMed 12514208. Source: UniProtKB elevation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Traceable author statement PubMed 15758184. Source: UniProtKB learning Inferred from electronic annotation. Source: Compara locomotory behavior Inferred from electronic annotation. Source: Compara negative regulation of locomotion Inferred from direct assay PubMed 12189203. Source: RGD phosphatidylinositol-mediated signaling Traceable author statement PubMed 15758184. Source: UniProtKB positive regulation of long-term neuronal synaptic plasticity Inferred from direct assay PubMed 12740378. Source: RGD protein kinase C-activating G-protein coupled receptor signaling pathway Inferred from direct assay PubMed 12514208. Source: UniProtKB protein phosphorylation Inferred from direct assay PubMed 15758184. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from direct assay PubMed 12189203. Source: RGD synaptic transmission Inferred from mutant phenotype PubMed 12514208. Source: RGD
Cellular_component	astrocyte projection Inferred from direct assay PubMed 21753079. Source: RGD cytoplasm Inferred from electronic annotation. Source: Compara dendritic shaft Inferred from direct assay PubMed 18582438. Source: RGD integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic density Inferred from direct assay PubMed 18582438. Source: RGD postsynaptic membrane Traceable author statement PubMed 10936169. Source: UniProtKB
Molecular_function	G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW PDZ domain binding Traceable author statement PubMed 10936169. Source: UniProtKB PLC activating G-protein coupled glutamate receptor activity Traceable author statement PubMed 12514208PubMed 15758184. Source: UniProtKB calmodulin binding Traceable author statement PubMed 12021391. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ADORA2A	P29274	3	EBI-2902778,EBI-2902702	From a different organism.

Alternative products

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

Isoform 2 (identifier: P31424-1)

Also known as: 5b;

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 1 (identifier: P31424-2)

Also known as: 5a;

The sequence of this isoform differs from the canonical sequence as follows:
     876-907: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Chain

21 – 1203

1183

Metabotropic glutamate receptor 5

PRO_0000012933

Regions

Topological domain

22 – 578

557

Extracellular Potential

Transmembrane

579 – 601

23

Helical; Name=1; Potential

Topological domain

602 – 615

14

Cytoplasmic Potential

Transmembrane

616 – 636

21

Helical; Name=2; Potential

Topological domain

637 – 647

11

Extracellular Potential

Transmembrane

648 – 666

19

Helical; Name=3; Potential

Topological domain

667 – 692

26

Cytoplasmic Potential

Transmembrane

693 – 713

21

Helical; Name=4; Potential

Topological domain

714 – 736

23

Extracellular Potential

Transmembrane

737 – 758

22

Helical; Name=5; Potential

Topological domain

759 – 771

13

Cytoplasmic Potential

Transmembrane

772 – 794

23

Helical; Name=6; Potential

Topological domain

795 – 800

6

Extracellular Potential

Transmembrane

801 – 826

26

Helical; Name=7; Potential

Topological domain

827 – 1203

377

Cytoplasmic Potential

Amino acid modifications

Glycosylation

88

1

N-linked (GlcNAc...) Potential

Glycosylation

209

1

N-linked (GlcNAc...) Potential

Glycosylation

377

1

N-linked (GlcNAc...) Potential

Glycosylation

381

1

N-linked (GlcNAc...) Potential

Glycosylation

444

1

N-linked (GlcNAc...) Potential

Glycosylation

733

1

N-linked (GlcNAc...) Potential

Disulfide bond

57 ↔ 99

By similarity

Disulfide bond

240 ↔ 529

By similarity

Disulfide bond

364 ↔ 380

By similarity

Disulfide bond

418 ↔ 425

By similarity

Disulfide bond

510 ↔ 530

By similarity

Disulfide bond

514 ↔ 533

By similarity

Disulfide bond

536 ↔ 548

By similarity

Disulfide bond

551 ↔ 564

By similarity

Natural variations

Alternative sequence

876 – 907

32

Missing in isoform 1.

VSP_002031

Experimental info

Mutagenesis

1154

1

L → V: Normal binding to HOMER1. Ref.3

Mutagenesis

1156

1

P → K: Disrupts binding to HOMER1. Ref.3

Mutagenesis

1157

1

P → E: Disrupts binding to HOMER1. Ref.3

Mutagenesis

1157

1

P → L: Disrupts binding to HOMER1. Ref.3

Mutagenesis

1158

1

S → F: Normal binding to HOMER1. Ref.3

Mutagenesis

1159

1

P → A: Normal binding to HOMER1. Ref.3

Mutagenesis

1160

1

F → R: Disrupts binding to HOMER1.

Mutagenesis

1161

1

R → T: Normal binding to HOMER1. Ref.3

Secondary structure

1

.

.

.

1203

Helix Strand Turn

Details...

Turn

1158 – 1159

2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (5b) [UniParc]. Last modified November 1, 1995. Version 2. Checksum: 99CA51E9E11C1EA4	FASTA	1,203	131,885
	10 20 30 40 50 60 MVLLLILSVL LLKEDVRGSA QSSERRVVAH MPGDIIIGAL FSVHHQPTVD KVHERKCGAV 70 80 90 100 110 120 REQYGIQRVE AMLHTLERIN SDPTLLPNIT LGCEIRDSCW HSAVALEQSI EFIRDSLISS 130 140 150 160 170 180 EEEEGLVRCV DGSSSFRSKK PIVGVIGPGS SSVAIQVQNL LQLFNIPQIA YSATSMDLSD 190 200 210 220 230 240 KTLFKYFMRV VPSDAQQARA MVDIVKRYNW TYVSAVHTEG NYGESGMEAF KDMSAKEGIC 250 260 270 280 290 300 IAHSYKIYSN AGEQSFDKLL KKLRSHLPKA RVVACFCEGM TVRGLLMAMR RLGLAGEFLL 310 320 330 340 350 360 LGSDGWADRY DVTDGYQREA VGGITIKLQS PDVKWFDDYY LKLRPETNLR NPWFQEFWQH 370 380 390 400 410 420 RFQCRLEGFA QENSKYNKTC NSSLTLRTHH VQDSKMGFVI NAIYSMAYGL HNMQMSLCPG 430 440 450 460 470 480 YAGLCDAMKP IDGRKLLDSL MKTNFTGVSG DMILFDENGD SPGRYEIMNF KEMGKDYFDY 490 500 510 520 530 540 INVGSWDNGE LKMDDDEVWS KKNNIIRSVC SEPCEKGQIK VIRKGEVSCC WTCTPCKENE 550 560 570 580 590 600 YVFDEYTCKA CQLGSWPTDD LTGCDLIPVQ YLRWGDPEPI AAVVFACLGL LATLFVTVIF 610 620 630 640 650 660 IIYRDTPVVK SSSRELCYII LAGICLGYLC TFCLIAKPKQ IYCYLQRIGI GLSPAMSYSA 670 680 690 700 710 720 LVTKTNRIAR ILAGSKKKIC TKKPRFMSAC AQLVIAFILI CIQLGIIVAL FIMEPPDIMH 730 740 750 760 770 780 DYPSIREVYL ICNTTNLGVV TPLGYNGLLI LSCTFYAFKT RNVPANFNEA KYIAFTMYTT 790 800 810 820 830 840 CIIWLAFVPI YFGSNYKIIT MCFSVSLSAT VALGCMFVPK VYIILAKPER NVRSAFTTST 850 860 870 880 890 900 VVRMHVGDGK SSSAASRSSS LVNLWKRRGS SGETLRYKDR RLAQHKSEIE CFTPKGSMGN 910 920 930 940 950 960 GGRATMSSSN GKSVTWAQNE KSTRGQHLWQ RLSVHINKKE NPNQTAVIKP FPKSTENRGP 970 980 990 1000 1010 1020 GAAAGGGSGP GVAGAGNAGC TATGGPEPPD AGPKALYDVA EAEESFPAAA RPRSPSPIST 1030 1040 1050 1060 1070 1080 LSHLAGSAGR TDDDAPSLHS ETAARSSSSQ GSLMEQISSV VTRFTANISE LNSMMLSTAA 1090 1100 1110 1120 1130 1140 TPGPPGTPIC SSYLIPKEIQ LPTTMTTFAE IQPLPAIEVT GGAQGATGVS PAQETPTGAE 1150 1160 1170 1180 1190 1200 SAPGKPDLEE LVALTPPSPF RDSVDSGSTT PNSPVSESAL CIPSSPKYDT LIIRDYTQSS SSL
	Isoform 1 (5a) [UniParc]. Checksum: 8B43A7D33497C3AC	FASTA	1,171	128,290
	10 20 30 40 50 60 MVLLLILSVL LLKEDVRGSA QSSERRVVAH MPGDIIIGAL FSVHHQPTVD KVHERKCGAV 70 80 90 100 110 120 REQYGIQRVE AMLHTLERIN SDPTLLPNIT LGCEIRDSCW HSAVALEQSI EFIRDSLISS 130 140 150 160 170 180 EEEEGLVRCV DGSSSFRSKK PIVGVIGPGS SSVAIQVQNL LQLFNIPQIA YSATSMDLSD 190 200 210 220 230 240 KTLFKYFMRV VPSDAQQARA MVDIVKRYNW TYVSAVHTEG NYGESGMEAF KDMSAKEGIC 250 260 270 280 290 300 IAHSYKIYSN AGEQSFDKLL KKLRSHLPKA RVVACFCEGM TVRGLLMAMR RLGLAGEFLL 310 320 330 340 350 360 LGSDGWADRY DVTDGYQREA VGGITIKLQS PDVKWFDDYY LKLRPETNLR NPWFQEFWQH 370 380 390 400 410 420 RFQCRLEGFA QENSKYNKTC NSSLTLRTHH VQDSKMGFVI NAIYSMAYGL HNMQMSLCPG 430 440 450 460 470 480 YAGLCDAMKP IDGRKLLDSL MKTNFTGVSG DMILFDENGD SPGRYEIMNF KEMGKDYFDY 490 500 510 520 530 540 INVGSWDNGE LKMDDDEVWS KKNNIIRSVC SEPCEKGQIK VIRKGEVSCC WTCTPCKENE 550 560 570 580 590 600 YVFDEYTCKA CQLGSWPTDD LTGCDLIPVQ YLRWGDPEPI AAVVFACLGL LATLFVTVIF 610 620 630 640 650 660 IIYRDTPVVK SSSRELCYII LAGICLGYLC TFCLIAKPKQ IYCYLQRIGI GLSPAMSYSA 670 680 690 700 710 720 LVTKTNRIAR ILAGSKKKIC TKKPRFMSAC AQLVIAFILI CIQLGIIVAL FIMEPPDIMH 730 740 750 760 770 780 DYPSIREVYL ICNTTNLGVV TPLGYNGLLI LSCTFYAFKT RNVPANFNEA KYIAFTMYTT 790 800 810 820 830 840 CIIWLAFVPI YFGSNYKIIT MCFSVSLSAT VALGCMFVPK VYIILAKPER NVRSAFTTST 850 860 870 880 890 900 VVRMHVGDGK SSSAASRSSS LVNLWKRRGS SGETLSSNGK SVTWAQNEKS TRGQHLWQRL 910 920 930 940 950 960 SVHINKKENP NQTAVIKPFP KSTENRGPGA AAGGGSGPGV AGAGNAGCTA TGGPEPPDAG 970 980 990 1000 1010 1020 PKALYDVAEA EESFPAAARP RSPSPISTLS HLAGSAGRTD DDAPSLHSET AARSSSSQGS 1030 1040 1050 1060 1070 1080 LMEQISSVVT RFTANISELN SMMLSTAATP GPPGTPICSS YLIPKEIQLP TTMTTFAEIQ 1090 1100 1110 1120 1130 1140 PLPAIEVTGG AQGATGVSPA QETPTGAESA PGKPDLEELV ALTPPSPFRD SVDSGSTTPN 1150 1160 1170 SPVSESALCI PSSPKYDTLI IRDYTQSSSS L

References

[1]	"Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction." Abe T., Sugihara H., Nawa H., Shigemoto R., Mizuno N., Nakanishi S. J. Biol. Chem. 267:13361-13368(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"A variant of metabotropic glutamate receptor subtype 5: an evolutionally conserved insertion with no termination codon." Minakami R., Katsuki F., Sugiyama H. Biochem. Biophys. Res. Commun. 194:622-627(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 859-923, ALTERNATIVE SPLICING. Tissue: Brain.
[3]	"Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors." Tu J.C., Xiao B., Yuan J.P., Lanahan A.A., Leoffert K., Li M., Linden D.J., Worley P.F. Neuron 21:717-726(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HOMER1; HOMER2 AND HOMER3, MUTAGENESIS OF LEU-1154; PRO-1156; PRO-1157; SER-1158; PRO-1159 AND ARG-1161.
[4]	"Competitive interaction of seven in absentia homolog-1A and Ca2+/calmodulin with the cytoplasmic tail of group 1 metabotropic glutamate receptors." Ishikawa K., Nash S.R., Nishimune A., Neki A., Kaneko S., Nakanishi S. Genes Cells 4:381-390(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SIAH1.
[5]	"Norbin is an endogenous regulator of metabotropic glutamate receptor 5 signaling." Wang H., Westin L., Nong Y., Birnbaum S., Bendor J., Brismar H., Nestler E., Aperia A., Flajolet M., Greengard P. Science 326:1554-1557(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NCDN.
[6]	"Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition." Beneken J., Tu J.C., Xiao B., Nuriya M., Yuan J.P., Worley P.F., Leahy D.J. Neuron 26:143-154(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1155 IN COMPLEX WITH HOMER1.
[7]	"Tamalin, a PDZ domain-containing protein, links a protein complex formation of group 1 metabotropic glutamate receptors and the guanine nucleotide exchange factor cytohesins." Kitano J., Kimura K., Yamazaki Y., Soda T., Shigemoto R., Nakajima Y., Nakanishi S. J. Neurosci. 22:1280-1289(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRASP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D10891 mRNA. Translation: BAA01711.1.
S64315 mRNA. Translation: AAB27666.1.

IPI

IPI00212621.
IPI00231472.

PIR

A42916.
PN0549.

RefSeq

NP_058708.1. NM_017012.1.

UniGene

Rn.29972.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DDV	X-ray	1.90	B	1155-1160	[»]

ProteinModelPortal

P31424.

SMR

P31424. Positions 25-498.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41263N.

IntAct

P31424. 2 interactions.

MINT

MINT-235173.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P31424.

Proteomic databases

PaxDb

P31424.

PRIDE

P31424.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000022060; ENSRNOP00000022059; ENSRNOG00000016429.
ENSRNOT00000050639; ENSRNOP00000040016; ENSRNOG00000016429.

GeneID

24418.

KEGG

rno:24418.

UCSC

RGD:2746. rat.

Organism-specific databases

CTD

2915.

RGD

2746. Grm5.

Phylogenomic databases

eggNOG

NOG295200.

GeneTree

ENSGT00660000095505.

HOGENOM

HOG000218636.

HOVERGEN

HBG107965.

InParanoid

P31424.

KO

K04604.

OMA

LRPETNH.

OrthoDB

EOG476JZC.

Gene expression databases

ArrayExpress

P31424.

Genevestigator

P31424.

GermOnline

ENSRNOG00000016429. Rattus norvegicus.

Family and domain databases

InterPro

IPR001828. ANF_lig-bd_rcpt.
IPR000337. GPCR_3.
IPR011500. GPCR_3_9-Cys_dom.
IPR017978. GPCR_3_C.
IPR017979. GPCR_3_CS.
IPR000162. GPCR_3_mtglu_rcpt.
IPR000202. GPCR_3_mtglu_rcpt_5.
IPR019588. Metabotropic_Glu_rcpt_Homer-bd.
[Graphical view]

Pfam

PF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF10606. GluR_Homer-bdg. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]

PRINTS

PR00248. GPCRMGR.
PR01055. MTABOTROPC5R.
PR00593. MTABOTROPICR.

PROSITE

PS00979. G_PROTEIN_RECEP_F3_1. 1 hit.
PS00980. G_PROTEIN_RECEP_F3_2. 1 hit.
PS00981. G_PROTEIN_RECEP_F3_3. 1 hit.
PS50259. G_PROTEIN_RECEP_F3_4. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P31424.

ChEMBL

CHEMBL2564.

EvolutionaryTrace

P31424.

NextBio

603267.

Entry information

Entry name

GRM5_RAT

Accession

Primary (citable) accession number: P31424

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 128 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program