P41594 (GRM5_HUMAN) 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

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	1212 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 SIAH1, RYR1, RYR2, ITPR1, SHANK1, SHANK3 and GRASP. Interacts with NCDN By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein.
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 electronic annotation. Source: Compara desensitization of G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: Compara learning Inferred from electronic annotation. Source: Compara locomotory behavior Inferred from electronic annotation. Source: Compara negative regulation of locomotion Inferred from electronic annotation. Source: Compara phospholipase C-activating G-protein coupled glutamate receptor signaling pathway Traceable author statement Ref.1. Source: ProtInc positive regulation of long-term neuronal synaptic plasticity Inferred from electronic annotation. Source: Compara protein kinase C-activating G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara protein phosphorylation Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara dendritic shaft Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc postsynaptic density Inferred from electronic annotation. Source: Compara
Molecular_function	G-protein coupled receptor activity Traceable author statement Ref.1. Source: UniProtKB glutamate receptor activity Traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 2 (identifier: P41594-1)

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: P41594-2)

Also known as: 5a;

The sequence of this isoform differs from the canonical sequence as follows:
     877-908: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Chain

21 – 1212

1192

Metabotropic glutamate receptor 5

PRO_0000012932

Regions

Topological domain

22 – 579

558

Extracellular Potential

Transmembrane

580 – 602

23

Helical; Name=1; Potential

Topological domain

603 – 616

14

Cytoplasmic Potential

Transmembrane

617 – 637

21

Helical; Name=2; Potential

Topological domain

638 – 648

11

Extracellular Potential

Transmembrane

649 – 667

19

Helical; Name=3; Potential

Topological domain

668 – 693

26

Cytoplasmic Potential

Transmembrane

694 – 714

21

Helical; Name=4; Potential

Topological domain

715 – 737

23

Extracellular Potential

Transmembrane

738 – 759

22

Helical; Name=5; Potential

Topological domain

760 – 772

13

Cytoplasmic Potential

Transmembrane

773 – 795

23

Helical; Name=6; Potential

Topological domain

796 – 801

6

Extracellular Potential

Transmembrane

802 – 827

26

Helical; Name=7; Potential

Topological domain

828 – 1212

385

Cytoplasmic Potential

Amino acid modifications

Glycosylation

88

1

N-linked (GlcNAc...) Potential

Glycosylation

210

1

N-linked (GlcNAc...) Potential

Glycosylation

378

1

N-linked (GlcNAc...) Potential

Glycosylation

382

1

N-linked (GlcNAc...) Potential

Glycosylation

445

1

N-linked (GlcNAc...) Potential

Glycosylation

734

1

N-linked (GlcNAc...) Potential

Disulfide bond

57 ↔ 99

By similarity

Disulfide bond

241 ↔ 530

By similarity

Disulfide bond

365 ↔ 381

By similarity

Disulfide bond

419 ↔ 426

By similarity

Disulfide bond

511 ↔ 531

By similarity

Disulfide bond

515 ↔ 534

By similarity

Disulfide bond

537 ↔ 549

By similarity

Disulfide bond

552 ↔ 565

By similarity

Natural variations

Alternative sequence

877 – 908

32

Missing in isoform 1.

VSP_002030

Secondary structure

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1212

Helix Strand Turn

Details...

Beta strand

29 – 31

3

Beta strand

34 – 41

8

Beta strand

49 – 51

3

Turn

52 – 55

4

Turn

62 – 65

4

Helix

66 – 81

16

Beta strand

91 – 97

7

Helix

102 – 112

11

Beta strand

143 – 147

5

Helix

152 – 162

11

Helix

163 – 165

3

Beta strand

169 – 173

5

Helix

177 – 180

4

Turn

182 – 184

3

Beta strand

188 – 192

5

Helix

195 – 208

14

Beta strand

213 – 219

7

Helix

222 – 235

14

Turn

236 – 239

4

Beta strand

241 – 248

8

Helix

254 – 267

14

Turn

268 – 270

3

Beta strand

273 – 277

5

Helix

280 – 293

14

Beta strand

300 – 303

4

Turn

307 – 309

3

Helix

311 – 314

4

Helix

318 – 321

4

Beta strand

325 – 329

5

Helix

335 – 342

8

Turn

346 – 348

3

Helix

355 – 363

9

Turn

387 – 390

4

Helix

397 – 418

22

Helix

427 – 429

3

Helix

434 – 441

8

Beta strand

445 – 447

3

Beta strand

449 – 451

3

Beta strand

453 – 455

3

Beta strand

466 – 475

10

Beta strand

479 – 488

10

Beta strand

491 – 494

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (5b) [UniParc]. Last modified October 1, 1996. Version 2. Checksum: A3C73606681C6A25	FASTA	1,212	132,469
	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 DGSSSSFRSK KPIVGVIGPG SSSVAIQVQN LLQLFNIPQI AYSATSMDLS 190 200 210 220 230 240 DKTLFKYFMR VVPSDAQQAR AMVDIVKRYN WTYVSAVHTE GNYGESGMEA FKDMSAKEGI 250 260 270 280 290 300 CIAHSYKIYS NAGEQSFDKL LKKLTSHLPK ARVVACFCEG MTVRGLLMAM RRLGLAGEFL 310 320 330 340 350 360 LLGSDGWADR YDVTDGYQRE AVGGITIKLQ SPDVKWFDDY YLKLRPETNH RNPWFQEFWQ 370 380 390 400 410 420 HRFQCRLEGF PQENSKYNKT CNSSLTLKTH HVQDSKMGFV INAIYSMAYG LHNMQMSLCP 430 440 450 460 470 480 GYAGLCDAMK PIDGRKLLES LMKTNFTGVS GDTILFDENG DSPGRYEIMN FKEMGKDYFD 490 500 510 520 530 540 YINVGSWDNG ELKMDDDEVW SKKSNIIRSV CSEPCEKGQI KVIRKGEVSC CWTCTPCKEN 550 560 570 580 590 600 EYVFDEYTCK ACQLGSWPTD DLTGCDLIPV QYLRWGDPEP IAAVVFACLG LLATLFVTVV 610 620 630 640 650 660 FIIYRDTPVV KSSSRELCYI ILAGICLGYL CTFCLIAKPK QIYCYLQRIG IGLSPAMSYS 670 680 690 700 710 720 ALVTKTNRIA RILAGSKKKI CTKKPRFMSA CAQLVIAFIL ICIQLGIIVA LFIMEPPDIM 730 740 750 760 770 780 HDYPSIREVY LICNTTNLGV VTPLGYNGLL ILSCTFYAFK TRNVPANFNE AKYIAFTMYT 790 800 810 820 830 840 TCIIWLAFVP IYFGSNYKII TMCFSVSLSA TVALGCMFVP KVYIILAKPE RNVRSAFTTS 850 860 870 880 890 900 TVVRMHVGDG KSSSAASRSS SLVNLWKRRG SSGETLRYKD RRLAQHKSEI ECFTPKGSMG 910 920 930 940 950 960 NGGRATMSSS NGKSVTWAQN EKSSRGQHLW QRLSIHINKK ENPNQTAVIK PFPKSTESRG 970 980 990 1000 1010 1020 LGAGAGAGGS AGGVGATGGA GCAGAGPGGP ESPDAGPKAL YDVAEAEEHF PAPARPRSPS 1030 1040 1050 1060 1070 1080 PISTLSHRAG SASRTDDDVP SLHSEPVARS SSSQGSLMEQ ISSVVTRFTA NISELNSMML 1090 1100 1110 1120 1130 1140 STAAPSPGVG APLCSSYLIP KEIQLPTTMT TFAEIQPLPA IEVTGGAQPA AGAQAAGDAA 1150 1160 1170 1180 1190 1200 RESPAAGPEA AAAKPDLEEL VALTPPSPFR DSVDSGSTTP NSPVSESALC IPSSPKYDTL 1210 IIRDYTQSSS SL
	Isoform 1 (5a) [UniParc]. Checksum: 3DBACB2E8B341647	FASTA	1,180	128,874
	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 DGSSSSFRSK KPIVGVIGPG SSSVAIQVQN LLQLFNIPQI AYSATSMDLS 190 200 210 220 230 240 DKTLFKYFMR VVPSDAQQAR AMVDIVKRYN WTYVSAVHTE GNYGESGMEA FKDMSAKEGI 250 260 270 280 290 300 CIAHSYKIYS NAGEQSFDKL LKKLTSHLPK ARVVACFCEG MTVRGLLMAM RRLGLAGEFL 310 320 330 340 350 360 LLGSDGWADR YDVTDGYQRE AVGGITIKLQ SPDVKWFDDY YLKLRPETNH RNPWFQEFWQ 370 380 390 400 410 420 HRFQCRLEGF PQENSKYNKT CNSSLTLKTH HVQDSKMGFV INAIYSMAYG LHNMQMSLCP 430 440 450 460 470 480 GYAGLCDAMK PIDGRKLLES LMKTNFTGVS GDTILFDENG DSPGRYEIMN FKEMGKDYFD 490 500 510 520 530 540 YINVGSWDNG ELKMDDDEVW SKKSNIIRSV CSEPCEKGQI KVIRKGEVSC CWTCTPCKEN 550 560 570 580 590 600 EYVFDEYTCK ACQLGSWPTD DLTGCDLIPV QYLRWGDPEP IAAVVFACLG LLATLFVTVV 610 620 630 640 650 660 FIIYRDTPVV KSSSRELCYI ILAGICLGYL CTFCLIAKPK QIYCYLQRIG IGLSPAMSYS 670 680 690 700 710 720 ALVTKTNRIA RILAGSKKKI CTKKPRFMSA CAQLVIAFIL ICIQLGIIVA LFIMEPPDIM 730 740 750 760 770 780 HDYPSIREVY LICNTTNLGV VTPLGYNGLL ILSCTFYAFK TRNVPANFNE AKYIAFTMYT 790 800 810 820 830 840 TCIIWLAFVP IYFGSNYKII TMCFSVSLSA TVALGCMFVP KVYIILAKPE RNVRSAFTTS 850 860 870 880 890 900 TVVRMHVGDG KSSSAASRSS SLVNLWKRRG SSGETLSSNG KSVTWAQNEK SSRGQHLWQR 910 920 930 940 950 960 LSIHINKKEN PNQTAVIKPF PKSTESRGLG AGAGAGGSAG GVGATGGAGC AGAGPGGPES 970 980 990 1000 1010 1020 PDAGPKALYD VAEAEEHFPA PARPRSPSPI STLSHRAGSA SRTDDDVPSL HSEPVARSSS 1030 1040 1050 1060 1070 1080 SQGSLMEQIS SVVTRFTANI SELNSMMLST AAPSPGVGAP LCSSYLIPKE IQLPTTMTTF 1090 1100 1110 1120 1130 1140 AEIQPLPAIE VTGGAQPAAG AQAAGDAARE SPAAGPEAAA AKPDLEELVA LTPPSPFRDS 1150 1160 1170 1180 VDSGSTTPNS PVSESALCIP SSPKYDTLII RDYTQSSSSL

References

[1]	"Molecular cloning and the functional expression of two isoforms of human metabotropic glutamate receptor subtype 5." Minakami R., Katsuki F., Yamamoto T., Nakamura K., Sugiyama H. Biochem. Biophys. Res. Commun. 199:1136-1143(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	Katsuki F. Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"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 860-952. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D28538 mRNA. Translation: BAA05891.1.
D28539 mRNA. Translation: BAA05892.1.
S64316 mRNA. Translation: AAD13954.1.

IPI

IPI00220277.
IPI00296244.

PIR

JC2131.
JC2132.

RefSeq

NP_000833.1. NM_000842.3.
NP_001137303.1. NM_001143831.2.

UniGene

Hs.147361.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3LMK	X-ray	2.44	A/B	18-505	[»]

ProteinModelPortal

P41594.

SMR

P41594. Positions 26-569.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000306138.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P41594.

Polymorphism databases

DMDM

1709020.

Proteomic databases

PaxDb

P41594.

PRIDE

P41594.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000305432; ENSP00000305905; ENSG00000168959.
ENST00000305447; ENSP00000306138; ENSG00000168959.
ENST00000418177; ENSP00000402912; ENSG00000168959.
ENST00000455756; ENSP00000405690; ENSG00000168959.

GeneID

2915.

KEGG

hsa:2915.

UCSC

uc001pcq.3. human.
uc009yvm.3. human.

Organism-specific databases

CTD

2915.

GeneCards

GC11M088237.

HGNC

HGNC:4597. GRM5.

HPA

HPA014096.

MIM

604102. gene.

neXtProt

NX_P41594.

PharmGKB

PA28994.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG295200.

HOGENOM

HOG000218636.

HOVERGEN

HBG107965.

InParanoid

P41594.

KO

K04604.

OMA

LRPETNH.

PhylomeDB

P41594.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P41594.

Bgee

P41594.

CleanEx

HS_GRM5.

Genevestigator

P41594.

GermOnline

ENSG00000168959. Homo sapiens.

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

P41594.

ChEMBL

CHEMBL3227.

ChiTaRS

GRM5. human.

DrugBank

DB00659. Acamprosate.

EvolutionaryTrace

P41594.

GenomeRNAi

2915.

NextBio

11555.

SOURCE

Search...

Entry information

Entry name

GRM5_HUMAN

Accession

Primary (citable) accession number: P41594

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 122 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.