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Protein

Metabotropic glutamate receptor 3

Gene

GRM3

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

Functioni

G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei151GlutamateBy similarity1
Binding sitei222GlutamateBy similarity1
Binding sitei301GlutamateBy similarity1
Binding sitei389GlutamateBy similarity1

GO - Molecular functioni

  • calcium channel regulator activity Source: Ensembl
  • glutamate receptor activity Source: UniProtKB
  • G-protein coupled receptor activity Source: UniProtKB
  • group II metabotropic glutamate receptor activity Source: Ensembl

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:G66-33000-MONOMER.
ReactomeiR-HSA-418594. G alpha (i) signalling events.
R-HSA-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).
SignaLinkiQ14832.
SIGNORiQ14832.

Names & Taxonomyi

Protein namesi
Recommended name:
Metabotropic glutamate receptor 3
Short name:
mGluR3
Gene namesi
Name:GRM3
Synonyms:GPRC1C, MGLUR3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:4595. GRM3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 576ExtracellularSequence analysisAdd BLAST554
Transmembranei577 – 599Helical; Name=1Sequence analysisAdd BLAST23
Topological domaini600 – 613CytoplasmicSequence analysisAdd BLAST14
Transmembranei614 – 634Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini635 – 645ExtracellularSequence analysisAdd BLAST11
Transmembranei646 – 664Helical; Name=3Sequence analysisAdd BLAST19
Topological domaini665 – 688CytoplasmicSequence analysisAdd BLAST24
Transmembranei689 – 709Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini710 – 734ExtracellularSequence analysisAdd BLAST25
Transmembranei735 – 756Helical; Name=5Sequence analysisAdd BLAST22
Topological domaini757 – 769CytoplasmicSequence analysisAdd BLAST13
Transmembranei770 – 792Helical; Name=6Sequence analysisAdd BLAST23
Topological domaini793 – 802ExtracellularSequence analysis10
Transmembranei803 – 828Helical; Name=7Sequence analysisAdd BLAST26
Topological domaini829 – 879CytoplasmicSequence analysisAdd BLAST51

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi2913.
OpenTargetsiENSG00000198822.
PharmGKBiPA28992.

Chemistry databases

ChEMBLiCHEMBL2888.
GuidetoPHARMACOLOGYi291.

Polymorphism and mutation databases

BioMutaiGRM3.
DMDMi76803803.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000001292723 – 879Metabotropic glutamate receptor 3Add BLAST857

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi57 ↔ 991 Publication
Glycosylationi209N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi240 ↔ 527By similarity
Glycosylationi292N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi361 ↔ 3731 Publication
Disulfide bondi412 ↔ 4191 Publication
Glycosylationi414N-linked (GlcNAc...)Sequence analysis1
Glycosylationi439N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi509 ↔ 528By similarity
Disulfide bondi513 ↔ 531By similarity
Disulfide bondi534 ↔ 546By similarity
Disulfide bondi549 ↔ 562By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ14832.
PeptideAtlasiQ14832.
PRIDEiQ14832.

PTM databases

iPTMnetiQ14832.
PhosphoSitePlusiQ14832.

Expressioni

Tissue specificityi

Detected in brain cortex, thalamus, subthalamic nucleus, substantia nigra, hypothalamus, hippocampus, corpus callosum, caudate nucleus and amygdala.1 Publication

Gene expression databases

BgeeiENSG00000198822.
CleanExiHS_GRM3.
ExpressionAtlasiQ14832. baseline and differential.
GenevisibleiQ14832. HS.

Interactioni

Subunit structurei

Interacts with GRASP.By similarity

Protein-protein interaction databases

BioGridi109170. 5 interactors.
STRINGi9606.ENSP00000355316.

Chemistry databases

BindingDBiQ14832.

Structurei

Secondary structure

1879
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi33 – 35Combined sources3
Beta strandi38 – 45Combined sources8
Beta strandi48 – 50Combined sources3
Beta strandi56 – 60Combined sources5
Turni62 – 65Combined sources4
Helixi66 – 81Combined sources16
Beta strandi83 – 86Combined sources4
Beta strandi91 – 97Combined sources7
Helixi102 – 114Combined sources13
Beta strandi142 – 146Combined sources5
Helixi151 – 161Combined sources11
Helixi162 – 164Combined sources3
Beta strandi168 – 172Combined sources5
Helixi176 – 179Combined sources4
Turni181 – 186Combined sources6
Beta strandi187 – 191Combined sources5
Helixi195 – 207Combined sources13
Beta strandi212 – 220Combined sources9
Helixi221 – 235Combined sources15
Turni236 – 238Combined sources3
Beta strandi240 – 247Combined sources8
Helixi253 – 264Combined sources12
Beta strandi271 – 275Combined sources5
Helixi278 – 290Combined sources13
Beta strandi296 – 299Combined sources4
Turni301 – 305Combined sources5
Helixi307 – 310Combined sources4
Turni314 – 319Combined sources6
Beta strandi321 – 325Combined sources5
Helixi331 – 338Combined sources8
Turni342 – 344Combined sources3
Helixi351 – 359Combined sources9
Turni381 – 383Combined sources3
Helixi390 – 411Combined sources22
Helixi420 – 423Combined sources4
Helixi427 – 433Combined sources7
Helixi435 – 437Combined sources3
Beta strandi438 – 440Combined sources3
Helixi450 – 452Combined sources3
Beta strandi453 – 455Combined sources3
Beta strandi466 – 476Combined sources11
Beta strandi478 – 492Combined sources15
Helixi494 – 496Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1S8Mmodel-A30-499[»]
3SM9X-ray2.26A26-504[»]
4XARX-ray2.26A2-508[»]
5CNKX-ray3.15A/B/C2-507[»]
5CNMX-ray2.84A2-507[»]
ProteinModelPortaliQ14832.
SMRiQ14832.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni172 – 174Glutamate bindingBy similarity3

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1056. Eukaryota.
ENOG410XR6W. LUCA.
GeneTreeiENSGT00760000118884.
HOGENOMiHOG000218635.
HOVERGENiHBG107965.
InParanoidiQ14832.
KOiK04605.
OMAiCTCIVVT.
OrthoDBiEOG091G177R.
PhylomeDBiQ14832.
TreeFamiTF313240.

Family and domain databases

InterProiIPR001828. 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.
IPR001234. GPCR_3_mtglu_rcpt_3.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSiPR00248. GPCRMGR.
PR01053. MTABOTROPC3R.
PR00593. MTABOTROPICR.
SUPFAMiSSF53822. SSF53822. 1 hit.
PROSITEiPS00979. 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]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: Q14832-1) [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
MKMLTRLQVL TLALFSKGFL LSLGDHNFLR REIKIEGDLV LGGLFPINEK
60 70 80 90 100
GTGTEECGRI NEDRGIQRLE AMLFAIDEIN KDDYLLPGVK LGVHILDTCS
110 120 130 140 150
RDTYALEQSL EFVRASLTKV DEAEYMCPDG SYAIQENIPL LIAGVIGGSY
160 170 180 190 200
SSVSIQVANL LRLFQIPQIS YASTSAKLSD KSRYDYFART VPPDFYQAKA
210 220 230 240 250
MAEILRFFNW TYVSTVASEG DYGETGIEAF EQEARLRNIC IATAEKVGRS
260 270 280 290 300
NIRKSYDSVI RELLQKPNAR VVVLFMRSDD SRELIAAASR ANASFTWVAS
310 320 330 340 350
DGWGAQESII KGSEHVAYGA ITLELASQPV RQFDRYFQSL NPYNNHRNPW
360 370 380 390 400
FRDFWEQKFQ CSLQNKRNHR RVCDKHLAID SSNYEQESKI MFVVNAVYAM
410 420 430 440 450
AHALHKMQRT LCPNTTKLCD AMKILDGKKL YKDYLLKINF TAPFNPNKDA
460 470 480 490 500
DSIVKFDTFG DGMGRYNVFN FQNVGGKYSY LKVGHWAETL SLDVNSIHWS
510 520 530 540 550
RNSVPTSQCS DPCAPNEMKN MQPGDVCCWI CIPCEPYEYL ADEFTCMDCG
560 570 580 590 600
SGQWPTADLT GCYDLPEDYI RWEDAWAIGP VTIACLGFMC TCMVVTVFIK
610 620 630 640 650
HNNTPLVKAS GRELCYILLF GVGLSYCMTF FFIAKPSPVI CALRRLGLGS
660 670 680 690 700
SFAICYSALL TKTNCIARIF DGVKNGAQRP KFISPSSQVF ICLGLILVQI
710 720 730 740 750
VMVSVWLILE APGTRRYTLA EKRETVILKC NVKDSSMLIS LTYDVILVIL
760 770 780 790 800
CTVYAFKTRK CPENFNEAKF IGFTMYTTCI IWLAFLPIFY VTSSDYRVQT
810 820 830 840 850
TTMCISVSLS GFVVLGCLFA PKVHIILFQP QKNVVTHRLH LNRFSVSGTG
860 870
TTYSQSSAST YVPTVCNGRE VLDSTTSSL
Length:879
Mass (Da):98,879
Last modified:September 27, 2005 - v2
Checksum:i7EB84521676E8304
GO
Isoform 2 (identifier: Q14832-2) [UniParc]FASTAAdd to basket
Also known as: GRM3Delta4

The sequence of this isoform differs from the canonical sequence as follows:
     442-537: APFNPNKDAD...CWICIPCEPY → GADDNHVHLC...CSSVLVFLDC
     538-879: Missing.

Note: Appears to be membrane-associated, despite the absence of the seven-transmembrane domain.
Show »
Length:537
Mass (Da):60,749
Checksum:i47F5D3ED1DF5A9E1
GO

Sequence cautioni

The sequence AAD15616 differs from that shown. Reason: Erroneous initiation.Curated
The sequence ABC47402 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAA54796 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti96L → F in AAH41407 (PubMed:15489334).Curated1
Sequence conflicti446P → T in AAH22496 (PubMed:15489334).Curated1
Sequence conflicti512P → A in AAH22496 (PubMed:15489334).Curated1
Sequence conflicti856S → Y in AAH22496 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049274475G → D.Corresponds to variant rs17161026dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047679442 – 537APFNP…PCEPY → GADDNHVHLCQPEWLCGLGL FVCTQGSHHPVSTPEECCHT QTAPQQVQCQWNWDHILSVL CKHVCANGVQWAGSPRLHHL ISVIVNCSSVLVFLDC in isoform 2. 1 PublicationAdd BLAST96
Alternative sequenceiVSP_047680538 – 879Missing in isoform 2. 1 PublicationAdd BLAST342

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X77748 mRNA. Translation: CAA54796.1. Different initiation.
DQ315361 mRNA. Translation: ABC47402.1. Different initiation.
AC004829 Genomic DNA. No translation available.
AC005009 Genomic DNA. Translation: AAD15616.1. Different initiation.
AC002081 Genomic DNA. Translation: AAC60379.2.
BC022496 mRNA. Translation: AAH22496.2.
BC041407 mRNA. Translation: AAH41407.1.
CCDSiCCDS5600.1. [Q14832-1]
RefSeqiNP_000831.2. NM_000840.2. [Q14832-1]
XP_011514390.1. XM_011516088.1. [Q14832-2]
UniGeneiHs.590575.

Genome annotation databases

EnsembliENST00000361669; ENSP00000355316; ENSG00000198822. [Q14832-1]
ENST00000439827; ENSP00000398767; ENSG00000198822. [Q14832-2]
GeneIDi2913.
KEGGihsa:2913.
UCSCiuc003uid.4. human. [Q14832-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X77748 mRNA. Translation: CAA54796.1. Different initiation.
DQ315361 mRNA. Translation: ABC47402.1. Different initiation.
AC004829 Genomic DNA. No translation available.
AC005009 Genomic DNA. Translation: AAD15616.1. Different initiation.
AC002081 Genomic DNA. Translation: AAC60379.2.
BC022496 mRNA. Translation: AAH22496.2.
BC041407 mRNA. Translation: AAH41407.1.
CCDSiCCDS5600.1. [Q14832-1]
RefSeqiNP_000831.2. NM_000840.2. [Q14832-1]
XP_011514390.1. XM_011516088.1. [Q14832-2]
UniGeneiHs.590575.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1S8Mmodel-A30-499[»]
3SM9X-ray2.26A26-504[»]
4XARX-ray2.26A2-508[»]
5CNKX-ray3.15A/B/C2-507[»]
5CNMX-ray2.84A2-507[»]
ProteinModelPortaliQ14832.
SMRiQ14832.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109170. 5 interactors.
STRINGi9606.ENSP00000355316.

Chemistry databases

BindingDBiQ14832.
ChEMBLiCHEMBL2888.
GuidetoPHARMACOLOGYi291.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ14832.
PhosphoSitePlusiQ14832.

Polymorphism and mutation databases

BioMutaiGRM3.
DMDMi76803803.

Proteomic databases

PaxDbiQ14832.
PeptideAtlasiQ14832.
PRIDEiQ14832.

Protocols and materials databases

DNASUi2913.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361669; ENSP00000355316; ENSG00000198822. [Q14832-1]
ENST00000439827; ENSP00000398767; ENSG00000198822. [Q14832-2]
GeneIDi2913.
KEGGihsa:2913.
UCSCiuc003uid.4. human. [Q14832-1]

Organism-specific databases

CTDi2913.
DisGeNETi2913.
GeneCardsiGRM3.
HGNCiHGNC:4595. GRM3.
MIMi601115. gene.
neXtProtiNX_Q14832.
OpenTargetsiENSG00000198822.
PharmGKBiPA28992.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1056. Eukaryota.
ENOG410XR6W. LUCA.
GeneTreeiENSGT00760000118884.
HOGENOMiHOG000218635.
HOVERGENiHBG107965.
InParanoidiQ14832.
KOiK04605.
OMAiCTCIVVT.
OrthoDBiEOG091G177R.
PhylomeDBiQ14832.
TreeFamiTF313240.

Enzyme and pathway databases

BioCyciZFISH:G66-33000-MONOMER.
ReactomeiR-HSA-418594. G alpha (i) signalling events.
R-HSA-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).
SignaLinkiQ14832.
SIGNORiQ14832.

Miscellaneous databases

ChiTaRSiGRM3. human.
GeneWikiiMetabotropic_glutamate_receptor_3.
GenomeRNAii2913.
PROiQ14832.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198822.
CleanExiHS_GRM3.
ExpressionAtlasiQ14832. baseline and differential.
GenevisibleiQ14832. HS.

Family and domain databases

InterProiIPR001828. 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.
IPR001234. GPCR_3_mtglu_rcpt_3.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSiPR00248. GPCRMGR.
PR01053. MTABOTROPC3R.
PR00593. MTABOTROPICR.
SUPFAMiSSF53822. SSF53822. 1 hit.
PROSITEiPS00979. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiGRM3_HUMAN
AccessioniPrimary (citable) accession number: Q14832
Secondary accession number(s): Q2PNZ6
, Q75MV4, Q75N17, Q86YG6, Q8TBH9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 27, 2005
Last modified: November 2, 2016
This is version 152 of the entry and version 2 of the sequence. [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

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.