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Q14832 (GRM3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Metabotropic glutamate receptor 3

Short name=mGluR3
Gene names
Name:GRM3
Synonyms:GPRC1C, MGLUR3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length879 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1

Subunit structure

Interacts with GRASP By similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.1.

Tissue specificity

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

Sequence similarities

Belongs to the G-protein coupled receptor 3 family.

Sequence caution

The sequence AAD15616.1 differs from that shown. Reason: Erroneous initiation.

The sequence ABC47402.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence CAA54796.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processnegative regulation of adenylate cyclase activity

Traceable author statement Ref.1. Source: ProtInc

regulation of synaptic transmission

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentastrocyte projection

Inferred from electronic annotation. Source: Ensembl

axon

Inferred from electronic annotation. Source: Ensembl

dendritic spine

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic density

Inferred from electronic annotation. Source: Ensembl

postsynaptic membrane

Inferred from electronic annotation. Source: Ensembl

presynaptic membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionG-protein coupled receptor activity

Traceable author statement Ref.1. Source: UniProtKB

calcium channel regulator activity

Inferred from electronic annotation. Source: Ensembl

glutamate receptor activity

Traceable author statement Ref.1. Source: UniProtKB

group II metabotropic glutamate receptor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q14832-1)

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: Q14832-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 879857Metabotropic glutamate receptor 3
PRO_0000012927

Regions

Topological domain23 – 576554Extracellular Potential
Transmembrane577 – 59923Helical; Name=1; Potential
Topological domain600 – 61314Cytoplasmic Potential
Transmembrane614 – 63421Helical; Name=2; Potential
Topological domain635 – 64511Extracellular Potential
Transmembrane646 – 66419Helical; Name=3; Potential
Topological domain665 – 68824Cytoplasmic Potential
Transmembrane689 – 70921Helical; Name=4; Potential
Topological domain710 – 73425Extracellular Potential
Transmembrane735 – 75622Helical; Name=5; Potential
Topological domain757 – 76913Cytoplasmic Potential
Transmembrane770 – 79223Helical; Name=6; Potential
Topological domain793 – 80210Extracellular Potential
Transmembrane803 – 82826Helical; Name=7; Potential
Topological domain829 – 87951Cytoplasmic Potential
Region172 – 1743Glutamate binding By similarity

Sites

Binding site1511Glutamate By similarity
Binding site2221Glutamate By similarity
Binding site3011Glutamate By similarity
Binding site3891Glutamate By similarity

Amino acid modifications

Glycosylation2091N-linked (GlcNAc...) Potential
Glycosylation2921N-linked (GlcNAc...) Potential
Glycosylation4141N-linked (GlcNAc...) Potential
Glycosylation4391N-linked (GlcNAc...) Potential
Disulfide bond57 ↔ 99 Ref.5
Disulfide bond240 ↔ 527 By similarity
Disulfide bond361 ↔ 373 Ref.5
Disulfide bond412 ↔ 419 Ref.5
Disulfide bond509 ↔ 528 By similarity
Disulfide bond513 ↔ 531 By similarity
Disulfide bond534 ↔ 546 By similarity
Disulfide bond549 ↔ 562 By similarity

Natural variations

Alternative sequence442 – 53796APFNP…PCEPY → GADDNHVHLCQPEWLCGLGL FVCTQGSHHPVSTPEECCHT QTAPQQVQCQWNWDHILSVL CKHVCANGVQWAGSPRLHHL ISVIVNCSSVLVFLDC in isoform 2.
VSP_047679
Alternative sequence538 – 879342Missing in isoform 2.
VSP_047680
Natural variant4751G → D.
Corresponds to variant rs17161026 [ dbSNP | Ensembl ].
VAR_049274

Experimental info

Sequence conflict961L → F in AAH41407. Ref.4
Sequence conflict4461P → T in AAH22496. Ref.4
Sequence conflict5121P → A in AAH22496. Ref.4
Sequence conflict8561S → Y in AAH22496. Ref.4

Secondary structure

............................................................................ 879
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 27, 2005. Version 2.
Checksum: 7EB84521676E8304

FASTA87998,879
        10         20         30         40         50         60 
MKMLTRLQVL TLALFSKGFL LSLGDHNFLR REIKIEGDLV LGGLFPINEK GTGTEECGRI 

        70         80         90        100        110        120 
NEDRGIQRLE AMLFAIDEIN KDDYLLPGVK LGVHILDTCS RDTYALEQSL EFVRASLTKV 

       130        140        150        160        170        180 
DEAEYMCPDG SYAIQENIPL LIAGVIGGSY SSVSIQVANL LRLFQIPQIS YASTSAKLSD 

       190        200        210        220        230        240 
KSRYDYFART VPPDFYQAKA MAEILRFFNW TYVSTVASEG DYGETGIEAF EQEARLRNIC 

       250        260        270        280        290        300 
IATAEKVGRS NIRKSYDSVI RELLQKPNAR VVVLFMRSDD SRELIAAASR ANASFTWVAS 

       310        320        330        340        350        360 
DGWGAQESII KGSEHVAYGA ITLELASQPV RQFDRYFQSL NPYNNHRNPW FRDFWEQKFQ 

       370        380        390        400        410        420 
CSLQNKRNHR RVCDKHLAID SSNYEQESKI MFVVNAVYAM AHALHKMQRT LCPNTTKLCD 

       430        440        450        460        470        480 
AMKILDGKKL YKDYLLKINF TAPFNPNKDA DSIVKFDTFG DGMGRYNVFN FQNVGGKYSY 

       490        500        510        520        530        540 
LKVGHWAETL SLDVNSIHWS RNSVPTSQCS DPCAPNEMKN MQPGDVCCWI CIPCEPYEYL 

       550        560        570        580        590        600 
ADEFTCMDCG SGQWPTADLT GCYDLPEDYI RWEDAWAIGP VTIACLGFMC TCMVVTVFIK 

       610        620        630        640        650        660 
HNNTPLVKAS GRELCYILLF GVGLSYCMTF FFIAKPSPVI CALRRLGLGS SFAICYSALL 

       670        680        690        700        710        720 
TKTNCIARIF DGVKNGAQRP KFISPSSQVF ICLGLILVQI VMVSVWLILE APGTRRYTLA 

       730        740        750        760        770        780 
EKRETVILKC NVKDSSMLIS LTYDVILVIL CTVYAFKTRK CPENFNEAKF IGFTMYTTCI 

       790        800        810        820        830        840 
IWLAFLPIFY VTSSDYRVQT TTMCISVSLS GFVVLGCLFA PKVHIILFQP QKNVVTHRLH 

       850        860        870 
LNRFSVSGTG TTYSQSSAST YVPTVCNGRE VLDSTTSSL 

« Hide

Isoform 2 (GRM3Delta4) [UniParc].

Checksum: 47F5D3ED1DF5A9E1
Show »

FASTA53760,749

References

« Hide 'large scale' references
[1]"Molecular characterization and localization of human metabotropic glutamate receptor type 3."
Makoff A., Volpe F., Lelchuk R., Harrington K., Emson P.
Brain Res. Mol. Brain Res. 40:55-63(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Brain.
[2]"Alternative splicing of human metabotropic glutamate receptor 3."
Sartorius L.J., Nagappan G., Lipska B.K., Lu B., Sei Y., Ren-Patterson R., Li Z., Weinberger D.R., Harrison P.J.
J. Neurochem. 96:1139-1148(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
Tissue: Lymphoblast.
[3]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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).
Tissue: Brain.
[5]"Crystal structure of metabotropic glutamate receptor 3 precursor in presence of LY341495 antagonist."
Structural genomics consortium (SGC)
Submitted (JUL-2011) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.26 ANGSTROMS) OF 26-504 OF MUTANT SER-240, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_000831.2. NM_000840.2.
UniGeneHs.590575.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1S8Mmodel-A30-499[»]
3SM9X-ray2.26A26-504[»]
ProteinModelPortalQ14832.
SMRQ14832. Positions 28-567.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109170. 4 interactions.
STRING9606.ENSP00000355316.

Chemistry

BindingDBQ14832.
ChEMBLCHEMBL2888.
DrugBankDB00659. Acamprosate.
DB00184. Nicotine.
GuidetoPHARMACOLOGY291.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ14832.

Polymorphism databases

DMDM76803803.

Proteomic databases

PaxDbQ14832.
PRIDEQ14832.

Protocols and materials databases

DNASU2913.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000361669; ENSP00000355316; ENSG00000198822. [Q14832-1]
ENST00000394720; ENSP00000378209; ENSG00000198822.
ENST00000439827; ENSP00000398767; ENSG00000198822. [Q14832-2]
GeneID2913.
KEGGhsa:2913.
UCSCuc003uid.3. human. [Q14832-1]

Organism-specific databases

CTD2913.
GeneCardsGC07P086274.
HGNCHGNC:4595. GRM3.
HPAHPA045227.
MIM601115. gene.
neXtProtNX_Q14832.
PharmGKBPA28992.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG295200.
HOGENOMHOG000218635.
HOVERGENHBG107965.
InParanoidQ14832.
KOK04605.
OMACTCIVVT.
OrthoDBEOG7Z0JXG.
PhylomeDBQ14832.
TreeFamTF313240.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ14832.

Gene expression databases

ArrayExpressQ14832.
BgeeQ14832.
CleanExHS_GRM3.
GenevestigatorQ14832.

Family and domain databases

InterProIPR001828. 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]
PfamPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSPR00248. GPCRMGR.
PR01053. MTABOTROPC3R.
PR00593. MTABOTROPICR.
SUPFAMSSF53822. SSF53822. 1 hit.
PROSITEPS00979. 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]
ProtoNetSearch...

Other

GeneWikiMetabotropic_glutamate_receptor_3.
GenomeRNAi2913.
NextBio11547.
PROQ14832.
SOURCESearch...

Entry information

Entry nameGRM3_HUMAN
AccessionPrimary (citable) accession number: Q14832
Secondary accession number(s): Q2PNZ6 expand/collapse secondary AC list , Q75MV4, Q75N17, Q86YG6, Q8TBH9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 27, 2005
Last modified: April 16, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries