RBCC

Full text data of GRM4

GRM4 (GPRC1D, MGLUR4) [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Metabotropic glutamate receptor 4; mGluR4; Flags: Precursor

hRBCD IPI00442030
IPI00442030 Hypothetical protein FLJ16766 Hypothetical protein FLJ16766 membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a integral membrane protein n/a found at its expected molecular weight found at molecular weight

UniProt Q14833
ID GRM4_HUMAN Reviewed; 912 AA.
AC Q14833; B3KVL9; B7Z1T9; B7Z1U6; F5GXM5; Q5SZ84; Q6ZMQ2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1997, sequence version 1.
DT 22-JAN-2014, entry version 122.
DE RecName: Full=Metabotropic glutamate receptor 4;
DE Short=mGluR4;
DE Flags: Precursor;
GN Name=GRM4; Synonyms=GPRC1D, MGLUR4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=8738157; DOI=10.1016/0169-328X(95)00321-I;
RA Makoff A., Lelchuk R., Oxer M., Harrington K., Emson P.;
RT "Molecular characterization and localization of human metabotropic
RT glutamate receptor type 4.";
RL Brain Res. Mol. Brain Res. 37:239-248(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=9473604; DOI=10.1016/S0169-328X(97)00277-5;
RA Wu S., Wright R.A., Rockey P.K., Burgett S.G., Arnold J.S.,
RA Rosteck P.R. Jr., Johnson B.G., Schoepp D.D., Belagaje R.M.;
RT "Group III human metabotropic glutamate receptors 4, 7 and 8:
RT molecular cloning, functional expression, and comparison of
RT pharmacological properties in RGT cells.";
RL Brain Res. Mol. Brain Res. 53:88-97(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=7617140; DOI=10.1016/0028-3908(94)00149-M;
RA Flor P.J., Lukic S., Rueegg D., Leonhardt T., Knoepfel T., Kuhn R.;
RT "Molecular cloning, functional expression and pharmacological
RT characterization of the human metabotropic glutamate receptor type
RT 4.";
RL Neuropharmacology 34:149-155(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 5).
RC TISSUE=Brain, and Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP VARIANT ILE-797.
RX PubMed=11525421; DOI=10.1097/00041444-200106000-00004;
RA Ohtsuki T., Toru M., Arinami T.;
RT "Mutation screening of the metabotropic glutamate receptor mGluR4
RT (GRM4) gene in patients with schizophrenia.";
RL Psychiatr. Genet. 11:79-83(2001).
CC -!- FUNCTION: G-protein coupled receptor for glutamate. Ligand binding
CC causes a conformation change that triggers signaling via guanine
CC nucleotide-binding proteins (G proteins) and modulates the
CC activity of down-stream effectors. Signaling inhibits adenylate
CC cyclase activity.
CC -!- SUBUNIT: Interacts with PICK1 (By similarity).
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q14833-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14833-2; Sequence=VSP_044740, VSP_044741;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q14833-3; Sequence=VSP_045218;
CC Name=4;
CC IsoId=Q14833-4; Sequence=VSP_046762;
CC Note=No experimental confirmation available;
CC Name=5;
CC IsoId=Q14833-5; Sequence=VSP_046761, VSP_046763;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Strongly expressed in the cerebellum.
CC Expressed at low levels in hippocampus, hypothalamus and thalamus.
CC No expression detected in liver.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family.
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DR EMBL; X80818; CAA56784.1; -; mRNA.
DR EMBL; U92457; AAB51762.1; -; mRNA.
DR EMBL; AK122982; BAG53831.1; -; mRNA.
DR EMBL; AK131536; BAD18673.1; -; mRNA.
DR EMBL; AK293913; BAH11625.1; -; mRNA.
DR EMBL; AK293949; BAH11632.1; -; mRNA.
DR EMBL; AL354740; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590403; CAI17348.1; -; Genomic_DNA.
DR RefSeq; NP_000832.1; NM_000841.3.
DR RefSeq; NP_001243738.1; NM_001256809.2.
DR RefSeq; NP_001243740.1; NM_001256811.2.
DR RefSeq; NP_001243741.1; NM_001256812.2.
DR RefSeq; NP_001243742.1; NM_001256813.2.
DR RefSeq; NP_001269776.1; NM_001282847.1.
DR UniGene; Hs.429018; -.
DR UniGene; Hs.736330; -.
DR ProteinModelPortal; Q14833; -.
DR SMR; Q14833; 38-577.
DR STRING; 9606.ENSP00000363296; -.
DR BindingDB; Q14833; -.
DR ChEMBL; CHEMBL2736; -.
DR DrugBank; DB00142; L-Glutamic Acid.
DR GuidetoPHARMACOLOGY; 292; -.
DR PhosphoSite; Q14833; -.
DR DMDM; 2495077; -.
DR PaxDb; Q14833; -.
DR PRIDE; Q14833; -.
DR DNASU; 2914; -.
DR Ensembl; ENST00000374177; ENSP00000363292; ENSG00000124493.
DR Ensembl; ENST00000374181; ENSP00000363296; ENSG00000124493.
DR Ensembl; ENST00000455714; ENSP00000398456; ENSG00000124493.
DR Ensembl; ENST00000535756; ENSP00000437925; ENSG00000124493.
DR Ensembl; ENST00000538487; ENSP00000440556; ENSG00000124493.
DR Ensembl; ENST00000544773; ENSP00000437730; ENSG00000124493.
DR GeneID; 2914; -.
DR KEGG; hsa:2914; -.
DR UCSC; uc003oiq.4; human.
DR CTD; 2914; -.
DR GeneCards; GC06M035230; -.
DR HGNC; HGNC:4596; GRM4.
DR HPA; CAB022096; -.
DR MIM; 604100; gene.
DR neXtProt; NX_Q14833; -.
DR PharmGKB; PA28993; -.
DR eggNOG; NOG295200; -.
DR HOGENOM; HOG000218635; -.
DR HOVERGEN; HBG107965; -.
DR InParanoid; Q14833; -.
DR KO; K04607; -.
DR OMA; GWGWWWA; -.
DR OrthoDB; EOG7Z0JXG; -.
DR PhylomeDB; Q14833; -.
DR Reactome; REACT_111102; Signal Transduction.
DR ChiTaRS; GRM4; human.
DR GeneWiki; Metabotropic_glutamate_receptor_4; -.
DR GenomeRNAi; 2914; -.
DR NextBio; 11551; -.
DR PRO; PR:Q14833; -.
DR ArrayExpress; Q14833; -.
DR Bgee; Q14833; -.
DR CleanEx; HS_GRM4; -.
DR Genevestigator; Q14833; -.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0043198; C:dendritic shaft; IEA:Ensembl.
DR GO; GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
DR GO; GO:0048787; C:presynaptic active zone membrane; IEA:Ensembl.
DR GO; GO:0043195; C:terminal bouton; IEA:Ensembl.
DR GO; GO:0004930; F:G-protein coupled receptor activity; IMP:UniProtKB.
DR GO; GO:0008066; F:glutamate receptor activity; IMP:UniProtKB.
DR GO; GO:0000187; P:activation of MAPK activity; IDA:UniProtKB.
DR GO; GO:0007196; P:adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007612; P:learning; IEA:Ensembl.
DR GO; GO:0007269; P:neurotransmitter secretion; TAS:UniProtKB.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; TAS:UniProtKB.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR000337; GPCR_3.
DR InterPro; IPR011500; GPCR_3_9-Cys_dom.
DR InterPro; IPR017978; GPCR_3_C.
DR InterPro; IPR017979; GPCR_3_CS.
DR InterPro; IPR000162; GPCR_3_mtglu_rcpt.
DR InterPro; IPR001786; GPCR_3_mtglu_rcpt_4.
DR InterPro; IPR028082; Peripla_BP_I.
DR Pfam; PF00003; 7tm_3; 1.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF07562; NCD3G; 1.
DR PRINTS; PR00248; GPCRMGR.
DR PRINTS; PR01054; MTABOTROPC4R.
DR PRINTS; PR00593; MTABOTROPICR.
DR SUPFAM; SSF53822; SSF53822; 1.
DR PROSITE; PS00979; G_PROTEIN_RECEP_F3_1; 1.
DR PROSITE; PS00980; G_PROTEIN_RECEP_F3_2; 1.
DR PROSITE; PS00981; G_PROTEIN_RECEP_F3_3; 1.
DR PROSITE; PS50259; G_PROTEIN_RECEP_F3_4; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Complete proteome;
KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane;
KW Polymorphism; Receptor; Reference proteome; Signal; Transducer;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1 32 Potential.
FT CHAIN 33 912 Metabotropic glutamate receptor 4.
FT /FTId=PRO_0000012930.
FT TOPO_DOM 33 587 Extracellular (Potential).
FT TRANSMEM 588 610 Helical; Name=1; (Potential).
FT TOPO_DOM 611 624 Cytoplasmic (Potential).
FT TRANSMEM 625 645 Helical; Name=2; (Potential).
FT TOPO_DOM 646 656 Extracellular (Potential).
FT TRANSMEM 657 675 Helical; Name=3; (Potential).
FT TOPO_DOM 676 699 Cytoplasmic (Potential).
FT TRANSMEM 700 720 Helical; Name=4; (Potential).
FT TOPO_DOM 721 750 Extracellular (Potential).
FT TRANSMEM 751 772 Helical; Name=5; (Potential).
FT TOPO_DOM 773 785 Cytoplasmic (Potential).
FT TRANSMEM 786 808 Helical; Name=6; (Potential).
FT TOPO_DOM 809 821 Extracellular (Potential).
FT TRANSMEM 822 847 Helical; Name=7; (Potential).
FT TOPO_DOM 848 912 Cytoplasmic (Potential).
FT REGION 180 182 Glutamate binding (By similarity).
FT BINDING 159 159 Glutamate (By similarity).
FT BINDING 230 230 Glutamate (By similarity).
FT BINDING 312 312 Glutamate (By similarity).
FT BINDING 405 405 Glutamate (By similarity).
FT CARBOHYD 98 98 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 301 301 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 454 454 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 484 484 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 569 569 N-linked (GlcNAc...) (Potential).
FT DISULFID 67 109 By similarity.
FT DISULFID 249 538 By similarity.
FT DISULFID 372 388 By similarity.
FT DISULFID 428 435 By similarity.
FT DISULFID 520 539 By similarity.
FT DISULFID 524 542 By similarity.
FT DISULFID 545 557 By similarity.
FT DISULFID 560 573 By similarity.
FT VAR_SEQ 1 173 MPGKRGLGWWWARLPLCLLLSLYGPWMPSSLGKPKGHPHMN
FT SIRIDGDITLGGLFPVHGRGSEGKPCGELKKEKGIHRLEAM
FT LFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTFV
FT QALIEKDGTEVRCGSGGPPIITKPERVVGVIGASGSSVSIM
FT VANILRLFK -> MPAWEPGVAASCGWRAPPCSPLRLCIAP
FT HPCTPPSSHQGNLTCRLPPRSFGFCRCVWVRTRGPSLPGEQ
FT VSLAAHESEGAAAQLGSSPEIDPRRPRCLLPESAQ (in
FT isoform 5).
FT /FTId=VSP_046761.
FT VAR_SEQ 1 172 MPGKRGLGWWWARLPLCLLLSLYGPWMPSSLGKPKGHPHMN
FT SIRIDGDITLGGLFPVHGRGSEGKPCGELKKEKGIHRLEAM
FT LFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTFV
FT QALIEKDGTEVRCGSGGPPIITKPERVVGVIGASGSSVSIM
FT VANILRLF -> MSC (in isoform 3).
FT /FTId=VSP_045218.
FT VAR_SEQ 1 172 MPGKRGLGWWWARLPLCLLLSLYGPWMPSSLGKPKGHPHMN
FT SIRIDGDITLGGLFPVHGRGSEGKPCGELKKEKGIHRLEAM
FT LFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTFV
FT QALIEKDGTEVRCGSGGPPIITKPERVVGVIGASGSSVSIM
FT VANILRLF -> MAVPLGAPCWASALPAWAPPGLPHRSLLT
FT RLLSQHVKPA (in isoform 4).
FT /FTId=VSP_046762.
FT VAR_SEQ 1 33 MPGKRGLGWWWARLPLCLLLSLYGPWMPSSLGK -> MVQT
FT LPKLFPHDGAKRKKRTLRTSGPCFGGGGQ (in isoform
FT 2).
FT /FTId=VSP_044740.
FT VAR_SEQ 34 173 Missing (in isoform 2).
FT /FTId=VSP_044741.
FT VAR_SEQ 343 390 GFDRYFSSRTLDNNRRNIWFAEFWEDNFHCKLSRHALKKGS
FT HVKKCTN -> D (in isoform 5).
FT /FTId=VSP_046763.
FT VARIANT 169 169 L -> F (in dbSNP:rs452752).
FT /FTId=VAR_049275.
FT VARIANT 797 797 V -> I.
FT /FTId=VAR_012992.
FT CONFLICT 449 449 Y -> H (in Ref. 4; BAH11632).
SQ SEQUENCE 912 AA; 101868 MW; 4A2F36E63A2EAF5A CRC64;
MPGKRGLGWW WARLPLCLLL SLYGPWMPSS LGKPKGHPHM NSIRIDGDIT LGGLFPVHGR
GSEGKPCGEL KKEKGIHRLE AMLFALDRIN NDPDLLPNIT LGARILDTCS RDTHALEQSL
TFVQALIEKD GTEVRCGSGG PPIITKPERV VGVIGASGSS VSIMVANILR LFKIPQISYA
STAPDLSDNS RYDFFSRVVP SDTYQAQAMV DIVRALKWNY VSTVASEGSY GESGVEAFIQ
KSREDGGVCI AQSVKIPREP KAGEFDKIIR RLLETSNARA VIIFANEDDI RRVLEAARRA
NQTGHFFWMG SDSWGSKIAP VLHLEEVAEG AVTILPKRMS VRGFDRYFSS RTLDNNRRNI
WFAEFWEDNF HCKLSRHALK KGSHVKKCTN RERIGQDSAY EQEGKVQFVI DAVYAMGHAL
HAMHRDLCPG RVGLCPRMDP VDGTQLLKYI RNVNFSGIAG NPVTFNENGD APGRYDIYQY
QLRNDSAEYK VIGSWTDHLH LRIERMHWPG SGQQLPRSIC SLPCQPGERK KTVKGMPCCW
HCEPCTGYQY QVDRYTCKTC PYDMRPTENR TGCRPIPIIK LEWGSPWAVL PLFLAVVGIA
ATLFVVITFV RYNDTPIVKA SGRELSYVLL AGIFLCYATT FLMIAEPDLG TCSLRRIFLG
LGMSISYAAL LTKTNRIYRI FEQGKRSVSA PRFISPASQL AITFSLISLQ LLGICVWFVV
DPSHSVVDFQ DQRTLDPRFA RGVLKCDISD LSLICLLGYS MLLMVTCTVY AIKTRGVPET
FNEAKPIGFT MYTTCIVWLA FIPIFFGTSQ SADKLYIQTT TLTVSVSLSA SVSLGMLYMP
KVYIILFHPE QNVPKRKRSL KAVVTAATMS NKFTQKGNFR PNGEAKSELC ENLEAPALAT
KQTYVTYTNH AI
//

MIM 604100
*RECORD*
*FIELD* NO
604100
*FIELD* TI
*604100 GLUTAMATE RECEPTOR, METABOTROPIC, 4; GRM4
;;MGLUR4
*FIELD* TX

DESCRIPTION
read more
L-glutamate is the major excitatory neurotransmitter in the central
nervous system and activates both ionotropic and metabotropic glutamate
receptors, such as GRM4. The metabotropic glutamate receptors (mGluRs),
which are G protein-coupled receptors, have been divided into 3 groups
on the basis of sequence homology, putative signal transduction
mechanisms, and pharmacologic properties. Group II and group III mGluRs
are linked to the inhibition of the cyclic AMP cascade, but differ in
their agonist selectivities. Group III agonists include
L-2-amino-4-phosphonobutyrate (L-AP4) and L-serine-O-phosphate (summary
by Wu et al., 1998).

CLONING

Using a PCR strategy with primers based on consensus regions of rat
mGluR1-5, Makoff et al. (1996) isolated partial cDNAs corresponding to
the human homologs of these genes. By probing a cerebellum library with
the partial human mGluR4 cDNA, the authors isolated additional mGluR4
cDNAs which between them contained the complete coding sequence for the
human protein. The predicted 912-amino acid human mGluR4 protein shares
90% identity with rat mGluR4. Northern blot analysis of human tissues
revealed that the approximately 5-kb mGluR4 mRNA was only expressed in
brain. In situ hybridization to brain tissues indicated that human
mGluR4 mRNA, like that of rat mGluR4, has a narrow distribution. In both
organisms, the highest level of expression was detected in the granule
cells of the cerebellum. Wu et al. (1998) isolated cDNAs encoding 3
human group III mGluRs, mGluR4, mGluR7 (604101) and mGluR8 (601116), and
compared the pharmacologic properties of these receptors.

By database analysis, Bjarnadottir et al. (2005) identified GRM4
orthologs in mouse and fish. The deduced mouse protein contains 912
amino acids.

GENE STRUCTURE

Bjarnadottir et al. (2005) determined that the GRM4 gene contains 7
exons.

MAPPING

Barbon et al. (2000) mapped the GRM4 gene to chromosome 6p21.3 by
radiation hybrid mapping.

Bjarnadottir et al. (2005) mapped the mouse Grm4 gene to chromosome 17.

ANIMAL MODEL

To provide a better understanding of the L-AP4 receptors, Pekhletski et
al. (1996) generated knockout mice lacking the mGluR4 gene. The mutant
mice did not display any gross motor abnormalities, impairments of
novelty-induced exploratory behaviors, or alterations in fine motor
coordination. However, they were deficient on the rotating rod
motor-learning test, suggesting that they may have an impaired ability
to learn complex motor tasks. Analysis of presynaptic short-term
synaptic plasticity at the parallel fiber-Purkinje cell synapse
demonstrated that paired-pulse facilitation and post-tetanic
potentiation were impaired in the mutant mice, although long-term
depression was unaffected. Pekhletski et al. (1996) concluded that an
important function of mGluR4 is to provide a presynaptic mechanism for
maintaining synaptic efficacy during repetitive activation, and that the
presence of mGluR4 at the parallel fiber-Purkinje cell synapse is
required for maintaining normal motor function. Gerlai et al. (1998)
found that mGluR4 mutant mice exhibited significantly accelerated
learning performance in a spatial reversal learning task. In a probe
trial administered 6 weeks posttraining, the mice showed impaired
spatial accuracy. These results suggested that mGluR4 mutant mice differ
in their ability to learn and integrate new spatial information into
previously formed memory traces and that their use of stored spatial
information is altered.

Fallarino et al. (2010) observed that mGluR4-null mice were markedly
vulnerable to experimental autoimmune encephalomyelitis (EAE), a mouse
model of multiple sclerosis (MS; 126200), and developed immune responses
dominated by IL17 (603149)-producing T helper (TH17) cells. MGluR4 was
constitutively expressed on dendritic cells isolated from wildtype mice.
Signaling through mGluR4 decreased commitment to the TH17 phenotype by
decreasing intracellular cAMP. Treatment of wildtype mice with a
selective mGluR4 enhancer increased EAE resistance and offered a
protective response via a shift toward regulatory CD4+ T cells. In
contrast, dendritic cells from mGluR4-null mice showed defective mGluR4
signaling with resultant bias toward the TH17 phenotype. The findings
provided evidence that glutamate acts at the interface between the
nervous and immune systems, with mGluR4 present on dendritic cells in
the central nervous system. Fallarino et al. (2010) suggested that the
high amounts of glutamate associated with neuroinflammation might
reflect a counterregulatory mechanism that is protective in nature by
decreasing activation of pathogenic IL17-producing T cells.

*FIELD* RF
1. Barbon, A.; Ferraboli, S.; Barlati, S.: Assignment of the human
metabotropic glutamate receptor gene GRM4 to chromosome 6 band p21.3
by radiation hybrid mapping. Cytogenet. Cell Genet. 88: 210 only,
2000.

2. Bjarnadottir, T. K.; Fredriksson, R.; Schioth, H. B.: The gene
repertoire and the common evolutionary history of glutamate, pheromone
(V2R), taste(1) and other related G protein-coupled receptors. Gene 362:
70-84, 2005.

3. Fallarino, F.; Volpi, C.; Fazio, F.; Notartomaso, S.; Vacca, C.;
Busceti, C.; Bicciato, S.; Battaglia, G.; Bruno, V.; Puccetti, P.;
Fioretti, M. C.; Nicoletti, F.; Grohmann, U.; Di Marco, R.: Metabotropic
glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammation. Nature
Med. 16: 897-902, 2010.

4. Gerlai, R.; Roder, J. C.; Hampson, D. R.: Altered spatial learning
and memory in mice lacking the mGluR4 subtype of metabotropic glutamate
receptor. Behav. Neurosci. 112: 525-532, 1998.

5. Makoff, A.; Lelchuk, R.; Oxer, M.; Harrington, K.; Emson, P.:
Molecular characterization and localization of human metabotropic
glutamate receptor type 4. Molec. Brain Res. 37: 239-248, 1996.

6. Pekhletski, R.; Gerlai, R.; Overstreet, L. S.; Huang, X. P.; Agopyan,
N.; Slater, N. T.; Abramow-Newerly, W.; Roder, J. C.; Hampson, D.
R.: Impaired cerebellar synaptic plasticity and motor performance
in mice lacking the mGluR4 subtype of metabotropic glutamate receptor. J.
Neurosci. 16: 6364-6373, 1996.

7. Wu, S.; Wright, R. A.; Rockey, P. K.; Burgett, S. G.; Arnold, J.
S.; Rosteck, P. R., Jr.; Johnson, B. G.; Schoepp, D. D.; Belagaje,
R. M.: Group III human metabotropic glutamate receptors 4, 7 and
8: molecular cloning, functional expression, and comparison of pharmacological
properties in RGT cells. Molec. Brain Res. 53: 88-97, 1998.

*FIELD* CN
Patricia A. Hartz - updated: 3/12/2012
Cassandra L. Kniffin - updated: 10/4/2010
Joanna S. Amberger - updated: 3/7/2001

*FIELD* CD
Rebekah S. Rasooly: 8/4/1999

*FIELD* ED
mgross: 04/17/2012
terry: 3/12/2012
wwang: 10/11/2010
ckniffin: 10/4/2010
terry: 3/8/2001
joanna: 3/7/2001
mgross: 8/5/1999
mgross: 8/4/1999

RBCC Red Blood Cell Collection

Full text data of GRM4