GRM5_HUMAN
ID GRM5_HUMAN Reviewed; 1212 AA.
AC P41594; Q6J164;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Metabotropic glutamate receptor 5;
DE Short=mGluR5;
DE Flags: Precursor;
GN Name=GRM5; Synonyms=GPRC1E, MGLUR5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Brain;
RX PubMed=7908515; DOI=10.1006/bbrc.1994.1349;
RA Minakami R., Katsuki F., Yamamoto T., Nakamura K., Sugiyama H.;
RT "Molecular cloning and the functional expression of two isoforms of human
RT metabotropic glutamate receptor subtype 5.";
RL Biochem. Biophys. Res. Commun. 199:1136-1143(1994).
RN [2]
RP SEQUENCE REVISION.
RA Katsuki F.;
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Levinthal C., Storjohann L., Hammerland L.G., Hung B.C.P., Krapcho K.J.,
RA Logan M.A., Smith D.L., Trovato R., Vanwagenen B.C., Stormannn T.M.;
RT "Molecular cloning and characterization of human metabotropic glutamate
RT receptor 5d; a splice variant with reduced desensitization properties.";
RL Abstr. - Soc. Neurosci. 25:976-976(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 860-952 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=7688218; DOI=10.1006/bbrc.1993.1866;
RA Minakami R., Katsuki F., Sugiyama H.;
RT "A variant of metabotropic glutamate receptor subtype 5: an evolutionally
RT conserved insertion with no termination codon.";
RL Biochem. Biophys. Res. Commun. 194:622-627(1993).
RN [6]
RP INTERACTION WITH NECAB2.
RX PubMed=19694902; DOI=10.1111/j.1471-4159.2009.06348.x;
RA Canela L., Fernandez-Duenas V., Albergaria C., Watanabe M., Lluis C.,
RA Mallol J., Canela E.I., Franco R., Lujan R., Ciruela F.;
RT "The association of metabotropic glutamate receptor type 5 with the
RT neuronal Ca2+-binding protein 2 modulates receptor function.";
RL J. Neurochem. 111:555-567(2009).
RN [7]
RP INTERACTION WITH CAMK2A.
RX PubMed=28130356; DOI=10.1523/jneurosci.2068-16.2017;
RA Stephenson J.R., Wang X., Perfitt T.L., Parrish W.P., Shonesy B.C.,
RA Marks C.R., Mortlock D.P., Nakagawa T., Sutcliffe J.S., Colbran R.J.;
RT "Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and
RT Causes ASD-Related Behaviors.";
RL J. Neurosci. 37:2216-2233(2017).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 18-505 IN COMPLEX WITH GLUTAMATE,
RP GLYCOSYLATION AT ASN-445, AND DISULFIDE BONDS.
RG Structural genomics consortium (SGC);
RT "Metabotropic glutamate receptor MGluR5 complexed with glutamate.";
RL Submitted (JUL-2011) to the PDB data bank.
RN [9] {ECO:0007744|PDB:4OO9}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 569-836 IN COMPLEX WITH
RP ALLOSTERIC EFFECTOR MAVOGLURANT, FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY,
RP DISULFIDE BONDS, AND MUTAGENESIS OF SER-613; SER-614; LYS-665 AND GLU-770.
RX PubMed=25042998; DOI=10.1038/nature13396;
RA Dore A.S., Okrasa K., Patel J.C., Serrano-Vega M., Bennett K., Cooke R.M.,
RA Errey J.C., Jazayeri A., Khan S., Tehan B., Weir M., Wiggin G.R.,
RA Marshall F.H.;
RT "Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane
RT domain.";
RL Nature 511:557-562(2014).
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 activity of
CC down-stream effectors. Signaling activates a phosphatidylinositol-
CC calcium second messenger system and generates a calcium-activated
CC chloride current. Plays an important role in the regulation of synaptic
CC plasticity and the modulation of the neural network activity.
CC {ECO:0000269|PubMed:25042998, ECO:0000269|PubMed:7908515}.
CC -!- SUBUNIT: The PPXXF motif binds HOMER1, HOMER2 and HOMER3. Interacts
CC with SIAH1, RYR1, RYR2, ITPR1, SHANK1, SHANK3 and TAMALIN. Interacts
CC with NCDN (By similarity). Isoform 2 interacts with NECAB2
CC (PubMed:19694902). Interacts with CAMK2A (PubMed:28130356).
CC {ECO:0000250, ECO:0000269|PubMed:19694902,
CC ECO:0000269|PubMed:28130356}.
CC -!- INTERACTION:
CC P41594; P41594: GRM5; NbExp=3; IntAct=EBI-6595175, EBI-6595175;
CC P41594-1; Q7Z6G3: NECAB2; NbExp=2; IntAct=EBI-14039683, EBI-950070;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25042998,
CC ECO:0000269|PubMed:7908515}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:25042998, ECO:0000269|PubMed:7908515}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=2; Synonyms=5b;
CC IsoId=P41594-1; Sequence=Displayed;
CC Name=1; Synonyms=5a;
CC IsoId=P41594-2; Sequence=VSP_002030;
CC Name=3; Synonyms=5d;
CC IsoId=P41594-3; Sequence=VSP_047710;
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family.
CC {ECO:0000305}.
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DR EMBL; D28538; BAA05891.1; -; mRNA.
DR EMBL; D28539; BAA05892.1; -; mRNA.
DR EMBL; AY608336; AAT37960.1; -; mRNA.
DR EMBL; AP000626; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001482; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001828; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003120; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP006214; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP006215; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; S64316; AAD13954.1; -; mRNA.
DR CCDS; CCDS44694.1; -. [P41594-1]
DR CCDS; CCDS8283.1; -. [P41594-2]
DR PIR; JC2131; JC2131.
DR PIR; JC2132; JC2132.
DR RefSeq; NP_000833.1; NM_000842.4. [P41594-2]
DR RefSeq; NP_001137303.1; NM_001143831.2. [P41594-1]
DR RefSeq; XP_006718891.1; XM_006718828.3.
DR RefSeq; XP_011541094.1; XM_011542792.1. [P41594-1]
DR RefSeq; XP_016873116.1; XM_017017627.1.
DR PDB; 3LMK; X-ray; 2.44 A; A/B=18-505.
DR PDB; 4OO9; X-ray; 2.60 A; A=569-836.
DR PDB; 5CGC; X-ray; 3.10 A; A=569-836.
DR PDB; 5CGD; X-ray; 2.60 A; A=569-836.
DR PDB; 6N4X; X-ray; 4.00 A; A/B=20-865.
DR PDB; 6N4Y; X-ray; 3.26 A; A/B/C/D=21-571.
DR PDB; 6N50; X-ray; 3.75 A; A/B/C=21-571.
DR PDB; 6N51; EM; 4.00 A; A/B=23-826.
DR PDB; 6N52; EM; 4.00 A; A/B=20-839.
DR PDB; 7FD8; EM; 3.80 A; A/B=21-856.
DR PDB; 7FD9; EM; 4.00 A; A/B=21-856.
DR PDBsum; 3LMK; -.
DR PDBsum; 4OO9; -.
DR PDBsum; 5CGC; -.
DR PDBsum; 5CGD; -.
DR PDBsum; 6N4X; -.
DR PDBsum; 6N4Y; -.
DR PDBsum; 6N50; -.
DR PDBsum; 6N51; -.
DR PDBsum; 6N52; -.
DR PDBsum; 7FD8; -.
DR PDBsum; 7FD9; -.
DR AlphaFoldDB; P41594; -.
DR SMR; P41594; -.
DR BioGRID; 109172; 20.
DR IntAct; P41594; 5.
DR STRING; 9606.ENSP00000306138; -.
DR BindingDB; P41594; -.
DR ChEMBL; CHEMBL3227; -.
DR DrugBank; DB00659; Acamprosate.
DR DrugBank; DB05070; ADX10059.
DR DrugBank; DB12733; Dipraglurant.
DR DrugBank; DB06201; Rufinamide.
DR DrugCentral; P41594; -.
DR GuidetoPHARMACOLOGY; 293; -.
DR TCDB; 9.A.14.7.8; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P41594; 8 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P41594; -.
DR PhosphoSitePlus; P41594; -.
DR BioMuta; GRM5; -.
DR DMDM; 1709020; -.
DR EPD; P41594; -.
DR jPOST; P41594; -.
DR MassIVE; P41594; -.
DR PaxDb; P41594; -.
DR PeptideAtlas; P41594; -.
DR PRIDE; P41594; -.
DR ProteomicsDB; 55471; -. [P41594-1]
DR ProteomicsDB; 55472; -. [P41594-2]
DR ProteomicsDB; 66504; -.
DR ABCD; P41594; 5 sequenced antibodies.
DR Antibodypedia; 2950; 553 antibodies from 44 providers.
DR DNASU; 2915; -.
DR Ensembl; ENST00000305432.9; ENSP00000305905.5; ENSG00000168959.15. [P41594-2]
DR Ensembl; ENST00000305447.5; ENSP00000306138.4; ENSG00000168959.15. [P41594-1]
DR Ensembl; ENST00000455756.6; ENSP00000405690.2; ENSG00000168959.15. [P41594-2]
DR GeneID; 2915; -.
DR KEGG; hsa:2915; -.
DR MANE-Select; ENST00000305447.5; ENSP00000306138.4; NM_001143831.3; NP_001137303.1.
DR UCSC; uc001pcq.4; human. [P41594-1]
DR CTD; 2915; -.
DR DisGeNET; 2915; -.
DR GeneCards; GRM5; -.
DR HGNC; HGNC:4597; GRM5.
DR HPA; ENSG00000168959; Tissue enriched (brain).
DR MIM; 604102; gene.
DR neXtProt; NX_P41594; -.
DR OpenTargets; ENSG00000168959; -.
DR PharmGKB; PA28994; -.
DR VEuPathDB; HostDB:ENSG00000168959; -.
DR eggNOG; KOG1056; Eukaryota.
DR GeneTree; ENSGT01030000234595; -.
DR HOGENOM; CLU_005389_0_1_1; -.
DR InParanoid; P41594; -.
DR OMA; EVEEHYP; -.
DR OrthoDB; 107675at2759; -.
DR PhylomeDB; P41594; -.
DR TreeFam; TF313240; -.
DR PathwayCommons; P41594; -.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR Reactome; R-HSA-420499; Class C/3 (Metabotropic glutamate/pheromone receptors).
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR SignaLink; P41594; -.
DR SIGNOR; P41594; -.
DR BioGRID-ORCS; 2915; 14 hits in 1070 CRISPR screens.
DR ChiTaRS; GRM5; human.
DR EvolutionaryTrace; P41594; -.
DR GenomeRNAi; 2915; -.
DR Pharos; P41594; Tchem.
DR PRO; PR:P41594; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P41594; protein.
DR Bgee; ENSG00000168959; Expressed in endothelial cell and 73 other tissues.
DR ExpressionAtlas; P41594; baseline and differential.
DR Genevisible; P41594; HS.
DR GO; GO:0097449; C:astrocyte projection; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0043198; C:dendritic shaft; IEA:Ensembl.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098839; C:postsynaptic density membrane; IBA:GO_Central.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl.
DR GO; GO:0031687; F:A2A adenosine receptor binding; IEA:Ensembl.
DR GO; GO:0001640; F:adenylate cyclase inhibiting G protein-coupled glutamate receptor activity; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IMP:UniProtKB.
DR GO; GO:0099530; F:G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central.
DR GO; GO:0008066; F:glutamate receptor activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0099583; F:neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:0030296; F:protein tyrosine kinase activator activity; TAS:ARUK-UCL.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISS:ARUK-UCL.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IGI:ARUK-UCL.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IGI:ARUK-UCL.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0050890; P:cognition; IMP:UniProtKB.
DR GO; GO:0002029; P:desensitization of G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0007216; P:G protein-coupled glutamate receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007612; P:learning; IEA:Ensembl.
DR GO; GO:0007611; P:learning or memory; ISS:ARUK-UCL.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0040013; P:negative regulation of locomotion; IEA:Ensembl.
DR GO; GO:0007206; P:phospholipase C-activating G protein-coupled glutamate receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISS:ARUK-UCL.
DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR GO; GO:1902938; P:regulation of intracellular calcium activated chloride channel activity; IGI:ARUK-UCL.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IGI:ARUK-UCL.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0006417; P:regulation of translation; TAS:ARUK-UCL.
DR GO; GO:0006448; P:regulation of translational elongation; IGI:ARUK-UCL.
DR GO; GO:0050808; P:synapse organization; ISS:ARUK-UCL.
DR GO; GO:0099553; P:trans-synaptic signaling by endocannabinoid, modulating synaptic transmission; IBA:GO_Central.
DR Gene3D; 2.10.50.30; -; 1.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR000337; GPCR_3.
DR InterPro; IPR011500; GPCR_3_9-Cys_dom.
DR InterPro; IPR038550; GPCR_3_9-Cys_sf.
DR InterPro; IPR017978; GPCR_3_C.
DR InterPro; IPR017979; GPCR_3_CS.
DR InterPro; IPR000202; GPCR_3_mGluR5.
DR InterPro; IPR000162; GPCR_3_mtglu_rcpt.
DR InterPro; IPR019588; Metabotropic_Glu_rcpt_Homer-bd.
DR InterPro; IPR028082; Peripla_BP_I.
DR Pfam; PF00003; 7tm_3; 1.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF10606; GluR_Homer-bdg; 1.
DR Pfam; PF07562; NCD3G; 1.
DR PRINTS; PR00248; GPCRMGR.
DR PRINTS; PR01055; MTABOTROPC5R.
DR PRINTS; PR00593; MTABOTROPICR.
DR SMART; SM01229; GluR_Homer-bdg; 1.
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 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Membrane; Methylation;
KW Phosphoprotein; Receptor; Reference proteome; Signal; Transducer;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..1212
FT /note="Metabotropic glutamate receptor 5"
FT /id="PRO_0000012932"
FT TOPO_DOM 22..580
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:25042998"
FT TRANSMEM 581..603
FT /note="Helical; Name=1"
FT TOPO_DOM 604..613
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:25042998"
FT TRANSMEM 614..636
FT /note="Helical; Name=2"
FT TOPO_DOM 637..644
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:25042998"
FT TRANSMEM 645..667
FT /note="Helical; Name=3"
FT TOPO_DOM 668..693
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:25042998"
FT TRANSMEM 694..714
FT /note="Helical; Name=4"
FT TOPO_DOM 715..737
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:25042998"
FT TRANSMEM 738..759
FT /note="Helical; Name=5"
FT TOPO_DOM 760..772
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:25042998"
FT TRANSMEM 773..795
FT /note="Helical; Name=6"
FT TOPO_DOM 796..798
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:25042998"
FT TRANSMEM 799..820
FT /note="Helical; Name=7"
FT TOPO_DOM 821..1212
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:25042998"
FT REGION 937..971
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1010..1056
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1132..1191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 937..952
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1170..1189
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 64
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 152
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 173..175
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT BINDING 223
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 305
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000269|Ref.8"
FT BINDING 396
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000269|Ref.8"
FT MOD_RES 861
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31424"
FT MOD_RES 869
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q3UVX5"
FT MOD_RES 925
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q3UVX5"
FT MOD_RES 1018
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UVX5"
FT MOD_RES 1020
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UVX5"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 378
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 445
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|Ref.8"
FT CARBOHYD 734
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 57..99
FT DISULFID 241..530
FT /evidence="ECO:0000250"
FT DISULFID 276..278
FT DISULFID 365..381
FT DISULFID 419..426
FT DISULFID 511..531
FT /evidence="ECO:0000250"
FT DISULFID 515..534
FT /evidence="ECO:0000250"
FT DISULFID 537..549
FT /evidence="ECO:0000250"
FT DISULFID 552..565
FT /evidence="ECO:0000250"
FT DISULFID 644..733
FT VAR_SEQ 877..908
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:7908515"
FT /id="VSP_002030"
FT VAR_SEQ 896..1165
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_047710"
FT MUTAGEN 613
FT /note="S->A,K: Increased constitutive signaling activity."
FT /evidence="ECO:0000269|PubMed:25042998"
FT MUTAGEN 614
FT /note="S->D: Decreased constitutive signaling activity."
FT /evidence="ECO:0000269|PubMed:25042998"
FT MUTAGEN 665
FT /note="K->A: Increased constitutive signaling activity."
FT /evidence="ECO:0000269|PubMed:25042998"
FT MUTAGEN 770
FT /note="E->A: Increased constitutive signaling activity."
FT /evidence="ECO:0000269|PubMed:25042998"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:3LMK"
FT TURN 52..55
FT /evidence="ECO:0007829|PDB:3LMK"
FT TURN 62..65
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 66..81
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 83..86
FT /evidence="ECO:0007829|PDB:6N4Y"
FT STRAND 91..97
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 102..112
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 143..147
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 152..162
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 169..173
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 177..180
FT /evidence="ECO:0007829|PDB:3LMK"
FT TURN 182..184
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 195..208
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 213..219
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 222..235
FT /evidence="ECO:0007829|PDB:3LMK"
FT TURN 236..239
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 241..248
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 254..267
FT /evidence="ECO:0007829|PDB:3LMK"
FT TURN 268..270
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 273..277
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 280..293
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 300..303
FT /evidence="ECO:0007829|PDB:3LMK"
FT TURN 307..309
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 311..314
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 318..321
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 335..342
FT /evidence="ECO:0007829|PDB:3LMK"
FT TURN 346..348
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 355..363
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:6N4Y"
FT TURN 387..390
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 397..418
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 427..429
FT /evidence="ECO:0007829|PDB:3LMK"
FT HELIX 434..441
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 445..447
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 449..451
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 453..455
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 466..475
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 479..488
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 491..494
FT /evidence="ECO:0007829|PDB:3LMK"
FT STRAND 522..524
FT /evidence="ECO:0007829|PDB:6N4Y"
FT STRAND 532..534
FT /evidence="ECO:0007829|PDB:6N4Y"
FT STRAND 545..547
FT /evidence="ECO:0007829|PDB:6N4Y"
FT HELIX 569..575
FT /evidence="ECO:0007829|PDB:4OO9"
FT HELIX 579..603
FT /evidence="ECO:0007829|PDB:4OO9"
FT TURN 604..606
FT /evidence="ECO:0007829|PDB:4OO9"
FT HELIX 608..611
FT /evidence="ECO:0007829|PDB:4OO9"
FT HELIX 615..630
FT /evidence="ECO:0007829|PDB:4OO9"
FT HELIX 632..635
FT /evidence="ECO:0007829|PDB:4OO9"
FT HELIX 641..678
FT /evidence="ECO:0007829|PDB:4OO9"
FT HELIX 690..714
FT /evidence="ECO:0007829|PDB:4OO9"
FT HELIX 738..760
FT /evidence="ECO:0007829|PDB:4OO9"
FT TURN 761..763
FT /evidence="ECO:0007829|PDB:4OO9"
FT HELIX 766..793
FT /evidence="ECO:0007829|PDB:4OO9"
FT HELIX 798..817
FT /evidence="ECO:0007829|PDB:4OO9"
FT HELIX 819..827
FT /evidence="ECO:0007829|PDB:4OO9"
FT TURN 829..831
FT /evidence="ECO:0007829|PDB:4OO9"
SQ SEQUENCE 1212 AA; 132469 MW; A3C73606681C6A25 CRC64;
MVLLLILSVL LLKEDVRGSA QSSERRVVAH MPGDIIIGAL FSVHHQPTVD KVHERKCGAV
REQYGIQRVE AMLHTLERIN SDPTLLPNIT LGCEIRDSCW HSAVALEQSI EFIRDSLISS
EEEEGLVRCV DGSSSSFRSK KPIVGVIGPG SSSVAIQVQN LLQLFNIPQI AYSATSMDLS
DKTLFKYFMR VVPSDAQQAR AMVDIVKRYN WTYVSAVHTE GNYGESGMEA FKDMSAKEGI
CIAHSYKIYS NAGEQSFDKL LKKLTSHLPK ARVVACFCEG MTVRGLLMAM RRLGLAGEFL
LLGSDGWADR YDVTDGYQRE AVGGITIKLQ SPDVKWFDDY YLKLRPETNH RNPWFQEFWQ
HRFQCRLEGF PQENSKYNKT CNSSLTLKTH HVQDSKMGFV INAIYSMAYG LHNMQMSLCP
GYAGLCDAMK PIDGRKLLES LMKTNFTGVS GDTILFDENG DSPGRYEIMN FKEMGKDYFD
YINVGSWDNG ELKMDDDEVW SKKSNIIRSV CSEPCEKGQI KVIRKGEVSC CWTCTPCKEN
EYVFDEYTCK ACQLGSWPTD DLTGCDLIPV QYLRWGDPEP IAAVVFACLG LLATLFVTVV
FIIYRDTPVV KSSSRELCYI ILAGICLGYL CTFCLIAKPK QIYCYLQRIG IGLSPAMSYS
ALVTKTNRIA RILAGSKKKI CTKKPRFMSA CAQLVIAFIL ICIQLGIIVA LFIMEPPDIM
HDYPSIREVY LICNTTNLGV VTPLGYNGLL ILSCTFYAFK TRNVPANFNE AKYIAFTMYT
TCIIWLAFVP IYFGSNYKII TMCFSVSLSA TVALGCMFVP KVYIILAKPE RNVRSAFTTS
TVVRMHVGDG KSSSAASRSS SLVNLWKRRG SSGETLRYKD RRLAQHKSEI ECFTPKGSMG
NGGRATMSSS NGKSVTWAQN EKSSRGQHLW QRLSIHINKK ENPNQTAVIK PFPKSTESRG
LGAGAGAGGS AGGVGATGGA GCAGAGPGGP ESPDAGPKAL YDVAEAEEHF PAPARPRSPS
PISTLSHRAG SASRTDDDVP SLHSEPVARS SSSQGSLMEQ ISSVVTRFTA NISELNSMML
STAAPSPGVG APLCSSYLIP KEIQLPTTMT TFAEIQPLPA IEVTGGAQPA AGAQAAGDAA
RESPAAGPEA AAAKPDLEEL VALTPPSPFR DSVDSGSTTP NSPVSESALC IPSSPKYDTL
IIRDYTQSSS SL
