GRM7_HUMAN
ID GRM7_HUMAN Reviewed; 915 AA.
AC Q14831; Q8NFS2; Q8NFS3; Q8NFS4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Metabotropic glutamate receptor 7;
DE Short=mGluR7;
DE Flags: Precursor;
GN Name=GRM7; Synonyms=GPRC1G, MGLUR7;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=8840028; DOI=10.1016/0169-328x(96)00110-6;
RA Makoff A., Pilling C., Harrington K., Emson P.;
RT "Human metabotropic glutamate receptor type 7: molecular cloning and mRNA
RT distribution in the CNS.";
RL Brain Res. Mol. Brain Res. 40:165-170(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=9144652; DOI=10.1016/s0028-3908(96)00176-1;
RA Flor P.J., Van Der Putten H., Ruegg D., Lukic S., Leonhardt T., Bence M.,
RA Sansig G., Knoepfel T., Kuhn R.;
RT "A novel splice variant of a metabotropic glutamate receptor, human
RT mGluR7b.";
RL Neuropharmacology 36:153-159(1997).
RN [3]
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: molecular
RT cloning, functional expression, and comparison of pharmacological
RT properties in RGT cells.";
RL Brain Res. Mol. Brain Res. 53:88-97(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4 AND 5), AND TISSUE SPECIFICITY.
RX PubMed=12052533; DOI=10.1016/s0304-3940(02)00306-3;
RA Schulz H.L., Stoehr H., Weber B.H.F.;
RT "Characterization of three novel isoforms of the metabotropic glutamate
RT receptor 7 (GRM7).";
RL Neurosci. Lett. 326:37-40(2002).
RN [5]
RP INVOLVEMENT IN NEDSHBA, AND VARIANTS NEDSHBA THR-154; TRP-658 AND LYS-675.
RX PubMed=27435318; DOI=10.1186/s12920-016-0208-3;
RA Charng W.L., Karaca E., Coban Akdemir Z., Gambin T., Atik M.M., Gu S.,
RA Posey J.E., Jhangiani S.N., Muzny D.M., Doddapaneni H., Hu J.,
RA Boerwinkle E., Gibbs R.A., Rosenfeld J.A., Cui H., Xia F., Manickam K.,
RA Yang Y., Faqeih E.A., Al Asmari A., Saleh M.A., El-Hattab A.W.,
RA Lupski J.R.;
RT "Exome sequencing in mostly consanguineous Arab families with neurologic
RT disease provides a high potential molecular diagnosis rate.";
RL BMC Med. Genomics 9:42-42(2016).
RN [6]
RP VARIANTS NEDSHBA 586-TRP--ILE-915 DEL AND 856-VAL--ILE-915 DEL.
RX PubMed=28097321; DOI=10.1001/jamapsychiatry.2016.3798;
RA Reuter M.S., Tawamie H., Buchert R., Hosny Gebril O., Froukh T., Thiel C.,
RA Uebe S., Ekici A.B., Krumbiegel M., Zweier C., Hoyer J., Eberlein K.,
RA Bauer J., Scheller U., Strom T.M., Hoffjan S., Abdelraouf E.R.,
RA Meguid N.A., Abboud A., Al Khateeb M.A., Fakher M., Hamdan S., Ismael A.,
RA Muhammad S., Abdallah E., Sticht H., Wieczorek D., Reis A., Abou Jamra R.;
RT "Diagnostic yield and novel candidate genes by exome sequencing in 152
RT consanguineous families with neurodevelopmental disorders.";
RL JAMA Psychiatry 74:293-299(2017).
RN [7]
RP VARIANTS NEDSHBA THR-154; 586-TRP--ILE-915 DEL; GLN-658; TRP-658;
RP 659-ARG--ILE-915 DEL; LYS-675 AND LYS-891.
RX PubMed=32286009; DOI=10.1002/acn3.51003;
RA Marafi D., Mitani T., Isikay S., Hertecant J., Almannai M., Manickam K.,
RA Abou Jamra R., El-Hattab A.W., Rajah J., Fatih J.M., Du H., Karaca E.,
RA Bayram Y., Punetha J., Rosenfeld J.A., Jhangiani S.N., Boerwinkle E.,
RA Akdemir Z.C., Erdin S., Hunter J.V., Gibbs R.A., Pehlivan D., Posey J.E.,
RA Lupski J.R.;
RT "Biallelic GRM7 variants cause epilepsy, microcephaly, and cerebral
RT atrophy.";
RL Ann. Clin. Transl. Neurol. 7:610-627(2020).
RN [8]
RP VARIANT NEDSHBA THR-154, CHARACTERIZATION OF VARIANT NEDSHBA THR-154, AND
RP SUBUNIT.
RX PubMed=33476302; DOI=10.1172/jci.insight.143324;
RA Fisher N.M., Alhashim A., Buch A.B., Badivuku H., Samman M.M., Weiss K.M.,
RA Cestero G.I., Does M.D., Rook J.M., Lindsley C.W., Conn P.J.,
RA Gogliotti R.G., Niswender C.M.;
RT "A GRM7 mutation associated with developmental delay reduces mGlu7
RT expression and produces neurological phenotypes.";
RL JCI Insight 6:0-0(2021).
RN [9]
RP CHARACTERIZATION OF VARIANTS NEDSHBA THR-154 AND 586-TRP--ILE-915 DEL,
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, GLYCOSYLATION, AND MUTAGENESIS OF
RP ARG-622; ARG-658 AND THR-675.
RX PubMed=33500274; DOI=10.1523/jneurosci.2108-20.2021;
RA Song J.M., Kang M., Park D.H., Park S., Lee S., Suh Y.H.;
RT "Pathogenic GRM7 mutations associated with neurodevelopmental disorders
RT impair axon outgrowth and presynaptic terminal development.";
RL J. Neurosci. 41:2344-2359(2021).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 37-513.
RG Structural genomics consortium (SGC);
RT "MGluR7 complexed with LY341495.";
RL Submitted (JUN-2010) to the PDB data bank.
RN [11]
RP VARIANT PHE-433.
RX PubMed=11163549; DOI=10.1016/s0920-9964(99)00235-2;
RA Bolonna A.A., Kerwin R.W., Munro J., Arranz M.J., Makoff A.J.;
RT "Polymorphisms in the genes for mGluR types 7 and 8: association studies
RT with schizophrenia.";
RL Schizophr. Res. 47:99-103(2001).
CC -!- FUNCTION: G-protein coupled receptor activated by glutamate that
CC regulates axon outgrowth through the MAPK-cAMP-PKA signaling pathway
CC during neuronal development (PubMed:33500274). Ligand binding causes a
CC conformation change that triggers signaling via guanine nucleotide-
CC binding proteins (G proteins) and modulates the activity of downstream
CC effectors, such as adenylate cyclase that it inhibits (PubMed:9473604).
CC {ECO:0000269|PubMed:33500274, ECO:0000269|PubMed:9473604}.
CC -!- SUBUNIT: Homodimer (PubMed:33476302, PubMed:33500274). Interacts with
CC PICK1. {ECO:0000250|UniProtKB:P35400, ECO:0000269|PubMed:33476302,
CC ECO:0000269|PubMed:33500274}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:33500274};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=GRM7_v1, mGluR7a;
CC IsoId=Q14831-1; Sequence=Displayed;
CC Name=2; Synonyms=GRM7_v2, mGluR7b;
CC IsoId=Q14831-2; Sequence=VSP_015735;
CC Name=3; Synonyms=GRM7_v3;
CC IsoId=Q14831-3; Sequence=VSP_015732;
CC Name=4; Synonyms=GRM7_v4;
CC IsoId=Q14831-4; Sequence=VSP_015733;
CC Name=5; Synonyms=GRM7_v5;
CC IsoId=Q14831-5; Sequence=VSP_015734;
CC -!- TISSUE SPECIFICITY: Expressed in many areas of the brain, especially in
CC the cerebral cortex, hippocampus, and cerebellum. Expression of GRM7
CC isoforms in non-neuronal tissues appears to be restricted to isoform 3
CC and isoform 4. {ECO:0000269|PubMed:12052533,
CC ECO:0000269|PubMed:8840028}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:33500274}.
CC -!- DISEASE: Neurodevelopmental disorder with seizures, hypotonia, and
CC brain imaging abnormalities (NEDSHBA) [MIM:618922]: An autosomal
CC recessive neurodevelopmental disorder characterized by global
CC developmental delay, hypotonia, severe to profound intellectual
CC disability, early-onset epilepsy, and microcephaly. Neuroimaging shows
CC cerebral atrophy, thin corpus callosum and hypomyelination in a
CC majority of cases. Death in childhood may occur.
CC {ECO:0000269|PubMed:27435318, ECO:0000269|PubMed:28097321,
CC ECO:0000269|PubMed:32286009, ECO:0000269|PubMed:33476302,
CC ECO:0000269|PubMed:33500274}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION: [Isoform 3]:
CC Sequence=AAM47557.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X94552; CAA64245.1; -; mRNA.
DR EMBL; U92458; AAB51763.1; -; mRNA.
DR EMBL; AF458052; AAM47557.1; ALT_FRAME; mRNA.
DR EMBL; AF458053; AAM47558.1; -; mRNA.
DR EMBL; AF458054; AAM47559.1; -; mRNA.
DR CCDS; CCDS43042.1; -. [Q14831-1]
DR RefSeq; NP_000835.1; NM_000844.3. [Q14831-1]
DR RefSeq; NP_870989.1; NM_181874.2. [Q14831-2]
DR PDB; 3MQ4; X-ray; 2.80 A; A=37-513.
DR PDB; 5C5C; X-ray; 1.86 A; A=37-513.
DR PDB; 7EPC; EM; 4.00 A; A/B=35-859.
DR PDB; 7EPD; EM; 3.90 A; B=15-859.
DR PDBsum; 3MQ4; -.
DR PDBsum; 5C5C; -.
DR PDBsum; 7EPC; -.
DR PDBsum; 7EPD; -.
DR AlphaFoldDB; Q14831; -.
DR SMR; Q14831; -.
DR BioGRID; 109174; 6.
DR CORUM; Q14831; -.
DR STRING; 9606.ENSP00000350348; -.
DR BindingDB; Q14831; -.
DR ChEMBL; CHEMBL3777; -.
DR DrugBank; DB00142; Glutamic acid.
DR DrugCentral; Q14831; -.
DR GuidetoPHARMACOLOGY; 295; -.
DR GlyGen; Q14831; 4 sites.
DR iPTMnet; Q14831; -.
DR PhosphoSitePlus; Q14831; -.
DR BioMuta; GRM7; -.
DR DMDM; 2495078; -.
DR EPD; Q14831; -.
DR MassIVE; Q14831; -.
DR PaxDb; Q14831; -.
DR PeptideAtlas; Q14831; -.
DR PRIDE; Q14831; -.
DR ProteomicsDB; 60197; -. [Q14831-1]
DR ProteomicsDB; 60198; -. [Q14831-2]
DR ProteomicsDB; 60199; -. [Q14831-3]
DR ProteomicsDB; 60200; -. [Q14831-4]
DR ProteomicsDB; 60201; -. [Q14831-5]
DR Antibodypedia; 10079; 428 antibodies from 35 providers.
DR DNASU; 2917; -.
DR Ensembl; ENST00000357716.9; ENSP00000350348.4; ENSG00000196277.16. [Q14831-1]
DR Ensembl; ENST00000389335.7; ENSP00000373986.3; ENSG00000196277.16. [Q14831-4]
DR Ensembl; ENST00000389336.8; ENSP00000373987.4; ENSG00000196277.16. [Q14831-5]
DR Ensembl; ENST00000467425.5; ENSP00000419835.1; ENSG00000196277.16. [Q14831-2]
DR Ensembl; ENST00000486284.5; ENSP00000417536.1; ENSG00000196277.16. [Q14831-2]
DR GeneID; 2917; -.
DR KEGG; hsa:2917; -.
DR MANE-Select; ENST00000357716.9; ENSP00000350348.4; NM_000844.4; NP_000835.1.
DR UCSC; uc003bql.3; human. [Q14831-1]
DR CTD; 2917; -.
DR DisGeNET; 2917; -.
DR GeneCards; GRM7; -.
DR HGNC; HGNC:4599; GRM7.
DR HPA; ENSG00000196277; Tissue enhanced (brain, parathyroid gland).
DR MalaCards; GRM7; -.
DR MIM; 604101; gene.
DR MIM; 618922; phenotype.
DR neXtProt; NX_Q14831; -.
DR OpenTargets; ENSG00000196277; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR Orphanet; 1934; Early infantile epileptic encephalopathy.
DR PharmGKB; PA28996; -.
DR VEuPathDB; HostDB:ENSG00000196277; -.
DR eggNOG; KOG1056; Eukaryota.
DR GeneTree; ENSGT01030000234648; -.
DR HOGENOM; CLU_005389_0_0_1; -.
DR InParanoid; Q14831; -.
DR OMA; QWGRGVR; -.
DR PhylomeDB; Q14831; -.
DR TreeFam; TF313240; -.
DR PathwayCommons; Q14831; -.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-420499; Class C/3 (Metabotropic glutamate/pheromone receptors).
DR SignaLink; Q14831; -.
DR SIGNOR; Q14831; -.
DR BioGRID-ORCS; 2917; 14 hits in 1073 CRISPR screens.
DR ChiTaRS; GRM7; human.
DR EvolutionaryTrace; Q14831; -.
DR GeneWiki; Metabotropic_glutamate_receptor_7; -.
DR GenomeRNAi; 2917; -.
DR Pharos; Q14831; Tchem.
DR PRO; PR:Q14831; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q14831; protein.
DR Bgee; ENSG00000196277; Expressed in endothelial cell and 120 other tissues.
DR ExpressionAtlas; Q14831; baseline and differential.
DR Genevisible; Q14831; HS.
DR GO; GO:0032279; C:asymmetric synapse; ISS:UniProtKB.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0043198; C:dendritic shaft; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IMP:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; ISS:UniProtKB.
DR GO; GO:0048786; C:presynaptic active zone; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0001640; F:adenylate cyclase inhibiting G protein-coupled glutamate receptor activity; IBA:GO_Central.
DR GO; GO:0010855; F:adenylate cyclase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0016595; F:glutamate binding; IDA:UniProtKB.
DR GO; GO:0008066; F:glutamate receptor activity; IDA:UniProtKB.
DR GO; GO:0001642; F:group III metabotropic glutamate receptor activity; IDA:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; NAS:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IMP:UniProtKB.
DR GO; GO:0070905; F:serine binding; IDA:UniProtKB.
DR GO; GO:0007196; P:adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0061564; P:axon development; IMP:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; IDA:UniProtKB.
DR GO; GO:0007216; P:G protein-coupled glutamate receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0070085; P:glycosylation; IDA:UniProtKB.
DR GO; GO:0014050; P:negative regulation of glutamate secretion; ISS:UniProtKB.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IBA:GO_Central.
DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
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; IPR001883; GPCR_3_mGluR7.
DR InterPro; IPR000162; GPCR_3_mtglu_rcpt.
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; PR01057; MTABOTROPC7R.
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 3D-structure; Alternative splicing; Cardiomyopathy; Cell membrane;
KW Disease variant; Disulfide bond; Epilepsy; G-protein coupled receptor;
KW Glycoprotein; Intellectual disability; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Sensory transduction; Signal; Transducer;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..34
FT /evidence="ECO:0000255"
FT CHAIN 35..915
FT /note="Metabotropic glutamate receptor 7"
FT /id="PRO_0000012938"
FT TOPO_DOM 35..590
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 591..615
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 616..627
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 628..648
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 649..654
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 655..675
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 676..702
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 703..723
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 724..753
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 754..775
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 776..788
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 789..810
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 811..825
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 826..850
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 851..915
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 874..895
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 159
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 180..182
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 230
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 314
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 407
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT MOD_RES 900
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68ED2"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 458
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 486
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 572
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 67..109
FT /evidence="ECO:0000250"
FT DISULFID 249..541
FT /evidence="ECO:0000250"
FT DISULFID 374..390
FT /evidence="ECO:0000250"
FT DISULFID 430..437
FT /evidence="ECO:0000250"
FT DISULFID 523..542
FT /evidence="ECO:0000250"
FT DISULFID 527..545
FT /evidence="ECO:0000250"
FT DISULFID 548..560
FT /evidence="ECO:0000250"
FT DISULFID 563..576
FT /evidence="ECO:0000250"
FT VAR_SEQ 900..915
FT /note="SPAAKKKYVSYNNLVI -> NCIPPVRKSVQKSVTWYTIPPTV (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:9144652"
FT /id="VSP_015735"
FT VAR_SEQ 900..915
FT /note="SPAAKKKYVSYNNLVI -> NFFFWLYSGTW (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12052533"
FT /id="VSP_015732"
FT VAR_SEQ 900..915
FT /note="SPAAKKKYVSYNNLVI -> ITSEDLSLHKED (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12052533"
FT /id="VSP_015733"
FT VAR_SEQ 900..915
FT /note="SPAAKKKYVSYNNLVI -> SEKCNCY (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:12052533"
FT /id="VSP_015734"
FT VARIANT 154
FT /note="I -> T (in NEDSHBA; does not rescue axon outgrowth
FT defects when expressed in an heterologous system; decreased
FT protein abundance; increased proteasomal degradation;
FT decreased homodimerization; decreased localization to the
FT cell membrane; dbSNP:rs1114167298)"
FT /evidence="ECO:0000269|PubMed:27435318,
FT ECO:0000269|PubMed:32286009, ECO:0000269|PubMed:33476302,
FT ECO:0000269|PubMed:33500274"
FT /id="VAR_084620"
FT VARIANT 433
FT /note="Y -> F (in dbSNP:rs2229902)"
FT /evidence="ECO:0000269|PubMed:11163549"
FT /id="VAR_003584"
FT VARIANT 495
FT /note="I -> V (in dbSNP:rs7634846)"
FT /id="VAR_049276"
FT VARIANT 586..915
FT /note="Missing (in NEDSHBA; does not rescue axon outgrowth
FT defects when expressed in an heterologous system)"
FT /evidence="ECO:0000269|PubMed:28097321,
FT ECO:0000269|PubMed:32286009"
FT /id="VAR_084621"
FT VARIANT 658
FT /note="R -> Q (in NEDSHBA; unknown pathological
FT significance; dbSNP:rs769709112)"
FT /evidence="ECO:0000269|PubMed:32286009"
FT /id="VAR_084622"
FT VARIANT 658
FT /note="R -> W (in NEDSHBA; unknown pathological
FT significance; dbSNP:rs1114167300)"
FT /evidence="ECO:0000269|PubMed:27435318,
FT ECO:0000269|PubMed:32286009, ECO:0000269|PubMed:33500274"
FT /id="VAR_084623"
FT VARIANT 659..915
FT /note="Missing (in NEDSHBA)"
FT /evidence="ECO:0000269|PubMed:32286009"
FT /id="VAR_084624"
FT VARIANT 675
FT /note="T -> K (in NEDSHBA; unknown pathological
FT significance; dbSNP:rs1114167301)"
FT /evidence="ECO:0000269|PubMed:27435318,
FT ECO:0000269|PubMed:32286009, ECO:0000269|PubMed:33500274"
FT /id="VAR_084625"
FT VARIANT 745
FT /note="G -> E (in dbSNP:rs1485174)"
FT /id="VAR_049277"
FT VARIANT 856..915
FT /note="Missing (in NEDSHBA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28097321"
FT /id="VAR_084626"
FT VARIANT 891
FT /note="E -> K (in NEDSHBA; unknown pathological
FT significance; dbSNP:rs746833089)"
FT /evidence="ECO:0000269|PubMed:32286009"
FT /id="VAR_084627"
FT MUTAGEN 622
FT /note="R->Q: Rescues axon outgrowth defects when expressed
FT in an heterologous system. Unchanged protein abundance.
FT Does not affect localization to the plasma membrane. Does
FT not affect N-glycosylation. Does not affect
FT homodimerization."
FT /evidence="ECO:0000269|PubMed:33500274"
FT MUTAGEN 658
FT /note="R->W: Does not rescue axon outgrowth defects when
FT expressed in an heterologous system; when associated with
FT K-675. Decreased protein abundance due to increased
FT proteasomal degradation; when associated with K-675. Loss
FT of localization to the cell membrane; when associated with
FT K-675."
FT /evidence="ECO:0000269|PubMed:33500274"
FT MUTAGEN 675
FT /note="T->K: Does not rescue axon outgrowth defects when
FT expressed in an heterologous system; when associated with
FT W-658. Decreased protein abundance due to increased
FT proteasomal degradation; when associated with W-658. Loss
FT of localization to the cell membrane; when associated with
FT W-658."
FT /evidence="ECO:0000269|PubMed:33500274"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 48..55
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:5C5C"
FT TURN 72..75
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 76..90
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 93..98
FT /evidence="ECO:0007829|PDB:3MQ4"
FT STRAND 101..107
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 112..119
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:5C5C"
FT TURN 124..126
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 150..154
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 159..171
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 184..187
FT /evidence="ECO:0007829|PDB:5C5C"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 195..199
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 202..215
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 220..228
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 229..245
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 249..256
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 267..275
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 282..287
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 289..301
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 308..314
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 334..338
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 344..351
FT /evidence="ECO:0007829|PDB:5C5C"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 364..371
FT /evidence="ECO:0007829|PDB:5C5C"
FT TURN 396..398
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 408..429
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 438..453
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 456..458
FT /evidence="ECO:0007829|PDB:3MQ4"
FT STRAND 462..465
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 477..483
FT /evidence="ECO:0007829|PDB:5C5C"
FT STRAND 491..504
FT /evidence="ECO:0007829|PDB:5C5C"
FT HELIX 506..508
FT /evidence="ECO:0007829|PDB:5C5C"
SQ SEQUENCE 915 AA; 102251 MW; CFF94E06BF7F4919 CRC64;
MVQLRKLLRV LTLMKFPCCV LEVLLCALAA AARGQEMYAP HSIRIEGDVT LGGLFPVHAK
GPSGVPCGDI KRENGIHRLE AMLYALDQIN SDPNLLPNVT LGARILDTCS RDTYALEQSL
TFVQALIQKD TSDVRCTNGE PPVFVKPEKV VGVIGASGSS VSIMVANILR LFQIPQISYA
STAPELSDDR RYDFFSRVVP PDSFQAQAMV DIVKALGWNY VSTLASEGSY GEKGVESFTQ
ISKEAGGLCI AQSVRIPQER KDRTIDFDRI IKQLLDTPNS RAVVIFANDE DIKQILAAAK
RADQVGHFLW VGSDSWGSKI NPLHQHEDIA EGAITIQPKR ATVEGFDAYF TSRTLENNRR
NVWFAEYWEE NFNCKLTISG SKKEDTDRKC TGQERIGKDS NYEQEGKVQF VIDAVYAMAH
ALHHMNKDLC ADYRGVCPEM EQAGGKKLLK YIRNVNFNGS AGTPVMFNKN GDAPGRYDIF
QYQTTNTSNP GYRLIGQWTD ELQLNIEDMQ WGKGVREIPA SVCTLPCKPG QRKKTQKGTP
CCWTCEPCDG YQYQFDEMTC QHCPYDQRPN ENRTGCQDIP IIKLEWHSPW AVIPVFLAML
GIIATIFVMA TFIRYNDTPI VRASGRELSY VLLTGIFLCY IITFLMIAKP DVAVCSFRRV
FLGLGMCISY AALLTKTNRI YRIFEQGKKS VTAPRLISPT SQLAITSSLI SVQLLGVFIW
FGVDPPNIII DYDEHKTMNP EQARGVLKCD ITDLQIICSL GYSILLMVTC TVYAIKTRGV
PENFNEAKPI GFTMYTTCIV WLAFIPIFFG TAQSAEKLYI QTTTLTISMN LSASVALGML
YMPKVYIIIF HPELNVQKRK RSFKAVVTAA TMSSRLSHKP SDRPNGEAKT ELCENVDPNS
PAAKKKYVSY NNLVI
