ID GPM6A_RAT Reviewed; 278 AA. AC Q812E9; DT 13-JUN-2012, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 1. DT 24-JAN-2024, entry version 118. DE RecName: Full=Neuronal membrane glycoprotein M6-a; DE Short=M6a; GN Name=Gpm6a; Synonyms=m6a; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION. RX PubMed=12359212; DOI=10.1016/s0006-291x(02)02284-2; RA Mukobata S., Hibino T., Sugiyama A., Urano Y., Inatomi A., Kanai Y., RA Endo H., Tashiro F.; RT "M6a acts as a nerve growth factor-gated Ca(2+) channel in neuronal RT differentiation."; RL Biochem. Biophys. Res. Commun. 297:722-728(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-188 (ISOFORM 2). RX PubMed=15326124; DOI=10.1167/iovs.04-0302; RA Ahmed F., Torrado M., Zinovieva R.D., Senatorov V.V., Wistow G., RA Tomarev S.I.; RT "Gene expression profile of the rat eye iridocorneal angle: NEIBank RT expressed sequence tag analysis."; RL Invest. Ophthalmol. Vis. Sci. 45:3081-3090(2004). RN [5] RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=16286650; DOI=10.1073/pnas.0504262102; RA Alfonso J., Fernandez M.E., Cooper B., Flugge G., Frasch A.C.; RT "The stress-regulated protein M6a is a key modulator for neurite outgrowth RT and filopodium/spine formation."; RL Proc. Natl. Acad. Sci. U.S.A. 102:17196-17201(2005). RN [6] RP FUNCTION, AND INTERACTION WITH OPRM1. RX PubMed=17548356; DOI=10.1074/jbc.m700941200; RA Wu D.F., Koch T., Liang Y.J., Stumm R., Schulz S., Schroder H., Hollt V.; RT "Membrane glycoprotein M6a interacts with the micro-opioid receptor and RT facilitates receptor endocytosis and recycling."; RL J. Biol. Chem. 282:22239-22247(2007). RN [7] RP FUNCTION, TOPOLOGY, DISULFIDE BOND, AND MUTAGENESIS OF CYS-162; CYS-174; RP CYS-192 AND CYS-202. RX PubMed=19737934; DOI=10.1074/jbc.m109.012377; RA Fuchsova B., Fernandez M.E., Alfonso J., Frasch A.C.; RT "Cysteine residues in the large extracellular loop (EC2) are essential for RT the function of the stress-regulated glycoprotein M6a."; RL J. Biol. Chem. 284:32075-32088(2009). RN [8] RP ALTERNATIVE SPLICING (ISOFORM 2), TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=19180239; DOI=10.1371/journal.pone.0003659; RA Cooper B., Fuchs E., Flugge G.; RT "Expression of the axonal membrane glycoprotein M6a is regulated by chronic RT stress."; RL PLoS ONE 4:E3659-E3659(2009). RN [9] RP FUNCTION, MUTAGENESIS OF THR-10; SER-256; SER-267 AND THR-268, AND RP SUBCELLULAR LOCATION. RX PubMed=20074218; DOI=10.1111/j.1460-9568.2009.07064.x; RA Brocco M.A., Fernandez M.E., Frasch A.C.; RT "Filopodial protrusions induced by glycoprotein M6a exhibit high motility RT and aids synapse formation."; RL Eur. J. Neurosci. 31:195-202(2010). RN [10] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=21426347; DOI=10.1111/j.1471-4159.2011.07252.x; RA Scorticati C., Formoso K., Frasch A.C.; RT "Neuronal glycoprotein M6a induces filopodia formation via association with RT cholesterol-rich lipid rafts."; RL J. Neurochem. 119:521-531(2011). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-256 AND THR-278, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Involved in neuronal differentiation, including CC differentiation and migration of neuronal stem cells (By similarity). CC Plays a role in neuronal plasticity and is involved in neurite and CC filopodia outgrowth, filopodia motility and probably synapse formation. CC Gpm6a-induced filopodia formation involves mitogen-activated protein CC kinase (MAPK) and Src signaling pathways. May be involved in neuronal CC NGF-dependent Ca(2+) influx. May be involved in regulation of CC endocytosis and intracellular trafficking of G-protein-coupled CC receptors (GPCRs); enhances internalization and recycling of mu-type CC opioid receptor. {ECO:0000250, ECO:0000269|PubMed:12359212, CC ECO:0000269|PubMed:16286650, ECO:0000269|PubMed:17548356, CC ECO:0000269|PubMed:19737934, ECO:0000269|PubMed:20074218, CC ECO:0000269|PubMed:21426347}. CC -!- SUBUNIT: Interacts with OPRM1 (PubMed:17548356). Interacts with CC palmitoyltransferase ZDHHC17/HIP14; the interaction leads to CC palmitoylation of GPM6A (By similarity). {ECO:0000250|UniProtKB:P51674, CC ECO:0000269|PubMed:17548356}. CC -!- INTERACTION: CC Q812E9; P33535: Oprm1; NbExp=7; IntAct=EBI-6113756, EBI-4392569; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16286650, CC ECO:0000269|PubMed:21426347}; Multi-pass membrane protein. Cell CC projection, axon {ECO:0000269|PubMed:20074218}. Cell projection, growth CC cone {ECO:0000250|UniProtKB:P35802}. Cell projection, dendritic spine CC {ECO:0000269|PubMed:16286650}. Cell projection, filopodium CC {ECO:0000269|PubMed:16286650}. Cell projection, neuron projection CC {ECO:0000269|PubMed:16286650, ECO:0000269|PubMed:21426347}. CC Note=Localizes to cholesterol-rich lipid rafts of the plasma membrane CC of hippocampal neurons (PubMed:21426347). Localized to plasma membrane CC of cell bodies and neurites of hippocampal neurons (PubMed:16286650). CC Localized in membrane protrusions (filopodia and spines) of primary CC hippocampal neurons (PubMed:16286650). Localized to the growth cone CC edge membrane of elongating axons (By similarity). CC {ECO:0000250|UniProtKB:P35802, ECO:0000269|PubMed:16286650, CC ECO:0000269|PubMed:21426347}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Ib; CC IsoId=Q812E9-1; Sequence=Displayed; CC Name=2; Synonyms=Ia; CC IsoId=Q812E9-2; Sequence=VSP_043957; CC -!- TISSUE SPECIFICITY: Expressed in hippocampus (at protein level). CC Isoform 1 is the predominant isoform expressed in brain, specifically CC in hippocampus. Isoform 2 is expressed at low levels in brain and CC kidney. {ECO:0000269|PubMed:16286650, ECO:0000269|PubMed:19180239}. CC -!- INDUCTION: [Isoform 1]: Down-regulated by chronic stress in dentate CC gyrus granule neurons and CA3 pyramidal neurons. CC {ECO:0000269|PubMed:19180239}. CC -!- INDUCTION: [Isoform 2]: Up-regulated in the medial prefrontal cortex. CC {ECO:0000269|PubMed:19180239}. CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P51674}. CC -!- PTM: Palmitoylated by ZDHHC17/HIP14. {ECO:0000250|UniProtKB:P51674}. CC -!- SIMILARITY: Belongs to the myelin proteolipid protein family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB089242; BAC56699.1; -; mRNA. DR EMBL; CH473995; EDL78956.1; -; Genomic_DNA. DR EMBL; BC088862; AAH88862.1; -; mRNA. DR EMBL; DV216104; -; NOT_ANNOTATED_CDS; mRNA. DR RefSeq; NP_835206.1; NM_178105.2. [Q812E9-1] DR AlphaFoldDB; Q812E9; -. DR BioGRID; 258452; 1. DR IntAct; Q812E9; 1. DR STRING; 10116.ENSRNOP00000014312; -. DR GlyCosmos; Q812E9; 2 sites, No reported glycans. DR GlyGen; Q812E9; 2 sites. DR iPTMnet; Q812E9; -. DR PhosphoSitePlus; Q812E9; -. DR SwissPalm; Q812E9; -. DR PaxDb; 10116-ENSRNOP00000014312; -. DR Ensembl; ENSRNOT00000014312.8; ENSRNOP00000014312.4; ENSRNOG00000010731.8. [Q812E9-1] DR Ensembl; ENSRNOT00000092971.2; ENSRNOP00000075962.1; ENSRNOG00000010731.8. [Q812E9-2] DR Ensembl; ENSRNOT00055013096; ENSRNOP00055010475; ENSRNOG00055007814. [Q812E9-1] DR Ensembl; ENSRNOT00060011789; ENSRNOP00060008879; ENSRNOG00060007153. [Q812E9-1] DR Ensembl; ENSRNOT00065024489; ENSRNOP00065019120; ENSRNOG00065014802. [Q812E9-1] DR GeneID; 306439; -. DR KEGG; rno:306439; -. DR AGR; RGD:631368; -. DR CTD; 2823; -. DR RGD; 631368; Gpm6a. DR eggNOG; KOG4800; Eukaryota. DR GeneTree; ENSGT00390000006915; -. DR HOGENOM; CLU_064167_2_0_1; -. DR InParanoid; Q812E9; -. DR OMA; IQDENTH; -. DR OrthoDB; 3091734at2759; -. DR PhylomeDB; Q812E9; -. DR TreeFam; TF315162; -. DR PRO; PR:Q812E9; -. DR Proteomes; UP000002494; Chromosome 16. DR Proteomes; UP000234681; Chromosome 16. DR Bgee; ENSRNOG00000010731; Expressed in frontal cortex and 19 other cell types or tissues. DR ExpressionAtlas; Q812E9; baseline and differential. DR GO; GO:0044295; C:axonal growth cone; ISS:UniProtKB. DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell. DR GO; GO:0030175; C:filopodium; IDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB. DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IDA:SynGO. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0098793; C:presynapse; IDA:SynGO. DR GO; GO:0048787; C:presynaptic active zone membrane; IDA:SynGO. DR GO; GO:0005262; F:calcium channel activity; IDA:RGD. DR GO; GO:0003407; P:neural retina development; ISS:UniProtKB. DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB. DR GO; GO:0031175; P:neuron projection development; IBA:GO_Central. DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:UniProtKB. DR GO; GO:0051491; P:positive regulation of filopodium assembly; IDA:UniProtKB. DR GO; GO:0050807; P:regulation of synapse organization; IDA:SynGO. DR GO; GO:0009617; P:response to bacterium; ISO:RGD. DR GO; GO:0048863; P:stem cell differentiation; ISS:UniProtKB. DR GO; GO:0007416; P:synapse assembly; IDA:UniProtKB. DR InterPro; IPR001614; Myelin_PLP. DR InterPro; IPR018237; Myelin_PLP_CS. DR PANTHER; PTHR11683; MYELIN PROTEOLIPID; 1. DR PANTHER; PTHR11683:SF4; NEURONAL MEMBRANE GLYCOPROTEIN M6-A; 1. DR Pfam; PF01275; Myelin_PLP; 1. DR PRINTS; PR00214; MYELINPLP. DR SMART; SM00002; PLP; 1. DR PROSITE; PS00575; MYELIN_PLP_1; 1. DR PROSITE; PS01004; MYELIN_PLP_2; 1. DR Genevisible; Q812E9; RN. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Cell membrane; Cell projection; KW Disulfide bond; Glycoprotein; Lipoprotein; Membrane; Neurogenesis; KW Palmitate; Phosphoprotein; Reference proteome; Synapse; Transmembrane; KW Transmembrane helix. FT CHAIN 1..278 FT /note="Neuronal membrane glycoprotein M6-a" FT /id="PRO_0000418016" FT TOPO_DOM 1..22 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 23..43 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 44..84 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 85..105 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 106..127 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 128..148 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 149..213 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:19737934" FT TRANSMEM 214..234 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 235..278 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000250|UniProtKB:P51674" FT MOD_RES 256 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 278 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:22673903" FT CARBOHYD 164 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 208 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 174..192 FT /evidence="ECO:0000269|PubMed:19737934" FT VAR_SEQ 1..12 FT /note="MEENMEEGQTQK -> M (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15326124" FT /id="VSP_043957" FT MUTAGEN 10 FT /note="T->A: Reduces motility of Gpm6a-induced filopodia; FT when associated with A-256, A-267 and A-268." FT /evidence="ECO:0000269|PubMed:20074218" FT MUTAGEN 162 FT /note="C->A: Abolishess cell surface expression." FT /evidence="ECO:0000269|PubMed:19737934" FT MUTAGEN 174 FT /note="C->A: Impairs Gpm6a-induced filopodium formation." FT /evidence="ECO:0000269|PubMed:19737934" FT MUTAGEN 174 FT /note="C->A: Impairs synaptic density in primary FT hippocampal neurons; when associated with A-192." FT /evidence="ECO:0000269|PubMed:19737934" FT MUTAGEN 192 FT /note="C->A: Impairs Gpm6a-induced filopodium formation." FT /evidence="ECO:0000269|PubMed:19737934" FT MUTAGEN 192 FT /note="C->A: Impairs synaptic density in primary FT hippocampal neurons; when associated with A-174." FT /evidence="ECO:0000269|PubMed:19737934" FT MUTAGEN 202 FT /note="C->A: Abolishess cell surface expression." FT /evidence="ECO:0000269|PubMed:19737934" FT MUTAGEN 256 FT /note="S->A: Reduces motility of Gpm6a-induced filopodia; FT when associated with A-10, A-267 and A-268." FT /evidence="ECO:0000269|PubMed:20074218" FT MUTAGEN 267 FT /note="S->A: Reduces motility of Gpm6a-induced filopodia; FT when associated with A-10, A-256 and A-268." FT /evidence="ECO:0000269|PubMed:20074218" FT MUTAGEN 268 FT /note="T->A: Reduces motility of Gpm6a-induced filopodia; FT when associated with A-10, A-256 and A-267." FT /evidence="ECO:0000269|PubMed:20074218" SQ SEQUENCE 278 AA; 31196 MW; D2EDAF98C0E8715D CRC64; MEENMEEGQT QKGCFECCIK CLGGIPYASL IATILLYAGV ALFCGCGHEA LSGTVNILQT YFEMARTAGD TLDVFTMIDI FKYVIYGIAA AFFVYGILLM VEGFFTTGAI KDLYGDFKIT TCGRCVSAWF IMLTYLFMLA WLGVTAFTSL PVYMYFNVWT ICRNTTLVEG ANLCLDLRQF GIVTIGEEKK ICTVSENFLR MCESTELNMT FHLFIVALAG AGAAVIAMVH YLMVLSANWA YVKDACRMQK YEDIKSKEEQ ELHDIHSTRS KERLNAYT //