GPM6A_RAT
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 03-AUG-2022, entry version 111.
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}.
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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 RefSeq; XP_017455597.1; XM_017600108.1. [Q812E9-2]
DR AlphaFoldDB; Q812E9; -.
DR BioGRID; 258452; 1.
DR IntAct; Q812E9; 1.
DR STRING; 10116.ENSRNOP00000014312; -.
DR GlyGen; Q812E9; 2 sites.
DR iPTMnet; Q812E9; -.
DR PhosphoSitePlus; Q812E9; -.
DR SwissPalm; Q812E9; -.
DR PaxDb; Q812E9; -.
DR PRIDE; Q812E9; -.
DR Ensembl; ENSRNOT00000014312; ENSRNOP00000014312; ENSRNOG00000010731. [Q812E9-1]
DR Ensembl; ENSRNOT00000092971; ENSRNOP00000075962; ENSRNOG00000010731. [Q812E9-2]
DR GeneID; 306439; -.
DR KEGG; rno:306439; -.
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; YFEMTRA; -.
DR OrthoDB; 914457at2759; -.
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 tissues.
DR ExpressionAtlas; Q812E9; baseline and differential.
DR Genevisible; Q812E9; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:0099059; C:integral component of presynaptic active zone membrane; IDA:SynGO.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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; PTHR11683; 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.
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
