GPM6A_MOUSE
ID GPM6A_MOUSE Reviewed; 278 AA.
AC P35802;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Neuronal membrane glycoprotein M6-a;
DE Short=M6a;
GN Name=Gpm6a; Synonyms=M6a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 67-78.
RC TISSUE=Brain;
RX PubMed=8398137; DOI=10.1016/0896-6273(93)90147-j;
RA Yan Y., Lagenaur C., Narayanan V.;
RT "Molecular cloning of M6: identification of a PLP/DM20 gene family.";
RL Neuron 11:423-431(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, Eye, and Retina;
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 [3]
RP PROTEIN SEQUENCE OF 13-20; 67-82; 112-118; 179-200 AND 256-269, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP FUNCTION, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=18776950;
RA Zhao J., Iida A., Ouchi Y., Satoh S., Watanabe S.;
RT "M6a is expressed in the murine neural retina and regulates neurite
RT extension.";
RL Mol. Vis. 14:1623-1630(2008).
RN [5]
RP FUNCTION.
RX PubMed=18522499; DOI=10.1089/scd.2008.0088;
RA Michibata H., Okuno T., Konishi N., Wakimoto K., Kyono K., Aoki K.,
RA Kondo Y., Takata K., Kitamura Y., Taniguchi T.;
RT "Inhibition of mouse GPM6A expression leads to decreased differentiation of
RT neurons derived from mouse embryonic stem cells.";
RL Stem Cells Dev. 17:641-651(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-256, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=21714103; DOI=10.1002/dneu.20941;
RA Sato Y., Mita S., Fukushima N., Fujisawa H., Saga Y., Hirata T.;
RT "Induction of axon growth arrest without growth cone collapse through the
RT N-terminal region of four-transmembrane glycoprotein M6a.";
RL Dev. Neurobiol. 71:733-746(2011).
RN [8]
RP FUNCTION.
RX PubMed=22162747; DOI=10.1371/journal.pone.0026702;
RA Sato Y., Watanabe N., Fukushima N., Mita S., Hirata T.;
RT "Actin-independent behavior and membrane deformation exhibited by the four-
RT transmembrane protein M6a.";
RL PLoS ONE 6:E26702-E26702(2011).
CC -!- FUNCTION: Involved in neuronal differentiation, including
CC differentiation and migration of neuronal stem cells. Plays a role in
CC neuronal plasticity and is involved in neurite and filopodia outgrowth,
CC filopodia motility and probably synapse formation. Gpm6a-induced
CC filopodia formation involves mitogen-activated protein kinase (MAPK)
CC and Src signaling pathways. Conflictingly, PubMed:22162747 reports that
CC induced cellular protrusions are simple membrane-wrapped tubules
CC without actin or tubulin-based cytoskeletons and with Gpm6a gliding
CC along membrane edges indicative for a function in actin-independent
CC membrane deformation. May be involved in neuronal NGF-dependent Ca(2+)
CC influx. May be involved in regulation of endocytosis and intracellular
CC trafficking of G-protein-coupled receptors (GPCRs); enhances
CC internalization and recycling of mu-type opioid receptor.
CC {ECO:0000269|PubMed:18522499, ECO:0000269|PubMed:18776950,
CC ECO:0000269|PubMed:22162747}.
CC -!- SUBUNIT: Interacts with OPRM1 (By similarity). Interacts with
CC palmitoyltransferase ZDHHC17/HIP14; the interaction leads to
CC palmitoylation of GPM6A (By similarity). {ECO:0000250|UniProtKB:P51674,
CC ECO:0000250|UniProtKB:Q812E9}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21714103};
CC Multi-pass membrane protein {ECO:0000269|PubMed:21714103}. Cell
CC projection, axon {ECO:0000269|PubMed:21714103}. Cell projection, growth
CC cone {ECO:0000269|PubMed:21714103}. Cell projection, dendritic spine
CC {ECO:0000250|UniProtKB:Q812E9}. Cell projection, filopodium
CC {ECO:0000250|UniProtKB:Q812E9}. Cell projection, neuron projection
CC {ECO:0000250|UniProtKB:Q812E9}. Note=Localizes to cholesterol-rich
CC lipid rafts of the plasma membrane of hippocampal neurons. Localized to
CC plasma membrane of cell bodies and neurites of hippocampal neurons.
CC Localized in membrane protrusions (filopodia and spines) of primary
CC hippocampal neurons (By similarity). Localized to the growth cone edge
CC membrane of elongating axons (PubMed:21714103).
CC {ECO:0000250|UniProtKB:Q812E9, ECO:0000269|PubMed:21714103}.
CC -!- TISSUE SPECIFICITY: Widely expressed in the CNS. Found especially in
CC the granule cell layer of the cerebellum but not in the molecular layer
CC or white matter. Expressed in the immature embryonic retina including
CC the nerve fiber layer (NFL), inner plexiform layer (IPL), and outer
CC plexiform layer (OPL). Weakly expressed in processes of Mueller glia
CC cells. {ECO:0000269|PubMed:18776950}.
CC -!- DEVELOPMENTAL STAGE: First detected in presumptive postmitotic neurons
CC in the developing neural tube at embryonic day 9. Expressed in 14 dpc
CC retinas, and expression continued after birth with a slight decrease
CC between P12 and P15. In the 14 dpc retina is mainly and strongly
CC expressed in the NFL. In P1 and P5 retinas strong expression is
CC confined to the IPL and also in NFL. At P10 and in the adult retina
CC strong expression is detected in the IPL, and weak expression in NFL,
CC OPL, and inner nuclear layer. Is expressed on postmitotic mature
CC neurons. {ECO:0000269|PubMed:18776950}.
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; S65735; AAB28350.1; -; mRNA.
DR EMBL; BC024759; AAH24759.1; -; mRNA.
DR EMBL; BC029683; AAH29683.1; -; mRNA.
DR EMBL; BC029711; AAH29711.1; -; mRNA.
DR EMBL; BC033357; AAH33357.1; -; mRNA.
DR EMBL; BC033394; AAH33394.1; -; mRNA.
DR EMBL; BC043130; AAH43130.1; -; mRNA.
DR CCDS; CCDS22310.1; -.
DR RefSeq; NP_001240683.1; NM_001253754.1.
DR RefSeq; NP_001240685.1; NM_001253756.1.
DR RefSeq; NP_705809.1; NM_153581.6.
DR AlphaFoldDB; P35802; -.
DR BioGRID; 231507; 25.
DR IntAct; P35802; 3.
DR MINT; P35802; -.
DR STRING; 10090.ENSMUSP00000033915; -.
DR TCDB; 9.B.38.1.1; the myelin proteolipid protein (mplp) family.
DR GlyGen; P35802; 2 sites.
DR iPTMnet; P35802; -.
DR PhosphoSitePlus; P35802; -.
DR SwissPalm; P35802; -.
DR jPOST; P35802; -.
DR PaxDb; P35802; -.
DR PeptideAtlas; P35802; -.
DR PRIDE; P35802; -.
DR ProteomicsDB; 271144; -.
DR Antibodypedia; 17235; 314 antibodies from 32 providers.
DR DNASU; 234267; -.
DR Ensembl; ENSMUST00000033915; ENSMUSP00000033915; ENSMUSG00000031517.
DR GeneID; 234267; -.
DR KEGG; mmu:234267; -.
DR UCSC; uc009lsl.2; mouse.
DR CTD; 2823; -.
DR MGI; MGI:107671; Gpm6a.
DR VEuPathDB; HostDB:ENSMUSG00000031517; -.
DR eggNOG; KOG4800; Eukaryota.
DR GeneTree; ENSGT00390000006915; -.
DR HOGENOM; CLU_064167_2_0_1; -.
DR InParanoid; P35802; -.
DR OMA; YFEMTRA; -.
DR OrthoDB; 914457at2759; -.
DR PhylomeDB; P35802; -.
DR TreeFam; TF315162; -.
DR BioGRID-ORCS; 234267; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Gpm6a; mouse.
DR PRO; PR:P35802; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P35802; protein.
DR Bgee; ENSMUSG00000031517; Expressed in subiculum and 219 other tissues.
DR ExpressionAtlas; P35802; baseline and differential.
DR Genevisible; P35802; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0044295; C:axonal growth cone; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0099059; C:integral component of presynaptic active zone membrane; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005262; F:calcium channel activity; ISO:MGI.
DR GO; GO:0003407; P:neural retina development; IDA: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; IDA:UniProtKB.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISS:UniProtKB.
DR GO; GO:0050807; P:regulation of synapse organization; ISO:MGI.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0048863; P:stem cell differentiation; ISS:UniProtKB.
DR GO; GO:0007416; P:synapse assembly; ISS: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; Cell membrane; Cell projection; Direct protein sequencing;
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_0000159019"
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:0000250"
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:21183079"
FT MOD_RES 278
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q812E9"
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:0000250"
SQ SEQUENCE 278 AA; 31149 MW; CEE0688873E786CE CRC64;
MEENMEEGQT QKGCFECCIK CLGGIPYASL IATILLYAGV ALFCGCGHEA LSGTVNILQT
YFELARTAGD TLDVFTMIDI FKYVIYGIAA AFFVYGILLM VEGFFTTGAI KDLYGDFKIT
TCGRCVSAWF IMLTYLFMLA WLGVTAFTSL PVYMYFNVWT ICRNTTLVEG ANLCLDLRQF
GIVTIGEEKK ICTASENFLR MCESTELNMT FHLFIVALAG AGAAVIAMVH YLMVLSANWA
YVKDACRMQK YEDIKSKEEQ ELHDIHSTRS KERLNAYT
