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   24-JAN-2024, entry version 174.
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}.
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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; 30.
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   GlyCosmos; P35802; 2 sites, No reported glycans.
DR   GlyGen; P35802; 3 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; P35802; -.
DR   MetOSite; P35802; -.
DR   PhosphoSitePlus; P35802; -.
DR   SwissPalm; P35802; -.
DR   jPOST; P35802; -.
DR   PaxDb; 10090-ENSMUSP00000033915; -.
DR   PeptideAtlas; P35802; -.
DR   ProteomicsDB; 271144; -.
DR   Antibodypedia; 17235; 363 antibodies from 32 providers.
DR   DNASU; 234267; -.
DR   Ensembl; ENSMUST00000033915.9; ENSMUSP00000033915.8; ENSMUSG00000031517.9.
DR   GeneID; 234267; -.
DR   KEGG; mmu:234267; -.
DR   UCSC; uc009lsl.2; mouse.
DR   AGR; MGI:107671; -.
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; IQDENTH; -.
DR   OrthoDB; 3091734at2759; -.
DR   PhylomeDB; P35802; -.
DR   TreeFam; TF315162; -.
DR   BioGRID-ORCS; 234267; 1 hit in 76 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 221 other cell types or tissues.
DR   ExpressionAtlas; P35802; baseline and differential.
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:0043005; C:neuron projection; ISS:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR   GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0098793; C:presynapse; ISO:MGI.
DR   GO; GO:0048787; C:presynaptic active zone membrane; ISO:MGI.
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; 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; P35802; MM.
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
//