GPM6A_HUMAN
ID GPM6A_HUMAN Reviewed; 278 AA.
AC P51674; B7Z642; E9PHI5; Q92602;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Neuronal membrane glycoprotein M6-a;
DE Short=M6a;
GN Name=GPM6A; Synonyms=M6A;
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).
RC TISSUE=Fetal brain;
RX PubMed=8893821; DOI=10.1159/000134401;
RA Shimizu F., Watanabe T.K., Fujiwara T., Takahashi E., Nakamura Y.,
RA Maekawa H.;
RT "Isolation and mapping of the human glycoprotein M6 gene (GPM6A) to
RT 4q33-->q34.";
RL Cytogenet. Cell Genet. 74:138-139(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 100-278.
RC TISSUE=Spinal cord;
RX PubMed=8661015; DOI=10.1006/geno.1996.0231;
RA Olinsky S., Loop B.T., Dekosky A., Ripepi B., Weng W., Cummins J.,
RA Wenger S.L., Yan Y., Lagenaur C., Narayanan V.;
RT "Chromosomal mapping of the human M6 genes.";
RL Genomics 33:532-536(1996).
RN [7]
RP FUNCTION.
RX PubMed=19298174; DOI=10.1089/scd.2008.0215;
RA Michibata H., Okuno T., Konishi N., Kyono K., Wakimoto K., Aoki K.,
RA Kondo Y., Takata K., Kitamura Y., Taniguchi T.;
RT "Human GPM6A is associated with differentiation and neuronal migration of
RT neurons derived from human embryonic stem cells.";
RL Stem Cells Dev. 18:629-639(2009).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [9]
RP INTERACTION WITH ZDHHC17, GLYCOSYLATION, AND PALMITOYLATION.
RX PubMed=24705354; DOI=10.1093/hmg/ddu137;
RA Butland S.L., Sanders S.S., Schmidt M.E., Riechers S.P., Lin D.T.,
RA Martin D.D., Vaid K., Graham R.K., Singaraja R.R., Wanker E.E.,
RA Conibear E., Hayden M.R.;
RT "The palmitoyl acyltransferase HIP14 shares a high proportion of
RT interactors with huntingtin: implications for a role in the pathogenesis of
RT Huntington's disease.";
RL Hum. Mol. Genet. 23:4142-4160(2014).
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. May be involved in neuronal NGF-dependent
CC Ca(2+) influx. May be involved in regulation of endocytosis and
CC intracellular trafficking of G-protein-coupled receptors (GPCRs);
CC enhances internalization and recycling of mu-type opioid receptor.
CC {ECO:0000269|PubMed:19298174}.
CC -!- SUBUNIT: Interacts with OPRM1 (By similarity). Interacts with
CC palmitoyltransferase ZDHHC17/HIP14; the interaction leads to
CC palmitoylation of GPM6A (PubMed:24705354).
CC {ECO:0000250|UniProtKB:Q812E9, ECO:0000269|PubMed:24705354}.
CC -!- INTERACTION:
CC P51674; P42858: HTT; NbExp=4; IntAct=EBI-7187133, EBI-466029;
CC P51674; Q9UMF0: ICAM5; NbExp=3; IntAct=EBI-7187133, EBI-6398041;
CC P51674; O14901: KLF11; NbExp=3; IntAct=EBI-7187133, EBI-948266;
CC P51674; P37173: TGFBR2; NbExp=3; IntAct=EBI-7187133, EBI-296151;
CC P51674; Q5T9L3-1: WLS; NbExp=2; IntAct=EBI-7187133, EBI-22114623;
CC P51674; Q8IUH5: ZDHHC17; NbExp=5; IntAct=EBI-7187133, EBI-524753;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P35802};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P35802}. Cell
CC projection, axon {ECO:0000250|UniProtKB:P35802}. Cell projection,
CC growth cone {ECO:0000250|UniProtKB:P35802}. Cell projection, dendritic
CC spine {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 (By similarity).
CC {ECO:0000250|UniProtKB:P35802, ECO:0000250|UniProtKB:Q812E9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P51674-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P51674-2; Sequence=VSP_045109;
CC Name=3;
CC IsoId=P51674-3; Sequence=VSP_046098;
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:24705354}.
CC -!- PTM: Palmitoylated by ZDHHC17/HIP14. {ECO:0000269|PubMed:24705354}.
CC -!- SIMILARITY: Belongs to the myelin proteolipid protein family.
CC {ECO:0000305}.
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DR EMBL; D49958; BAA08712.1; -; mRNA.
DR EMBL; AK299788; BAH13128.1; -; mRNA.
DR EMBL; AK226176; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC093819; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC097537; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110794; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC022508; AAH22508.1; -; mRNA.
DR EMBL; BC022528; AAH22528.1; -; mRNA.
DR EMBL; U45956; AAB16889.1; -; mRNA.
DR CCDS; CCDS3824.1; -. [P51674-1]
DR CCDS; CCDS54822.1; -. [P51674-3]
DR CCDS; CCDS58936.1; -. [P51674-2]
DR RefSeq; NP_001248377.1; NM_001261448.1. [P51674-2]
DR RefSeq; NP_005268.1; NM_005277.4. [P51674-1]
DR RefSeq; NP_963885.1; NM_201591.2. [P51674-1]
DR RefSeq; NP_963886.1; NM_201592.2. [P51674-3]
DR AlphaFoldDB; P51674; -.
DR BioGRID; 109084; 146.
DR IntAct; P51674; 29.
DR MINT; P51674; -.
DR STRING; 9606.ENSP00000280187; -.
DR GlyGen; P51674; 2 sites.
DR iPTMnet; P51674; -.
DR PhosphoSitePlus; P51674; -.
DR SwissPalm; P51674; -.
DR BioMuta; GPM6A; -.
DR DMDM; 2506889; -.
DR jPOST; P51674; -.
DR MassIVE; P51674; -.
DR PaxDb; P51674; -.
DR PeptideAtlas; P51674; -.
DR PRIDE; P51674; -.
DR ProteomicsDB; 20544; -.
DR ProteomicsDB; 56364; -. [P51674-1]
DR ProteomicsDB; 6743; -.
DR Antibodypedia; 17235; 314 antibodies from 32 providers.
DR DNASU; 2823; -.
DR Ensembl; ENST00000280187.11; ENSP00000280187.7; ENSG00000150625.17. [P51674-1]
DR Ensembl; ENST00000393658.7; ENSP00000377268.2; ENSG00000150625.17. [P51674-1]
DR Ensembl; ENST00000506894.5; ENSP00000421578.1; ENSG00000150625.17. [P51674-3]
DR Ensembl; ENST00000515090.5; ENSP00000423984.1; ENSG00000150625.17. [P51674-2]
DR GeneID; 2823; -.
DR KEGG; hsa:2823; -.
DR MANE-Select; ENST00000393658.7; ENSP00000377268.2; NM_201591.3; NP_963885.1.
DR UCSC; uc003iuf.5; human. [P51674-1]
DR CTD; 2823; -.
DR DisGeNET; 2823; -.
DR GeneCards; GPM6A; -.
DR HGNC; HGNC:4460; GPM6A.
DR HPA; ENSG00000150625; Group enriched (brain, choroid plexus, retina).
DR MIM; 601275; gene.
DR neXtProt; NX_P51674; -.
DR OpenTargets; ENSG00000150625; -.
DR PharmGKB; PA28843; -.
DR VEuPathDB; HostDB:ENSG00000150625; -.
DR eggNOG; KOG4800; Eukaryota.
DR GeneTree; ENSGT00390000006915; -.
DR HOGENOM; CLU_064167_2_0_1; -.
DR InParanoid; P51674; -.
DR OMA; YFEMTRA; -.
DR OrthoDB; 914457at2759; -.
DR PhylomeDB; P51674; -.
DR TreeFam; TF315162; -.
DR PathwayCommons; P51674; -.
DR SignaLink; P51674; -.
DR SIGNOR; P51674; -.
DR BioGRID-ORCS; 2823; 9 hits in 1066 CRISPR screens.
DR ChiTaRS; GPM6A; human.
DR GeneWiki; GPM6A; -.
DR GenomeRNAi; 2823; -.
DR Pharos; P51674; Tbio.
DR PRO; PR:P51674; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P51674; protein.
DR Bgee; ENSG00000150625; Expressed in endothelial cell and 167 other tissues.
DR ExpressionAtlas; P51674; baseline and differential.
DR Genevisible; P51674; HS.
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:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0099059; C:integral component of presynaptic active zone membrane; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0003407; P:neural retina development; ISS:UniProtKB.
DR GO; GO:0001764; P:neuron migration; IDA: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; ISS:UniProtKB.
DR GO; GO:0050807; P:regulation of synapse organization; IEA:Ensembl.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR GO; GO:0048863; P:stem cell differentiation; IDA: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; 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_0000159018"
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:0007744|PubMed:22223895"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35802"
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"
FT VAR_SEQ 1..12
FT /note="MEENMEEGQTQK -> MTDLE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045109"
FT VAR_SEQ 1..12
FT /note="MEENMEEGQTQK -> M (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_046098"
FT VARIANT 242
FT /note="V -> L (in dbSNP:rs1049820)"
FT /id="VAR_014895"
FT CONFLICT 102
FT /note="E -> A (in Ref. 6; AAB16889)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 278 AA; 31210 MW; DD0DB598C0E86B5D CRC64;
MEENMEEGQT QKGCFECCIK CLGGIPYASL IATILLYAGV ALFCGCGHEA LSGTVNILQT
YFEMARTAGD TLDVFTMIDI FKYVIYGIAA AFFVYGILLM VEGFFTTGAI KDLYGDFKIT
TCGRCVSAWF IMLTYLFMLA WLGVTAFTSL PVYMYFNLWT ICRNTTLVEG ANLCLDLRQF
GIVTIGEEKK ICTVSENFLR MCESTELNMT FHLFIVALAG AGAAVIAMVH YLMVLSANWA
YVKDACRMQK YEDIKSKEEQ ELHDIHSTRS KERLNAYT
