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Q812E9 (GPM6A_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 71. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neuronal membrane glycoprotein M6-a

Short name=M6a
Gene names
Name:Gpm6a
Synonyms:m6a
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length278 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in neuronal differentiation, including differentiation and migration of neuronal stem cells By similarity. Plays a role in neuronal plasticity and is involved in neurite and filopodia outgrowth, filopodia motility and probably synapse formation. Gpm6a-induced filopodia formation involves mitogen-activated protein kinase (MAPK) and Src signaling pathways. May be involved in neuronal NGF-dependent Ca2+ influx. May be involved in regulation of endocytosis and intracellular trafficking of G-protein-coupled receptors (GPCRs); enhances internalization and recycling of mu-type opioid receptor. Ref.1 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10

Subunit structure

Interacts with OPRM1. Ref.6

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell projectionaxon By similarity. Cell projectiondendritic spine. Cell projectionfilopodium. Note: Localizes to cholesterol-rich lipid rafts of the plasma membrane of hippocampal neurons. Localized to plasma membrane of cell bodies and neurites of hippocampal neurons. Localized in membrane protrusions (filopodia and spines) of primary hippocampal neurons. Localized to the growth cone edge membrane of elongating axons By similarity. Ref.5 Ref.10

Tissue specificity

Expressed in hippocampus (at protein level). Isoform 1 is the predominant isoform expressedin brain, specifically in hippocampus. Isoform 2 is expressed at low levels in brain and kidney. Ref.5 Ref.8

Induction

Isoform 1 is down-regulated by chronic stress in dentate gyrus granule neurons and CA3 pyramidal neurons whereas isoform 2 is up-regulated in the medial prefrontal cortex. Ref.8

Sequence similarities

Belongs to the myelin proteolipid protein family.

Ontologies

Keywords
   Biological processNeurogenesis
   Cellular componentCell membrane
Cell projection
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   PTMAcetylation
Disulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcalcium ion transmembrane transport

Inferred from direct assay Ref.1. Source: GOC

neural retina development

Inferred from sequence or structural similarity. Source: UniProtKB

neuron migration

Inferred from sequence or structural similarity. Source: UniProtKB

neuron projection morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of filopodium assembly

Inferred from direct assay Ref.10. Source: UniProtKB

stem cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

synapse assembly

Inferred from direct assay Ref.7. Source: UniProtKB

   Cellular_componentaxonal growth cone

Inferred from sequence or structural similarity. Source: UniProtKB

dendritic spine

Inferred from electronic annotation. Source: UniProtKB-SubCell

filopodium

Inferred from direct assay Ref.5. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

neuron projection

Inferred from direct assay Ref.10. Source: UniProtKB

neuronal cell body

Inferred from direct assay Ref.10. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.5Ref.10. Source: UniProtKB

   Molecular_functioncalcium channel activity

Inferred from direct assay Ref.1. Source: RGD

protein binding

Inferred from physical interaction Ref.6. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Oprm1P335357EBI-6113756,EBI-4392569

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q812E9-1)

Also known as: Ib;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q812E9-2)

Also known as: Ia;

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MEENMEEGQTQK → M

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 278278Neuronal membrane glycoprotein M6-a
PRO_0000418016

Regions

Topological domain1 – 2222Cytoplasmic Potential
Transmembrane23 – 4321Helical; Potential
Topological domain44 – 8441Extracellular Potential
Transmembrane85 – 10521Helical; Potential
Topological domain106 – 12722Cytoplasmic Potential
Transmembrane128 – 14821Helical; Potential
Topological domain149 – 21365Extracellular Ref.7
Transmembrane214 – 23421Helical; Potential
Topological domain235 – 27844Cytoplasmic Potential

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Glycosylation1641N-linked (GlcNAc...) Potential
Glycosylation2081N-linked (GlcNAc...) Potential
Disulfide bond174 ↔ 192 Ref.7

Natural variations

Alternative sequence1 – 1212MEENM…GQTQK → M in isoform 2.
VSP_043957

Experimental info

Mutagenesis101T → A: Reduces motility of Gpm6a-induced filopodia; when associated with A-256, A-267 and A-268. Ref.9
Mutagenesis1621C → A: Abolishess cell surface expression. Ref.7
Mutagenesis1741C → A: Impairs Gpm6a-induced filopodium formation. Ref.7
Mutagenesis1741C → A: Impairs synaptic density in primary hippocampal neurons; when associated with A-192. Ref.7
Mutagenesis1921C → A: Impairs Gpm6a-induced filopodium formation. Ref.7
Mutagenesis1921C → A: Impairs synaptic density in primary hippocampal neurons; when associated with A-174. Ref.7
Mutagenesis2021C → A: Abolishess cell surface expression. Ref.7
Mutagenesis2561S → A: Reduces motility of Gpm6a-induced filopodia; when associated with A-10, A-267 and A-268. Ref.9
Mutagenesis2671S → A: Reduces motility of Gpm6a-induced filopodia; when associated with A-10, A-256 and A-268. Ref.9
Mutagenesis2681T → A: Reduces motility of Gpm6a-induced filopodia; when associated with A-10, A-256 and A-267. Ref.9

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Ib) [UniParc].

Last modified June 1, 2003. Version 1.
Checksum: D2EDAF98C0E8715D

FASTA27831,196
        10         20         30         40         50         60 
MEENMEEGQT QKGCFECCIK CLGGIPYASL IATILLYAGV ALFCGCGHEA LSGTVNILQT 

        70         80         90        100        110        120 
YFEMARTAGD TLDVFTMIDI FKYVIYGIAA AFFVYGILLM VEGFFTTGAI KDLYGDFKIT 

       130        140        150        160        170        180 
TCGRCVSAWF IMLTYLFMLA WLGVTAFTSL PVYMYFNVWT ICRNTTLVEG ANLCLDLRQF 

       190        200        210        220        230        240 
GIVTIGEEKK ICTVSENFLR MCESTELNMT FHLFIVALAG AGAAVIAMVH YLMVLSANWA 

       250        260        270 
YVKDACRMQK YEDIKSKEEQ ELHDIHSTRS KERLNAYT 

« Hide

Isoform 2 (Ia) [UniParc].

Checksum: 9B3D31D6AFADF061
Show »

FASTA26729,891

References

« Hide 'large scale' references
[1]"M6a acts as a nerve growth factor-gated Ca(2+) channel in neuronal differentiation."
Mukobata S., Hibino T., Sugiyama A., Urano Y., Inatomi A., Kanai Y., Endo H., Tashiro F.
Biochem. Biophys. Res. Commun. 297:722-728(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
[2]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[4]"Gene expression profile of the rat eye iridocorneal angle: NEIBank expressed sequence tag analysis."
Ahmed F., Torrado M., Zinovieva R.D., Senatorov V.V., Wistow G., Tomarev S.I.
Invest. Ophthalmol. Vis. Sci. 45:3081-3090(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-188 (ISOFORM 2).
[5]"The stress-regulated protein M6a is a key modulator for neurite outgrowth and filopodium/spine formation."
Alfonso J., Fernandez M.E., Cooper B., Flugge G., Frasch A.C.
Proc. Natl. Acad. Sci. U.S.A. 102:17196-17201(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[6]"Membrane glycoprotein M6a interacts with the micro-opioid receptor and facilitates receptor endocytosis and recycling."
Wu D.F., Koch T., Liang Y.J., Stumm R., Schulz S., Schroder H., Hollt V.
J. Biol. Chem. 282:22239-22247(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH OPRM1.
[7]"Cysteine residues in the large extracellular loop (EC2) are essential for the function of the stress-regulated glycoprotein M6a."
Fuchsova B., Fernandez M.E., Alfonso J., Frasch A.C.
J. Biol. Chem. 284:32075-32088(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TOPOLOGY, DISULFIDE BOND, MUTAGENESIS OF CYS-162; CYS-174; CYS-192 AND CYS-202.
[8]"Expression of the axonal membrane glycoprotein M6a is regulated by chronic stress."
Cooper B., Fuchs E., Flugge G.
PLoS ONE 4:E3659-E3659(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 2), TISSUE SPECIFICITY, INDUCTION.
[9]"Filopodial protrusions induced by glycoprotein M6a exhibit high motility and aids synapse formation."
Brocco M.A., Fernandez M.E., Frasch A.C.
Eur. J. Neurosci. 31:195-202(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF THR-10; SER-256; SER-267 AND THR-268.
[10]"Neuronal glycoprotein M6a induces filopodia formation via association with cholesterol-rich lipid rafts."
Scorticati C., Formoso K., Frasch A.C.
J. Neurochem. 119:521-531(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB089242 mRNA. Translation: BAC56699.1.
CH473995 Genomic DNA. Translation: EDL78956.1.
BC088862 mRNA. Translation: AAH88862.1.
DV216104 mRNA. No translation available.
RefSeqNP_835206.1. NM_178105.2. [Q812E9-1]
XP_006253156.1. XM_006253094.1. [Q812E9-2]
UniGeneRn.34370.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ812E9. 1 interaction.
STRING10116.ENSRNOP00000014312.

PTM databases

PhosphoSiteQ812E9.

Proteomic databases

PaxDbQ812E9.
PRIDEQ812E9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000014312; ENSRNOP00000014312; ENSRNOG00000010731. [Q812E9-1]
GeneID306439.
KEGGrno:306439.

Organism-specific databases

CTD2823.
RGD631368. Gpm6a.

Phylogenomic databases

eggNOGNOG322245.
GeneTreeENSGT00390000006915.
HOGENOMHOG000231338.
HOVERGENHBG000096.
InParanoidQ812E9.
OMAEEKKVCT.
OrthoDBEOG7X3QRG.
PhylomeDBQ812E9.
TreeFamTF315162.

Gene expression databases

GenevestigatorQ812E9.

Family and domain databases

InterProIPR001614. Myelin_PLP.
IPR018237. Myelin_PLP_CS.
[Graphical view]
PANTHERPTHR11683. PTHR11683. 1 hit.
PfamPF01275. Myelin_PLP. 1 hit.
[Graphical view]
PRINTSPR00214. MYELINPLP.
SMARTSM00002. PLP. 1 hit.
[Graphical view]
PROSITEPS00575. MYELIN_PLP_1. 1 hit.
PS01004. MYELIN_PLP_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio656030.
PROQ812E9.

Entry information

Entry nameGPM6A_RAT
AccessionPrimary (citable) accession number: Q812E9
Entry history
Integrated into UniProtKB/Swiss-Prot: June 13, 2012
Last sequence update: June 1, 2003
Last modified: June 11, 2014
This is version 71 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families