Q812E9 (GPM6A_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neuronal membrane glycoprotein M6-a
Short name=M6a

Gene names

Name:	Gpm6a
Synonyms:	m6a

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	278 AA.
Sequence status	Complete.
Protein existence	Evidence 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 projection › axon By similarity. Cell projection › dendritic spine. Cell projection › filopodium. 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 expressed in 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 process	Neurogenesis
Cellular component	Cell membrane Cell projection Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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_component	axonal growth cone Inferred from sequence or structural similarity. Source: UniProtKB cell surface Inferred from electronic annotation. Source: Compara dendritic spine Inferred from electronic annotation. Source: UniProtKB-SubCell filopodium Inferred from direct assay Ref.5. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuronal cell body Inferred from direct assay Ref.10. Source: UniProtKB plasma membrane Inferred from direct assay Ref.5Ref.10. Source: UniProtKB
Molecular_function	calcium channel activity Inferred from direct assay Ref.1. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Oprm1	P33535	7	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 278	278	Neuronal membrane glycoprotein M6-a		PRO_0000418016
Regions
	Topological domain	1 – 22	22	Cytoplasmic Potential
	Transmembrane	23 – 43	21	Helical; Potential
	Topological domain	44 – 84	41	Extracellular Potential
	Transmembrane	85 – 105	21	Helical; Potential
	Topological domain	106 – 127	22	Cytoplasmic Potential
	Transmembrane	128 – 148	21	Helical; Potential
	Topological domain	149 – 213	65	Extracellular Ref.7
	Transmembrane	214 – 234	21	Helical; Potential
	Topological domain	235 – 278	44	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	164	1	N-linked (GlcNAc...) Potential
	Glycosylation	208	1	N-linked (GlcNAc...) Potential
	Disulfide bond	174 ↔ 192		Ref.7
Natural variations
	Alternative sequence	1 – 12	12	MEENM…GQTQK → M in isoform 2.		VSP_043957
Experimental info
	Mutagenesis	10	1	T → A: Reduces motility of Gpm6a-induced filopodia; when associated with A-256, A-267 and A-268. Ref.9
	Mutagenesis	162	1	C → A: Abolishess cell surface expression. Ref.7
	Mutagenesis	174	1	C → A: Impairs Gpm6a-induced filopodium formation. Ref.7
	Mutagenesis	174	1	C → A: Impairs synaptic density in primary hippocampal neurons; when associated with A-192. Ref.7
	Mutagenesis	192	1	C → A: Impairs Gpm6a-induced filopodium formation. Ref.7
	Mutagenesis	192	1	C → A: Impairs synaptic densityin primary hippocampal neurons; when associated with A-174. Ref.7
	Mutagenesis	202	1	C → A: Abolishess cell surface expression. Ref.7
	Mutagenesis	256	1	S → A: Reduces motility of Gpm6a-induced filopodia; when associated with A-10, A-267 and A-268. Ref.9
	Mutagenesis	267	1	S → A: Reduces motility of Gpm6a-induced filopodia; when associated with A-10, A-256 and A-268. Ref.9
	Mutagenesis	268	1	T → A: Reduces motility of Gpm6a-induced filopodia; when associated with A-10, A-256 and A-267. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Ib) [UniParc]. Last modified June 1, 2003. Version 1. Checksum: D2EDAF98C0E8715D	FASTA	278	31,196
	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
	Isoform 2 (Ia) [UniParc]. Checksum: 9B3D31D6AFADF061	FASTA	267	29,891
	10 20 30 40 50 60 MGCFECCIKC LGGIPYASLI ATILLYAGVA LFCGCGHEAL SGTVNILQTY FEMARTAGDT 70 80 90 100 110 120 LDVFTMIDIF KYVIYGIAAA FFVYGILLMV EGFFTTGAIK DLYGDFKITT CGRCVSAWFI 130 140 150 160 170 180 MLTYLFMLAW LGVTAFTSLP VYMYFNVWTI CRNTTLVEGA NLCLDLRQFG IVTIGEEKKI 190 200 210 220 230 240 CTVSENFLRM CESTELNMTF HLFIVALAGA GAAVIAMVHY LMVLSANWAY VKDACRMQKY 250 260 EDIKSKEEQE LHDIHSTRSK ERLNAYT

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00287309.
RefSeq	NP_835206.1. NM_178105.2.
UniGene	Rn.34370.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q812E9. 1 interaction.
PTM databases
PhosphoSite	Q812E9.
Proteomic databases
PaxDb	Q812E9.
PRIDE	Q812E9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000014312; ENSRNOP00000014312; ENSRNOG00000010731.
GeneID	306439.
KEGG	rno:306439.
Organism-specific databases
CTD	2823.
RGD	631368. Gpm6a.
Phylogenomic databases
eggNOG	NOG322245.
GeneTree	ENSGT00390000006915.
HOGENOM	HOG000231338.
HOVERGEN	HBG000096.
InParanoid	Q812E9.
OMA	NELEYSA.
OrthoDB	EOG4KSPKC.
Gene expression databases
Genevestigator	Q812E9.
Family and domain databases
InterPro	IPR001614. Myelin_PLP. IPR018237. Myelin_PLP_CS. [Graphical view]
PANTHER	PTHR11683. PTHR11683. 1 hit.
Pfam	PF01275. Myelin_PLP. 1 hit. [Graphical view]
PRINTS	PR00214. MYELINPLP.
SMART	SM00002. PLP. 1 hit. [Graphical view]
PROSITE	PS00575. MYELIN_PLP_1. 1 hit. PS01004. MYELIN_PLP_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	656030.

Entry information

Entry name

GPM6A_RAT

Accession

Primary (citable) accession number: Q812E9

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 13, 2012
Last sequence update:	June 1, 2003
Last modified:	April 3, 2013
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program