P51674 (GPM6A_HUMAN) 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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	278 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Involved in neuronal differentiation, including differentiation and migration of neuronal stem cells. 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.7
Subunit structure	Interacts with OPRM1 By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein By similarity. Cell projection › axon By similarity. Cell projection › dendritic spine By similarity. Cell projection › filopodium By similarity. 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.
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 Polymorphism
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 direct assay Ref.7. Source: UniProtKB neuron projection morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of filopodium assembly Inferred from sequence or structural similarity. Source: UniProtKB stem cell differentiation Inferred from direct assay Ref.7. Source: UniProtKB synapse assembly Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	axonal growth cone Inferred from sequence or structural similarity. Source: UniProtKB cell surface Inferred from direct assay PubMed 12493773. Source: UniProtKB dendritic spine Inferred from electronic annotation. Source: UniProtKB-SubCell filopodium Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuronal cell body Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	calcium channel activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P51674-1)

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: P51674-2)

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

Isoform 3 (identifier: P51674-3)

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

Note: No experimental confirmation available.

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_0000159018
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 By similarity
	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		By similarity
Natural variations
	Alternative sequence	1 – 12	12	MEENM…GQTQK → MTDLE in isoform 2.		VSP_045109
	Alternative sequence	1 – 12	12	MEENM…GQTQK → M in isoform 3.		VSP_046098
	Natural variant	242	1	V → L. Corresponds to variant rs1049820 [ dbSNP | Ensembl ].		VAR_014895
Experimental info
	Sequence conflict	102	1	E → A in AAB16889. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: DD0DB598C0E86B5D	FASTA	278	31,210
	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 PVYMYFNLWT ICRNTTLVEG ANLCLDLRQF 190 200 210 220 230 240 GIVTIGEEKK ICTVSENFLR MCESTELNMT FHLFIVALAG AGAAVIAMVH YLMVLSANWA 250 260 270 YVKDACRMQK YEDIKSKEEQ ELHDIHSTRS KERLNAYT
	Isoform 2 [UniParc]. Checksum: AA2999D92620BD4A	FASTA	271	30,364
	10 20 30 40 50 60 MTDLEGCFEC CIKCLGGIPY ASLIATILLY AGVALFCGCG HEALSGTVNI LQTYFEMART 70 80 90 100 110 120 AGDTLDVFTM IDIFKYVIYG IAAAFFVYGI LLMVEGFFTT GAIKDLYGDF KITTCGRCVS 130 140 150 160 170 180 AWFIMLTYLF MLAWLGVTAF TSLPVYMYFN LWTICRNTTL VEGANLCLDL RQFGIVTIGE 190 200 210 220 230 240 EKKICTVSEN FLRMCESTEL NMTFHLFIVA LAGAGAAVIA MVHYLMVLSA NWAYVKDACR 250 260 270 MQKYEDIKSK EEQELHDIHS TRSKERLNAY T
	Isoform 3 [UniParc]. Checksum: 94DD2BD6AFADEA61	FASTA	267	29,905
	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 VYMYFNLWTI 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]	"Isolation and mapping of the human glycoprotein M6 gene (GPM6A) to 4q33-->q34." Shimizu F., Watanabe T.K., Fujiwara T., Takahashi E., Nakamura Y., Maekawa H. Cytogenet. Cell Genet. 74:138-139(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[3]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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.
[6]	"Chromosomal mapping of the human M6 genes." Olinsky S., Loop B.T., Dekosky A., Ripepi B., Weng W., Cummins J., Wenger S.L., Yan Y., Lagenaur C., Narayanan V. Genomics 33:532-536(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 100-278. Tissue: Spinal cord.
[7]	"Human GPM6A is associated with differentiation and neuronal migration of neurons derived from human embryonic stem cells." Michibata H., Okuno T., Konishi N., Kyono K., Wakimoto K., Aoki K., Kondo Y., Takata K., Kitamura Y., Taniguchi T. Stem Cells Dev. 18:629-639(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D49958 mRNA. Translation: BAA08712.1. AK299788 mRNA. Translation: BAH13128.1. AK226176 mRNA. No translation available. AC093819 Genomic DNA. No translation available. AC097537 Genomic DNA. No translation available. AC110794 Genomic DNA. No translation available. BC022508 mRNA. Translation: AAH22508.1. BC022528 mRNA. Translation: AAH22528.1. U45956 mRNA. Translation: AAB16889.1.
IPI	IPI00019952. IPI00967359.
RefSeq	NP_001248377.1. NM_001261448.1. NP_005268.1. NM_005277.4. NP_963885.1. NM_201591.2. NP_963886.1. NM_201592.2.
UniGene	Hs.75819.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000280187.
PTM databases
PhosphoSite	P51674.
Polymorphism databases
DMDM	2506889.
Proteomic databases
PaxDb	P51674.
PRIDE	P51674.
Protocols and materials databases
DNASU	2823.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000280187; ENSP00000280187; ENSG00000150625. ENST00000393658; ENSP00000377268; ENSG00000150625. ENST00000506894; ENSP00000421578; ENSG00000150625. ENST00000515090; ENSP00000423984; ENSG00000150625.
GeneID	2823.
KEGG	hsa:2823.
UCSC	uc003iuf.3. human.
Organism-specific databases
CTD	2823.
GeneCards	GC04M176554.
HGNC	HGNC:4460. GPM6A.
HPA	HPA017338.
MIM	601275. gene.
neXtProt	NX_P51674.
PharmGKB	PA28843.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG322245.
HOGENOM	HOG000231338.
HOVERGEN	HBG000096.
InParanoid	P51674.
OMA	NELEYSA.
OrthoDB	EOG4KSPKC.
Gene expression databases
ArrayExpress	P51674.
Bgee	P51674.
CleanEx	HS_GPM6A.
Genevestigator	P51674.
GermOnline	ENSG00000150625. Homo sapiens.
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
ChiTaRS	GPM6A. human.
GenomeRNAi	2823.
NextBio	11127.
SOURCE	Search...

Entry information

Entry name

GPM6A_HUMAN

Accession

Primary (citable) accession number: P51674
Secondary accession number(s): B7Z642, E9PHI5, Q92602

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 117 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.