Q6PCX7 (RGMA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Repulsive guidance molecule A

Alternative name(s):
RGM domain family member A

Gene names

Name:

Rgma

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	454 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Member of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system. Regulates cephalic neural tube closure, inhibits neurite outgrowth and cortical neuron branching, and the formation of mature synapses. Binding to its receptor NEO1/neogenin induces activation of RHOA-ROCK1/Rho-kinase signaling pathway through UNC5B-ARHGEF12/LARG-PTK2/FAK1 cascade, leading to collapse of the neuronal growth cone and neurite outgrowth inhibition. Furthermore, RGMA binding to NEO1/neogenin leads to HRAS inactivation by influencing HRAS1-PTK2/FAK1-AKT1 pathway. It also functions as a bone morphogenetic protein (BMP) coreceptor that may signal through SMAD1, SMAD5, and SMAD8. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9
Subunit structure	Interacts with NEO1, BMP2 and BMP4. Ref.5 Ref.6 Ref.7
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor By similarity.
Tissue specificity	Expressed in gradient in periventricular layers of the developing nervous system. In adult, expressed in scattered cells throughout the brain.
Developmental stage	Expressed in the early developing nervous system, with the exception of prominent gaps in the mid-hindbrain and the fore-midbrain boundaries. By E10.5, expression in the nervous system decreases slightly and a segmented pattern of expression appears, marking the ventral sites of somitic buds. At that stage, the expression shows a strong dorsal to ventral gradient. In the neural tubes, strong expression is detected at the level of the floor plate and in the medial portion of the neural tubes. Lower expression is detected in the dorsal neural tube and the ventral aspect corresponding to the area of motoneuron differentiation. In the developing eye, expressed in the perioptic mesenchyme. Ref.1 Ref.4
Sequence similarities	Belongs to the repulsive guidance molecule (RGM) family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal
PTM	GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	neural tube closure Inferred from mutant phenotype Ref.3. Source: MGI regulation of BMP signaling pathway Inferred from direct assay Ref.7. Source: MGI
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW cell surface Inferred from direct assay Ref.3. Source: MGI plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6PCX7-1)

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: Q6PCX7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-16: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 47	47	Potential
	Propeptide	48 – 169	122	Removed in mature form By similarity		PRO_0000030388
	Chain	170 – 427	258	Repulsive guidance molecule A		PRO_0000030389
	Propeptide	428 – 454	27	Removed in mature form Potential		PRO_0000030390
Regions
	Compositional bias	422 – 430	9	Poly-Ala
Amino acid modifications
	Lipidation	427	1	GPI-anchor amidated alanine Potential
	Glycosylation	115	1	N-linked (GlcNAc...) Potential
	Glycosylation	160	1	N-linked (GlcNAc...) Potential
	Glycosylation	388	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 16	16	Missing in isoform 2.		VSP_011316
Experimental info
	Sequence conflict	424	1	Missing in AAH23870. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 3AD1C72D8A70E177	FASTA	454	49,676
	10 20 30 40 50 60 MQPPRERLVV TGRAGWMGMG RGAGRSALGL WPTLAFLLCS FPAAISPCKI LKCNSEFWSA 70 80 90 100 110 120 TSSGSHAPAS DDVPEFCAAL RTYALCTRRT ARTCRGDLAY HSAVHGIEDL MSQHNCSKDG 130 140 150 160 170 180 PTSQPRVRTL PPAGDSQERS DSPEICHYEK SFHKHSAAPN YTHCGLFGDP HLRTFTDHFQ 190 200 210 220 230 240 TCKVQGAWPL IDNNYLNVQV TNTPVLPGSA ATATSKLTII FKNFQECVDQ KVYQAEMDEL 250 260 270 280 290 300 PSAFADGSKN GGDKHGANSL KITEKVSGQH VEIQAKYIGT TIVVRQVGRY LTFAVRMPEE 310 320 330 340 350 360 VVNAVEDRDS QGLYLCLRGC PLNQQIDFQA FRANAESPRR PAAASPSPVV PETFPYETAV 370 380 390 400 410 420 AKCKEKLPVE DLYYQACVFD LLTTGDVNFT LAAYYALEDG KMLHSNKDKL HLFERTRELP 430 440 450 GAVAAAAAAA TTFPLAPQIL LGTIPLLVLL PVLW
	Isoform 2 [UniParc]. Checksum: FF8ED11BA8C9CDDE	FASTA	438	47,840
	10 20 30 40 50 60 MGMGRGAGRS ALGLWPTLAF LLCSFPAAIS PCKILKCNSE FWSATSSGSH APASDDVPEF 70 80 90 100 110 120 CAALRTYALC TRRTARTCRG DLAYHSAVHG IEDLMSQHNC SKDGPTSQPR VRTLPPAGDS 130 140 150 160 170 180 QERSDSPEIC HYEKSFHKHS AAPNYTHCGL FGDPHLRTFT DHFQTCKVQG AWPLIDNNYL 190 200 210 220 230 240 NVQVTNTPVL PGSAATATSK LTIIFKNFQE CVDQKVYQAE MDELPSAFAD GSKNGGDKHG 250 260 270 280 290 300 ANSLKITEKV SGQHVEIQAK YIGTTIVVRQ VGRYLTFAVR MPEEVVNAVE DRDSQGLYLC 310 320 330 340 350 360 LRGCPLNQQI DFQAFRANAE SPRRPAAASP SPVVPETFPY ETAVAKCKEK LPVEDLYYQA 370 380 390 400 410 420 CVFDLLTTGD VNFTLAAYYA LEDGKMLHSN KDKLHLFERT RELPGAVAAA AAAATTFPLA 430 PQILLGTIPL LVLLPVLW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and expression pattern of three mouse homologues of chick Rgm." Schmidtmer J., Engelkamp D. Gene Expr. Patterns 4:105-110(2004) [PubMed: 14678836] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), DEVELOPMENTAL STAGE.
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6 and FVB/N. Tissue: Brain and Mammary gland.
[3]	"Repulsive guidance molecule (RGM) gene function is required for neural tube closure but not retinal topography in the mouse visual system." Niederkofler V., Salie R., Sigrist M., Arber S. J. Neurosci. 24:808-818(2004) [PubMed: 14749425] [Abstract] Cited for: FUNCTION.
[4]	"The repulsive guidance molecule RGMa is involved in the formation of afferent connections in the dentate gyrus." Brinks H., Conrad S., Vogt J., Oldekamp J., Sierra A., Deitinghoff L., Bechmann I., Alvarez-Bolado G., Heimrich B., Monnier P.P., Mueller B.K., Skutella T. J. Neurosci. 24:3862-3869(2004) [PubMed: 15084667] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE.
[5]	"Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic protein co-receptor." Babitt J.L., Zhang Y., Samad T.A., Xia Y., Tang J., Campagna J.A., Schneyer A.L., Woolf C.J., Lin H.Y. J. Biol. Chem. 280:29820-29827(2005) [PubMed: 15975920] [Abstract] Cited for: FUNCTION, INTERACTION WITH BMP2 AND BMP4.
[6]	"Neogenin-RGMa signaling at the growth cone is bone morphogenetic protein-independent and involves RhoA, ROCK, and PKC." Conrad S., Genth H., Hofmann F., Just I., Skutella T. J. Biol. Chem. 282:16423-16433(2007) [PubMed: 17389603] [Abstract] Cited for: FUNCTION, INTERACTION WITH NEO1.
[7]	"Repulsive guidance molecule RGMa alters utilization of bone morphogenetic protein (BMP) type II receptors by BMP2 and BMP4." Xia Y., Yu P.B., Sidis Y., Beppu H., Bloch K.D., Schneyer A.L., Lin H.Y. J. Biol. Chem. 282:18129-18140(2007) [PubMed: 17472960] [Abstract] Cited for: FUNCTION, INTERACTION WITH BMP2 AND BMP4.
[8]	"RGMa inhibits neurite outgrowth of neuronal progenitors from murine enteric nervous system via the neogenin receptor in vitro." Metzger M., Conrad S., Skutella T., Just L. J. Neurochem. 103:2665-2678(2007) [PubMed: 17953666] [Abstract] Cited for: FUNCTION.
[9]	"Inhibition of branching and spine maturation by repulsive guidance molecule in cultured cortical neurons." Yoshida J., Kubo T., Yamashita T. Biochem. Biophys. Res. Commun. 372:725-729(2008) [PubMed: 18519029] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ557513 mRNA. Translation: CAD89718.1. BC023870 mRNA. Translation: AAH23870.2. BC059072 mRNA. Translation: AAH59072.1.
IPI	IPI00453947. IPI00462622.
RefSeq	NP_808408.2. NM_177740.5.
UniGene	Mm.333943.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q6PCX7.
Proteomic databases
PRIDE	Q6PCX7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000094312; ENSMUSP00000091870; ENSMUSG00000070509.
GeneID	244058.
KEGG	mmu:244058.
UCSC	uc009hra.2. mouse. uc009hrb.2. mouse.
Organism-specific databases
CTD	56963.
MGI	MGI:2679262. Rgma.
Phylogenomic databases
eggNOG	roNOG10282.
HOGENOM	HBG505677.
HOVERGEN	HBG057627.
InParanoid	Q6PCX7.
OMA	CTALRAY.
OrthoDB	EOG4001JB.
Gene expression databases
ArrayExpress	Q6PCX7.
Bgee	Q6PCX7.
CleanEx	MM_RGMA.
Genevestigator	Q6PCX7.
GermOnline	ENSMUSG00000070509. Mus musculus.
Family and domain databases
InterPro	IPR009496. RGM_C. IPR010536. RGM_N. [Graphical view]
KO	K06847.
Pfam	PF06534. RGM_C. 1 hit. PF06535. RGM_N. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	386094.
SOURCE	Search...

Entry information

Entry name

RGMA_MOUSE

Accession

Primary (citable) accession number: Q6PCX7
Secondary accession number(s): Q7TQ34, Q8CIH6

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2004
Last sequence update:	July 5, 2004
Last modified:	January 25, 2012
This is version 62 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program