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Protein

Repulsive guidance molecule A

Gene

Rgma

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 HRAS-PTK2/FAK1-AKT1 pathway. It also functions as a bone morphogenetic protein (BMP) coreceptor that may signal through SMAD1, SMAD5, and SMAD8.7 Publications

GO - Molecular functioni

  • coreceptor activity Source: MGI
  • glycoprotein binding Source: MGI
  • transferrin receptor binding Source: MGI

GO - Biological processi

Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Repulsive guidance molecule A
Alternative name(s):
RGM domain family member A
Gene namesi
Name:Rgma
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2679262. Rgma.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 4747Sequence analysisAdd
BLAST
Propeptidei48 – 169122Removed in mature formBy similarityPRO_0000030388Add
BLAST
Chaini170 – 427258Repulsive guidance molecule APRO_0000030389Add
BLAST
Propeptidei428 – 45427Removed in mature formSequence analysisPRO_0000030390Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi115 – 1151N-linked (GlcNAc...)Sequence analysis
Disulfide bondi146 ↔ 227By similarity
Glycosylationi160 – 1601N-linked (GlcNAc...)Sequence analysis
Disulfide bondi164 ↔ 316By similarity
Glycosylationi388 – 3881N-linked (GlcNAc...)Sequence analysis
Lipidationi427 – 4271GPI-anchor amidated alanineSequence analysis

Post-translational modificationi

Autocatalytically cleaved at low pH; the two chains remain linked via two disulfide bonds.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei169 – 1702Cleavage; by autolysisBy similarity

Keywords - PTMi

Autocatalytic cleavage, Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

MaxQBiQ6PCX7.
PaxDbiQ6PCX7.
PeptideAtlasiQ6PCX7.
PRIDEiQ6PCX7.

PTM databases

PhosphoSiteiQ6PCX7.
SwissPalmiQ6PCX7.

Expressioni

Tissue specificityi

Expressed in gradient in periventricular layers of the developing nervous system. In adult, expressed in scattered cells throughout the brain.

Developmental stagei

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.2 Publications

Gene expression databases

BgeeiQ6PCX7.
CleanExiMM_RGMA.
ExpressionAtlasiQ6PCX7. baseline and differential.
GenevisibleiQ6PCX7. MM.

Interactioni

Subunit structurei

Interacts with NEO1, BMP2 and BMP4.3 Publications

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000091870.

Structurei

3D structure databases

ProteinModelPortaliQ6PCX7.
SMRiQ6PCX7. Positions 47-327.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi422 – 4309Poly-Ala

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IFAH. Eukaryota.
ENOG410ZT7E. LUCA.
GeneTreeiENSGT00390000008488.
HOGENOMiHOG000013072.
HOVERGENiHBG057627.
InParanoidiQ6PCX7.
KOiK06847.
OMAiQQIDFQA.
OrthoDBiEOG7VQJDC.
PhylomeDBiQ6PCX7.
TreeFamiTF329836.

Family and domain databases

InterProiIPR009496. RGM_C.
IPR010536. RGM_N.
IPR033607. RGMA.
[Graphical view]
PANTHERiPTHR31428:SF4. PTHR31428:SF4. 1 hit.
PfamiPF06534. RGM_C. 1 hit.
PF06535. RGM_N. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6PCX7-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MQPPRERLVV TGRAGWMGMG RGAGRSALGL WPTLAFLLCS FPAAISPCKI
60 70 80 90 100
LKCNSEFWSA TSSGSHAPAS DDVPEFCAAL RTYALCTRRT ARTCRGDLAY
110 120 130 140 150
HSAVHGIEDL MSQHNCSKDG PTSQPRVRTL PPAGDSQERS DSPEICHYEK
160 170 180 190 200
SFHKHSAAPN YTHCGLFGDP HLRTFTDHFQ TCKVQGAWPL IDNNYLNVQV
210 220 230 240 250
TNTPVLPGSA ATATSKLTII FKNFQECVDQ KVYQAEMDEL PSAFADGSKN
260 270 280 290 300
GGDKHGANSL KITEKVSGQH VEIQAKYIGT TIVVRQVGRY LTFAVRMPEE
310 320 330 340 350
VVNAVEDRDS QGLYLCLRGC PLNQQIDFQA FRANAESPRR PAAASPSPVV
360 370 380 390 400
PETFPYETAV AKCKEKLPVE DLYYQACVFD LLTTGDVNFT LAAYYALEDG
410 420 430 440 450
KMLHSNKDKL HLFERTRELP GAVAAAAAAA TTFPLAPQIL LGTIPLLVLL

PVLW
Length:454
Mass (Da):49,676
Last modified:July 5, 2004 - v1
Checksum:i3AD1C72D8A70E177
GO
Isoform 2 (identifier: Q6PCX7-2) [UniParc]FASTAAdd to basket

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

Show »
Length:438
Mass (Da):47,840
Checksum:iFF8ED11BA8C9CDDE
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti424 – 4241Missing in AAH23870 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1616Missing in isoform 2. 2 PublicationsVSP_011316Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ557513 mRNA. Translation: CAD89718.1.
BC023870 mRNA. Translation: AAH23870.2.
BC059072 mRNA. Translation: AAH59072.1.
CCDSiCCDS21362.2. [Q6PCX7-1]
RefSeqiNP_808408.2. NM_177740.5. [Q6PCX7-1]
XP_006540965.1. XM_006540902.1. [Q6PCX7-2]
UniGeneiMm.333943.

Genome annotation databases

EnsembliENSMUST00000094312; ENSMUSP00000091870; ENSMUSG00000070509. [Q6PCX7-1]
ENSMUST00000139780; ENSMUSP00000145758; ENSMUSG00000070509. [Q6PCX7-2]
GeneIDi244058.
KEGGimmu:244058.
UCSCiuc009hqz.2. mouse. [Q6PCX7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ557513 mRNA. Translation: CAD89718.1.
BC023870 mRNA. Translation: AAH23870.2.
BC059072 mRNA. Translation: AAH59072.1.
CCDSiCCDS21362.2. [Q6PCX7-1]
RefSeqiNP_808408.2. NM_177740.5. [Q6PCX7-1]
XP_006540965.1. XM_006540902.1. [Q6PCX7-2]
UniGeneiMm.333943.

3D structure databases

ProteinModelPortaliQ6PCX7.
SMRiQ6PCX7. Positions 47-327.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000091870.

PTM databases

PhosphoSiteiQ6PCX7.
SwissPalmiQ6PCX7.

Proteomic databases

MaxQBiQ6PCX7.
PaxDbiQ6PCX7.
PeptideAtlasiQ6PCX7.
PRIDEiQ6PCX7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000094312; ENSMUSP00000091870; ENSMUSG00000070509. [Q6PCX7-1]
ENSMUST00000139780; ENSMUSP00000145758; ENSMUSG00000070509. [Q6PCX7-2]
GeneIDi244058.
KEGGimmu:244058.
UCSCiuc009hqz.2. mouse. [Q6PCX7-1]

Organism-specific databases

CTDi56963.
MGIiMGI:2679262. Rgma.

Phylogenomic databases

eggNOGiENOG410IFAH. Eukaryota.
ENOG410ZT7E. LUCA.
GeneTreeiENSGT00390000008488.
HOGENOMiHOG000013072.
HOVERGENiHBG057627.
InParanoidiQ6PCX7.
KOiK06847.
OMAiQQIDFQA.
OrthoDBiEOG7VQJDC.
PhylomeDBiQ6PCX7.
TreeFamiTF329836.

Miscellaneous databases

ChiTaRSiRgma. mouse.
PROiQ6PCX7.
SOURCEiSearch...

Gene expression databases

BgeeiQ6PCX7.
CleanExiMM_RGMA.
ExpressionAtlasiQ6PCX7. baseline and differential.
GenevisibleiQ6PCX7. MM.

Family and domain databases

InterProiIPR009496. RGM_C.
IPR010536. RGM_N.
IPR033607. RGMA.
[Graphical view]
PANTHERiPTHR31428:SF4. PTHR31428:SF4. 1 hit.
PfamiPF06534. RGM_C. 1 hit.
PF06535. RGM_N. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and expression pattern of three mouse homologues of chick Rgm."
    Schmidtmer J., Engelkamp D.
    Gene Expr. Patterns 4:105-110(2004) [PubMed] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiRGMA_MOUSE
AccessioniPrimary (citable) accession number: Q6PCX7
Secondary accession number(s): Q7TQ34, Q8CIH6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: July 5, 2004
Last modified: July 6, 2016
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.