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Protein

Repulsive guidance molecule A

Gene

Rgma

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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
  • signaling receptor binding Source: MGI
  • transferrin receptor binding Source: MGI

GO - Biological processi

  • BMP signaling pathway Source: MGI
  • negative regulation of axon regeneration Source: Ensembl
  • negative regulation of collateral sprouting Source: Ensembl
  • negative regulation of neuron projection development Source: MGI
  • negative regulation of receptor binding Source: MGI
  • neural tube closure Source: MGI
  • neuron projection development Source: MGI
  • positive regulation of GTPase activity Source: MGI
  • positive regulation of membrane protein ectodomain proteolysis Source: MGI
  • positive regulation of neuron projection development Source: Ensembl
  • positive regulation of protein phosphorylation Source: MGI
  • positive regulation of transcription by RNA polymerase II Source: MGI
  • regulation of BMP signaling pathway Source: MGI

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2679262 Rgma

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 47Sequence analysisAdd BLAST47
PropeptideiPRO_000003038848 – 169Removed in mature formBy similarityAdd BLAST122
ChainiPRO_0000030389170 – 427Repulsive guidance molecule AAdd BLAST258
PropeptideiPRO_0000030390428 – 454Removed in mature formSequence analysisAdd BLAST27

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi115N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi146 ↔ 227By similarity
Glycosylationi160N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi164 ↔ 316By similarity
Glycosylationi388N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi427GPI-anchor amidated alanineSequence analysis1

Post-translational modificationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei169 – 170Cleavage; by autolysisBy similarity2

Keywords - PTMi

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

Proteomic databases

PaxDbiQ6PCX7
PeptideAtlasiQ6PCX7
PRIDEiQ6PCX7

PTM databases

PhosphoSitePlusiQ6PCX7
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

BgeeiENSMUSG00000070509
CleanExiMM_RGMA
ExpressionAtlasiQ6PCX7 baseline and differential
GenevisibleiQ6PCX7 MM

Interactioni

Subunit structurei

Interacts with NEO1, BMP2 and BMP4.3 Publications

GO - Molecular functioni

  • signaling receptor binding Source: MGI
  • transferrin receptor binding Source: MGI

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000091870

Structurei

3D structure databases

ProteinModelPortaliQ6PCX7
SMRiQ6PCX7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi422 – 430Poly-Ala9

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IFAH Eukaryota
ENOG410ZT7E LUCA
GeneTreeiENSGT00390000008488
HOGENOMiHOG000013072
HOVERGENiHBG057627
InParanoidiQ6PCX7
KOiK06847
OMAiPNYTHCG
OrthoDBiEOG091G0NF6
PhylomeDBiQ6PCX7
TreeFamiTF329836

Family and domain databases

Gene3Di3.40.1000.10, 1 hit
InterProiView protein in InterPro
IPR016123 Mog1/PsbP_a/b/a-sand
IPR009496 RGM_C
IPR010536 RGM_N
IPR033607 RGMA
PANTHERiPTHR31428:SF4 PTHR31428:SF4, 1 hit
PfamiView protein in Pfam
PF06534 RGM_C, 1 hit
PF06535 RGM_N, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti424Missing in AAH23870 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0113161 – 16Missing in isoform 2. 2 PublicationsAdd BLAST16

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

Similar proteinsi

Entry informationi

Entry nameiRGMA_MOUSE
AccessioniPrimary (citable) accession number: Q6PCX7
Secondary accession number(s): Q7TQ34, Q8CIH6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: July 5, 2004
Last modified: May 23, 2018
This is version 112 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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