ID   RGMA_MOUSE              Reviewed;         454 AA.
AC   Q6PCX7; Q7TQ34; Q8CIH6;
DT   16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   25-JAN-2012, entry version 62.
DE   RecName: Full=Repulsive guidance molecule A;
DE   AltName: Full=RGM domain family member A;
DE   Flags: Precursor;
GN   Name=Rgma;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND DEVELOPMENTAL STAGE.
RX   PubMed=14678836; DOI=10.1016/S1567-133X(03)00144-3;
RA   Schmidtmer J., Engelkamp D.;
RT   "Isolation and expression pattern of three mouse homologues of chick
RT   Rgm.";
RL   Gene Expr. Patterns 4:105-110(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6, and FVB/N; TISSUE=Brain, and Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   FUNCTION.
RX   PubMed=14749425; DOI=10.1523/JNEUROSCI.4610-03.2004;
RA   Niederkofler V., Salie R., Sigrist M., Arber S.;
RT   "Repulsive guidance molecule (RGM) gene function is required for
RT   neural tube closure but not retinal topography in the mouse visual
RT   system.";
RL   J. Neurosci. 24:808-818(2004).
RN   [4]
RP   FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=15084667; DOI=10.1523/JNEUROSCI.5296-03.2004;
RA   Brinks H., Conrad S., Vogt J., Oldekamp J., Sierra A., Deitinghoff L.,
RA   Bechmann I., Alvarez-Bolado G., Heimrich B., Monnier P.P.,
RA   Mueller B.K., Skutella T.;
RT   "The repulsive guidance molecule RGMa is involved in the formation of
RT   afferent connections in the dentate gyrus.";
RL   J. Neurosci. 24:3862-3869(2004).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH BMP2 AND BMP4.
RX   PubMed=15975920; DOI=10.1074/jbc.M503511200;
RA   Babitt J.L., Zhang Y., Samad T.A., Xia Y., Tang J., Campagna J.A.,
RA   Schneyer A.L., Woolf C.J., Lin H.Y.;
RT   "Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone
RT   morphogenetic protein co-receptor.";
RL   J. Biol. Chem. 280:29820-29827(2005).
RN   [6]
RP   FUNCTION, AND INTERACTION WITH NEO1.
RX   PubMed=17389603; DOI=10.1074/jbc.M610901200;
RA   Conrad S., Genth H., Hofmann F., Just I., Skutella T.;
RT   "Neogenin-RGMa signaling at the growth cone is bone morphogenetic
RT   protein-independent and involves RhoA, ROCK, and PKC.";
RL   J. Biol. Chem. 282:16423-16433(2007).
RN   [7]
RP   FUNCTION, AND INTERACTION WITH BMP2 AND BMP4.
RX   PubMed=17472960; DOI=10.1074/jbc.M701679200;
RA   Xia Y., Yu P.B., Sidis Y., Beppu H., Bloch K.D., Schneyer A.L.,
RA   Lin H.Y.;
RT   "Repulsive guidance molecule RGMa alters utilization of bone
RT   morphogenetic protein (BMP) type II receptors by BMP2 and BMP4.";
RL   J. Biol. Chem. 282:18129-18140(2007).
RN   [8]
RP   FUNCTION.
RX   PubMed=17953666; DOI=10.1111/j.1471-4159.2007.04994.x;
RA   Metzger M., Conrad S., Skutella T., Just L.;
RT   "RGMa inhibits neurite outgrowth of neuronal progenitors from murine
RT   enteric nervous system via the neogenin receptor in vitro.";
RL   J. Neurochem. 103:2665-2678(2007).
RN   [9]
RP   FUNCTION.
RX   PubMed=18519029; DOI=10.1016/j.bbrc.2008.05.124;
RA   Yoshida J., Kubo T., Yamashita T.;
RT   "Inhibition of branching and spine maturation by repulsive guidance
RT   molecule in cultured cortical neurons.";
RL   Biochem. Biophys. Res. Commun. 372:725-729(2008).
CC   -!- FUNCTION: Member of the repulsive guidance molecule (RGM) family
CC       that performs several functions in the developing and adult
CC       nervous system. Regulates cephalic neural tube closure, inhibits
CC       neurite outgrowth and cortical neuron branching, and the formation
CC       of mature synapses. Binding to its receptor NEO1/neogenin induces
CC       activation of RHOA-ROCK1/Rho-kinase signaling pathway through
CC       UNC5B-ARHGEF12/LARG-PTK2/FAK1 cascade, leading to collapse of the
CC       neuronal growth cone and neurite outgrowth inhibition.
CC       Furthermore, RGMA binding to NEO1/neogenin leads to HRAS
CC       inactivation by influencing HRAS1-PTK2/FAK1-AKT1 pathway. It also
CC       functions as a bone morphogenetic protein (BMP) coreceptor that
CC       may signal through SMAD1, SMAD5, and SMAD8.
CC   -!- SUBUNIT: Interacts with NEO1, BMP2 and BMP4.
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor (By
CC       similarity).
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q6PCX7-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q6PCX7-2; Sequence=VSP_011316;
CC   -!- TISSUE SPECIFICITY: Expressed in gradient in periventricular
CC       layers of the developing nervous system. In adult, expressed in
CC       scattered cells throughout the brain.
CC   -!- DEVELOPMENTAL STAGE: Expressed in the early developing nervous
CC       system, with the exception of prominent gaps in the mid-hindbrain
CC       and the fore-midbrain boundaries. By E10.5, expression in the
CC       nervous system decreases slightly and a segmented pattern of
CC       expression appears, marking the ventral sites of somitic buds. At
CC       that stage, the expression shows a strong dorsal to ventral
CC       gradient. In the neural tubes, strong expression is detected at
CC       the level of the floor plate and in the medial portion of the
CC       neural tubes. Lower expression is detected in the dorsal neural
CC       tube and the ventral aspect corresponding to the area of
CC       motoneuron differentiation. In the developing eye, expressed in
CC       the perioptic mesenchyme.
CC   -!- SIMILARITY: Belongs to the repulsive guidance molecule (RGM)
CC       family.
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DR   EMBL; AJ557513; CAD89718.1; -; mRNA.
DR   EMBL; BC023870; AAH23870.2; -; mRNA.
DR   EMBL; BC059072; AAH59072.1; -; mRNA.
DR   IPI; IPI00453947; -.
DR   IPI; IPI00462622; -.
DR   RefSeq; NP_808408.2; NM_177740.5.
DR   UniGene; Mm.333943; -.
DR   STRING; Q6PCX7; -.
DR   PRIDE; Q6PCX7; -.
DR   Ensembl; ENSMUST00000094312; ENSMUSP00000091870; ENSMUSG00000070509.
DR   GeneID; 244058; -.
DR   KEGG; mmu:244058; -.
DR   UCSC; uc009hra.2; mouse.
DR   UCSC; uc009hrb.2; mouse.
DR   CTD; 56963; -.
DR   MGI; MGI:2679262; Rgma.
DR   eggNOG; roNOG10282; -.
DR   HOGENOM; HBG505677; -.
DR   HOVERGEN; HBG057627; -.
DR   InParanoid; Q6PCX7; -.
DR   OMA; CTALRAY; -.
DR   OrthoDB; EOG4001JB; -.
DR   NextBio; 386094; -.
DR   ArrayExpress; Q6PCX7; -.
DR   Bgee; Q6PCX7; -.
DR   CleanEx; MM_RGMA; -.
DR   Genevestigator; Q6PCX7; -.
DR   GermOnline; ENSMUSG00000070509; Mus musculus.
DR   GO; GO:0031225; C:anchored to membrane; IEA:UniProtKB-KW.
DR   GO; GO:0009986; C:cell surface; IDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR   GO; GO:0030510; P:regulation of BMP signaling pathway; IDA:MGI.
DR   InterPro; IPR009496; RGM_C.
DR   InterPro; IPR010536; RGM_N.
DR   KO; K06847; -.
DR   Pfam; PF06534; RGM_C; 1.
DR   Pfam; PF06535; RGM_N; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Complete proteome; Glycoprotein;
KW   GPI-anchor; Lipoprotein; Membrane; Reference proteome; Signal.
FT   SIGNAL        1     47       Potential.
FT   PROPEP       48    169       Removed in mature form (By similarity).
FT                                /FTId=PRO_0000030388.
FT   CHAIN       170    427       Repulsive guidance molecule A.
FT                                /FTId=PRO_0000030389.
FT   PROPEP      428    454       Removed in mature form (Potential).
FT                                /FTId=PRO_0000030390.
FT   COMPBIAS    422    430       Poly-Ala.
FT   LIPID       427    427       GPI-anchor amidated alanine (Potential).
FT   CARBOHYD    115    115       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    160    160       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    388    388       N-linked (GlcNAc...) (Potential).
FT   VAR_SEQ       1     16       Missing (in isoform 2).
FT                                /FTId=VSP_011316.
FT   CONFLICT    424    424       Missing (in Ref. 2; AAH23870).
SQ   SEQUENCE   454 AA;  49676 MW;  3AD1C72D8A70E177 CRC64;
     MQPPRERLVV TGRAGWMGMG RGAGRSALGL WPTLAFLLCS FPAAISPCKI LKCNSEFWSA
     TSSGSHAPAS DDVPEFCAAL RTYALCTRRT ARTCRGDLAY HSAVHGIEDL MSQHNCSKDG
     PTSQPRVRTL PPAGDSQERS DSPEICHYEK SFHKHSAAPN YTHCGLFGDP HLRTFTDHFQ
     TCKVQGAWPL IDNNYLNVQV TNTPVLPGSA ATATSKLTII FKNFQECVDQ KVYQAEMDEL
     PSAFADGSKN GGDKHGANSL KITEKVSGQH VEIQAKYIGT TIVVRQVGRY LTFAVRMPEE
     VVNAVEDRDS QGLYLCLRGC PLNQQIDFQA FRANAESPRR PAAASPSPVV PETFPYETAV
     AKCKEKLPVE DLYYQACVFD LLTTGDVNFT LAAYYALEDG KMLHSNKDKL HLFERTRELP
     GAVAAAAAAA TTFPLAPQIL LGTIPLLVLL PVLW
//