RGMA_MOUSE
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 03-AUG-2022, entry version 133.
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; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC 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 Rgm.";
RL Gene Expr. Patterns 4:105-110(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, 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 project:
RT 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 neural
RT tube closure but not retinal topography in the mouse visual 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., Mueller B.K.,
RA 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 protein-
RT 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., Lin H.Y.;
RT "Repulsive guidance molecule RGMa alters utilization of bone morphogenetic
RT 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 that
CC performs several functions in the developing and adult nervous system.
CC Regulates cephalic neural tube closure, inhibits neurite outgrowth and
CC cortical neuron branching, and the formation of mature synapses.
CC Binding to its receptor NEO1/neogenin induces activation of RHOA-
CC ROCK1/Rho-kinase signaling pathway through UNC5B-ARHGEF12/LARG-
CC PTK2/FAK1 cascade, leading to collapse of the neuronal growth cone and
CC neurite outgrowth inhibition. Furthermore, RGMA binding to
CC NEO1/neogenin leads to HRAS inactivation by influencing HRAS-PTK2/FAK1-
CC AKT1 pathway. It also functions as a bone morphogenetic protein (BMP)
CC coreceptor that may signal through SMAD1, SMAD5, and SMAD8.
CC {ECO:0000269|PubMed:14749425, ECO:0000269|PubMed:15084667,
CC ECO:0000269|PubMed:15975920, ECO:0000269|PubMed:17389603,
CC ECO:0000269|PubMed:17472960, ECO:0000269|PubMed:17953666,
CC ECO:0000269|PubMed:18519029}.
CC -!- SUBUNIT: Interacts with NEO1, BMP2 and BMP4.
CC {ECO:0000269|PubMed:15975920, ECO:0000269|PubMed:17389603,
CC ECO:0000269|PubMed:17472960}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor, GPI-
CC anchor {ECO:0000250}.
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 layers of
CC the developing nervous system. In adult, expressed in scattered cells
CC throughout the brain.
CC -!- DEVELOPMENTAL STAGE: Expressed in the early developing nervous system,
CC with the exception of prominent gaps in the mid-hindbrain and the fore-
CC midbrain boundaries. By 10.5 dpc, expression in the nervous system
CC decreases slightly and a segmented pattern of expression appears,
CC marking the ventral sites of somitic buds. At that stage, the
CC expression shows a strong dorsal to ventral gradient. In the neural
CC tubes, strong expression is detected at the level of the floor plate
CC and in the medial portion of the neural tubes. Lower expression is
CC detected in the dorsal neural tube and the ventral aspect corresponding
CC to the area of motoneuron differentiation. In the developing eye,
CC expressed in the perioptic mesenchyme. {ECO:0000269|PubMed:14678836,
CC ECO:0000269|PubMed:15084667}.
CC -!- PTM: Autocatalytically cleaved at low pH; the two chains remain linked
CC via two disulfide bonds. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the repulsive guidance molecule (RGM) family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ557513; CAD89718.1; -; mRNA.
DR EMBL; BC023870; AAH23870.2; -; mRNA.
DR EMBL; BC059072; AAH59072.1; -; mRNA.
DR CCDS; CCDS21362.2; -. [Q6PCX7-1]
DR RefSeq; NP_808408.2; NM_177740.5. [Q6PCX7-1]
DR RefSeq; XP_006540965.1; XM_006540902.1. [Q6PCX7-2]
DR AlphaFoldDB; Q6PCX7; -.
DR SMR; Q6PCX7; -.
DR STRING; 10090.ENSMUSP00000091870; -.
DR GlyGen; Q6PCX7; 3 sites.
DR PhosphoSitePlus; Q6PCX7; -.
DR SwissPalm; Q6PCX7; -.
DR MaxQB; Q6PCX7; -.
DR PaxDb; Q6PCX7; -.
DR PeptideAtlas; Q6PCX7; -.
DR PRIDE; Q6PCX7; -.
DR ProteomicsDB; 255322; -. [Q6PCX7-1]
DR ProteomicsDB; 255323; -. [Q6PCX7-2]
DR Antibodypedia; 43886; 240 antibodies from 27 providers.
DR DNASU; 244058; -.
DR Ensembl; ENSMUST00000094312; ENSMUSP00000091870; ENSMUSG00000070509. [Q6PCX7-1]
DR Ensembl; ENSMUST00000139780; ENSMUSP00000145758; ENSMUSG00000070509. [Q6PCX7-2]
DR GeneID; 244058; -.
DR KEGG; mmu:244058; -.
DR UCSC; uc009hqz.2; mouse. [Q6PCX7-1]
DR CTD; 56963; -.
DR MGI; MGI:2679262; Rgma.
DR VEuPathDB; HostDB:ENSMUSG00000070509; -.
DR eggNOG; ENOG502QSTJ; Eukaryota.
DR GeneTree; ENSGT00950000183112; -.
DR HOGENOM; CLU_032775_1_1_1; -.
DR InParanoid; Q6PCX7; -.
DR OMA; CPLNEQI; -.
DR OrthoDB; 1300661at2759; -.
DR PhylomeDB; Q6PCX7; -.
DR TreeFam; TF329836; -.
DR BioGRID-ORCS; 244058; 6 hits in 73 CRISPR screens.
DR ChiTaRS; Rgma; mouse.
DR PRO; PR:Q6PCX7; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q6PCX7; protein.
DR Bgee; ENSMUSG00000070509; Expressed in embryonic brain and 209 other tissues.
DR ExpressionAtlas; Q6PCX7; baseline and differential.
DR Genevisible; Q6PCX7; MM.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0015026; F:coreceptor activity; IGI:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IPI:MGI.
DR GO; GO:1990459; F:transferrin receptor binding; ISO:MGI.
DR GO; GO:0030509; P:BMP signaling pathway; IGI:MGI.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:MGI.
DR GO; GO:0048681; P:negative regulation of axon regeneration; ISO:MGI.
DR GO; GO:0048671; P:negative regulation of collateral sprouting; ISO:MGI.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IMP:MGI.
DR GO; GO:1900121; P:negative regulation of receptor binding; IMP:MGI.
DR GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR GO; GO:0031175; P:neuron projection development; IMP:MGI.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:MGI.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IDA:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0030510; P:regulation of BMP signaling pathway; IDA:MGI.
DR InterPro; IPR040287; RGM.
DR InterPro; IPR009496; RGM_C.
DR InterPro; IPR010536; RGM_N.
DR InterPro; IPR033607; RGMA.
DR PANTHER; PTHR31428; PTHR31428; 1.
DR PANTHER; PTHR31428:SF4; PTHR31428:SF4; 1.
DR Pfam; PF06534; RGM_C; 1.
DR Pfam; PF06535; RGM_N; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autocatalytic cleavage; Cell membrane;
KW Disulfide bond; Glycoprotein; GPI-anchor; Lipoprotein; Membrane;
KW Reference proteome; Signal.
FT SIGNAL 1..47
FT /evidence="ECO:0000255"
FT PROPEP 48..169
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000030388"
FT CHAIN 170..427
FT /note="Repulsive guidance molecule A"
FT /id="PRO_0000030389"
FT PROPEP 428..454
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000030390"
FT REGION 114..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 169..170
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT LIPID 427
FT /note="GPI-anchor amidated alanine"
FT /evidence="ECO:0000255"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 388
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 146..227
FT /evidence="ECO:0000250"
FT DISULFID 164..316
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..16
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14678836,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_011316"
FT CONFLICT 424
FT /note="Missing (in Ref. 2; AAH23870)"
FT /evidence="ECO:0000305"
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
