ID   RGMA_HUMAN              Reviewed;         450 AA.
AC   Q96B86; Q0JV97; Q8NC80; Q9H0E6; Q9NPM3;
DT   16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2004, sequence version 2.
DT   24-NOV-2009, entry version 54.
DE   RecName: Full=Repulsive guidance molecule A;
DE   AltName: Full=RGM domain family member A;
DE   Flags: Precursor;
GN   Name=RGMA; Synonyms=RGM;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Testis;
RX   MEDLINE=21154917; PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA   Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA   Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA   Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA   Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA   Wambutt R., Korn B., Klein M., Poustka A.;
RT   "Towards a catalog of human genes and proteins: sequencing and
RT   analysis of 500 novel complete protein coding human cDNAs.";
RL   Genome Res. 11:422-435(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND PARTIAL
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Teratocarcinoma;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Retina;
RG   The European IMAGE consortium;
RL   Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Uterus;
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   [5]
RP   FUNCTION.
RX   PubMed=19273616; DOI=10.1083/jcb.200807029;
RA   Hata K., Kaibuchi K., Inagaki S., Yamashita T.;
RT   "Unc5B associates with LARG to mediate the action of repulsive
RT   guidance molecule.";
RL   J. Cell Biol. 184:737-750(2009).
RN   [6]
RP   FUNCTION.
RX   PubMed=19458235; DOI=10.1523/JNEUROSCI.0927-09.2009;
RA   Endo M., Yamashita T.;
RT   "Inactivation of Ras by p120GAP via focal adhesion kinase
RT   dephosphorylation mediates RGMa-induced growth cone collapse.";
RL   J. Neurosci. 29:6649-6662(2009).
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 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-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 (By similarity).
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=Q96B86-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q96B86-2; Sequence=VSP_022294;
CC         Note=Incomplete sequence. No experimental confirmation
CC         available;
CC   -!- SIMILARITY: Belongs to the repulsive guidance molecule (RGM)
CC       family.
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DR   EMBL; AL136826; CAB66760.1; -; mRNA.
DR   EMBL; AK074910; BAC11285.1; -; mRNA.
DR   EMBL; AK074966; BAC11321.1; -; mRNA.
DR   EMBL; AK074980; BAC11330.1; -; mRNA.
DR   EMBL; AL390083; CAB98207.1; -; mRNA.
DR   EMBL; BC015886; AAH15886.2; -; mRNA.
DR   IPI; IPI00015049; -.
DR   IPI; IPI00478417; -.
DR   RefSeq; NP_064596.1; -.
DR   UniGene; Hs.271277; -.
DR   IntAct; Q96B86; 2.
DR   STRING; Q96B86; -.
DR   PRIDE; Q96B86; -.
DR   Ensembl; ENST00000329082; ENSP00000330005; ENSG00000182175; Homo sapiens.
DR   GeneID; 56963; -.
DR   KEGG; hsa:56963; -.
DR   CTD; 56963; -.
DR   GeneCards; GC15M091387; -.
DR   HGNC; HGNC:30308; RGMA.
DR   HPA; CAB012343; -.
DR   MIM; 607362; gene.
DR   PharmGKB; PA128394693; -.
DR   HOGENOM; Q96B86; -.
DR   HOVERGEN; Q96B86; -.
DR   Pathway_Interaction_DB; bmppathway; BMP receptor signaling.
DR   NextBio; 62595; -.
DR   ArrayExpress; Q96B86; -.
DR   Bgee; Q96B86; -.
DR   CleanEx; HS_RGMA; -.
DR   Genevestigator; Q96B86; -.
DR   GermOnline; ENSG00000182175; Homo sapiens.
DR   GO; GO:0031225; C:anchored to membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-KW.
DR   InterPro; IPR009496; RGM_C.
DR   InterPro; IPR010536; RGM_N.
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; Polymorphism; Signal.
FT   SIGNAL        1     47       Potential.
FT   PROPEP       48    168       Removed in mature form (By similarity).
FT                                /FTId=PRO_0000030385.
FT   CHAIN       169    424       Repulsive guidance molecule A.
FT                                /FTId=PRO_0000030386.
FT   PROPEP      425    450       Removed in mature form (Potential).
FT                                /FTId=PRO_0000030387.
FT   LIPID       424    424       GPI-anchor amidated alanine (Potential).
FT   CARBOHYD    114    114       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    159    159       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    389    389       N-linked (GlcNAc...) (Potential).
FT   VAR_SEQ       1      4       MQPP -> ARGRGGRSLPARCSRRRSEAALSSQRDLFSSPF
FT                                FLNSSS (in isoform 2).
FT                                /FTId=VSP_022294.
FT   VARIANT     431    431       A -> V (in dbSNP:rs4778078).
FT                                /FTId=VAR_060105.
FT   CONFLICT    199    199       V -> A (in Ref. 2; BAC11285).
SQ   SEQUENCE   450 AA;  49361 MW;  E3244FA591182DCF CRC64;
     MQPPRERLVV TGRAGWMGMG RGAGRSALGF WPTLAFLLCS FPAATSPCKI LKCNSEFWSA
     TSGSHAPASD DTPEFCAALR SYALCTRRTA RTCRGDLAYH SAVHGIEDLM SQHNCSKDGP
     TSQPRLRTLP PAGDSQERSD SPEICHYEKS FHKHSATPNY THCGLFGDPH LRTFTDRFQT
     CKVQGAWPLI DNNYLNVQVT NTPVLPGSAA TATSKLTIIF KNFQECVDQK VYQAEMDELP
     AAFVDGSKNG GDKHGANSLK ITEKVSGQHV EIQAKYIGTT IVVRQVGRYL TFAVRMPEEV
     VNAVEDWDSQ GLYLCLRGCP LNQQIDFQAF HTNAEGTGAR RLAAASPAPT APETFPYETA
     VAKCKEKLPV EDLYYQACVF DLLTTGDVNF TLAAYYALED VKMLHSNKDK LHLYERTRDL
     PGRAAAGLPL APRPLLGALV PLLALLPVFC
//