RGMA_HUMAN
ID RGMA_HUMAN Reviewed; 450 AA.
AC Q96B86; B2RTW1; B7Z5S8; F5GXQ7; F5GZU6; G3V518; Q0JV97; Q8NC80; Q9H0E6;
AC Q9NPM3;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 4.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Repulsive guidance molecule A {ECO:0000305};
DE AltName: Full=RGM domain family member A;
DE Flags: Precursor;
GN Name=RGMA {ECO:0000312|HGNC:HGNC:30308}; Synonyms=RGM;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX 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., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
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 guidance
RT molecule.";
RL J. Cell Biol. 184:737-750(2009).
RN [8]
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 dephosphorylation
RT mediates RGMa-induced growth cone collapse.";
RL J. Neurosci. 29:6649-6662(2009).
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:19273616, ECO:0000269|PubMed:19458235}.
CC -!- SUBUNIT: Interacts with NEO1, BMP2 and BMP4. {ECO:0000250}.
CC -!- INTERACTION:
CC Q96B86; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-722102, EBI-750109;
CC Q96B86-1; P12643: BMP2; NbExp=2; IntAct=EBI-16155394, EBI-1029262;
CC Q96B86-3; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-14497860, EBI-11952721;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor, GPI-
CC anchor {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96B86-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96B86-3; Sequence=VSP_054070;
CC Name=3;
CC IsoId=Q96B86-4; Sequence=VSP_054071;
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 -!- SEQUENCE CAUTION:
CC Sequence=AAH15886.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB98207.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL390083; CAB98207.1; ALT_INIT; mRNA.
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; AK299363; BAH13014.1; -; mRNA.
DR EMBL; AC087641; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471101; EAX02167.1; -; Genomic_DNA.
DR EMBL; BC015886; AAH15886.2; ALT_INIT; mRNA.
DR EMBL; BC140838; AAI40839.1; -; mRNA.
DR EMBL; BC151132; AAI51133.1; -; mRNA.
DR CCDS; CCDS45357.1; -. [Q96B86-1]
DR CCDS; CCDS53973.1; -. [Q96B86-3]
DR CCDS; CCDS53974.1; -. [Q96B86-4]
DR RefSeq; NP_001159755.1; NM_001166283.1.
DR RefSeq; NP_001159758.1; NM_001166286.1.
DR RefSeq; NP_001159759.1; NM_001166287.1.
DR RefSeq; NP_001159760.1; NM_001166288.1.
DR RefSeq; NP_001159761.1; NM_001166289.1.
DR RefSeq; NP_064596.2; NM_020211.2.
DR PDB; 4UHY; X-ray; 3.20 A; C=46-139.
DR PDB; 6Z3G; X-ray; 2.78 A; B=54-139.
DR PDBsum; 4UHY; -.
DR PDBsum; 6Z3G; -.
DR AlphaFoldDB; Q96B86; -.
DR BioGRID; 121284; 16.
DR DIP; DIP-61606N; -.
DR IntAct; Q96B86; 16.
DR STRING; 9606.ENSP00000452126; -.
DR ChEMBL; CHEMBL4630886; -.
DR GlyGen; Q96B86; 4 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q96B86; -.
DR PhosphoSitePlus; Q96B86; -.
DR BioMuta; RGMA; -.
DR DMDM; 296452979; -.
DR EPD; Q96B86; -.
DR MassIVE; Q96B86; -.
DR PaxDb; Q96B86; -.
DR PeptideAtlas; Q96B86; -.
DR PRIDE; Q96B86; -.
DR ProteomicsDB; 25133; -.
DR ProteomicsDB; 33395; -.
DR ProteomicsDB; 76054; -. [Q96B86-1]
DR ABCD; Q96B86; 1 sequenced antibody.
DR Antibodypedia; 43886; 240 antibodies from 27 providers.
DR DNASU; 56963; -.
DR Ensembl; ENST00000329082.12; ENSP00000330005.7; ENSG00000182175.15. [Q96B86-1]
DR Ensembl; ENST00000425933.6; ENSP00000404442.2; ENSG00000182175.15. [Q96B86-3]
DR Ensembl; ENST00000542321.6; ENSP00000440025.2; ENSG00000182175.15. [Q96B86-3]
DR Ensembl; ENST00000543599.5; ENSP00000442498.1; ENSG00000182175.15. [Q96B86-3]
DR Ensembl; ENST00000557301.2; ENSP00000452126.1; ENSG00000182175.15. [Q96B86-4]
DR GeneID; 56963; -.
DR KEGG; hsa:56963; -.
DR MANE-Select; ENST00000329082.12; ENSP00000330005.7; NM_020211.3; NP_064596.2.
DR UCSC; uc002bsq.3; human. [Q96B86-1]
DR CTD; 56963; -.
DR DisGeNET; 56963; -.
DR GeneCards; RGMA; -.
DR HGNC; HGNC:30308; RGMA.
DR HPA; ENSG00000182175; Tissue enhanced (skeletal).
DR MIM; 607362; gene.
DR neXtProt; NX_Q96B86; -.
DR OpenTargets; ENSG00000182175; -.
DR PharmGKB; PA128394693; -.
DR VEuPathDB; HostDB:ENSG00000182175; -.
DR eggNOG; ENOG502QSTJ; Eukaryota.
DR GeneTree; ENSGT00950000183112; -.
DR HOGENOM; CLU_032775_1_1_1; -.
DR InParanoid; Q96B86; -.
DR OrthoDB; 1300661at2759; -.
DR PhylomeDB; Q96B86; -.
DR TreeFam; TF329836; -.
DR PathwayCommons; Q96B86; -.
DR Reactome; R-HSA-373752; Netrin-1 signaling.
DR SignaLink; Q96B86; -.
DR SIGNOR; Q96B86; -.
DR BioGRID-ORCS; 56963; 15 hits in 1064 CRISPR screens.
DR ChiTaRS; RGMA; human.
DR GeneWiki; RGMA; -.
DR GenomeRNAi; 56963; -.
DR Pharos; Q96B86; Tbio.
DR PRO; PR:Q96B86; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q96B86; protein.
DR Bgee; ENSG00000182175; Expressed in lower esophagus muscularis layer and 161 other tissues.
DR ExpressionAtlas; Q96B86; baseline and differential.
DR Genevisible; Q96B86; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0015026; F:coreceptor activity; IBA:GO_Central.
DR GO; GO:1990459; F:transferrin receptor binding; IPI:BHF-UCL.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IEA:Ensembl.
DR GO; GO:0048681; P:negative regulation of axon regeneration; IEA:InterPro.
DR GO; GO:1900121; P:negative regulation of receptor binding; IEA:Ensembl.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:Ensembl.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0030510; P:regulation of BMP signaling pathway; IEA:Ensembl.
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 3D-structure; 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..168
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000030385"
FT CHAIN 169..424
FT /note="Repulsive guidance molecule A"
FT /id="PRO_0000030386"
FT PROPEP 425..450
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000030387"
FT REGION 113..140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 168..169
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT LIPID 424
FT /note="GPI-anchor amidated alanine"
FT /evidence="ECO:0000255"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 145..226
FT /evidence="ECO:0000250"
FT DISULFID 163..315
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..16
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1"
FT /id="VSP_054070"
FT VAR_SEQ 1..4
FT /note="MQPP -> MGGLGPRRAGTS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054071"
FT VARIANT 415
FT /note="E -> D (in dbSNP:rs4238485)"
FT /id="VAR_062144"
FT VARIANT 431
FT /note="A -> V (in dbSNP:rs4778078)"
FT /id="VAR_060105"
FT CONFLICT 199
FT /note="V -> A (in Ref. 3; BAC11285)"
FT /evidence="ECO:0000305"
FT CONFLICT 314
FT /note="L -> P (in Ref. 3; BAH13014)"
FT /evidence="ECO:0000305"
FT TURN 57..59
FT /evidence="ECO:0007829|PDB:6Z3G"
FT HELIX 79..87
FT /evidence="ECO:0007829|PDB:6Z3G"
FT TURN 88..93
FT /evidence="ECO:0007829|PDB:6Z3G"
FT HELIX 97..110
FT /evidence="ECO:0007829|PDB:6Z3G"
FT TURN 111..114
FT /evidence="ECO:0007829|PDB:6Z3G"
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
