RGMB_HUMAN
ID RGMB_HUMAN Reviewed; 437 AA.
AC Q6NW40; D6R9A0; Q8NC92;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 3.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Repulsive guidance molecule B {ECO:0000303|PubMed:19324014};
DE AltName: Full=DRG11-responsive axonal guidance and outgrowth of neurite {ECO:0000250|UniProtKB:Q7TQ33};
DE Short=DRAGON {ECO:0000250|UniProtKB:Q7TQ33};
DE Flags: Precursor;
GN Name=RGMB {ECO:0000303|PubMed:19324014, ECO:0000312|HGNC:HGNC:26896};
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].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [4]
RP FUNCTION.
RX PubMed=19324014; DOI=10.1016/j.bbrc.2009.03.115;
RA Liu X., Hashimoto M., Horii H., Yamaguchi A., Naito K., Yamashita T.;
RT "Repulsive guidance molecule b inhibits neurite growth and is increased
RT after spinal cord injury.";
RL Biochem. Biophys. Res. Commun. 382:795-800(2009).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 50-410 IN COMPLEX WITH MOUSE NEO1
RP RECEPTOR, AUTOCATALYTIC CLEAVAGE, MUTAGENESIS OF ALA-186 AND PRO-206, AND
RP DISULFIDE BONDS.
RX PubMed=23744777; DOI=10.1126/science.1232322;
RA Bell C.H., Healey E., van Erp S., Bishop B., Tang C., Gilbert R.J.,
RA Aricescu A.R., Pasterkamp R.J., Siebold C.;
RT "Structure of the repulsive guidance molecule (RGM)-neogenin signaling
RT hub.";
RL Science 341:77-80(2013).
CC -!- FUNCTION: Member of the repulsive guidance molecule (RGM) family that
CC contributes to the patterning of the developing nervous system (By
CC similarity). Acts as a bone morphogenetic protein (BMP) coreceptor that
CC potentiates BMP signaling (By similarity). Promotes neuronal adhesion
CC (By similarity). May inhibit neurite outgrowth.
CC {ECO:0000250|UniProtKB:Q7TQ33, ECO:0000269|PubMed:19324014}.
CC -!- SUBUNIT: Homooligomer (By similarity). Interacts with DRGX (By
CC similarity). Interacts with BMP2 and BMP4 (By similarity). Interacts
CC with the BMP type I receptors ACVR1, BMPR1A and BMPR1B and with the BMP
CC type II receptor ACVR2B (By similarity). The functional complex with
CC its receptor NEO1/neogenin appears to be a heterotetramer with a 2:2
CC stoichiometry, RGM molecules acting as staples that bring two NEO1
CC receptors together without interacting themselves, this arrangement
CC leads to activation of downstream signaling via RhoA.
CC {ECO:0000250|UniProtKB:Q7TQ33, ECO:0000269|PubMed:23744777}.
CC -!- INTERACTION:
CC Q6NW40; P12643: BMP2; NbExp=7; IntAct=EBI-16155464, EBI-1029262;
CC Q6NW40; P97798: Neo1; Xeno; NbExp=2; IntAct=EBI-16155464, EBI-774991;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q7TQ33};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:Q7TQ33}. Membrane raft
CC {ECO:0000250|UniProtKB:Q7TQ33}.
CC -!- PTM: GPI-anchored. {ECO:0000250|UniProtKB:Q7TQ33}.
CC -!- PTM: Autocatalytically cleaved at low pH; the two chains remain linked
CC via two disulfide bonds. {ECO:0000269|PubMed:23744777}.
CC -!- SIMILARITY: Belongs to the repulsive guidance molecule (RGM) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH67736.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC11268.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={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; AK074887; BAC11268.1; ALT_SEQ; mRNA.
DR EMBL; AC008522; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC067736; AAH67736.1; ALT_INIT; mRNA.
DR RefSeq; NP_001012779.2; NM_001012761.2.
DR PDB; 4BQ6; X-ray; 2.30 A; C/E=50-168, D/F=169-410.
DR PDB; 4BQ7; X-ray; 6.60 A; C/E=50-168, D/F=169-410.
DR PDB; 4BQ8; X-ray; 2.80 A; B=50-168, C=169-410.
DR PDB; 4UHZ; X-ray; 2.85 A; B=53-136.
DR PDB; 4UI0; X-ray; 2.80 A; C=53-136.
DR PDB; 4UI2; X-ray; 3.15 A; C=50-168, D=169-410.
DR PDB; 6Z3H; X-ray; 3.16 A; B=53-136.
DR PDB; 6Z3J; X-ray; 1.65 A; C/D=53-136.
DR PDB; 6Z3M; X-ray; 5.50 A; C/D/I/J/O/P/S/T/U/V/W/X/c/d/i/j/o/p=53-412.
DR PDBsum; 4BQ6; -.
DR PDBsum; 4BQ7; -.
DR PDBsum; 4BQ8; -.
DR PDBsum; 4UHZ; -.
DR PDBsum; 4UI0; -.
DR PDBsum; 4UI2; -.
DR PDBsum; 6Z3H; -.
DR PDBsum; 6Z3J; -.
DR PDBsum; 6Z3M; -.
DR AlphaFoldDB; Q6NW40; -.
DR SMR; Q6NW40; -.
DR BioGRID; 130185; 7.
DR DIP; DIP-61607N; -.
DR IntAct; Q6NW40; 2.
DR STRING; 9606.ENSP00000308219; -.
DR GlyGen; Q6NW40; 2 sites.
DR iPTMnet; Q6NW40; -.
DR PhosphoSitePlus; Q6NW40; -.
DR BioMuta; RGMB; -.
DR DMDM; 327478562; -.
DR MassIVE; Q6NW40; -.
DR PaxDb; Q6NW40; -.
DR PeptideAtlas; Q6NW40; -.
DR PRIDE; Q6NW40; -.
DR ProteomicsDB; 66740; -.
DR Antibodypedia; 2207; 216 antibodies from 30 providers.
DR DNASU; 285704; -.
DR Ensembl; ENST00000513185.3; ENSP00000423256.1; ENSG00000174136.13.
DR GeneID; 285704; -.
DR KEGG; hsa:285704; -.
DR MANE-Select; ENST00000513185.3; ENSP00000423256.1; NM_001366508.1; NP_001353437.1.
DR UCSC; uc063frq.1; human.
DR CTD; 285704; -.
DR DisGeNET; 285704; -.
DR GeneCards; RGMB; -.
DR HGNC; HGNC:26896; RGMB.
DR HPA; ENSG00000174136; Low tissue specificity.
DR MIM; 612687; gene.
DR neXtProt; NX_Q6NW40; -.
DR OpenTargets; ENSG00000174136; -.
DR PharmGKB; PA134868641; -.
DR VEuPathDB; HostDB:ENSG00000174136; -.
DR eggNOG; ENOG502QSTJ; Eukaryota.
DR GeneTree; ENSGT00950000183112; -.
DR HOGENOM; CLU_032775_1_1_1; -.
DR InParanoid; Q6NW40; -.
DR PhylomeDB; Q6NW40; -.
DR PathwayCommons; Q6NW40; -.
DR Reactome; R-HSA-373752; Netrin-1 signaling.
DR SignaLink; Q6NW40; -.
DR BioGRID-ORCS; 285704; 13 hits in 1071 CRISPR screens.
DR ChiTaRS; RGMB; human.
DR GeneWiki; RGMB; -.
DR GenomeRNAi; 285704; -.
DR Pharos; Q6NW40; Tbio.
DR PRO; PR:Q6NW40; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q6NW40; protein.
DR Bgee; ENSG00000174136; Expressed in ileal mucosa and 188 other tissues.
DR ExpressionAtlas; Q6NW40; baseline and differential.
DR Genevisible; Q6NW40; HS.
DR GO; GO:0046658; C:anchored component of plasma membrane; ISS:HGNC-UCL.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISS:HGNC-UCL.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0015026; F:coreceptor activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISS:HGNC-UCL.
DR GO; GO:0030509; P:BMP signaling pathway; ISS:HGNC-UCL.
DR GO; GO:0007155; P:cell adhesion; ISS:HGNC-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:HGNC-UCL.
DR GO; GO:0007165; P:signal transduction; ISS:HGNC-UCL.
DR InterPro; IPR033608; DRAGON.
DR InterPro; IPR040287; RGM.
DR InterPro; IPR009496; RGM_C.
DR InterPro; IPR010536; RGM_N.
DR PANTHER; PTHR31428; PTHR31428; 1.
DR PANTHER; PTHR31428:SF5; PTHR31428:SF5; 1.
DR Pfam; PF06534; RGM_C; 1.
DR Pfam; PF06535; RGM_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Cell membrane; Disulfide bond;
KW Glycoprotein; GPI-anchor; Lipoprotein; Membrane; Reference proteome;
KW Signal.
FT SIGNAL 1..45
FT /evidence="ECO:0000255"
FT CHAIN 46..413
FT /note="Repulsive guidance molecule B"
FT /id="PRO_0000030394"
FT PROPEP 414..437
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000030395"
FT REGION 121..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 121..137
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 168..169
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:23744777"
FT LIPID 413
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 120
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 383
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 139..226
FT /evidence="ECO:0000269|PubMed:23744777"
FT DISULFID 163..312
FT /evidence="ECO:0000269|PubMed:23744777"
FT MUTAGEN 186
FT /note="A->R: Severely impairs interaction with NEO1."
FT /evidence="ECO:0000269|PubMed:23744777"
FT MUTAGEN 206
FT /note="P->N: Introduces a N-linked glycan; changes
FT interaction with NEO1 from a 2:2 to a 1:1 stoichiometry."
FT /evidence="ECO:0000269|PubMed:23744777"
FT CONFLICT 22
FT /note="S -> R (in Ref. 3; AAH67736)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="E -> G (in Ref. 3; AAH67736)"
FT /evidence="ECO:0000305"
FT HELIX 56..67
FT /evidence="ECO:0007829|PDB:6Z3J"
FT HELIX 77..94
FT /evidence="ECO:0007829|PDB:6Z3J"
FT HELIX 96..99
FT /evidence="ECO:0007829|PDB:6Z3J"
FT HELIX 103..118
FT /evidence="ECO:0007829|PDB:6Z3J"
FT STRAND 160..166
FT /evidence="ECO:0007829|PDB:4BQ6"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:4BQ6"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:4BQ6"
FT STRAND 185..205
FT /evidence="ECO:0007829|PDB:4BQ6"
FT STRAND 211..220
FT /evidence="ECO:0007829|PDB:4BQ6"
FT TURN 224..226
FT /evidence="ECO:0007829|PDB:4BQ6"
FT STRAND 230..235
FT /evidence="ECO:0007829|PDB:4BQ6"
FT STRAND 248..254
FT /evidence="ECO:0007829|PDB:4BQ6"
FT STRAND 257..261
FT /evidence="ECO:0007829|PDB:4BQ6"
FT TURN 264..267
FT /evidence="ECO:0007829|PDB:4UI2"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:4BQ6"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:4BQ6"
FT STRAND 278..285
FT /evidence="ECO:0007829|PDB:4BQ6"
FT STRAND 288..296
FT /evidence="ECO:0007829|PDB:4BQ6"
FT HELIX 297..300
FT /evidence="ECO:0007829|PDB:4BQ6"
FT HELIX 311..314
FT /evidence="ECO:0007829|PDB:4BQ6"
FT HELIX 318..320
FT /evidence="ECO:0007829|PDB:4BQ6"
FT HELIX 326..333
FT /evidence="ECO:0007829|PDB:4BQ8"
SQ SEQUENCE 437 AA; 47547 MW; 48C26166E68DCE5F CRC64;
MGLRAAPSSA AAAAAEVEQR RSPGLCPPPL ELLLLLLFSL GLLHAGDCQQ PAQCRIQKCT
TDFVSLTSHL NSAVDGFDSE FCKALRAYAG CTQRTSKACR GNLVYHSAVL GISDLMSQRN
CSKDGPTSST NPEVTHDPCN YHSHAGAREH RRGDQNPPSY LFCGLFGDPH LRTFKDNFQT
CKVEGAWPLI DNNYLSVQVT NVPVVPGSSA TATNKITIIF KAHHECTDQK VYQAVTDDLP
AAFVDGTTSG GDSDAKSLRI VERESGHYVE MHARYIGTTV FVRQVGRYLT LAIRMPEDLA
MSYEESQDLQ LCVNGCPLSE RIDDGQGQVS AILGHSLPRT SLVQAWPGYT LETANTQCHE
KMPVKDIYFQ SCVFDLLTTG DANFTAAAHS ALEDVEALHP RKERWHIFPS SGNGTPRGGS
DLSVSLGLTC LILIVFL
