ID RTN4R_HUMAN Reviewed; 473 AA. AC Q9BZR6; D3DX28; DT 25-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 24-JAN-2024, entry version 202. DE RecName: Full=Reticulon-4 receptor; DE AltName: Full=Nogo receptor; DE Short=NgR; DE AltName: Full=Nogo-66 receptor; DE Flags: Precursor; GN Name=RTN4R; Synonyms=NOGOR; ORFNames=UNQ330/PRO526; 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 [MRNA]. RC TISSUE=Brain; RX PubMed=11201742; DOI=10.1038/35053072; RA Fournier A.E., GrandPre T., Strittmatter S.M.; RT "Identification of a receptor mediating Nogo-66 inhibition of axonal RT regeneration."; RL Nature 409:341-346(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [6] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; 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 [8] RP PROTEIN SEQUENCE OF 27-41. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [9] RP FUNCTION, INTERACTION WITH NGR, AND SUBCELLULAR LOCATION. RX PubMed=12426574; DOI=10.1038/nn975; RA Wong S.T., Henley J.R., Kanning K.C., Huang K.H., Bothwell M., Poo M.M.; RT "A p75(NTR) and Nogo receptor complex mediates repulsive signaling by RT myelin-associated glycoprotein."; RL Nat. Neurosci. 5:1302-1308(2002). RN [10] RP FUNCTION, AND INTERACTION WITH RTN4. RX PubMed=12037567; DOI=10.1038/417547a; RA GrandPre T., Li S., Strittmatter S.M.; RT "Nogo-66 receptor antagonist peptide promotes axonal regeneration."; RL Nature 417:547-551(2002). RN [11] RP INTERACTION WITH OMG, AND FUNCTION. RX PubMed=12068310; DOI=10.1038/nature00867; RA Wang K.C., Koprivica V., Kim J.A., Sivasankaran R., Guo Y., Neve R.L., RA He Z.; RT "Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that RT inhibits neurite outgrowth."; RL Nature 417:941-944(2002). RN [12] RP INTERACTION WITH MAG, AND FUNCTION. RX PubMed=12089450; DOI=10.1126/science.1073031; RA Liu B.P., Fournier A., GrandPre T., Strittmatter S.M.; RT "Myelin-associated glycoprotein as a functional ligand for the Nogo-66 RT receptor."; RL Science 297:1190-1193(2002). RN [13] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=12694398; DOI=10.1046/j.1471-4159.2003.01710.x; RA Pignot V., Hein A.E., Barske C., Wiessner C., Walmsley A.R., Kaupmann K., RA Mayeur H., Sommer B., Mir A.K., Frentzel S.; RT "Characterization of two novel proteins, NgRH1 and NgRH2, structurally and RT biochemically homologous to the Nogo-66 receptor."; RL J. Neurochem. 85:717-728(2003). RN [14] RP INVOLVEMENT IN SCZD, AND VARIANTS SCZD TRP-119 AND HIS-196. RX PubMed=15532024; DOI=10.1002/humu.9292; RA Sinibaldi L., De Luca A., Bellacchio E., Conti E., Pasini A., Paloscia C., RA Spalletta G., Caltagirone C., Pizzuti A., Dallapiccola B.; RT "Mutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia."; RL Hum. Mutat. 24:534-535(2004). RN [15] RP FUNCTION, AND INTERACTION WITH LINGO1. RX PubMed=14966521; DOI=10.1038/nn1188; RA Mi S., Lee X., Shao Z., Thill G., Ji B., Relton J., Levesque M., RA Allaire N., Perrin S., Sands B., Crowell T., Cate R.L., McCoy J.M., RA Pepinsky R.B.; RT "LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex."; RL Nat. Neurosci. 7:221-228(2004). RN [16] RP REVIEW. RX PubMed=12183616; DOI=10.1126/science.1076247; RA Woolf C.J., Bloechlinger S.; RT "It takes more than two to Nogo."; RL Science 297:1132-1134(2002). RN [17] RP REVIEW. RX PubMed=11891768; DOI=10.1002/jnr.10134; RA Ng C.E.L., Tang B.L.; RT "Nogos and the Nogo-66 receptor: factors inhibiting CNS neuron RT regeneration."; RL J. Neurosci. Res. 67:559-565(2002). RN [18] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=16712417; DOI=10.1089/adt.2006.4.133; RA Teusch N., Kiefer C.; RT "A high-content screening assay for the Nogo receptor based on cellular Rho RT activation."; RL Assay Drug Dev. Technol. 4:133-141(2006). RN [19] RP INTERACTION WITH GANGLIOSIDE GT1B; GANGLIOSIDE GM1; NGFR; RTN4 AND MAG, RP SUBUNIT, SUBCELLULAR LOCATION, FUNCTION, AND MUTAGENESIS OF ARG-151; RP ARG-199; LYS-277 AND ARG-279. RX PubMed=18411262; DOI=10.1074/jbc.m802067200; RA Williams G., Wood A., Williams E.J., Gao Y., Mercado M.L., Katz A., RA Joseph-McCarthy D., Bates B., Ling H.P., Aulabaugh A., Zaccardi J., Xie Y., RA Pangalos M.N., Walsh F.S., Doherty P.; RT "Ganglioside inhibition of neurite outgrowth requires Nogo receptor RT function: identification of interaction sites and development of novel RT antagonists."; RL J. Biol. Chem. 283:16641-16652(2008). RN [20] RP FUNCTION, INTERACTION WITH MAG; RTN4; OMG; NGFR AND LINGO1, INVOLVEMENT IN RP SCZD, VARIANTS MET-53; HIS-68; SER-141; HIS-227; MET-263; SER-314; LEU-329 RP AND MET-363, VARIANTS SCZD TRP-119; HIS-196; CYS-227; GLN-377; TRP-377 AND RP TRP-399, AND CHARACTERIZATION OF VARIANTS SCZD TRP-119; HIS-196; GLN-377 RP AND TRP-377. RX PubMed=19052207; DOI=10.1523/jneurosci.3828-08.2008; RA Budel S., Padukkavidana T., Liu B.P., Feng Z., Hu F., Johnson S., RA Lauren J., Park J.H., McGee A.W., Liao J., Stillman A., Kim J.E., RA Yang B.Z., Sodi S., Gelernter J., Zhao H., Hisama F., Arnsten A.F., RA Strittmatter S.M.; RT "Genetic variants of Nogo-66 receptor with possible association to RT schizophrenia block myelin inhibition of axon growth."; RL J. Neurosci. 28:13161-13172(2008). RN [21] RP INTERACTION WITH KIAA0319L. RX PubMed=20697954; DOI=10.1007/s10571-010-9549-1; RA Poon M.W., Tsang W.H., Chan S.O., Li H.M., Ng H.K., Waye M.M.; RT "Dyslexia-associated kiaa0319-like protein interacts with axon guidance RT receptor nogo receptor 1."; RL Cell. Mol. Neurobiol. 31:27-35(2011). RN [22] RP FUNCTION. RX PubMed=22325200; DOI=10.1016/j.neuron.2011.11.029; RA Wills Z.P., Mandel-Brehm C., Mardinly A.R., McCord A.E., Giger R.J., RA Greenberg M.E.; RT "The Nogo receptor family restricts synapse number in the developing RT hippocampus."; RL Neuron 73:466-481(2012). RN [23] RP FUNCTION, VARIANTS HIS-68; ASN-259 AND MET-363, INVOLVEMENT IN SCZD, RP VARIANT SCZD HIS-292, AND CHARACTERIZATION OF VARIANT SCZD HIS-292. RX PubMed=28892071; DOI=10.1038/tp.2017.170; RA Kimura H., Fujita Y., Kawabata T., Ishizuka K., Wang C., Iwayama Y., RA Okahisa Y., Kushima I., Morikawa M., Uno Y., Okada T., Ikeda M., Inada T., RA Branko A., Mori D., Yoshikawa T., Iwata N., Nakamura H., Yamashita T., RA Ozaki N.; RT "A novel rare variant R292H in RTN4R affects growth cone formation and RT possibly contributes to schizophrenia susceptibility."; RL Transl. Psychiatry 7:E1214-E1214(2017). RN [24] RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 27-311, FUNCTION, INTERACTION WITH RP MAG; OMG AND RTN4, SUBCELLULAR LOCATION, DISULFIDE BONDS, AND GLYCOSYLATION RP AT ASN-82 AND ASN-179. RX PubMed=12839991; DOI=10.1093/emboj/cdg325; RA Barton W.A., Liu B.P., Tzvetkova D., Jeffrey P.D., Fournier A.E., Sah D., RA Cate R., Strittmatter S.M., Nikolov D.B.; RT "Structure and axon outgrowth inhibitor binding of the Nogo-66 receptor and RT related proteins."; RL EMBO J. 22:3291-3302(2003). RN [25] RP X-RAY CRYSTALLOGRAPHY (1.52 ANGSTROMS) OF 26-310, DISULFIDE BONDS, AND RP GLYCOSYLATION AT ASN-82 AND ASN-179. RX PubMed=12718853; DOI=10.1016/s0896-6273(03)00232-0; RA He X.L., Bazan J.F., McDermott G., Park J.B., Wang K., Tessier-Lavigne M., RA He Z., Garcia K.C.; RT "Structure of the Nogo receptor ectodomain: a recognition module implicated RT in myelin inhibition."; RL Neuron 38:177-185(2003). CC -!- FUNCTION: Receptor for RTN4, OMG and MAG (PubMed:12037567, CC PubMed:12068310, PubMed:12426574, PubMed:12089450, PubMed:16712417, CC PubMed:18411262, PubMed:12839991, PubMed:19052207). Functions as a CC receptor for the sialylated gangliosides GT1b and GM1 CC (PubMed:18411262). Besides, functions as a receptor for chondroitin CC sulfate proteoglycans (By similarity). Can also bind heparin (By CC similarity). Intracellular signaling cascades are triggered via the CC coreceptor NGFR (PubMed:12426574). Signaling mediates activation of Rho CC and downstream reorganization of the actin cytoskeleton CC (PubMed:16712417, PubMed:22325200). Mediates axonal growth inhibition CC (PubMed:12839991, PubMed:19052207, PubMed:28892071). Plays a role in CC regulating axon regeneration and neuronal plasticity in the adult CC central nervous system. Plays a role in postnatal brain development. CC Required for normal axon migration across the brain midline and normal CC formation of the corpus callosum. Protects motoneurons against CC apoptosis; protection against apoptosis is probably mediated via CC interaction with MAG. Acts in conjunction with RTN4 and LINGO1 in CC regulating neuronal precursor cell motility during cortical CC development. Like other family members, plays a role in restricting the CC number dendritic spines and the number of synapses that are formed CC during brain development (PubMed:22325200). CC {ECO:0000250|UniProtKB:Q99PI8, ECO:0000269|PubMed:12037567, CC ECO:0000269|PubMed:12426574, ECO:0000269|PubMed:12839991, CC ECO:0000269|PubMed:14966521, ECO:0000269|PubMed:16712417, CC ECO:0000269|PubMed:18411262, ECO:0000269|PubMed:19052207, CC ECO:0000269|PubMed:28892071}. CC -!- SUBUNIT: Homodimer (PubMed:18411262). Interacts with MAG CC (PubMed:12089450, PubMed:12839991, PubMed:18411262, PubMed:19052207). CC Interacts with RTN4 (PubMed:12839991, PubMed:19052207). Interacts with CC NGFR (PubMed:12426574, PubMed:18411262, PubMed:19052207). Interacts CC with LINGO1 (PubMed:14966521, PubMed:19052207). Interacts with CC KIAA0319L (PubMed:20697954). Interacts with OLFM1; this inhibits CC interaction with LINGO1 and NGFR (By similarity). Interacts with OMG CC (PubMed:12068310, PubMed:12839991, PubMed:19052207). CC {ECO:0000250|UniProtKB:Q99PI8, ECO:0000269|PubMed:12068310, CC ECO:0000269|PubMed:12089450, ECO:0000269|PubMed:12426574, CC ECO:0000269|PubMed:12839991, ECO:0000269|PubMed:14966521, CC ECO:0000269|PubMed:18411262, ECO:0000269|PubMed:19052207, CC ECO:0000269|PubMed:20697954}. CC -!- INTERACTION: CC Q9BZR6; P49639: HOXA1; NbExp=3; IntAct=EBI-5240240, EBI-740785; CC Q9BZR6; Q8IZA0: KIAA0319L; NbExp=4; IntAct=EBI-5240240, EBI-5240269; CC Q9BZR6; P32242: OTX1; NbExp=3; IntAct=EBI-5240240, EBI-740446; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12426574, CC ECO:0000269|PubMed:12694398, ECO:0000269|PubMed:12839991, CC ECO:0000269|PubMed:16712417, ECO:0000269|PubMed:18411262}; Lipid- CC anchor, GPI-anchor {ECO:0000269|PubMed:12694398}. Membrane raft CC {ECO:0000269|PubMed:12694398}. Cell projection, dendrite CC {ECO:0000250|UniProtKB:Q99PI8}. Cell projection, axon CC {ECO:0000250|UniProtKB:Q99PI8}. Perikaryon CC {ECO:0000250|UniProtKB:Q99M75}. Note=Detected along dendrites and CC axons, close to synapses, but clearly excluded from synapses. CC {ECO:0000250|UniProtKB:Q99PI8}. CC -!- TISSUE SPECIFICITY: Widespread in the brain but highest levels in the CC gray matter. Low levels in heart and kidney; not expressed in CC oligodendrocytes (white matter). {ECO:0000269|PubMed:12694398}. CC -!- PTM: N-glycosylated. O-glycosylated. Contains terminal sialic acid CC groups on its glycan chains. {ECO:0000250|UniProtKB:Q99M75}. CC -!- DISEASE: Schizophrenia (SCZD) [MIM:181500]: A complex, multifactorial CC psychotic disorder or group of disorders characterized by disturbances CC in the form and content of thought (e.g. delusions, hallucinations), in CC mood (e.g. inappropriate affect), in sense of self and relationship to CC the external world (e.g. loss of ego boundaries, withdrawal), and in CC behavior (e.g bizarre or apparently purposeless behavior). Although it CC affects emotions, it is distinguished from mood disorders in which such CC disturbances are primary. Similarly, there may be mild impairment of CC cognitive function, and it is distinguished from the dementias in which CC disturbed cognitive function is considered primary. Some patients CC manifest schizophrenic as well as bipolar disorder symptoms and are CC often given the diagnosis of schizoaffective disorder. CC {ECO:0000269|PubMed:15532024, ECO:0000269|PubMed:19052207, CC ECO:0000269|PubMed:28892071}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the Nogo receptor family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Nerve regrowth: nipped by a CC no-go - Issue 69 of April 2006; CC URL="https://web.expasy.org/spotlight/back_issues/069"; 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; AF283463; AAG53612.1; -; mRNA. DR EMBL; AL834449; CAD39109.1; -; mRNA. DR EMBL; AY358297; AAQ88664.1; -; mRNA. DR EMBL; CR456360; CAG30246.1; -; mRNA. DR EMBL; AC058790; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC007663; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471176; EAX02975.1; -; Genomic_DNA. DR EMBL; CH471176; EAX02976.1; -; Genomic_DNA. DR EMBL; BC011787; AAH11787.1; -; mRNA. DR CCDS; CCDS13777.1; -. DR RefSeq; NP_075380.1; NM_023004.5. DR PDB; 1OZN; X-ray; 1.52 A; A=26-310. DR PDB; 1P8T; X-ray; 3.20 A; A=27-311. DR PDBsum; 1OZN; -. DR PDBsum; 1P8T; -. DR AlphaFoldDB; Q9BZR6; -. DR EMDB; EMD-13149; -. DR SMR; Q9BZR6; -. DR BioGRID; 122388; 40. DR CORUM; Q9BZR6; -. DR IntAct; Q9BZR6; 10. DR MINT; Q9BZR6; -. DR STRING; 9606.ENSP00000043402; -. DR GlyCosmos; Q9BZR6; 3 sites, 1 glycan. DR GlyGen; Q9BZR6; 5 sites, 2 O-linked glycans (3 sites). DR iPTMnet; Q9BZR6; -. DR PhosphoSitePlus; Q9BZR6; -. DR BioMuta; RTN4R; -. DR EPD; Q9BZR6; -. DR jPOST; Q9BZR6; -. DR MassIVE; Q9BZR6; -. DR PaxDb; 9606-ENSP00000043402; -. DR PeptideAtlas; Q9BZR6; -. DR ProteomicsDB; 79894; -. DR Antibodypedia; 23162; 414 antibodies from 34 providers. DR DNASU; 65078; -. DR Ensembl; ENST00000043402.8; ENSP00000043402.7; ENSG00000040608.14. DR GeneID; 65078; -. DR KEGG; hsa:65078; -. DR MANE-Select; ENST00000043402.8; ENSP00000043402.7; NM_023004.6; NP_075380.1. DR UCSC; uc002zrv.4; human. DR AGR; HGNC:18601; -. DR CTD; 65078; -. DR DisGeNET; 65078; -. DR GeneCards; RTN4R; -. DR HGNC; HGNC:18601; RTN4R. DR HPA; ENSG00000040608; Tissue enriched (brain). DR MalaCards; RTN4R; -. DR MIM; 181500; phenotype. DR MIM; 605566; gene. DR neXtProt; NX_Q9BZR6; -. DR OpenTargets; ENSG00000040608; -. DR PharmGKB; PA38600; -. DR VEuPathDB; HostDB:ENSG00000040608; -. DR eggNOG; KOG0619; Eukaryota. DR GeneTree; ENSGT00940000160711; -. DR HOGENOM; CLU_000288_18_6_1; -. DR InParanoid; Q9BZR6; -. DR OMA; HPHAFHD; -. DR OrthoDB; 5394956at2759; -. DR PhylomeDB; Q9BZR6; -. DR TreeFam; TF330080; -. DR PathwayCommons; Q9BZR6; -. DR Reactome; R-HSA-193634; Axonal growth inhibition (RHOA activation). DR SignaLink; Q9BZR6; -. DR BioGRID-ORCS; 65078; 23 hits in 1155 CRISPR screens. DR ChiTaRS; RTN4R; human. DR EvolutionaryTrace; Q9BZR6; -. DR GeneWiki; Reticulon_4_receptor; -. DR GenomeRNAi; 65078; -. DR Pharos; Q9BZR6; Tbio. DR PRO; PR:Q9BZR6; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; Q9BZR6; Protein. DR Bgee; ENSG00000040608; Expressed in right hemisphere of cerebellum and 112 other cell types or tissues. DR ExpressionAtlas; Q9BZR6; baseline and differential. DR GO; GO:0044295; C:axonal growth cone; ISS:UniProtKB. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0043198; C:dendritic shaft; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb. DR GO; GO:0009897; C:external side of plasma membrane; IMP:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB. DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB. DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0098793; C:presynapse; IEA:Ensembl. DR GO; GO:0035374; F:chondroitin sulfate binding; ISS:UniProtKB. DR GO; GO:1905573; F:ganglioside GM1 binding; IDA:UniProtKB. DR GO; GO:1905576; F:ganglioside GT1b binding; IDA:UniProtKB. DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB. DR GO; GO:0038131; F:neuregulin receptor activity; ISS:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0038023; F:signaling receptor activity; ISS:UniProtKB. DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl. DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0022038; P:corpus callosum development; ISS:UniProtKB. DR GO; GO:0030517; P:negative regulation of axon extension; ISS:UniProtKB. DR GO; GO:0048681; P:negative regulation of axon regeneration; ISS:UniProtKB. DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:UniProtKB. DR GO; GO:0023041; P:neuronal signal transduction; ISS:UniProtKB. DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB. DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; IMP:UniProtKB. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR InterPro; IPR000483; Cys-rich_flank_reg_C. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp. DR InterPro; IPR032675; LRR_dom_sf. DR PANTHER; PTHR24369; ANTIGEN BSP, PUTATIVE-RELATED; 1. DR PANTHER; PTHR24369:SF174; RETICULON-4 RECEPTOR; 1. DR Pfam; PF13855; LRR_8; 2. DR SMART; SM00369; LRR_TYP; 8. DR SMART; SM00082; LRRCT; 1. DR SUPFAM; SSF52058; L domain-like; 1. DR PROSITE; PS51450; LRR; 6. DR Genevisible; Q9BZR6; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Cell projection; Direct protein sequencing; KW Disease variant; Disulfide bond; Glycoprotein; GPI-anchor; KW Leucine-rich repeat; Lipid-binding; Lipoprotein; Membrane; Receptor; KW Reference proteome; Repeat; Schizophrenia; Signal. FT SIGNAL 1..26 FT /evidence="ECO:0000269|PubMed:15340161" FT CHAIN 27..447 FT /note="Reticulon-4 receptor" FT /id="PRO_0000022253" FT PROPEP 448..473 FT /note="Removed in mature form" FT /evidence="ECO:0000255" FT /id="PRO_0000022254" FT DOMAIN 27..54 FT /note="LRRNT" FT REPEAT 55..79 FT /note="LRR 1" FT /evidence="ECO:0000255" FT REPEAT 81..103 FT /note="LRR 2" FT /evidence="ECO:0000255" FT REPEAT 104..128 FT /note="LRR 3" FT /evidence="ECO:0000255" FT REPEAT 129..152 FT /note="LRR 4" FT /evidence="ECO:0000255" FT REPEAT 153..176 FT /note="LRR 5" FT /evidence="ECO:0000255" FT REPEAT 178..200 FT /note="LRR 6" FT /evidence="ECO:0000255" FT REPEAT 202..224 FT /note="LRR 7" FT /evidence="ECO:0000255" FT REPEAT 225..248 FT /note="LRR 8" FT /evidence="ECO:0000255" FT REPEAT 250..273 FT /note="LRR 9" FT /evidence="ECO:0000255" FT DOMAIN 260..310 FT /note="LRRCT" FT /evidence="ECO:0000255" FT REGION 346..447 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT LIPID 447 FT /note="GPI-anchor amidated serine" FT /evidence="ECO:0000255" FT CARBOHYD 82 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12718853, FT ECO:0000269|PubMed:12839991, ECO:0007744|PDB:1OZN" FT CARBOHYD 179 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12718853, FT ECO:0000269|PubMed:12839991" FT DISULFID 27..33 FT /evidence="ECO:0000269|PubMed:12718853, FT ECO:0000269|PubMed:12839991, ECO:0007744|PDB:1OZN, FT ECO:0007744|PDB:1P8T" FT DISULFID 31..43 FT /evidence="ECO:0000269|PubMed:12718853, FT ECO:0000269|PubMed:12839991, ECO:0007744|PDB:1OZN, FT ECO:0007744|PDB:1P8T" FT DISULFID 264..287 FT /evidence="ECO:0000269|PubMed:12718853, FT ECO:0000269|PubMed:12839991, ECO:0007744|PDB:1OZN, FT ECO:0007744|PDB:1P8T" FT DISULFID 266..335 FT /evidence="ECO:0000250|UniProtKB:Q99PI8" FT DISULFID 309..336 FT /evidence="ECO:0000250|UniProtKB:Q99PI8" FT VARIANT 53 FT /note="V -> M (in dbSNP:rs145292678)" FT /evidence="ECO:0000269|PubMed:19052207" FT /id="VAR_079224" FT VARIANT 68 FT /note="R -> H (in dbSNP:rs145773589)" FT /evidence="ECO:0000269|PubMed:19052207, FT ECO:0000269|PubMed:28892071" FT /id="VAR_079225" FT VARIANT 119 FT /note="R -> W (in SCZD; associated with disease FT susceptibility; unable to mediate down-regulation of axonal FT growth; decreased interaction with MAG and OMG; no effect FT on interaction with RTN4; dbSNP:rs74315508)" FT /evidence="ECO:0000269|PubMed:15532024, FT ECO:0000269|PubMed:19052207" FT /id="VAR_079154" FT VARIANT 141 FT /note="G -> S (in dbSNP:rs760855779)" FT /evidence="ECO:0000269|PubMed:19052207" FT /id="VAR_079226" FT VARIANT 196 FT /note="R -> H (in SCZD; associated with disease FT susceptibility; unable to mediate down-regulation of axonal FT growth; does not affect interaction with MAG, RTN4 and OMG; FT dbSNP:rs74315509)" FT /evidence="ECO:0000269|PubMed:15532024, FT ECO:0000269|PubMed:19052207" FT /id="VAR_079155" FT VARIANT 227 FT /note="R -> C (in SCZD; uncertain significance; FT dbSNP:rs754793885)" FT /evidence="ECO:0000269|PubMed:19052207" FT /id="VAR_079227" FT VARIANT 227 FT /note="R -> H (in dbSNP:rs576939822)" FT /evidence="ECO:0000269|PubMed:19052207" FT /id="VAR_079228" FT VARIANT 259 FT /note="D -> N (in dbSNP:rs3747073)" FT /evidence="ECO:0000269|PubMed:28892071" FT /id="VAR_079229" FT VARIANT 263 FT /note="V -> M (in dbSNP:rs752810777)" FT /evidence="ECO:0000269|PubMed:19052207" FT /id="VAR_079230" FT VARIANT 292 FT /note="R -> H (in SCZD; associated with disease FT susceptibility; unable to mediate down-regulation of axonal FT growth; dbSNP:rs1432033565)" FT /evidence="ECO:0000269|PubMed:28892071" FT /id="VAR_079231" FT VARIANT 314 FT /note="G -> S (in dbSNP:rs112151786)" FT /evidence="ECO:0000269|PubMed:19052207" FT /id="VAR_079232" FT VARIANT 329 FT /note="P -> L (in dbSNP:rs757507039)" FT /evidence="ECO:0000269|PubMed:19052207" FT /id="VAR_079233" FT VARIANT 363 FT /note="V -> M (in dbSNP:rs149231717)" FT /evidence="ECO:0000269|PubMed:19052207, FT ECO:0000269|PubMed:28892071" FT /id="VAR_079234" FT VARIANT 377 FT /note="R -> Q (in SCZD; associated with disease FT susceptibility; unable to mediate down-regulation of axonal FT growth; does not affect interaction with MAG, RTN4, OMG, FT NGFR and LINGO1; dbSNP:rs779384862)" FT /evidence="ECO:0000269|PubMed:19052207" FT /id="VAR_079235" FT VARIANT 377 FT /note="R -> W (in SCZD; associated with disease FT susceptibility; unable to mediate down-regulation of axonal FT growth; does not affect interaction with MAG, RTN4, OMG, FT NGFR and LINGO1; dbSNP:rs748655075)" FT /evidence="ECO:0000269|PubMed:19052207" FT /id="VAR_079236" FT VARIANT 399 FT /note="R -> W (in SCZD; uncertain significance; FT dbSNP:rs200119628)" FT /evidence="ECO:0000269|PubMed:19052207" FT /id="VAR_079237" FT MUTAGEN 151 FT /note="R->E: Impaired ganglioside binding." FT /evidence="ECO:0000269|PubMed:18411262" FT MUTAGEN 199 FT /note="R->E: Impaired ganglioside binding." FT /evidence="ECO:0000269|PubMed:18411262" FT MUTAGEN 277 FT /note="K->A: No effect on interaction with MAG." FT /evidence="ECO:0000269|PubMed:18411262" FT MUTAGEN 277 FT /note="K->D: Decreases interaction with MAG; when FT associated with D-279." FT /evidence="ECO:0000269|PubMed:18411262" FT MUTAGEN 279 FT /note="R->A: Mildly decreases interaction with MAG." FT /evidence="ECO:0000269|PubMed:18411262" FT MUTAGEN 279 FT /note="R->D: Decreases interaction with MAG; when FT associated with D-277." FT /evidence="ECO:0000269|PubMed:18411262" FT MUTAGEN 279 FT /note="R->E: Impaired ganglioside binding." FT /evidence="ECO:0000269|PubMed:18411262" FT STRAND 32..34 FT /evidence="ECO:0007829|PDB:1OZN" FT STRAND 36..38 FT /evidence="ECO:0007829|PDB:1OZN" FT STRAND 40..42 FT /evidence="ECO:0007829|PDB:1OZN" FT STRAND 60..63 FT /evidence="ECO:0007829|PDB:1OZN" FT TURN 74..79 FT /evidence="ECO:0007829|PDB:1OZN" FT STRAND 85..87 FT /evidence="ECO:0007829|PDB:1OZN" FT TURN 98..103 FT /evidence="ECO:0007829|PDB:1OZN" FT STRAND 109..111 FT /evidence="ECO:0007829|PDB:1OZN" FT TURN 123..128 FT /evidence="ECO:0007829|PDB:1OZN" FT STRAND 134..136 FT /evidence="ECO:0007829|PDB:1OZN" FT TURN 147..152 FT /evidence="ECO:0007829|PDB:1OZN" FT STRAND 158..160 FT /evidence="ECO:0007829|PDB:1OZN" FT TURN 171..176 FT /evidence="ECO:0007829|PDB:1OZN" FT STRAND 182..184 FT /evidence="ECO:0007829|PDB:1OZN" FT TURN 195..200 FT /evidence="ECO:0007829|PDB:1OZN" FT STRAND 206..208 FT /evidence="ECO:0007829|PDB:1OZN" FT TURN 219..224 FT /evidence="ECO:0007829|PDB:1OZN" FT STRAND 230..232 FT /evidence="ECO:0007829|PDB:1OZN" FT HELIX 243..246 FT /evidence="ECO:0007829|PDB:1OZN" FT STRAND 254..256 FT /evidence="ECO:0007829|PDB:1OZN" FT HELIX 266..268 FT /evidence="ECO:0007829|PDB:1OZN" FT HELIX 269..277 FT /evidence="ECO:0007829|PDB:1OZN" FT STRAND 280..282 FT /evidence="ECO:0007829|PDB:1OZN" FT STRAND 286..290 FT /evidence="ECO:0007829|PDB:1OZN" FT HELIX 291..293 FT /evidence="ECO:0007829|PDB:1OZN" FT HELIX 298..300 FT /evidence="ECO:0007829|PDB:1OZN" FT HELIX 303..305 FT /evidence="ECO:0007829|PDB:1OZN" SQ SEQUENCE 473 AA; 50708 MW; CA5624B24C584702 CRC64; MKRASAGGSR LLAWVLWLQA WQVAAPCPGA CVCYNEPKVT TSCPQQGLQA VPVGIPAASQ RIFLHGNRIS HVPAASFRAC RNLTILWLHS NVLARIDAAA FTGLALLEQL DLSDNAQLRS VDPATFHGLG RLHTLHLDRC GLQELGPGLF RGLAALQYLY LQDNALQALP DDTFRDLGNL THLFLHGNRI SSVPERAFRG LHSLDRLLLH QNRVAHVHPH AFRDLGRLMT LYLFANNLSA LPTEALAPLR ALQYLRLNDN PWVCDCRARP LWAWLQKFRG SSSEVPCSLP QRLAGRDLKR LAANDLQGCA VATGPYHPIW TGRATDEEPL GLPKCCQPDA ADKASVLEPG RPASAGNALK GRVPPGDSPP GNGSGPRHIN DSPFGTLPGS AEPPLTAVRP EGSEPPGFPT SGPRRRPGCS RKNRTRSHCR LGQAGSGGGG TGDSEGSGAL PSLTCSLTPL GLALVLWTVL GPC //