RTN4R_HUMAN
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 03-AUG-2022, entry version 194.
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
CC receptor for the sialylated gangliosides GT1b and GM1
CC (PubMed:18411262). Besides, functions as 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";
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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 SMR; Q9BZR6; -.
DR BioGRID; 122388; 40.
DR CORUM; Q9BZR6; -.
DR IntAct; Q9BZR6; 10.
DR MINT; Q9BZR6; -.
DR STRING; 9606.ENSP00000043402; -.
DR GlyGen; Q9BZR6; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BZR6; -.
DR PhosphoSitePlus; Q9BZR6; -.
DR BioMuta; RTN4R; -.
DR EPD; Q9BZR6; -.
DR jPOST; Q9BZR6; -.
DR MassIVE; Q9BZR6; -.
DR PaxDb; Q9BZR6; -.
DR PeptideAtlas; Q9BZR6; -.
DR PRIDE; Q9BZR6; -.
DR ProteomicsDB; 79894; -.
DR Antibodypedia; 23162; 336 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 CTD; 65078; -.
DR DisGeNET; 65078; -.
DR GeneCards; RTN4R; -.
DR HGNC; HGNC:18601; RTN4R.
DR HPA; ENSG00000040608; Tissue enhanced (brain, liver).
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; MWLNLLP; -.
DR OrthoDB; 826997at2759; -.
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 1076 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 110 other tissues.
DR ExpressionAtlas; Q9BZR6; baseline and differential.
DR Genevisible; Q9BZR6; HS.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; IMP:UniProtKB.
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:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
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; IBA:GO_Central.
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; -; 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 Pfam; PF13855; LRR_8; 2.
DR SMART; SM00369; LRR_TYP; 8.
DR SMART; SM00082; LRRCT; 1.
DR PROSITE; PS51450; LRR; 6.
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; unknown pathological 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; unknown pathological 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
