RTN4R_RAT
ID RTN4R_RAT Reviewed; 473 AA.
AC Q99M75;
DT 25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 2.
DT 03-AUG-2022, entry version 165.
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Jin W.-L., Jia W., Long M., Ju G.;
RT "Identification and preparation of polyclonal antibody against rat Nogo
RT receptor.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Oertle T., van der Haar M.E., Bandtlow C.E., Huber A.B., Simonen M.,
RA Schnell L., Broesamle C., Schwab M.E.;
RT "Nogo-A: a molecule with two active sites and two membrane topologies.";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP INTERACTION WITH NGFR, TISSUE SPECIFICITY, 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 [5]
RP FUNCTION.
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAG; RTN4 AND OMG, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=15673660; DOI=10.1523/jneurosci.4464-04.2005;
RA Venkatesh K., Chivatakarn O., Lee H., Joshi P.S., Kantor D.B., Newman B.A.,
RA Mage R., Rader C., Giger R.J.;
RT "The Nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor
RT selective for myelin-associated glycoprotein.";
RL J. Neurosci. 25:808-822(2005).
RN [7]
RP FUNCTION.
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 [8]
RP INTERACTION WITH MAG; RTN4 AND OMG, GLYCOSYLATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=19420245; DOI=10.1523/jneurosci.4935-08.2009;
RA Robak L.A., Venkatesh K., Lee H., Raiker S.J., Duan Y., Lee-Osbourne J.,
RA Hofer T., Mage R.G., Rader C., Giger R.J.;
RT "Molecular basis of the interactions of the Nogo-66 receptor and its
RT homolog NgR2 with myelin-associated glycoprotein: development of NgROMNI-
RT Fc, a novel antagonist of CNS myelin inhibition.";
RL J. Neurosci. 29:5768-5783(2009).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [10]
RP FUNCTION.
RX PubMed=26335717; DOI=10.1038/cddis.2015.228;
RA Palandri A., Salvador V.R., Wojnacki J., Vivinetto A.L., Schnaar R.L.,
RA Lopez P.H.;
RT "Myelin-associated glycoprotein modulates apoptosis of motoneurons during
RT early postnatal development via NgR/p75(NTR) receptor-mediated activation
RT of RhoA signaling pathways.";
RL Cell Death Dis. 6:E1876-E1876(2015).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 27-312, AND DISULFIDE BONDS.
RX PubMed=20815818; DOI=10.1042/ba20100061;
RA Weinreb P.H., Wen D., Qian F., Wildes C.P., Garber E.A., Walus L.,
RA Jung M.Y., Wang J., Relton J.K., Amatucci J., Wang R., Porreca F.,
RA Silvian L., Meier W., Pepinsky R.B., Lee D.H.;
RT "Resolution of disulfide heterogeneity in Nogo receptor I fusion proteins
RT by molecular engineering.";
RL Biotechnol. Appl. Biochem. 57:31-45(2010).
CC -!- FUNCTION: Receptor for RTN4, OMG and MAG (PubMed:12037567,
CC PubMed:15673660, PubMed:19420245). Functions as receptor for the
CC sialylated gangliosides GT1b and GM1. Besides, functions as receptor
CC for chondroitin sulfate proteoglycans. Can also bind heparin.
CC Intracellular signaling cascades are triggered via the coreceptor NGFR
CC (By similarity). Signaling mediates activation of Rho and downstream
CC reorganization of the actin cytoskeleton (PubMed:18411262). Mediates
CC axonal growth inhibition (PubMed:12037567). May play 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 (By similarity). Protects motoneurons
CC against apoptosis; protection against apoptosis is probably mediated
CC via interaction with MAG (PubMed:26335717). Acts in conjunction with
CC RTN4 and LINGO1 in regulating neuronal precursor cell motility during
CC cortical development. Like other family members, plays a role in
CC restricting the number dendritic spines and the number of synapses that
CC are formed during brain development (PubMed:22325200).
CC {ECO:0000250|UniProtKB:Q99PI8, ECO:0000250|UniProtKB:Q9BZR6,
CC ECO:0000269|PubMed:12037567, ECO:0000269|PubMed:15673660,
CC ECO:0000269|PubMed:18411262, ECO:0000269|PubMed:22325200,
CC ECO:0000269|PubMed:26335717}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with MAG
CC (PubMed:15673660, PubMed:19420245). Interacts with RTN4 and OMG
CC (PubMed:15673660, PubMed:19420245). Interacts with LINGO1 and NGFR (By
CC similarity). Interacts with KIAA0319L (By similarity). Interacts with
CC OLFM1; this inhibits interaction with LINGO1 and NGFR (By similarity).
CC {ECO:0000250|UniProtKB:Q99PI8, ECO:0000250|UniProtKB:Q9BZR6,
CC ECO:0000269|PubMed:15673660, ECO:0000269|PubMed:19420245}.
CC -!- INTERACTION:
CC Q99M75; Q96FE5: LINGO1; Xeno; NbExp=2; IntAct=EBI-7370412, EBI-719955;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15673660,
CC ECO:0000269|PubMed:19420245, ECO:0000269|PubMed:22325200}; Lipid-
CC anchor, GPI-anchor {ECO:0000250|UniProtKB:Q99PI8}. Membrane raft
CC {ECO:0000269|PubMed:15673660}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q99PI8}. Perikaryon
CC {ECO:0000269|PubMed:15673660}. Cell projection, axon
CC {ECO:0000269|PubMed:12426574}. Note=Detected along dendrites and axons,
CC close to synapses, but clearly excluded from synapses.
CC {ECO:0000250|UniProtKB:Q99PI8}.
CC -!- TISSUE SPECIFICITY: Detected in embryonic cerebellum, in spinal cord
CC motor neurons and in dorsal root ganglia (PubMed:12426574). Detected in
CC adult brain, in neocortex, hippocampus, striatum, thalamus and dorsal
CC root ganglion neurons (at protein level).
CC {ECO:0000269|PubMed:15673660}.
CC -!- DEVELOPMENTAL STAGE: Expression is high in adult, but very low in
CC neonate dorsal root ganglion neurons (at protein level).
CC {ECO:0000269|PubMed:15673660}.
CC -!- PTM: N-glycosylated. O-glycosylated. Contains terminal sialic acid
CC groups on its glycan chains. {ECO:0000269|PubMed:19420245}.
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; AY028438; AAK20166.1; -; mRNA.
DR EMBL; AF462390; AAM46772.1; -; mRNA.
DR RefSeq; NP_446065.1; NM_053613.1.
DR PDB; 3KJ4; X-ray; 3.10 A; A/D=27-312.
DR PDBsum; 3KJ4; -.
DR AlphaFoldDB; Q99M75; -.
DR SMR; Q99M75; -.
DR BioGRID; 250215; 5.
DR IntAct; Q99M75; 1.
DR MINT; Q99M75; -.
DR STRING; 10116.ENSRNOP00000041517; -.
DR GlyGen; Q99M75; 2 sites.
DR iPTMnet; Q99M75; -.
DR PaxDb; Q99M75; -.
DR ABCD; Q99M75; 2 sequenced antibodies.
DR Ensembl; ENSRNOT00000051037; ENSRNOP00000041517; ENSRNOG00000030920.
DR GeneID; 113912; -.
DR KEGG; rno:113912; -.
DR CTD; 65078; -.
DR RGD; 620810; Rtn4r.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000160711; -.
DR HOGENOM; CLU_000288_18_6_1; -.
DR InParanoid; Q99M75; -.
DR OMA; MWLNLLP; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; Q99M75; -.
DR TreeFam; TF330080; -.
DR EvolutionaryTrace; Q99M75; -.
DR PRO; PR:Q99M75; -.
DR Proteomes; UP000002494; Chromosome 11.
DR Bgee; ENSRNOG00000030920; Expressed in frontal cortex and 17 other tissues.
DR Genevisible; Q99M75; RN.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; ISS: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; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0030426; C:growth cone; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA: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; ISO:RGD.
DR GO; GO:0098793; C:presynapse; IDA:SynGO.
DR GO; GO:0035374; F:chondroitin sulfate binding; ISS:UniProtKB.
DR GO; GO:1905573; F:ganglioside GM1 binding; ISS:UniProtKB.
DR GO; GO:1905576; F:ganglioside GT1b binding; ISS: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; IPI:RGD.
DR GO; GO:0048495; F:Roundabout binding; IBA:GO_Central.
DR GO; GO:0038023; F:signaling receptor activity; IMP:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007409; P:axonogenesis; ISO:RGD.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0022038; P:corpus callosum development; ISS:UniProtKB.
DR GO; GO:0050919; P:negative chemotaxis; IBA:GO_Central.
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:0050771; P:negative regulation of axonogenesis; TAS:RGD.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IMP: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; ISS: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; 8.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cell projection; Disulfide bond; Glycoprotein;
KW GPI-anchor; Leucine-rich repeat; Lipoprotein; Membrane; Receptor;
KW Reference proteome; Repeat; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..447
FT /note="Reticulon-4 receptor"
FT /id="PRO_0000022259"
FT PROPEP 448..473
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000022260"
FT DOMAIN 27..57
FT /note="LRRNT"
FT /evidence="ECO:0000255"
FT REPEAT 56..79
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 80..103
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 105..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..446
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 429..443
FT /note="Polar residues"
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:0000255"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 27..33
FT /evidence="ECO:0000269|PubMed:20815818,
FT ECO:0007744|PDB:3KJ4"
FT DISULFID 31..43
FT /evidence="ECO:0000269|PubMed:20815818,
FT ECO:0007744|PDB:3KJ4"
FT DISULFID 264..287
FT /evidence="ECO:0000269|PubMed:20815818,
FT ECO:0007744|PDB:3KJ4"
FT DISULFID 266..335
FT /evidence="ECO:0000250|UniProtKB:Q99PI8"
FT DISULFID 309..336
FT /evidence="ECO:0000250|UniProtKB:Q99PI8"
FT CONFLICT 12..13
FT /note="LA -> PT (in Ref. 1; AAK20166)"
FT /evidence="ECO:0000305"
FT CONFLICT 43
FT /note="C -> R (in Ref. 1; AAK20166)"
FT /evidence="ECO:0000305"
FT CONFLICT 53
FT /note="T -> A (in Ref. 1; AAK20166)"
FT /evidence="ECO:0000305"
FT CONFLICT 284
FT /note="E -> G (in Ref. 1; AAK20166)"
FT /evidence="ECO:0000305"
FT CONFLICT 287
FT /note="C -> S (in Ref. 1; AAK20166)"
FT /evidence="ECO:0000305"
FT CONFLICT 303
FT /note="A -> T (in Ref. 1; AAK20166)"
FT /evidence="ECO:0000305"
FT CONFLICT 355
FT /note="A -> V (in Ref. 1; AAK20166)"
FT /evidence="ECO:0000305"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:3KJ4"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:3KJ4"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:3KJ4"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:3KJ4"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:3KJ4"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:3KJ4"
FT TURN 98..103
FT /evidence="ECO:0007829|PDB:3KJ4"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:3KJ4"
FT TURN 123..128
FT /evidence="ECO:0007829|PDB:3KJ4"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:3KJ4"
FT TURN 147..152
FT /evidence="ECO:0007829|PDB:3KJ4"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:3KJ4"
FT TURN 171..176
FT /evidence="ECO:0007829|PDB:3KJ4"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:3KJ4"
FT TURN 195..200
FT /evidence="ECO:0007829|PDB:3KJ4"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:3KJ4"
FT TURN 219..224
FT /evidence="ECO:0007829|PDB:3KJ4"
FT STRAND 230..232
FT /evidence="ECO:0007829|PDB:3KJ4"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:3KJ4"
FT HELIX 268..277
FT /evidence="ECO:0007829|PDB:3KJ4"
FT HELIX 291..293
FT /evidence="ECO:0007829|PDB:3KJ4"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:3KJ4"
SQ SEQUENCE 473 AA; 50851 MW; 3DFD17EA4651FECB CRC64;
MKRASSGGSR LLAWVLWLQA WRVATPCPGA CVCYNEPKVT TSCPQQGLQA VPTGIPASSQ
RIFLHGNRIS YVPAASFQSC RNLTILWLHS NALAGIDAAA FTGLTLLEQL DLSDNAQLRV
VDPTTFRGLG HLHTLHLDRC GLQELGPGLF RGLAALQYLY LQDNNLQALP DNTFRDLGNL
THLFLHGNRI PSVPEHAFRG LHSLDRLLLH QNHVARVHPH AFRDLGRLMT LYLFANNLSM
LPAEVLVPLR SLQYLRLNDN PWVCDCRARP LWAWLQKFRG SSSEVPCNLP QRLAGRDLKR
LAASDLEGCA VASGPFRPFQ TNQLTDEELL GLPKCCQPDA ADKASVLEPG RPASAGNALK
GRVPPGDTPP GNGSGPRHIN DSPFGTLPGS AEPPLTALRP GGSEPPGLPT TGPRRRPGCS
RKNRTRSHCR LGQAGSGSSG TGDAEGSGAL PALACSLAPL GLALVLWTVL GPC
