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Protein

Reticulon-4 receptor

Gene

Rtn4r

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for RTN4, OMG and MAG (PubMed:11201742, PubMed:12089450, PubMed:15504325, PubMed:18411262, PubMed:22923615). Functions as receptor for the sialylated gangliosides GT1b and GM1 (PubMed:18411262). Besides, functions as receptor for chondroitin sulfate proteoglycans (PubMed:22406547). Can also bind heparin (PubMed:22406547). Intracellular signaling cascades are triggered via the coreceptor NGFR (By similarity). Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton (PubMed:22325200). Mediates axonal growth inhibition (By similarity). Mediates axonal growth inhibition and plays a role in regulating axon regeneration and neuronal plasticity in the adult central nervous system (PubMed:11201742, PubMed:12089450, PubMed:15504325, PubMed:22923615). Plays a role in postnatal brain development (PubMed:27339102). Required for normal axon migration across the brain midline and normal formation of the corpus callosum (PubMed:27339102). Protects motoneurons against apoptosis; protection against apoptosis is probably mediated via interaction with MAG (PubMed:26335717). Acts in conjunction with RTN4 and LINGO1 in regulating neuronal precursor cell motility during cortical development (PubMed:20093372). Like other family members, plays a role in restricting the number dendritic spines and the number of synapses that are formed during brain development (PubMed:22325200).By similarity9 Publications

GO - Molecular functioni

  • chondroitin sulfate binding Source: UniProtKB
  • ganglioside GM1 binding Source: UniProtKB
  • ganglioside GT1b binding Source: UniProtKB
  • heparin binding Source: UniProtKB
  • neuregulin receptor activity Source: UniProtKB
  • protein kinase inhibitor activity Source: GO_Central

GO - Biological processi

  • axonogenesis Source: MGI
  • cell surface receptor signaling pathway Source: UniProtKB
  • corpus callosum development Source: UniProtKB
  • cytokine-mediated signaling pathway Source: GO_Central
  • negative regulation of axon extension Source: UniProtKB
  • negative regulation of axon regeneration Source: UniProtKB
  • negative regulation of JAK-STAT cascade Source: GO_Central
  • negative regulation of neuron projection development Source: UniProtKB
  • negative regulation of protein kinase activity Source: GO_Central
  • neuronal signal transduction Source: UniProtKB
  • positive regulation of GTPase activity Source: UniProtKB
  • positive regulation of Rho protein signal transduction Source: UniProtKB

Keywordsi

Molecular functionHeparin-binding, Receptor

Enzyme and pathway databases

ReactomeiR-MMU-193634. Axonal growth inhibition (RHOA activation).

Names & Taxonomyi

Protein namesi
Recommended name:
Reticulon-4 receptor
Alternative name(s):
Nogo receptor
Short name:
NgR1 Publication
Nogo-66 receptor1 Publication
Nogo66 receptor-11 Publication
Short name:
NgR11 Publication
Gene namesi
Name:Rtn4r
Synonyms:Ngr1, Nogor
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:2136886. Rtn4r.

Subcellular locationi

GO - Cellular componenti

  • anchored component of external side of plasma membrane Source: UniProtKB
  • axonal growth cone Source: UniProtKB
  • cell surface Source: UniProtKB
  • cytoplasm Source: GO_Central
  • dendritic shaft Source: UniProtKB
  • endoplasmic reticulum Source: MGI
  • extracellular exosome Source: MGI
  • growth cone Source: MGI
  • integral component of plasma membrane Source: UniProtKB
  • membrane raft Source: UniProtKB
  • neuronal cell body Source: UniProtKB
  • neuron projection Source: UniProtKB
  • perikaryon Source: UniProtKB-SubCell
  • plasma membrane Source: MGI

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice are born at the expected Mendelian rate, are viable and fertile (PubMed:15504325, PubMed:15647357). They display subtle changes in exploratory behavior and impaired ability to stay on a rotarod (PubMed:15504325). Compared to wild-type littermates, cultured hippocampus neurons from mutant mice display an increased number of excitatory synapses (PubMed:22325200). Effects on neurite outgrowth are controversial and may depend on the mouse strain, cell type, and the experimental conditions (PubMed:15504325, PubMed:15647357, PubMed:18411262, PubMed:19367338). Cultured neurons display impaired axon growth cone collapse in response to myelin, MAG and RTN4 (PubMed:15504325). Mutant cerebellar and dorsal root ganglion neurons show no decrease of the inhibition of neurite outgrowth by myelin or RTN4 (PubMed:15647357). Mutant cerebellar neurons display decreased inhibition of neurite outgrowth mediated by MAG and by cross-linking ganglioside GT1b (in vitro) (PubMed:18411262). Likewise, mutant sensory neurons show no decrease of the inhibition of neurite outgrowth by MAG (PubMed:19367338). Mutant mice have improved functional recovery and increased regeneration of rubrospinal and raphespinal fibers after spinal cord transection. Still, there is no regeneration of corticospinal fibers (PubMed:15504325, PubMed:15647357). Mice lacking both Rtn4r and Rtn4rl2 display no visible phenotype (PubMed:19367338). Sensory neurons from mice lacking both Rtn4r and Rtn4rl2 show moderately decreased inhibition of neurite outgrowth by MAG (PubMed:19367338). Mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 have no visible phenotype, are healthy and viable (PubMed:22406547). Mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 have normal brain size and grossly normal brain anatomy, but display disruption of medial brain structures, including an absence of the fasciola cinereum, corpus callosum agenesis and formation of bilateral Probst bundles indicative of the failure of callosally projecting neurons to extend across the midline (PubMed:27339102). Mice with a triple gene disruption of Rtn4r, Rtn4rl1 and Rtn4rl2 display impaired ability to stay on a rotarod and increased spontaneous locomotion (PubMed:27339102). These mice display an increased number of excitatory synapses in the apical dendritic regions of hippocampus neurons, an increase in the complexity of dendrite structure and increased total dendrite length (PubMed:22325200). One month after birth, mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 show a significant reduction in the survival of motoneurons (PubMed:26335717). Compared to wild-type or single mutants, cerebellar granule cells from mice lacking Rtn4r, Rtn4rl1 and Rtn4rl2 show decreased myelin-mediated inhibition of neurite outgrowth, an inhibition that is strongly decreased on myelin deficient in Mag, Rtn4 and Omg (PubMed:22406547). Mice lacking both Rtn4r and Rtn4rl1 show increased axon regeneration after injury; the same effect is observed when Rtn4r, Rtn4rl1 and Rtn4rl2 are disrupted (PubMed:22406547). Combined disruption of Rtn4r, Rtn4rl1 and Ptprs further increases axon regeneration after injury (PubMed:22406547). Single gene disruption of Rtn4r, Rtn4rl1 and Rtn4rl2 and combined disruption of Rtn4r and Rtn4rl2 have no effect on axon regeneration (PubMed:22406547).8 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000002225727 – 447Reticulon-4 receptorAdd BLAST421
PropeptideiPRO_0000022258448 – 473Removed in mature formSequence analysisAdd BLAST26

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi27 ↔ 33By similarity
Disulfide bondi31 ↔ 43By similarity
Glycosylationi82N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi264 ↔ 287By similarity
Disulfide bondi266 ↔ 309By similarity
Glycosylationi372N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi447GPI-anchor amidated serineSequence analysis1

Post-translational modificationi

N-glycosylated. O-glycosylated. Contains terminal sialic acid groups on its glycan chains.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiQ99PI8.
PeptideAtlasiQ99PI8.
PRIDEiQ99PI8.

Expressioni

Tissue specificityi

Detected in embryonic hippocampus neurons (PubMed:22325200). Detected in brain (at protein level) (PubMed:15504325, PubMed:22406547). Detected in neurons in the neocortex, in hippocampus, dorsal thalamus, cerebellum granule cell layer and the mitral cell layer in the olfactory bulb (PubMed:15647357). Detected in brain, dorsal root ganglion and heart.6 Publications

Gene expression databases

BgeeiENSMUSG00000043811.
CleanExiMM_RTN4R.
GenevisibleiQ99PI8. MM.

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with MAG (PubMed:12089450). Interacts with RTN4 (PubMed:15504325). Interacts with NGFR(PubMed:22923615). Interacts with LINGO1(PubMed:22923615). Interacts with KIAA0319L (By similarity). Interacts with OLFM1; this inhibits interaction with LINGO1 and NGFR (PubMed:22923615).By similarity3 Publications

Protein-protein interaction databases

BioGridi211123. 1 interactor.
MINTiMINT-188355.
STRINGi10090.ENSMUSP00000062924.

Structurei

3D structure databases

ProteinModelPortaliQ99PI8.
SMRiQ99PI8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 57LRRNTAdd BLAST31
Repeati58 – 79LRR 1Add BLAST22
Repeati82 – 103LRR 2Add BLAST22
Repeati106 – 128LRR 3Add BLAST23
Repeati131 – 152LRR 4Add BLAST22
Repeati155 – 176LRR 5Add BLAST22
Repeati179 – 200LRR 6Add BLAST22
Repeati203 – 224LRR 7Add BLAST22
Repeati227 – 248LRR 8Add BLAST22
Domaini260 – 311LRRCTAdd BLAST52

Sequence similaritiesi

Belongs to the Nogo receptor family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00760000118777.
HOGENOMiHOG000116109.
HOVERGENiHBG063707.
InParanoidiQ99PI8.
KOiK16659.
OMAiNDSPFGT.
OrthoDBiEOG091G08II.
PhylomeDBiQ99PI8.
TreeFamiTF330080.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiView protein in InterPro
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
PfamiView protein in Pfam
PF13855. LRR_8. 2 hits.
SMARTiView protein in SMART
SM00369. LRR_TYP. 8 hits.
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiView protein in PROSITE
PS51450. LRR. 8 hits.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q99PI8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKRASSGGSR LLAWVLWLQA WRVATPCPGA CVCYNEPKVT TSCPQQGLQA
60 70 80 90 100
VPTGIPASSQ RIFLHGNRIS HVPAASFQSC RNLTILWLHS NALARIDAAA
110 120 130 140 150
FTGLTLLEQL DLSDNAQLHV VDPTTFHGLG HLHTLHLDRC GLRELGPGLF
160 170 180 190 200
RGLAALQYLY LQDNNLQALP DNTFRDLGNL THLFLHGNRI PSVPEHAFRG
210 220 230 240 250
LHSLDRLLLH QNHVARVHPH AFRDLGRLMT LYLFANNLSM LPAEVLMPLR
260 270 280 290 300
SLQYLRLNDN PWVCDCRARP LWAWLQKFRG SSSEVPCNLP QRLADRDLKR
310 320 330 340 350
LAASDLEGCA VASGPFRPIQ TSQLTDEELL SLPKCCQPDA ADKASVLEPG
360 370 380 390 400
RPASAGNALK GRVPPGDTPP GNGSGPRHIN DSPFGTLPSS AEPPLTALRP
410 420 430 440 450
GGSEPPGLPT TGPRRRPGCS RKNRTRSHCR LGQAGSGASG TGDAEGSGAL
460 470
PALACSLAPL GLALVLWTVL GPC
Length:473
Mass (Da):50,987
Last modified:June 1, 2001 - v1
Checksum:i14C5270EBF557E7C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF283462 mRNA. Translation: AAG53611.1.
BC052317 mRNA. Translation: AAH52317.2.
BC058381 mRNA. Translation: AAH58381.1.
CCDSiCCDS37279.1.
RefSeqiNP_075358.1. NM_022982.2.
UniGeneiMm.40149.

Genome annotation databases

EnsembliENSMUST00000059589; ENSMUSP00000062924; ENSMUSG00000043811.
ENSMUST00000213627; ENSMUSP00000149817; ENSMUSG00000111113.
GeneIDi65079.
KEGGimmu:65079.
UCSCiuc007ymv.1. mouse.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiRTN4R_MOUSE
AccessioniPrimary (citable) accession number: Q99PI8
Secondary accession number(s): Q80WQ1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 25, 2002
Last sequence update: June 1, 2001
Last modified: June 7, 2017
This is version 137 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  3. SIMILARITY comments
    Index of protein domains and families