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Protein

Reticulon-4 receptor

Gene

RTN4R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor for RTN4, OMG and MAG (PubMed:12037567, PubMed:12068310, PubMed:12426574, PubMed:12089450, PubMed:16712417, PubMed:18411262, PubMed:12839991, PubMed:19052207). Functions as receptor for the sialylated gangliosides GT1b and GM1 (PubMed:18411262). Besides, functions as receptor for chondroitin sulfate proteoglycans (By similarity). Can also bind heparin (By similarity). Intracellular signaling cascades are triggered via the coreceptor NGFR (PubMed:12426574). Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton (PubMed:16712417, PubMed:22325200). Mediates axonal growth inhibition (PubMed:12839991, PubMed:19052207, PubMed:28892071). Plays a role in regulating axon regeneration and neuronal plasticity in the adult central nervous system. Plays a role in postnatal brain development. Required for normal axon migration across the brain midline and normal formation of the corpus callosum. Protects motoneurons against apoptosis; protection against apoptosis is probably mediated via interaction with MAG. Acts in conjunction with RTN4 and LINGO1 in regulating neuronal precursor cell motility during cortical development. 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 similarity8 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionReceptor
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-193634 Axonal growth inhibition (RHOA activation)

Names & Taxonomyi

Protein namesi
Recommended name:
Reticulon-4 receptor
Alternative name(s):
Nogo receptor
Short name:
NgR
Nogo-66 receptor
Gene namesi
Name:RTN4R
Synonyms:NOGOR
ORF Names:UNQ330/PRO526
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000040608.13
HGNCiHGNC:18601 RTN4R
MIMi605566 gene
neXtProtiNX_Q9BZR6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Involvement in diseasei

Schizophrenia (SCZD)3 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder.
See also OMIM:181500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079154119R → W in SCZD; associated with disease susceptibility; unable to mediate down-regulation of axonal growth; decreased interaction with MAG and OMG; no effect on interaction with RTN4. 2 PublicationsCorresponds to variant dbSNP:rs74315508EnsemblClinVar.1
Natural variantiVAR_079155196R → H in SCZD; associated with disease susceptibility; unable to mediate down-regulation of axonal growth; does not affect interaction with MAG, RTN4 and OMG. 2 PublicationsCorresponds to variant dbSNP:rs74315509EnsemblClinVar.1
Natural variantiVAR_079227227R → C in SCZD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs754793885Ensembl.1
Natural variantiVAR_079231292R → H in SCZD; associated with disease susceptibility; unable to mediate down-regulation of axonal growth. 1 Publication1
Natural variantiVAR_079235377R → Q in SCZD; associated with disease susceptibility; unable to mediate down-regulation of axonal growth; does not affect interaction with MAG, RTN4, OMG, NGFR and LINGO1. 1 PublicationCorresponds to variant dbSNP:rs779384862Ensembl.1
Natural variantiVAR_079236377R → W in SCZD; associated with disease susceptibility; unable to mediate down-regulation of axonal growth; does not affect interaction with MAG, RTN4, OMG, NGFR and LINGO1. 1 PublicationCorresponds to variant dbSNP:rs748655075Ensembl.1
Natural variantiVAR_079237399R → W in SCZD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs200119628Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi151R → E: Impaired ganglioside binding. 1 Publication1
Mutagenesisi199R → E: Impaired ganglioside binding. 1 Publication1
Mutagenesisi277K → A: No effect on interaction with MAG. 1 Publication1
Mutagenesisi277K → D: Decreases interaction with MAG; when associated with D-279. 1 Publication1
Mutagenesisi279R → A: Mildly decreases interaction with MAG. 1 Publication1
Mutagenesisi279R → D: Decreases interaction with MAG; when associated with D-277. 1 Publication1
Mutagenesisi279R → E: Impaired ganglioside binding. 1 Publication1

Keywords - Diseasei

Disease mutation, Schizophrenia

Organism-specific databases

DisGeNETi65078
MalaCardsiRTN4R
MIMi181500 phenotype
OpenTargetsiENSG00000040608
PharmGKBiPA38600

Polymorphism and mutation databases

BioMutaiRTN4R

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 261 PublicationAdd BLAST26
ChainiPRO_000002225327 – 447Reticulon-4 receptorAdd BLAST421
PropeptideiPRO_0000022254448 – 473Removed in mature formSequence analysisAdd BLAST26

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi27 ↔ 33Combined sources2 Publications
Disulfide bondi31 ↔ 43Combined sources2 Publications
Glycosylationi82N-linked (GlcNAc...) asparagineCombined sources2 Publications1
Glycosylationi179N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi264 ↔ 287Combined sources2 Publications
Disulfide bondi266 ↔ 335By similarity
Disulfide bondi309 ↔ 336By similarity
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

EPDiQ9BZR6
PaxDbiQ9BZR6
PeptideAtlasiQ9BZR6
PRIDEiQ9BZR6
ProteomicsDBi79894

PTM databases

iPTMnetiQ9BZR6

Expressioni

Tissue specificityi

Widespread in the brain but highest levels in the gray matter. Low levels in heart and kidney; not expressed in oligodendrocytes (white matter).1 Publication

Gene expression databases

BgeeiENSG00000040608 Expressed in 109 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_RTN4R
ExpressionAtlasiQ9BZR6 baseline and differential
GenevisibleiQ9BZR6 HS

Organism-specific databases

HPAiCAB012443

Interactioni

Subunit structurei

Homodimer (PubMed:18411262). Interacts with MAG (PubMed:12089450, PubMed:12839991, PubMed:18411262, PubMed:19052207). Interacts with RTN4 (PubMed:12839991, PubMed:19052207). Interacts with NGFR (PubMed:12426574, PubMed:18411262, PubMed:19052207). Interacts with LINGO1 (PubMed:14966521, PubMed:19052207). Interacts with KIAA0319L (PubMed:20697954). Interacts with OLFM1; this inhibits interaction with LINGO1 and NGFR (By similarity). Interacts with OMG (PubMed:12068310, PubMed:12839991, PubMed:19052207).By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
KIAA0319LQ8IZA04EBI-5240240,EBI-5240269

Protein-protein interaction databases

BioGridi122388, 7 interactors
CORUMiQ9BZR6
IntActiQ9BZR6, 3 interactors
STRINGi9606.ENSP00000043402

Structurei

Secondary structure

1473
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9BZR6
SMRiQ9BZR6
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9BZR6

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 54LRRNTAdd BLAST28
Repeati55 – 79LRR 1Sequence analysisAdd BLAST25
Repeati81 – 103LRR 2Sequence analysisAdd BLAST23
Repeati104 – 128LRR 3Sequence analysisAdd BLAST25
Repeati129 – 152LRR 4Sequence analysisAdd BLAST24
Repeati153 – 176LRR 5Sequence analysisAdd BLAST24
Repeati178 – 200LRR 6Sequence analysisAdd BLAST23
Repeati202 – 224LRR 7Sequence analysisAdd BLAST23
Repeati225 – 248LRR 8Sequence analysisAdd BLAST24
Repeati250 – 273LRR 9Sequence analysisAdd BLAST24
Domaini260 – 310LRRCTSequence analysisAdd BLAST51

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi435 – 442Poly-Gly8

Sequence similaritiesi

Belongs to the Nogo receptor family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal

Phylogenomic databases

eggNOGiKOG0619 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00920000148971
HOGENOMiHOG000116109
HOVERGENiHBG063707
InParanoidiQ9BZR6
KOiK16659
PhylomeDBiQ9BZR6
TreeFamiTF330080

Family and domain databases

Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
PfamiView protein in Pfam
PF13855 LRR_8, 2 hits
SMARTiView protein in SMART
SM00369 LRR_TYP, 8 hits
SM00082 LRRCT, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 6 hits

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

Q9BZR6-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKRASAGGSR LLAWVLWLQA WQVAAPCPGA CVCYNEPKVT TSCPQQGLQA
60 70 80 90 100
VPVGIPAASQ RIFLHGNRIS HVPAASFRAC RNLTILWLHS NVLARIDAAA
110 120 130 140 150
FTGLALLEQL DLSDNAQLRS VDPATFHGLG RLHTLHLDRC GLQELGPGLF
160 170 180 190 200
RGLAALQYLY LQDNALQALP DDTFRDLGNL THLFLHGNRI SSVPERAFRG
210 220 230 240 250
LHSLDRLLLH QNRVAHVHPH AFRDLGRLMT LYLFANNLSA LPTEALAPLR
260 270 280 290 300
ALQYLRLNDN PWVCDCRARP LWAWLQKFRG SSSEVPCSLP QRLAGRDLKR
310 320 330 340 350
LAANDLQGCA VATGPYHPIW TGRATDEEPL GLPKCCQPDA ADKASVLEPG
360 370 380 390 400
RPASAGNALK GRVPPGDSPP GNGSGPRHIN DSPFGTLPGS AEPPLTAVRP
410 420 430 440 450
EGSEPPGFPT SGPRRRPGCS RKNRTRSHCR LGQAGSGGGG TGDSEGSGAL
460 470
PSLTCSLTPL GLALVLWTVL GPC
Length:473
Mass (Da):50,708
Last modified:June 1, 2001 - v1
Checksum:iCA5624B24C584702
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C0V4H7C0V4_HUMAN
Reticulon-4 receptor
RTN4R
493Annotation score:
H7C215H7C215_HUMAN
Reticulon-4 receptor
RTN4R
559Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07922453V → M1 PublicationCorresponds to variant dbSNP:rs145292678Ensembl.1
Natural variantiVAR_07922568R → H2 PublicationsCorresponds to variant dbSNP:rs145773589Ensembl.1
Natural variantiVAR_079154119R → W in SCZD; associated with disease susceptibility; unable to mediate down-regulation of axonal growth; decreased interaction with MAG and OMG; no effect on interaction with RTN4. 2 PublicationsCorresponds to variant dbSNP:rs74315508EnsemblClinVar.1
Natural variantiVAR_079226141G → S1 PublicationCorresponds to variant dbSNP:rs760855779Ensembl.1
Natural variantiVAR_079155196R → H in SCZD; associated with disease susceptibility; unable to mediate down-regulation of axonal growth; does not affect interaction with MAG, RTN4 and OMG. 2 PublicationsCorresponds to variant dbSNP:rs74315509EnsemblClinVar.1
Natural variantiVAR_079227227R → C in SCZD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs754793885Ensembl.1
Natural variantiVAR_079228227R → H1 PublicationCorresponds to variant dbSNP:rs576939822Ensembl.1
Natural variantiVAR_079229259D → N1 PublicationCorresponds to variant dbSNP:rs3747073Ensembl.1
Natural variantiVAR_079230263V → M1 PublicationCorresponds to variant dbSNP:rs752810777Ensembl.1
Natural variantiVAR_079231292R → H in SCZD; associated with disease susceptibility; unable to mediate down-regulation of axonal growth. 1 Publication1
Natural variantiVAR_079232314G → S1 PublicationCorresponds to variant dbSNP:rs112151786Ensembl.1
Natural variantiVAR_079233329P → L1 PublicationCorresponds to variant dbSNP:rs757507039Ensembl.1
Natural variantiVAR_079234363V → M2 PublicationsCorresponds to variant dbSNP:rs149231717Ensembl.1
Natural variantiVAR_079235377R → Q in SCZD; associated with disease susceptibility; unable to mediate down-regulation of axonal growth; does not affect interaction with MAG, RTN4, OMG, NGFR and LINGO1. 1 PublicationCorresponds to variant dbSNP:rs779384862Ensembl.1
Natural variantiVAR_079236377R → W in SCZD; associated with disease susceptibility; unable to mediate down-regulation of axonal growth; does not affect interaction with MAG, RTN4, OMG, NGFR and LINGO1. 1 PublicationCorresponds to variant dbSNP:rs748655075Ensembl.1
Natural variantiVAR_079237399R → W in SCZD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs200119628Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF283463 mRNA Translation: AAG53612.1
AL834449 mRNA Translation: CAD39109.1
AY358297 mRNA Translation: AAQ88664.1
CR456360 mRNA Translation: CAG30246.1
AC058790 Genomic DNA No translation available.
AC007663 Genomic DNA No translation available.
CH471176 Genomic DNA Translation: EAX02975.1
CH471176 Genomic DNA Translation: EAX02976.1
BC011787 mRNA Translation: AAH11787.1
CCDSiCCDS13777.1
RefSeqiNP_075380.1, NM_023004.5
UniGeneiHs.30868

Genome annotation databases

EnsembliENST00000043402; ENSP00000043402; ENSG00000040608
GeneIDi65078
KEGGihsa:65078
UCSCiuc002zrv.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Protein Spotlight

Nerve regrowth: nipped by a no-go - Issue 69 of April 2006

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF283463 mRNA Translation: AAG53612.1
AL834449 mRNA Translation: CAD39109.1
AY358297 mRNA Translation: AAQ88664.1
CR456360 mRNA Translation: CAG30246.1
AC058790 Genomic DNA No translation available.
AC007663 Genomic DNA No translation available.
CH471176 Genomic DNA Translation: EAX02975.1
CH471176 Genomic DNA Translation: EAX02976.1
BC011787 mRNA Translation: AAH11787.1
CCDSiCCDS13777.1
RefSeqiNP_075380.1, NM_023004.5
UniGeneiHs.30868

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1OZNX-ray1.52A26-310[»]
1P8TX-ray3.20A27-311[»]
ProteinModelPortaliQ9BZR6
SMRiQ9BZR6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122388, 7 interactors
CORUMiQ9BZR6
IntActiQ9BZR6, 3 interactors
STRINGi9606.ENSP00000043402

PTM databases

iPTMnetiQ9BZR6

Polymorphism and mutation databases

BioMutaiRTN4R

Proteomic databases

EPDiQ9BZR6
PaxDbiQ9BZR6
PeptideAtlasiQ9BZR6
PRIDEiQ9BZR6
ProteomicsDBi79894

Protocols and materials databases

DNASUi65078
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000043402; ENSP00000043402; ENSG00000040608
GeneIDi65078
KEGGihsa:65078
UCSCiuc002zrv.4 human

Organism-specific databases

CTDi65078
DisGeNETi65078
EuPathDBiHostDB:ENSG00000040608.13
GeneCardsiRTN4R
HGNCiHGNC:18601 RTN4R
HPAiCAB012443
MalaCardsiRTN4R
MIMi181500 phenotype
605566 gene
neXtProtiNX_Q9BZR6
OpenTargetsiENSG00000040608
PharmGKBiPA38600
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0619 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00920000148971
HOGENOMiHOG000116109
HOVERGENiHBG063707
InParanoidiQ9BZR6
KOiK16659
PhylomeDBiQ9BZR6
TreeFamiTF330080

Enzyme and pathway databases

ReactomeiR-HSA-193634 Axonal growth inhibition (RHOA activation)

Miscellaneous databases

ChiTaRSiRTN4R human
EvolutionaryTraceiQ9BZR6
GeneWikiiReticulon_4_receptor
GenomeRNAii65078
PROiPR:Q9BZR6
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000040608 Expressed in 109 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_RTN4R
ExpressionAtlasiQ9BZR6 baseline and differential
GenevisibleiQ9BZR6 HS

Family and domain databases

Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
PfamiView protein in Pfam
PF13855 LRR_8, 2 hits
SMARTiView protein in SMART
SM00369 LRR_TYP, 8 hits
SM00082 LRRCT, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 6 hits
ProtoNetiSearch...

Entry informationi

Entry nameiRTN4R_HUMAN
AccessioniPrimary (citable) accession number: Q9BZR6
Secondary accession number(s): D3DX28
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 25, 2002
Last sequence update: June 1, 2001
Last modified: October 10, 2018
This is version 171 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. SIMILARITY comments
    Index of protein domains and families
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
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Main funding by: National Institutes of Health

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