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Q9JK11 (RTN4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Reticulon-4
Alternative name(s):
Foocen
Glut4 vesicle 20 kDa protein
Neurite outgrowth inhibitor
Short name=Nogo protein
Gene names
Name:Rtn4
Synonyms:Nogo
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1163 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS. Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex. Isoform 2 and isoform 3 inhibit BACE1 activity and amyloid precursor protein processing. Ref.4 Ref.6 Ref.9

Subunit structure

Binds to RTN4R. Interacts with Bcl-xl and Bcl-2. Isoform 2 binds to NGBR and RTN3. Isoform 2 and isoform 3 interact ith BACE1 and BACE2 By similarity. Interacts with RTN4IP1 By similarity. Interacts in trans with CNTNAP1. Interacts with ATL1. Ref.5 Ref.8

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein By similarity. Note: Anchored to the membrane of the endoplasmic reticulum through 2 putative transmembrane domains By similarity.

Tissue specificity

Isoforms 1, 2 and 3 are present in optic nerve, spinal cord and cerebral cortex. Isoforms 1 and 2 are present in dorsal root ganglion, sciatic nerve and PC12 cells after longer exposure. Isoforms 2 and 3 are detected in kidney, cartilage, skin, lung and spleen. Isoform 3 is expressed at high level in skeletal muscle. In adult animals isoform 1 is expressed mainly in the nervous system.

Domain

Three regions, residues 59-172, 544-725 and the loop 66 amino acids, known as Nogo-66 loop, appear to be responsible for the inhibitory effect on neurite outgrowth and the spreading of neurons. This Nogo-66 loop, mediates also the binding of RTN4 to its receptor.

Sequence similarities

Contains 1 reticulon domain.

Ontologies

Keywords
   Biological processNeurogenesis
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from expression pattern PubMed 16738487. Source: RGD

axonal fasciculation

Inferred from direct assay Ref.9. Source: UniProtKB

cerebral cortex radial glia guided migration

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of axon extension

Inferred from direct assay Ref.9. Source: UniProtKB

negative regulation of axonogenesis

Inferred from direct assay Ref.2. Source: RGD

negative regulation of neuron differentiation

Inferred from direct assay PubMed 19379790. Source: RGD

negative regulation of neuron projection development

Inferred from direct assay PubMed 19386232. Source: RGD

negative regulation of neuron projection regeneration

Inferred from mutant phenotype PubMed 18973596. Source: RGD

olfactory nerve development

Inferred from expression pattern PubMed 16262653. Source: RGD

oligodendrocyte differentiation

Inferred from expression pattern PubMed 19236864. Source: RGD

positive regulation of dopamine secretion

Inferred from mutant phenotype PubMed 19112410. Source: RGD

positive regulation of glial cell differentiation

Inferred from direct assay PubMed 19379790. Source: RGD

regulation of axon regeneration

Inferred from direct assay PubMed 15282288. Source: RGD

regulation of branching morphogenesis of a nerve

Inferred from direct assay Ref.9. Source: UniProtKB

regulation of sensory perception of pain

Inferred from direct assay PubMed 17720311. Source: RGD

response to activity

Inferred from expression pattern PubMed 18093178. Source: RGD

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 19386232. Source: RGD

endoplasmic reticulum

Inferred from direct assay PubMed 16469703. Source: RGD

integral component of endoplasmic reticulum membrane

Inferred from direct assay Ref.1. Source: UniProtKB

integral component of membrane

Traceable author statement PubMed 12451136. Source: RGD

myelin sheath

Inferred from direct assay PubMed 19524873. Source: RGD

neuron projection

Inferred from direct assay PubMed 19386232. Source: RGD

neuronal cell body

Inferred from direct assay PubMed 19386232. Source: RGD

nuclear envelope

Inferred from sequence or structural similarity PubMed 11126360. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 19236864. Source: RGD

protein complex

Inferred from direct assay PubMed 15640160. Source: RGD

   Molecular_functionprotein complex binding

Inferred from direct assay PubMed 15640160. Source: RGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ATL1Q8WXF72EBI-920002,EBI-2410266From a different organism.
Atl1Q6PST46EBI-919989,EBI-2410213

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9JK11-1)

Also known as: Nogo-A; NI-220-250;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9JK11-2)

Also known as: Nogo-B; Foocen-M1;

The sequence of this isoform differs from the canonical sequence as follows:
     173-975: Missing.
Isoform 3 (identifier: Q9JK11-3)

Also known as: Nogo-C; VP20;

The sequence of this isoform differs from the canonical sequence as follows:
     1-964: Missing.
     965-975: AVLSAELSKTS → MDGQKKHWKDK
Isoform 4 (identifier: Q9JK11-4)

Also known as: Foocen-M2;

The sequence of this isoform differs from the canonical sequence as follows:
     192-975: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11631163Reticulon-4
PRO_0000168167

Regions

Topological domain1 – 989989Cytoplasmic Potential
Transmembrane990 – 101021Helical; Potential
Topological domain1011 – 110494Lumenal Potential
Transmembrane1105 – 112521Helical; Potential
Topological domain1126 – 116338Cytoplasmic Potential
Domain976 – 1163188Reticulon
Compositional bias33 – 4614Poly-Glu
Compositional bias73 – 764Poly-Ala
Compositional bias140 – 1456Poly-Pro

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue71Phosphoserine By similarity
Modified residue161Phosphoserine By similarity
Modified residue1071Phosphoserine Ref.7
Modified residue1491Phosphoserine By similarity
Modified residue1691Phosphoserine By similarity
Modified residue3431Phosphoserine By similarity
Modified residue4881Phosphoserine By similarity
Modified residue6891Phosphoserine By similarity
Modified residue10751N6-acetyllysine By similarity

Natural variations

Alternative sequence1 – 964964Missing in isoform 3.
VSP_005656
Alternative sequence173 – 975803Missing in isoform 2.
VSP_005658
Alternative sequence192 – 975784Missing in isoform 4.
VSP_005659
Alternative sequence965 – 97511AVLSAELSKTS → MDGQKKHWKDK in isoform 3.
VSP_005657

Experimental info

Sequence conflict1130 – 11312Missing in AAD31020. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Nogo-A) (NI-220-250) [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 8CB894B09E94F0B6

FASTA1,163126,388
        10         20         30         40         50         60 
MEDIDQSSLV SSSTDSPPRP PPAFKYQFVT EPEDEEDEEE EEDEEEDDED LEELEVLERK 

        70         80         90        100        110        120 
PAAGLSAAAV PPAAAAPLLD FSSDSVPPAP RGPLPAAPPA APERQPSWER SPAAPAPSLP 

       130        140        150        160        170        180 
PAAAVLPSKL PEDDEPPARP PPPPPAGASP LAEPAAPPST PAAPKRRGSG SVDETLFALP 

       190        200        210        220        230        240 
AASEPVIPSS AEKIMDLMEQ PGNTVSSGQE DFPSVLLETA ASLPSLSPLS TVSFKEHGYL 

       250        260        270        280        290        300 
GNLSAVSSSE GTIEETLNEA SKELPERATN PFVNRDLAEF SELEYSEMGS SFKGSPKGES 

       310        320        330        340        350        360 
AILVENTKEE VIVRSKDKED LVCSAALHSP QESPVGKEDR VVSPEKTMDI FNEMQMSVVA 

       370        380        390        400        410        420 
PVREEYADFK PFEQAWEVKD TYEGSRDVLA ARANVESKVD RKCLEDSLEQ KSLGKDSEGR 

       430        440        450        460        470        480 
NEDASFPSTP EPVKDSSRAY ITCASFTSAT ESTTANTFPL LEDHTSENKT DEKKIEERKA 

       490        500        510        520        530        540 
QIITEKTSPK TSNPFLVAVQ DSEADYVTTD TLSKVTEAAV SNMPEGLTPD LVQEACESEL 

       550        560        570        580        590        600 
NEATGTKIAY ETKVDLVQTS EAIQESLYPT AQLCPSFEEA EATPSPVLPD IVMEAPLNSL 

       610        620        630        640        650        660 
LPSAGASVVQ PSVSPLEAPP PVSYDSIKLE PENPPPYEEA MNVALKALGT KEGIKEPESF 

       670        680        690        700        710        720 
NAAVQETEAP YISIACDLIK ETKLSTEPSP DFSNYSEIAK FEKSVPEHAE LVEDSSPESE 

       730        740        750        760        770        780 
PVDLFSDDSI PEVPQTQEEA VMLMKESLTE VSETVAQHKE ERLSASPQEL GKPYLESFQP 

       790        800        810        820        830        840 
NLHSTKDAAS NDIPTLTKKE KISLQMEEFN TAIYSNDDLL SSKEDKIKES ETFSDSSPIE 

       850        860        870        880        890        900 
IIDEFPTFVS AKDDSPKLAK EYTDLEVSDK SEIANIQSGA DSLPCLELPC DLSFKNIYPK 

       910        920        930        940        950        960 
DEVHVSDEFS ENRSSVSKAS ISPSNVSALE PQTEMGSIVK SKSLTKEAEK KLPSDTEKED 

       970        980        990       1000       1010       1020 
RSLSAVLSAE LSKTSVVDLL YWRDIKKTGV VFGASLFLLL SLTVFSIVSV TAYIALALLS 

      1030       1040       1050       1060       1070       1080 
VTISFRIYKG VIQAIQKSDE GHPFRAYLES EVAISEELVQ KYSNSALGHV NSTIKELRRL 

      1090       1100       1110       1120       1130       1140 
FLVDDLVDSL KFAVLMWVFT YVGALFNGLT LLILALISLF SIPVIYERHQ VQIDHYLGLA 

      1150       1160 
NKSVKDAMAK IQAKIPGLKR KAD 

« Hide

Isoform 2 (Nogo-B) (Foocen-M1) [UniParc].

Checksum: 149714AD6C3D65A7
Show »

FASTA36038,822
Isoform 3 (Nogo-C) (VP20) [UniParc].

Checksum: 2FD805453543DC95
Show »

FASTA19922,403
Isoform 4 (Foocen-M2) [UniParc].

Checksum: 9F15AB942D36ED0F
Show »

FASTA37940,719

References

« Hide 'large scale' references
[1]"Cloning and characterization of a 22 kDa protein from rat adipocytes: a new member of the reticulon family."
Morris N.J., Ross S.A., Neveu J.M., Lane W.S., Lienhard G.E.
Biochim. Biophys. Acta 1450:68-76(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PARTIAL PROTEIN SEQUENCE.
Strain: Sprague-Dawley.
Tissue: Adipocyte.
[2]"Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1."
Chen M.S., Huber A.B., Van der Haar M.E., Frank M., Schnell L., Spillmann A.A., Christ F., Schwab M.E.
Nature 403:434-439(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
[3]"Cloning of a member of the reticulon gene family in rat: one of two minor splice variants."
Ito T., Schwartz S.M.
Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4).
Strain: Wistar Kyoto.
Tissue: Vascular smooth muscle.
[4]"Nogo-66 receptor antagonist peptide promotes axonal regeneration."
GrandPre T., Li S., Strittmatter S.M.
Nature 417:547-551(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation of K(+) channel localization."
Nie D.-Y., Zhou Z.-H., Ang B.-T., Teng F.Y.H., Xu G., Xiang T., Wang C.-Y., Zeng L., Takeda Y., Xu T.-L., Ng Y.K., Faivre-Sarrailh C., Popko B., Ling E.-A., Schachner M., Watanabe K., Pallen C.J., Tang B.L., Xiao Z.-C.
EMBO J. 22:5666-5678(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CNTNAP1.
[6]"Nogo-A inhibits neurite outgrowth and cell spreading with three discrete regions."
Oertle T., van der Haar M.E., Bandtlow C.E., Robeva A., Burfeind P., Buss A., Huber A.B., Simonen M., Schnell L., Brosamle C., Kaupmann K., Vallon R., Schwab M.E.
J. Neurosci. 23:5393-5406(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-107, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"A class of dynamin-like GTPases involved in the generation of the tubular ER network."
Hu J., Shibata Y., Zhu P.-P., Voss C., Rismanchi N., Prinz W.A., Rapoport T.A., Blackstone C.
Cell 138:549-561(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATL1.
[9]"Neuronal Nogo-A regulates neurite fasciculation, branching and extension in the developing nervous system."
Petrinovic M.M., Duncan C.S., Bourikas D., Weinman O., Montani L., Schroeter A., Maerki D., Sommer L., Stoeckli E.T., Schwab M.E.
Development 137:2539-2550(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Web resources

Protein Spotlight

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

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF051335 mRNA. Translation: AAF01564.1.
AJ242961 mRNA. Translation: CAB71027.1.
AJ242962 mRNA. Translation: CAB71028.1.
AJ242963 mRNA. Translation: CAB71029.1.
AF132045 mRNA. Translation: AAD31019.1.
AF132046 mRNA. Translation: AAD31020.1.
RefSeqNP_114019.1. NM_031831.1.
XP_006251671.1. XM_006251609.1.
UniGeneRn.1348.
Rn.163269.

3D structure databases

ProteinModelPortalQ9JK11.
SMRQ9JK11. Positions 1026-1085.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249825. 2 interactions.
IntActQ9JK11. 3 interactions.
MINTMINT-4998315.
STRING10116.ENSRNOP00000006443.

PTM databases

PhosphoSiteQ9JK11.

Proteomic databases

PaxDbQ9JK11.
PRIDEQ9JK11.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000006957; ENSRNOP00000006957; ENSRNOG00000004621. [Q9JK11-2]
ENSRNOT00000041638; ENSRNOP00000042870; ENSRNOG00000004621. [Q9JK11-4]
ENSRNOT00000042965; ENSRNOP00000040760; ENSRNOG00000004621. [Q9JK11-3]
GeneID83765.
KEGGrno:83765.
UCSCRGD:620989. rat. [Q9JK11-1]

Organism-specific databases

CTD57142.
RGD620989. Rtn4.

Phylogenomic databases

eggNOGNOG306139.
GeneTreeENSGT00390000009934.
HOGENOMHOG000148576.
HOVERGENHBG023134.
InParanoidQ9JK11.
PhylomeDBQ9JK11.

Gene expression databases

GenevestigatorQ9JK11.

Family and domain databases

InterProIPR003388. Reticulon.
[Graphical view]
PANTHERPTHR10994. PTHR10994. 1 hit.
PfamPF02453. Reticulon. 1 hit.
[Graphical view]
PROSITEPS50845. RETICULON. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio616333.
PROQ9JK11.

Entry information

Entry nameRTN4_RAT
AccessionPrimary (citable) accession number: Q9JK11
Secondary accession number(s): Q9JK10 expand/collapse secondary AC list , Q9R0D9, Q9WUE9, Q9WUF0
Entry history
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries