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Protein

Reticulon-4

Gene

Rtn4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Induces the formation and stabilization of endoplasmic reticulum (ER) tubules. Regulates membrane morphogenesis in the ER by promoting tubular ER production. Influences NE expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins (By similarity).By similarity3 Publications

GO - Molecular functioni

  • protein complex binding Source: RGD

GO - Biological processi

  • aging Source: RGD
  • axonal fasciculation Source: UniProtKB
  • cerebral cortex radial glia guided migration Source: UniProtKB
  • endoplasmic reticulum tubular network assembly Source: UniProtKB
  • endoplasmic reticulum tubular network organization Source: UniProtKB
  • negative regulation of axon extension Source: UniProtKB
  • negative regulation of axonogenesis Source: RGD
  • negative regulation of neuron differentiation Source: RGD
  • negative regulation of neuron projection development Source: RGD
  • negative regulation of neuron projection regeneration Source: RGD
  • nuclear pore complex assembly Source: UniProtKB
  • olfactory nerve development Source: RGD
  • oligodendrocyte differentiation Source: RGD
  • positive regulation of dopamine secretion Source: RGD
  • positive regulation of glial cell differentiation Source: RGD
  • regulation of branching morphogenesis of a nerve Source: UniProtKB
  • regulation of sensory perception of pain Source: RGD
  • response to activity Source: RGD
Complete GO annotation...

Keywords - Biological processi

Neurogenesis

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Reticulon-4
Alternative name(s):
Foocen
Glut4 vesicle 20 kDa protein
Neurite outgrowth inhibitor
Short name:
Nogo protein
Gene namesi
Name:Rtn4
Synonyms:Nogo
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 14

Organism-specific databases

RGDi620989. Rtn4.

Subcellular locationi

  • Endoplasmic reticulum membrane By similarity; Multi-pass membrane protein Sequence analysis

  • Note: Anchored to the membrane of the endoplasmic reticulum through 2 putative transmembrane domains. Co-localizes with TMEM33 at the ER sheets.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 989CytoplasmicSequence analysisAdd BLAST989
Transmembranei990 – 1010HelicalSequence analysisAdd BLAST21
Topological domaini1011 – 1104LumenalSequence analysisAdd BLAST94
Transmembranei1105 – 1125HelicalSequence analysisAdd BLAST21
Topological domaini1126 – 1163CytoplasmicSequence analysisAdd BLAST38

GO - Cellular componenti

  • cytoplasm Source: RGD
  • endoplasmic reticulum Source: RGD
  • integral component of endoplasmic reticulum membrane Source: UniProtKB
  • integral component of membrane Source: RGD
  • intracellular Source: UniProtKB
  • myelin sheath Source: RGD
  • neuronal cell body Source: RGD
  • neuron projection Source: RGD
  • nuclear envelope Source: UniProtKB
  • plasma membrane Source: RGD
  • protein complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001681671 – 1163Reticulon-4Add BLAST1163

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei7PhosphoserineBy similarity1
Modified residuei16PhosphoserineCombined sources1
Modified residuei107PhosphoserineCombined sources1
Modified residuei149PhosphoserineBy similarity1
Modified residuei169PhosphoserineBy similarity1
Modified residuei171PhosphoserineBy similarity1
Modified residuei329PhosphoserineCombined sources1
Modified residuei333PhosphoserineCombined sources1
Modified residuei343PhosphoserineBy similarity1
Modified residuei347PhosphothreonineBy similarity1
Modified residuei425PhosphoserineCombined sources1
Modified residuei429PhosphothreonineCombined sources1
Modified residuei488PhosphoserineBy similarity1
Modified residuei689PhosphoserineCombined sources1
Modified residuei726PhosphoserineBy similarity1
Modified residuei766PhosphoserineCombined sources1
Modified residuei830PhosphoserineCombined sources1
Modified residuei832PhosphothreonineCombined sources1
Modified residuei855PhosphoserineBy similarity1
Modified residuei922PhosphoserineCombined sources1
Modified residuei962PhosphoserineBy similarity1
Modified residuei1075N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ9JK11.
PRIDEiQ9JK11.

PTM databases

iPTMnetiQ9JK11.
PhosphoSitePlusiQ9JK11.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSRNOG00000004621.
ExpressionAtlasiQ9JK11. baseline and differential.
GenevisibleiQ9JK11. RN.

Interactioni

Subunit structurei

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. Interacts with TMEM170A and TMEM33 (By similarity).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ATL1Q8WXF72EBI-920002,EBI-2410266From a different organism.
Atl1Q6PST46EBI-919989,EBI-2410213
Hspa4lP487226EBI-919989,EBI-8314699From a different organism.

GO - Molecular functioni

  • protein complex binding Source: RGD

Protein-protein interaction databases

BioGridi249825. 2 interactors.
DIPiDIP-37179N.
IntActiQ9JK11. 12 interactors.
MINTiMINT-4998315.
STRINGi10116.ENSRNOP00000006443.

Structurei

3D structure databases

ProteinModelPortaliQ9JK11.
SMRiQ9JK11.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini976 – 1163ReticulonPROSITE-ProRule annotationAdd BLAST188

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi33 – 46Poly-GluAdd BLAST14
Compositional biasi73 – 76Poly-Ala4
Compositional biasi140 – 145Poly-Pro6

Domaini

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 similaritiesi

Contains 1 reticulon domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1792. Eukaryota.
ENOG410XPKH. LUCA.
GeneTreeiENSGT00390000009934.
HOGENOMiHOG000148576.
HOVERGENiHBG023134.
InParanoidiQ9JK11.
KOiK20720.
PhylomeDBiQ9JK11.

Family and domain databases

InterProiIPR003388. Reticulon.
[Graphical view]
PfamiPF02453. Reticulon. 1 hit.
[Graphical view]
PROSITEiPS50845. RETICULON. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9JK11-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MEDIDQSSLV SSSTDSPPRP PPAFKYQFVT EPEDEEDEEE EEDEEEDDED
60 70 80 90 100
LEELEVLERK PAAGLSAAAV PPAAAAPLLD FSSDSVPPAP RGPLPAAPPA
110 120 130 140 150
APERQPSWER SPAAPAPSLP PAAAVLPSKL PEDDEPPARP PPPPPAGASP
160 170 180 190 200
LAEPAAPPST PAAPKRRGSG SVDETLFALP AASEPVIPSS AEKIMDLMEQ
210 220 230 240 250
PGNTVSSGQE DFPSVLLETA ASLPSLSPLS TVSFKEHGYL GNLSAVSSSE
260 270 280 290 300
GTIEETLNEA SKELPERATN PFVNRDLAEF SELEYSEMGS SFKGSPKGES
310 320 330 340 350
AILVENTKEE VIVRSKDKED LVCSAALHSP QESPVGKEDR VVSPEKTMDI
360 370 380 390 400
FNEMQMSVVA PVREEYADFK PFEQAWEVKD TYEGSRDVLA ARANVESKVD
410 420 430 440 450
RKCLEDSLEQ KSLGKDSEGR NEDASFPSTP EPVKDSSRAY ITCASFTSAT
460 470 480 490 500
ESTTANTFPL LEDHTSENKT DEKKIEERKA QIITEKTSPK TSNPFLVAVQ
510 520 530 540 550
DSEADYVTTD TLSKVTEAAV SNMPEGLTPD LVQEACESEL NEATGTKIAY
560 570 580 590 600
ETKVDLVQTS EAIQESLYPT AQLCPSFEEA EATPSPVLPD IVMEAPLNSL
610 620 630 640 650
LPSAGASVVQ PSVSPLEAPP PVSYDSIKLE PENPPPYEEA MNVALKALGT
660 670 680 690 700
KEGIKEPESF NAAVQETEAP YISIACDLIK ETKLSTEPSP DFSNYSEIAK
710 720 730 740 750
FEKSVPEHAE LVEDSSPESE PVDLFSDDSI PEVPQTQEEA VMLMKESLTE
760 770 780 790 800
VSETVAQHKE ERLSASPQEL GKPYLESFQP NLHSTKDAAS NDIPTLTKKE
810 820 830 840 850
KISLQMEEFN TAIYSNDDLL SSKEDKIKES ETFSDSSPIE IIDEFPTFVS
860 870 880 890 900
AKDDSPKLAK EYTDLEVSDK SEIANIQSGA DSLPCLELPC DLSFKNIYPK
910 920 930 940 950
DEVHVSDEFS ENRSSVSKAS ISPSNVSALE PQTEMGSIVK SKSLTKEAEK
960 970 980 990 1000
KLPSDTEKED RSLSAVLSAE LSKTSVVDLL YWRDIKKTGV VFGASLFLLL
1010 1020 1030 1040 1050
SLTVFSIVSV TAYIALALLS VTISFRIYKG VIQAIQKSDE GHPFRAYLES
1060 1070 1080 1090 1100
EVAISEELVQ KYSNSALGHV NSTIKELRRL FLVDDLVDSL KFAVLMWVFT
1110 1120 1130 1140 1150
YVGALFNGLT LLILALISLF SIPVIYERHQ VQIDHYLGLA NKSVKDAMAK
1160
IQAKIPGLKR KAD
Length:1,163
Mass (Da):126,388
Last modified:October 1, 2000 - v1
Checksum:i8CB894B09E94F0B6
GO
Isoform 2 (identifier: Q9JK11-2) [UniParc]FASTAAdd to basket
Also known as: Nogo-B, Foocen-M1

The sequence of this isoform differs from the canonical sequence as follows:
     173-975: Missing.

Show »
Length:360
Mass (Da):38,822
Checksum:i149714AD6C3D65A7
GO
Isoform 3 (identifier: Q9JK11-3) [UniParc]FASTAAdd to basket
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

Show »
Length:199
Mass (Da):22,403
Checksum:i2FD805453543DC95
GO
Isoform 4 (identifier: Q9JK11-4) [UniParc]FASTAAdd to basket
Also known as: Foocen-M2

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

Show »
Length:379
Mass (Da):40,719
Checksum:i9F15AB942D36ED0F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1130 – 1131Missing in AAD31020 (Ref. 3) Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0056561 – 964Missing in isoform 3. 2 PublicationsAdd BLAST964
Alternative sequenceiVSP_005658173 – 975Missing in isoform 2. 2 PublicationsAdd BLAST803
Alternative sequenceiVSP_005659192 – 975Missing in isoform 4. 1 PublicationAdd BLAST784
Alternative sequenceiVSP_005657965 – 975AVLSAELSKTS → MDGQKKHWKDK in isoform 3. 2 PublicationsAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_114019.1. NM_031831.1. [Q9JK11-1]
XP_006251670.2. XM_006251608.2. [Q9JK11-2]
XP_006251671.1. XM_006251609.3. [Q9JK11-3]
XP_017454882.1. XM_017599393.1. [Q9JK11-4]
UniGeneiRn.1348.
Rn.163269.

Genome annotation databases

EnsembliENSRNOT00000006957; ENSRNOP00000006957; ENSRNOG00000004621. [Q9JK11-2]
ENSRNOT00000041638; ENSRNOP00000042870; ENSRNOG00000004621. [Q9JK11-4]
ENSRNOT00000042965; ENSRNOP00000040760; ENSRNOG00000004621. [Q9JK11-3]
GeneIDi83765.
KEGGirno:83765.
UCSCiRGD:620989. rat. [Q9JK11-1]

Keywords - Coding sequence diversityi

Alternative splicing

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
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.
RefSeqiNP_114019.1. NM_031831.1. [Q9JK11-1]
XP_006251670.2. XM_006251608.2. [Q9JK11-2]
XP_006251671.1. XM_006251609.3. [Q9JK11-3]
XP_017454882.1. XM_017599393.1. [Q9JK11-4]
UniGeneiRn.1348.
Rn.163269.

3D structure databases

ProteinModelPortaliQ9JK11.
SMRiQ9JK11.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249825. 2 interactors.
DIPiDIP-37179N.
IntActiQ9JK11. 12 interactors.
MINTiMINT-4998315.
STRINGi10116.ENSRNOP00000006443.

PTM databases

iPTMnetiQ9JK11.
PhosphoSitePlusiQ9JK11.

Proteomic databases

PaxDbiQ9JK11.
PRIDEiQ9JK11.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000006957; ENSRNOP00000006957; ENSRNOG00000004621. [Q9JK11-2]
ENSRNOT00000041638; ENSRNOP00000042870; ENSRNOG00000004621. [Q9JK11-4]
ENSRNOT00000042965; ENSRNOP00000040760; ENSRNOG00000004621. [Q9JK11-3]
GeneIDi83765.
KEGGirno:83765.
UCSCiRGD:620989. rat. [Q9JK11-1]

Organism-specific databases

CTDi57142.
RGDi620989. Rtn4.

Phylogenomic databases

eggNOGiKOG1792. Eukaryota.
ENOG410XPKH. LUCA.
GeneTreeiENSGT00390000009934.
HOGENOMiHOG000148576.
HOVERGENiHBG023134.
InParanoidiQ9JK11.
KOiK20720.
PhylomeDBiQ9JK11.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ9JK11.

Gene expression databases

BgeeiENSRNOG00000004621.
ExpressionAtlasiQ9JK11. baseline and differential.
GenevisibleiQ9JK11. RN.

Family and domain databases

InterProiIPR003388. Reticulon.
[Graphical view]
PfamiPF02453. Reticulon. 1 hit.
[Graphical view]
PROSITEiPS50845. RETICULON. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRTN4_RAT
AccessioniPrimary (citable) accession number: Q9JK11
Secondary accession number(s): Q9JK10
, Q9R0D9, Q9WUE9, Q9WUF0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: October 1, 2000
Last modified: November 30, 2016
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  2. SIMILARITY comments
    Index of protein domains and families

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.