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Protein

Reticulon-4

Gene

Rtn4

Organism
Mus musculus (Mouse)
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. May 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 similarity2 Publications

GO - Molecular functioni

GO - Biological processi

  • axonal fasciculation Source: UniProtKB
  • cardiac epithelial to mesenchymal transition Source: MGI
  • 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 cell growth Source: MGI
  • nervous system development Source: MGI
  • nuclear pore complex assembly Source: UniProtKB
  • regulation of branching morphogenesis of a nerve Source: UniProtKB
  • regulation of cell migration Source: MGI
  • regulation of nervous system development Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Neurogenesis

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Reticulon-4
Alternative name(s):
Neurite outgrowth inhibitor
Short name:
Nogo protein
Gene namesi
Name:Rtn4
Synonyms:Kiaa0886, Nogo
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1915835. 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 – 988CytoplasmicSequence analysisAdd BLAST988
Transmembranei989 – 1009HelicalSequence analysisAdd BLAST21
Topological domaini1010 – 1078LumenalSequence analysisAdd BLAST69
Transmembranei1079 – 1099HelicalSequence analysisAdd BLAST21
Topological domaini1100 – 1162CytoplasmicSequence analysisAdd BLAST63

GO - Cellular componenti

  • cell-cell adherens junction Source: MGI
  • cell projection Source: MGI
  • endoplasmic reticulum Source: MGI
  • endoplasmic reticulum membrane Source: UniProtKB
  • extracellular exosome Source: MGI
  • integral component of endoplasmic reticulum membrane Source: UniProtKB
  • intracellular Source: MGI
  • nuclear envelope Source: UniProtKB
  • postsynaptic density Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Disruption phenotypei

Embryos show defects in the development of fore- and hindlimb innervation. Increased fasciculation and decreased branching of nerves innervating fore- and hindlimbs seen. Disturbances of the radial migration pattern of neuronal precursor cells seen in embryonic cortex.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001681661 – 1162Reticulon-4Add BLAST1162

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei7PhosphoserineBy similarity1
Modified residuei16PhosphoserineCombined sources1
Modified residuei105PhosphoserineCombined sources1
Modified residuei145PhosphoserineCombined sources1
Modified residuei165PhosphoserineCombined sources1
Modified residuei167PhosphoserineCombined sources1
Modified residuei329PhosphoserineBy similarity1
Modified residuei344PhosphoserineCombined sources1
Modified residuei348PhosphothreonineCombined sources1
Modified residuei426PhosphoserineBy similarity1
Modified residuei430PhosphothreonineBy similarity1
Modified residuei489PhosphoserineCombined sources1
Modified residuei690PhosphoserineCombined sources1
Modified residuei727PhosphoserineCombined sources1
Modified residuei768PhosphoserineCombined sources1
Modified residuei832PhosphoserineBy similarity1
Modified residuei834PhosphothreonineBy similarity1
Modified residuei857PhosphoserineCombined sources1
Modified residuei961PhosphoserineBy similarity1
Modified residuei1074N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ99P72.
MaxQBiQ99P72.
PaxDbiQ99P72.
PeptideAtlasiQ99P72.
PRIDEiQ99P72.

PTM databases

iPTMnetiQ99P72.
PhosphoSitePlusiQ99P72.
SwissPalmiQ99P72.

Expressioni

Developmental stagei

Expressed in radial glial cells, migrating postmitotic as well as postmigratory neurons of the embryonic cortex.1 Publication

Gene expression databases

BgeeiENSMUSG00000020458.
CleanExiMM_RTN4.
ExpressionAtlasiQ99P72. baseline and differential.
GenevisibleiQ99P72. MM.

Interactioni

Subunit structurei

Binds to RTN4R. Interacts with Bcl-xl and Bcl-2. Interacts in trans with CNTNAP1. Interacts with ATL1 (By similarity). Interacts with RTN4IP1. Interacts with TMEM170A and TMEM33 (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Hspa4lP487224EBI-3869532,EBI-8314699

GO - Molecular functioni

Protein-protein interaction databases

BioGridi212938. 7 interactors.
DIPiDIP-41976N.
IntActiQ99P72. 5 interactors.
MINTiMINT-188330.
STRINGi10090.ENSMUSP00000099907.

Structurei

Secondary structure

11162
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1026 – 1029Combined sources4
Helixi1031 – 1035Combined sources5
Turni1037 – 1040Combined sources4
Helixi1044 – 1053Combined sources10
Helixi1057 – 1063Combined sources7
Turni1065 – 1067Combined sources3
Helixi1068 – 1082Combined sources15
Helixi1087 – 1089Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KO2NMR-A1025-1090[»]
ProteinModelPortaliQ99P72.
SMRiQ99P72.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99P72.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini975 – 1162ReticulonPROSITE-ProRule annotationAdd BLAST188

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi31 – 57Glu-richAdd BLAST27
Compositional biasi68 – 160Pro-richAdd BLAST93

Domaini

Three regions, residues 59-172, 544-725 and the loop 66 amino acids, between the two transmembrane domains, 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 (By similarity).By similarity

Sequence similaritiesi

Contains 1 reticulon domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1792. Eukaryota.
ENOG410XPKH. LUCA.
GeneTreeiENSGT00390000009934.
HOVERGENiHBG023134.
InParanoidiQ99P72.
KOiK20720.
OMAiHTSENKT.
OrthoDBiEOG091G0TIO.
PhylomeDBiQ99P72.
TreeFamiTF105431.

Family and domain databases

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

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99P72-2) [UniParc]FASTAAdd to basket

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 SSSADSPPRP PPAFKYQFVT EPEDEEDEED EEEEEDDEDL
60 70 80 90 100
EELEVLERKP AAGLSAAPVP PAAAPLLDFS SDSVPPAPRG PLPAAPPTAP
110 120 130 140 150
ERQPSWERSP AASAPSLPPA AAVLPSKLPE DDEPPARPPA PAGASPLAEP
160 170 180 190 200
AAPPSTPAAP KRRGSGSVDE TLFALPAASE PVIPSSAEKI MDLKEQPGNT
210 220 230 240 250
VSSGQEDFPS VLFETAASLP SLSPLSTVSF KEHGYLGNLS AVASTEGTIE
260 270 280 290 300
ETLNEASREL PERATNPFVN RESAEFSVLE YSEMGSSFNG SPKGESAMLV
310 320 330 340 350
ENTKEEVIVR SKDKEDLVCS AALHNPQESP ATLTKVVKED GVMSPEKTMD
360 370 380 390 400
IFNEMKMSVV APVREEYADF KPFEQAWEVK DTYEGSRDVL AARANMESKV
410 420 430 440 450
DKKCFEDSLE QKGHGKDSES RNENASFPRT PELVKDGSRA YITCDSFSSA
460 470 480 490 500
TESTAANIFP VLEDHTSENK TDEKKIEERK AQIITEKTSP KTSNPFLVAI
510 520 530 540 550
HDSEADYVTT DNLSKVTEAV VATMPEGLTP DLVQEACESE LNEATGTKIA
560 570 580 590 600
YETKVDLVQT SEAIQESIYP TAQLCPSFEE AEATPSPVLP DIVMEAPLNS
610 620 630 640 650
LLPSTGASVA QPSASPLEVP SPVSYDGIKL EPENPPPYEE AMSVALKTSD
660 670 680 690 700
SKEEIKEPES FNAAAQEAEA PYISIACDLI KETKLSTEPS PEFSNYSEIA
710 720 730 740 750
KFEKSVPDHC ELVDDSSPES EPVDLFSDDS IPEVPQTQEE AVMLMKESLT
760 770 780 790 800
EVSETVTQHK HKERLSASPQ EVGKPYLESF QPNLHITKDA ASNEIPTLTK
810 820 830 840 850
KETISLQMEE FNTAIYSNDD LLSSKEDKMK ESETFSDSSP IEIIDEFPTF
860 870 880 890 900
VSAKDDSPKE YTDLEVSNKS EIANVQSGAN SLPCSELPCD LSFKNTYPKD
910 920 930 940 950
EAHVSDEFSK SRSSVSKVPL LLPNVSALES QIEMGNIVKP KVLTKEAEEK
960 970 980 990 1000
LPSDTEKEDR SLTAVLSAEL NKTSVVDLLY WRDIKKTGVV FGASLFLLLS
1010 1020 1030 1040 1050
LTVFSIVSVT AYIALALLSV TISFRIYKGV IQAIQKSDEG HPFRAYLESE
1060 1070 1080 1090 1100
VAISEELVQK YSNSALGHVN STIKELRRLF LVDDLVDSLK FAVLMWVFTY
1110 1120 1130 1140 1150
VGALFNGLTL LILALISLFS IPVIYERHQA QIDHYLGLAN KSVKDAMAKI
1160
QAKIPGLKRK AE
Length:1,162
Mass (Da):126,613
Last modified:May 2, 2006 - v2
Checksum:i855697FBEE11781F
GO
Isoform 2 (identifier: Q99P72-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-116: Missing.
     117-169: LPPAAAVLPS...PKRRGSGSVD → MAPPLAGGGQ...RSSRLSAARN

Show »
Length:1,046
Mass (Da):114,222
Checksum:i8CE2E2238ED51222
GO
Isoform 3 (identifier: Q99P72-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-963: Missing.
     964-974: AVLSAELNKTS → MDDQKKRWKDK

Show »
Length:199
Mass (Da):22,466
Checksum:i07BE5D580059ED9C
GO

Sequence cautioni

The sequence AAH32192 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BC056373 differs from that shown. Reason: Erroneous termination at position 721. Translated as Glu.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4I → V in BAD90301 (Ref. 4) Curated1
Sequence conflicti16S → R in BAD90301 (Ref. 4) Curated1
Sequence conflicti21P → L in BAD90301 (Ref. 4) Curated1
Sequence conflicti67A → V in AAM77068 (Ref. 3) Curated1
Sequence conflicti413G → S in AAM77068 (Ref. 3) Curated1
Sequence conflicti413G → S in BAD90301 (Ref. 4) Curated1
Sequence conflicti429R → S in AAM77068 (Ref. 3) Curated1
Sequence conflicti429R → S in BAD90301 (Ref. 4) Curated1
Sequence conflicti448S → T in AAM77068 (Ref. 3) Curated1
Sequence conflicti448S → T in BAD90301 (Ref. 4) Curated1
Sequence conflicti487 – 490KTSP → HASA in AAH32192 (PubMed:15489334).Curated4
Sequence conflicti651S → A in AAM77068 (Ref. 3) Curated1
Sequence conflicti651S → A in AAH32192 (PubMed:15489334).Curated1
Sequence conflicti651S → A in BAD90301 (Ref. 4) Curated1
Sequence conflicti665A → V in BAD90301 (Ref. 4) Curated1
Sequence conflicti692E → G in AAM77068 (Ref. 3) Curated1
Sequence conflicti692E → G in BAC75974 (Ref. 7) Curated1
Sequence conflicti733E → D in BAD90301 (Ref. 4) Curated1
Sequence conflicti772V → L in BAD90301 (Ref. 4) Curated1
Sequence conflicti916S → F in BAC75974 (Ref. 7) Curated1
Sequence conflicti990V → VY in AAM77068 (Ref. 3) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0180881 – 963Missing in isoform 3. 1 PublicationAdd BLAST963
Alternative sequenceiVSP_0180891 – 116Missing in isoform 2. 1 PublicationAdd BLAST116
Alternative sequenceiVSP_018090117 – 169LPPAA…SGSVD → MAPPLAGGGQKGGAASEAWV PSLFVGVSGSTCTAAKSLVP IPARSSRLSAARN in isoform 2. 1 PublicationAdd BLAST53
Alternative sequenceiVSP_018091964 – 974AVLSAELNKTS → MDDQKKRWKDK in isoform 3. 1 PublicationAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY102280 mRNA. Translation: AAM73502.1.
AY102284 mRNA. Translation: AAM73506.1.
AY102286 Genomic DNA. Translation: AAM73507.1.
AY102286 Genomic DNA. Translation: AAM73511.1.
AF326337 mRNA. Translation: AAK08076.1.
AY114152 mRNA. Translation: AAM77068.1.
AK220511 mRNA. Translation: BAD90301.1.
AL929371 Genomic DNA. Translation: CAI24273.1.
AL929371 Genomic DNA. Translation: CAI24274.1.
BC032192 mRNA. Translation: AAH32192.1. Different initiation.
BC056373 mRNA. No translation available.
AB073672 mRNA. Translation: BAC75974.1.
AK003859 mRNA. No translation available.
CCDSiCCDS24501.1. [Q99P72-2]
CCDS24502.1. [Q99P72-3]
CCDS24503.1. [Q99P72-1]
RefSeqiNP_077188.1. NM_024226.4. [Q99P72-1]
NP_918940.1. NM_194051.3. [Q99P72-3]
NP_918943.1. NM_194054.3. [Q99P72-2]
UniGeneiMm.192580.
Mm.440639.
Mm.488364.

Genome annotation databases

EnsembliENSMUST00000060992; ENSMUSP00000053754; ENSMUSG00000020458. [Q99P72-1]
ENSMUST00000102841; ENSMUSP00000099905; ENSMUSG00000020458. [Q99P72-3]
ENSMUST00000102843; ENSMUSP00000099907; ENSMUSG00000020458. [Q99P72-2]
GeneIDi68585.
KEGGimmu:68585.
UCSCiuc007ihk.2. mouse. [Q99P72-2]
uc007ihn.2. mouse. [Q99P72-3]

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
AY102280 mRNA. Translation: AAM73502.1.
AY102284 mRNA. Translation: AAM73506.1.
AY102286 Genomic DNA. Translation: AAM73507.1.
AY102286 Genomic DNA. Translation: AAM73511.1.
AF326337 mRNA. Translation: AAK08076.1.
AY114152 mRNA. Translation: AAM77068.1.
AK220511 mRNA. Translation: BAD90301.1.
AL929371 Genomic DNA. Translation: CAI24273.1.
AL929371 Genomic DNA. Translation: CAI24274.1.
BC032192 mRNA. Translation: AAH32192.1. Different initiation.
BC056373 mRNA. No translation available.
AB073672 mRNA. Translation: BAC75974.1.
AK003859 mRNA. No translation available.
CCDSiCCDS24501.1. [Q99P72-2]
CCDS24502.1. [Q99P72-3]
CCDS24503.1. [Q99P72-1]
RefSeqiNP_077188.1. NM_024226.4. [Q99P72-1]
NP_918940.1. NM_194051.3. [Q99P72-3]
NP_918943.1. NM_194054.3. [Q99P72-2]
UniGeneiMm.192580.
Mm.440639.
Mm.488364.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KO2NMR-A1025-1090[»]
ProteinModelPortaliQ99P72.
SMRiQ99P72.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi212938. 7 interactors.
DIPiDIP-41976N.
IntActiQ99P72. 5 interactors.
MINTiMINT-188330.
STRINGi10090.ENSMUSP00000099907.

PTM databases

iPTMnetiQ99P72.
PhosphoSitePlusiQ99P72.
SwissPalmiQ99P72.

Proteomic databases

EPDiQ99P72.
MaxQBiQ99P72.
PaxDbiQ99P72.
PeptideAtlasiQ99P72.
PRIDEiQ99P72.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000060992; ENSMUSP00000053754; ENSMUSG00000020458. [Q99P72-1]
ENSMUST00000102841; ENSMUSP00000099905; ENSMUSG00000020458. [Q99P72-3]
ENSMUST00000102843; ENSMUSP00000099907; ENSMUSG00000020458. [Q99P72-2]
GeneIDi68585.
KEGGimmu:68585.
UCSCiuc007ihk.2. mouse. [Q99P72-2]
uc007ihn.2. mouse. [Q99P72-3]

Organism-specific databases

CTDi57142.
MGIiMGI:1915835. Rtn4.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG1792. Eukaryota.
ENOG410XPKH. LUCA.
GeneTreeiENSGT00390000009934.
HOVERGENiHBG023134.
InParanoidiQ99P72.
KOiK20720.
OMAiHTSENKT.
OrthoDBiEOG091G0TIO.
PhylomeDBiQ99P72.
TreeFamiTF105431.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiRtn4. mouse.
EvolutionaryTraceiQ99P72.
PROiQ99P72.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020458.
CleanExiMM_RTN4.
ExpressionAtlasiQ99P72. baseline and differential.
GenevisibleiQ99P72. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: Q99P72
Secondary accession number(s): Q5DTK9
, Q7TNB7, Q80W95, Q8BGK7, Q8BGM9, Q8K290, Q8K3G8, Q9CTE3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: May 2, 2006
Last modified: November 2, 2016
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  4. 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.