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Protein

Reticulon-4

Gene

Rtn4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

  • angiogenesis Source: MGI
  • axonal fasciculation Source: UniProtKB
  • cardiac epithelial to mesenchymal transition Source: MGI
  • cerebral cortex radial glia guided migration Source: UniProtKB
  • endoplasmic reticulum tubular network formation Source: UniProtKB
  • endoplasmic reticulum tubular network membrane organization Source: UniProtKB
  • endoplasmic reticulum tubular network organization Source: UniProtKB
  • negative regulation of axon extension Source: UniProtKB
  • negative regulation of axonogenesis Source: MGI
  • negative regulation of cell growth Source: MGI
  • negative regulation of dendrite extension Source: MGI
  • negative regulation of formation of growth cone in injured axon Source: MGI
  • negative regulation of neuron differentiation Source: MGI
  • negative regulation of neuron projection development Source: MGI
  • negative regulation of neuron projection regeneration Source: MGI
  • nervous system development Source: MGI
  • nuclear pore complex assembly Source: UniProtKB
  • positive regulation of collateral sprouting of injured axon Source: MGI
  • positive regulation of dopamine secretion Source: MGI
  • positive regulation of epithelial cell migration Source: MGI
  • positive regulation of ERBB3 signaling pathway Source: MGI
  • positive regulation of glial cell differentiation Source: MGI
  • positive regulation of mammary gland epithelial cell proliferation Source: MGI
  • positive regulation of protein kinase B signaling Source: MGI
  • positive regulation of protein localization to endoplasmic reticulum Source: MGI
  • protein stabilization Source: CAFA
  • regulation of branching morphogenesis of a nerve Source: UniProtKB
  • regulation of cell migration Source: MGI
  • regulation of nervous system development Source: UniProtKB
  • regulation of sensory perception of pain Source: MGI

Keywordsi

Biological processNeurogenesis

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1915835 Rtn4

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

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

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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi212938, 7 interactors
CORUMiQ99P72
DIPiDIP-41976N
IntActiQ99P72, 6 interactors
MINTiQ99P72
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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1792 Eukaryota
ENOG410XPKH LUCA
GeneTreeiENSGT00390000009934
HOVERGENiHBG023134
InParanoidiQ99P72
KOiK20720
OMAiPLLEDHT
OrthoDBiEOG091G0TIO
PhylomeDBiQ99P72
TreeFamiTF105431

Family and domain databases

InterProiView protein in InterPro
IPR003388 Reticulon
PfamiView protein in Pfam
PF02453 Reticulon, 1 hit
PROSITEiView protein in PROSITE
PS50845 RETICULON, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiRTN4_MOUSE
AccessioniPrimary (citable) accession number: Q99P72
Secondary accession number(s): Q5DTK9
, Q7TNB7, Q80W95, Q8BGK7, Q8BGM9, Q8K290, Q8K3G8, Q9CTE3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: May 2, 2006
Last modified: June 20, 2018
This is version 159 of the entry and version 2 of the sequence. See 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

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