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Protein

Reticulon-4 receptor-like 2

Gene

Rtn4rl2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Cell surface receptor that plays a functionally redundant role in the inhibition of neurite outgrowth mediated by MAG (By similarity). Plays a functionally redundant role in postnatal brain development (PubMed:27339102). Contributes to normal axon migration across the brain midline and normal formation of the corpus callosum (PubMed:27339102). Does not seem to play a significant role in regulating axon regeneration in the adult central nervous system (PubMed:22406547). Protects motoneurons against apoptosis; protection against apoptosis is probably mediated by MAG (PubMed:26335717). 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). Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton (PubMed:22325200).By similarity4 Publications

GO - Molecular functioni

GO - Biological processi

  • axon regeneration Source: UniProtKB
  • cell surface receptor signaling pathway Source: UniProtKB
  • corpus callosum development Source: UniProtKB
  • cytokine-mediated signaling pathway Source: GO_Central
  • negative regulation of JAK-STAT cascade Source: GO_Central
  • negative regulation of neuron projection development Source: UniProtKB
  • negative regulation of protein kinase activity Source: GO_Central

Keywordsi

Molecular functionReceptor

Enzyme and pathway databases

ReactomeiR-MMU-163125 Post-translational modification: synthesis of GPI-anchored proteins

Names & Taxonomyi

Protein namesi
Recommended name:
Reticulon-4 receptor-like 2
Alternative name(s):
Nogo receptor-like 3
Nogo-66 receptor homolog 1
Nogo-66 receptor-related protein 2
Short name:
NgR21 Publication
Gene namesi
Name:Rtn4rl2Imported
Synonyms:Ngrl3Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2669796 Rtn4rl2

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

Disruption phenotypei

No visible phenotype (PubMed:19367338). Mutant sensory neurons show no decrease of the inhibition of neurite outgrowth by MAG (PubMed:19367338). Compared to wild-type littermates, cultured hippocampus neurons from mutant mice display an increased number of excitatory synapses (PubMed:22325200). Likewise, mice lacking both Rtn4r and Rtn4rl2 display no visible phenotype (PubMed:19367338). Sensory neurons from mice lacking both Rtn4r and Rtn4rl2 show moderately decreased inhibition of neurite outgrowth by MAG (PubMed:19367338). Mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 have no visible phenotype, are healthy and viable (PubMed:22406547, PubMed:22325200). Mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 have normal brain size and grossly normal brain anatomy, but display disruption of medial brain structures, including an absence of the fasciola cinereum, corpus callosum agenesis and formation of bilateral Probst bundles indicative of the failure of callosally projecting neurons to extend across the midline (PubMed:27339102). Mice with a triple gene disruption of Rtn4r, Rtn4rl1 and Rtn4rl2 display impaired ability to stay on a rotarod and increased spontaneous locomotion (PubMed:27339102). These mice display an increased number of excitatory synapses in the apical dendritic regions of hippocampus neurons, an increase in the complexity of dendrite structure and increased total dendrite length (PubMed:22325200). One month after birth, mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 show a significant reduction in the survival of motoneurons (PubMed:26335717). Compared to wild-type or single mutants, cerebellar granule cells from mice lacking Rtn4r, Rtn4rl1 and Rtn4rl2 show decreased myelin-mediated inhibition of neurite outgrowth, an inhibition that is strongly decreased on myelin deficient in Mag, Rtn4 and Omg (PubMed:22406547). Mice lacking both Rtn4r and Rtn4rl1 show increased axon regeneration after injury; the same effect is observed when Rtn4r, Rtn4rl1 and Rtn4rl2 are disrupted (PubMed:22406547). Combined disruption of Rtn4r, Rtn4rl1 and Ptprs further increases axon regeneration after injury (PubMed:22406547). Single gene disruption of Rtn4r, Rtn4rl1 and Rtn4rl2 and combined disruption of Rtn4r and Rtn4rl2 have no effect on axon regeneration (PubMed:22406547).5 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 30Sequence analysisAdd BLAST30
ChainiPRO_000004605031 – 398Reticulon-4 receptor-like 2Add BLAST368
PropeptideiPRO_0000046051399 – 420Removed in mature formSequence analysisAdd BLAST22

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi31 ↔ 37By similarity
Disulfide bondi35 ↔ 46By similarity
Glycosylationi50N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi93N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi236N-linked (GlcNAc...) asparagineBy similarity1
Disulfide bondi265 ↔ 288By similarity
Disulfide bondi267 ↔ 310By similarity
Lipidationi398GPI-anchor amidated glycineSequence analysis1

Post-translational modificationi

Undergoes zinc metalloproteinase-mediated ectodomain shedding in neuroblastoma cells; is released both as a full-length ectodomain and an N-terminal fragment containing the leucine-rich repeat (LRR) region of the protein.By similarity
N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiQ7M6Z0
PRIDEiQ7M6Z0

PTM databases

iPTMnetiQ7M6Z0
PhosphoSitePlusiQ7M6Z0

Expressioni

Tissue specificityi

Detected in brain (PubMed:22406547). Detected in hippocampus neurons (at protein level) (PubMed:22325200).2 Publications

Developmental stagei

At E13.5, strongly expressed in PNS ganglia and developing heart, and weakly expressed in brain and spinal cord. By postnatal day 1, strongly expressed in dorsal root ganglia and in dorsal and gray matter areas of spinal cord. Expressed in various adult brain structures including the amygdala, cerebral cortex, cerebellum, hippocampus and olfactory bulb.1 Publication

Gene expression databases

BgeeiENSMUSG00000050896
CleanExiMM_RTN4RL2
ExpressionAtlasiQ7M6Z0 baseline and differential
GenevisibleiQ7M6Z0 MM

Interactioni

Subunit structurei

Interaction with MAG is controversial, and may be indirect (Probable). Interacts with MAG. Does not interact with OMG and RTN4 (By similarity).By similarityCurated

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000057725

Structurei

3D structure databases

ProteinModelPortaliQ7M6Z0
SMRiQ7M6Z0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini31 – 60LRRNTAdd BLAST30
Repeati61 – 82LRR 1Add BLAST22
Repeati83 – 104LRR 2Add BLAST22
Repeati107 – 129LRR 3Add BLAST23
Repeati132 – 153LRR 4Add BLAST22
Repeati156 – 177LRR 5Add BLAST22
Repeati180 – 201LRR 6Add BLAST22
Repeati204 – 225LRR 7Add BLAST22
Repeati228 – 249LRR 8Add BLAST22
Domaini261 – 312LRRCTAdd BLAST52

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni315 – 327Important for interaction with MAGBy similarityAdd BLAST13

Sequence similaritiesi

Belongs to the Nogo receptor family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal

Phylogenomic databases

eggNOGiKOG0619 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00760000118777
HOGENOMiHOG000116109
HOVERGENiHBG063707
InParanoidiQ7M6Z0
KOiK16661

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

Sequencei

Sequence statusi: Complete.

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

Q7M6Z0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLPGLRRLLQ GPASACLLLT LLALPSVTPS CPMLCTCYSS PPTVSCQANN
60 70 80 90 100
FSSVPLSLPP STQRLFLQNN LIRSLRPGTF GPNLLTLWLF SNNLSTIHPG
110 120 130 140 150
TFRHLQALEE LDLGDNRHLR SLEPDTFQGL ERLQSLHLYR CQLSSLPGNI
160 170 180 190 200
FRGLVSLQYL YLQENSLLHL QDDLFADLAN LSHLFLHGNR LRLLTEHVFR
210 220 230 240 250
GLGSLDRLLL HGNRLQGVHR AAFHGLSRLT ILYLFNNSLA SLPGEALADL
260 270 280 290 300
PALEFLRLNA NPWACDCRAR PLWAWFQRAR VSSSDVTCAT PPERQGRDLR
310 320 330 340 350
ALRDSDFQAC PPPTPTRPGS RARGNSSSNH LYGVAEAGAP PADPSTLYRD
360 370 380 390 400
LPAEDSRGRQ GGDAPTEDDY WGGYGGEDQR GEQTCPGAAC QAPADSRGPA
410 420
LSAGLRTPLL CLLPLALHHL
Length:420
Mass (Da):46,075
Last modified:December 15, 2003 - v1
Checksum:i412500FEE8154B47
GO

Sequence cautioni

The sequence BAE25181 differs from that shown. Reason: Erroneous translation. Wrong choice of frame.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY250220 mRNA Translation: AAP82837.1
BC132523 mRNA Translation: AAI32524.1
BC138154 mRNA Translation: AAI38155.1
AK142743 mRNA Translation: BAE25181.1 Sequence problems.
BK001303 mRNA Translation: DAA01386.1
CCDSiCCDS16197.1
RefSeqiNP_954693.1, NM_199223.1
UniGeneiMm.389289
Mm.86447

Genome annotation databases

EnsembliENSMUST00000054514; ENSMUSP00000057725; ENSMUSG00000050896
GeneIDi269295
KEGGimmu:269295
UCSCiuc008kjm.1 mouse

Similar proteinsi

Entry informationi

Entry nameiR4RL2_MOUSE
AccessioniPrimary (citable) accession number: Q7M6Z0
Secondary accession number(s): A2RTJ0, Q3UQ62
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: December 15, 2003
Last modified: May 23, 2018
This is version 121 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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