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RTN4RL2 Gene

protein-coding   GIFtS: 49
GCID: GC11P057228

Reticulon 4 Receptor-Like 2

  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Reticulon 4 Receptor-Like 21 2     Nogo-66 Receptor Homolog 12 3
NGRH12 3 5     Reticulon-4 Receptor-Like 22
Nogo Receptor-Like 32 3     NGRL33
Nogo-66 Receptor-Related Protein 22 3     NGR25
NgR22 3     

External Ids:    HGNC: 230531   Entrez Gene: 3496672   Ensembl: ENSG000001869077   OMIM: 6104625   UniProtKB: Q86UN33   

Export aliases for RTN4RL2 gene to outside databases

Previous GC identifers: GC11P057003 GC11P056984 GC11P053577


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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GeneCards Summary for RTN4RL2 Gene:
RTN4RL2 (reticulon 4 receptor-like 2) is a protein-coding gene. Diseases associated with RTN4RL2 include schizophrenia, and thyroiditis. GO annotations related to this gene include receptor activity. An important paralog of this gene is NYX.

UniProtKB/Swiss-Prot: R4RL2_HUMAN, Q86UN3
Function: May play a role in regulating axonal regeneration and plasticity in the adult central nervous system




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000011.10  NC_018922.2  NT_167190.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the RTN4RL2 gene promoter:
         Sp1   SREBP-1c   MyoD   SREBP-1b   Max   AREB6   POU2F1   SREBP-1a   POU2F1a   c-Myc   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidRTN4RL2 promoter sequence
   Search Chromatin IP Primers for RTN4RL2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat RTN4RL2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 11q12.1   Ensembl cytogenetic band:  11q12.1   HGNC cytogenetic band: 11q12.1

RTN4RL2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
RTN4RL2 gene location

GeneLoc information about chromosome 11         GeneLoc Exon Structure

GeneLoc location for GC11P057228:  view genomic region     (about GC identifiers)

Start:
57,228,022 bp from pter      End:
57,245,007 bp from pter
Size:
16,986 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: R4RL2_HUMAN, Q86UN3 (See protein sequence)
Recommended Name: Reticulon-4 receptor-like 2 precursor  
Size: 420 amino acids; 46106 Da
Secondary accessions: Q0GGW3 Q17RL9 Q6X813
Alternative splicing: 2 isoforms:  Q86UN3-1   Q86UN3-2   

Explore the universe of human proteins at neXtProt for RTN4RL2: NX_Q86UN3

Explore proteomics data for RTN4RL2 at MOPED

Post-translational modifications: 

  • Undergoes zinc metalloproteinase-mediated ectodomain shedding in neuroblastoma cells; where BRE is released as a
    full-length ectodomain and an N-terminal fragment containing the leucine-rich repeat (LRR) region of the protein1
  • Glycosylation2 at Asn50, Thr316
  • Modification sites at PhosphoSitePlus

  • See RTN4RL2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_848665.1  
    ENSEMBL proteins: 
     ENSP00000335397   ENSP00000435606   ENSP00000378552  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    3 InterPro protein domains:
     IPR000483 Cys-rich_flank_reg_C
     IPR000372 LRR-contain_N
     IPR003591 Leu-rich_rpt_typical-subtyp

    Graphical View of Domain Structure for InterPro Entry Q86UN3

    ProtoNet protein and cluster: Q86UN3

    3 Blocks protein domains:
    IPB000372 Cysteine-rich flanking region
    IPB000483 Cysteine-rich flanking region
    IPB001611 Leucine-rich repeat signature


    UniProtKB/Swiss-Prot: R4RL2_HUMAN, Q86UN3
    Similarity: Belongs to the Nogo receptor family
    Similarity: Contains 8 LRR (leucine-rich) repeats
    Similarity: Contains 1 LRRCT domain
    Similarity: Contains 1 LRRNT domain


    RTN4RL2 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: R4RL2_HUMAN, Q86UN3
    Function: May play a role in regulating axonal regeneration and plasticity in the adult central nervous system

         Gene Ontology (GO): 2 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004872receptor activity IDA12694398
    GO:0005515protein binding ----
         
    RTN4RL2 for ontologies           About GeneDecksing


    Phenotypes:
         3 GenomeRNAi human phenotypes for RTN4RL2:
     Cells with protrusions  Increased Salmonella enterica   Synthetic lethal with Ras 

         4 MGI mutant phenotypes (inferred from 5 alleles(MGI details for Rtn4rl2):
     nervous system  no phenotypic analysis  normal  other 

    RTN4RL2 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for RTN4RL2: Rtn4rl2tm1Yanr Rtn4rl2tm1Svk Rtn4rl2tm1Lex Rtn4rl2tm1.1Pado

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for RTN4RL2
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    R4RL2_HUMAN, Q86UN3: Cell membrane; Lipid-anchor, GPI-anchor. Note=Localized to the surface of neurons, including
    axons
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    extracellular3
    golgi apparatus1

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0009897external side of plasma membrane IEA--
    GO:0009986cell surface IDA--
    GO:0045121membrane raft IEA--
    GO:0046658anchored component of plasma membrane IDA12694398

    RTN4RL2 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for RTN4RL2
    Interactions:

        Search GeneGlobe Interaction Network for RTN4RL2

    STRING Interaction Network Preview (showing 2 interactants - click image to see more details)

    2 Interacting proteins for RTN4RL2 (ENSP000003353974) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CAB39ENSP000002584184STRING: ENSP00000258418
    CAB39LENSP000002616694STRING: ENSP00000261669
    About this table

    Gene Ontology (GO): 1 biological process term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0031103axon regeneration TAS14664809

    RTN4RL2 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for RTN4RL2 (R4RL2)



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for RTN4RL2 gene: 
    NM_178570.2  

    Unigene Cluster for RTN4RL2:

    Reticulon 4 receptor-like 2
    Hs.502618  [show with all ESTs]
    Unigene Representative Sequence: BM544597
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000335099(uc010rjt.2) ENST00000533205 ENST00000395120
    miRNA
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      QuantiTect SYBR Green Assays in human, mouse, rat RTN4RL2
      QuantiFast Probe-based Assays in human, mouse, rat RTN4RL2

    Additional mRNA sequence: 

    AF532858.1 AY250221.1 BC113673.1 BC117276.1 BC143818.1 DQ864979.1 

    3 DOTS entries:

    DT.40281369  DT.75133130  DT.86856121 

    Selected AceView cDNA sequences (see all 38):

    AI928856 BF115984 AY250221 BU620649 AI079320 BF940539 AF532858 AI633223 
    AI310350 AX751514 BE222737 BK001302 NM_178570 BF515550 AW131579 AI474722 
    AW293195 AW292999 BE858048 BU845536 AI929019 BF941745 AI346757 AW293985 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    RTN4RL2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CTCTGCACCT
    RTN4RL2 Expression
    About this image


    RTN4RL2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 2) fully expand
     
     Smooth Muscle (Muscoskeletal System)
             Juxtaglomerular Cells Afferent Arteriole
     
     Kidney (Urinary System)
             Juxtaglomerular Cells Afferent Arteriole
    RTN4RL2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    RTN4RL2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.502618

    UniProtKB/Swiss-Prot: R4RL2_HUMAN, Q86UN3
    Tissue specificity: Highly expressed in brain and liver. Expressed at lower levels in kidney, mammary gland,
    placenta, skeletal muscle, spleen and thyroid

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    In Situ
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for RTN4RL2 gene from Selected species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Rtn4rl21 , 5 reticulon 4 receptor-like 21, 5 91.25(n)1
    96.04(a)1
      2 (49.45 cM)5
    2692951  NM_199223.11  NP_954693.11 
     848719245 
    chicken
    (Gallus gallus)
    Aves RTN4RL21 reticulon 4 receptor-like 2 73.49(n)
    70.32(a)
      425201  XM_422985.4  XP_422985.4 
    lizard
    (Anolis carolinensis)
    Reptilia RTN4RL26
    reticulon 4 receptor-like 2
    68(a)
    1 ↔ 1
    1(91955142-91961793)
    zebrafish
    (Danio rerio)
    Actinopterygii rtn4rl2b1 reticulon 4 receptor-like 2b 57.08(n)
    54.25(a)
      403309  NM_203483.1  NP_982350.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG15046
    --
    20(a)
    1 → many
    X(20181336-20186734)
    worm
    (Caenorhabditis elegans)
    Secernentea lron-126
    Protein LRON-12 (lron-12) mRNA, complete cds
    17(a)
    1 → many
    III(12114564-12118470) WBGene00013542


    ENSEMBL Gene Tree for RTN4RL2 (if available)
    TreeFam Gene Tree for RTN4RL2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for RTN4RL2 gene
    NYX2  LRRC532  RTN4R2  LRRC702  RTN4RL12  
    4 SIMAP similar genes for RTN4RL2 using alignment to 3 protein entries:     R4RL2_HUMAN (see all proteins):
    RTN4RL1    RTN4R    LRRC24    SLIT2

    RTN4RL2 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for RTN4RL2 (see all 318)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 11 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1424973811,2
    C--57226521(+) GGGAAA/TCAGAC 1 -- us2k10--------
    rs2003179961,2
    C--57226542(+) AGAAAA/GGGTCC 1 -- us2k10--------
    rs1509247341,2
    C--57226557(+) GAGAGG/TGAGGG 1 -- us2k10--------
    rs1858046431,2
    --57226573(+) GGGAAC/GAGAGA 1 -- us2k10--------
    rs1395247251,2
    --57226773(+) GCGGCA/GCGGGC 1 -- us2k10--------
    rs1454158371,2
    C--57226838(+) GCCCC-/GGCA  
            
    CCGCC
    1 -- us2k10--------
    rs27293631,2
    C,F,H--57226854(-) GAGCCG/TCAGGT 1 -- us2k115Minor allele frequency- T:0.25NS NA CSA WA EA 1467
    rs1904734981,2
    --57227185(+) ATAAGG/TTCTCC 1 -- us2k10--------
    rs1181235961,2
    C,F--57227203(+) GACACA/CTCATA 1 -- us2k11Minor allele frequency- C:0.01EA 120
    rs1442670211,2
    --57227292(+) ACCGGC/GCACAT 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for RTN4RL2 (57228022 - 57245007 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for RTN4RL2:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2674981CNV Deletion23128226

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 610462    OMIM disorders: --

    3 diseases for RTN4RL2:    
    About MalaCards
    schizophrenia    thyroiditis    neuronitis


    RTN4RL2 for disorders           About GeneDecksing


    Export disorders for RTN4RL2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for RTN4RL2 gene, integrated from 10 sources (see all 12):
    (articles sorted by number of sources associating them with RTN4RL2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Structure and axon outgrowth inhibitor binding of the Nogo-66 receptor and related proteins. (PubMed id 12839991)1, 2, 9 Barton W.A.... Nikolov D.B. (EMBO J. 2003)
    2. Two novel mammalian nogo receptor homologs differentially expressed in the central and peripheral nervous systems. (PubMed id 14664809)1, 2, 9 Lauren J.... Timmusk T. (Mol. Cell. Neurosci. 2003)
    3. Human chromosome 11 DNA sequence and analysis including novel gene identification. (PubMed id 16554811)1, 2 Taylor T.D....Sakaki Y. (Nature 2006)
    4. Ectodomain shedding of human Nogo-66 receptor homologue-1 by zinc metalloproteinases. (PubMed id 15629437)1, 2 Walmsley A.R.... Frentzel S. (Biochem. Biophys. Res. Commun. 2005)
    5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    6. Characterization of two novel proteins, NgRH1 and NgRH2, structurally and biochemically homologous to the Nogo-66 receptor. (PubMed id 12694398)1, 2 Pignot V.... Frentzel S. (J. Neurochem. 2003)
    7. Synaptic function for the Nogo-66 receptor NgR1: regulation of dendritic spine morphology and activity-dependent synaptic strength. (PubMed id 18337405)1, 9 Lee H....Giger R.J. (J. Neurosci. 2008)
    8. Nogo receptor is involved in the adhesion of dendritic cells to myelin. (PubMed id 21906273)1 McDonald C.L....Reindl M. (J Neuroinflammation 2011)
    9. Systematic analysis of human protein complexes identifies chromosome segregation proteins. (PubMed id 20360068)1 Hutchins J.R.... Peters J.M. (Science 2010)
    10. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PubMed id 12477932)1 Strausberg R.L....Marra M.A. (Proc. Natl. Acad. Sci. U.S.A. 2002)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 349667 HGNC: 23053 AceView: RTN4RL2 Ensembl:ENSG00000186907 euGenes: HUgn349667
    ECgene: RTN4RL2 H-InvDB: RTN4RL2

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for RTN4RL2 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for RTN4RL2 gene:
    Search GeneIP for patents involving RTN4RL2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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