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RTN4 (reticulon 4)

Written2007-01Masuo Yutsudo
Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan

(Note : for Links provided by Atlas : click)

Identity

Other namesASY
NI220/250
NOGO
NOGO-A
NSP
NSP-CL
Nbla00271
Nbla10545
RTN-X
RTN4-A
RTN4-B1
RTN4-B2
RTN4-C
HGNC (Hugo) RTN4
LocusID (NCBI) 57142
Atlas_Id 42182
Location 2p16.1  [Link to chromosome band 2p16]
Location_base_pair Starts at 55199327 and ends at 55237470 bp from pter ( according to hg19-Feb_2009)  [Mapping RTN4.png]
Local_order Between FLJ42562 and FLJ31438.
 
  Local order.
Fusion genes
(updated 2016)
ADAM12 (10q26.2) / RTN4 (2p16.1)AFF3 (2q11.2) / RTN4 (2p16.1)ANAPC4 (4p15.2) / RTN4 (2p16.1)
CBFA2T2 (20q11.21) / RTN4 (2p16.1)CRY2 (11p11.2) / RTN4 (2p16.1)FRMD6 (14q22.1) / RTN4 (2p16.1)
ICAM1 (19p13.2) / RTN4 (2p16.1)KARS (16q23.1) / RTN4 (2p16.1)LDAH (2p24.1) / RTN4 (2p16.1)
RGL1 (1q25.3) / RTN4 (2p16.1)RTN4 (2p16.1) / ANAPC4 (4p15.2)RTN4 (2p16.1) / ATP5G2 (12q13.13)
RTN4 (2p16.1) / ENTPD1 (10q24.1)RTN4 (2p16.1) / MITD1 (2q11.2)RTN4 (2p16.1) / RTN4 (2p16.1)
RTN4 (2p16.1) / UTP3 (4q13.3)TIMM17A (1q32.1) / RTN4 (2p16.1)

DNA/RNA

 
  Genomic structure and transcriptional isoforms.
Description The RTN4 gene spans about 75kb, and contains 9 major exons and several different cap sites (Fig. 2a).
Transcription Three major, RTN4-A, B1 and C, (Fig. 2b) and several minor transcriptional isoforms result from alternative splicing and/or differential promoter usage. Although RTN4 mRNA is ubiquitously expressed, the expression of isoforms is tissue-specific, for example, RTN4-A and C in brain, RTN4-C in muscle, and RTN4-B1 in many other tissues.

Protein

Description Proteins with different sizes are synthesized from different mRNA isoforms: RTN4-A, 129.9 kDa (1192 amino acids); RTN4-B1, 40.3 kDa (373 amino acids); RTN4-B2, 42.3 kDa (392 amino acids); RTN4-C, 22.4 kDa (199 amino acids). All RTN4 protein isoforms retain a common C-terminal domain containing two trans-membrane domains and an endoplasmic reticulum (ER)-retrieval motif.
Expression Ubiquitously expressed (see Transcription).
Localisation RTN4 protein localizes predominantly in the ER and, to a lesser extent, in cytoplasmic membrane.
Function Although definitive functional mechanisms of RTN4 have not yet been clarified, RTN4 protein interacts with several other proteins, including RTN1, RTN3, DP1/Yop1p, BACE1, and Nogo receptor (NogoR). Interaction with DP1/Yop1p, an ER membrane protein, may be necessary for maintenance or stabilization of tubular ER. Binding with BACE1 (beta-amyloid converting enzyme 1) results in reduction in BACE1 activity and production of amyloid-beta. RTN4 also interacts with NogoR, and may lead to activation of RhoA and inhibition of neuronal regeneration in central nervous system. Further, overexpression of RTN4 may cause ER stress and apoptosis in certain cells.
Homology Four reticulon family members (RTN1, RTN2, RTN3 and RTN4) have been identified. They possess a highly conserved C-terminal domain named reticulon homology domain.

Implicated in

Note
Entity Various cancers.
Note Down-regulation of RTN4 expression was observed in small cell lung carcinomas and adult T-cell leukemia/lymphomas, and RTN3, one of RTN4 interacting proteins, was over-expressed in astrocytomas, suggesting involvement of RTN4 (and RTN3) in certain types of tumorigenesis. However, increased incidence of tumor formation has not been observed in RTN4 knock out mice.
RTN4 is also suspected to involve in schizophrenia and neuronal degenerative diseases.
  

Bibliography

A new role for Nogo as a regulator of vascular remodeling.
Acevedo L, Yu J, Erdjument-Bromage H, Miao RQ, Kim JE, Fulton D, Tempst P, Strittmatter SM, Sessa WC
Nature medicine. 2004 ; 10 (4) : 382-388.
PMID 15034570
 
Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1.
Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME
Nature. 2000 ; 403 (6768) : 434-439.
PMID 10667796
 
Human Nogo-C overexpression induces HEK293 cell apoptosis via a mechanism that involves JNK-c-Jun pathway.
Chen Y, Tang X, Cao X, Chen H, Zhang X
Biochemical and biophysical research communications. 2006 ; 348 (3) : 923-928.
PMID 16905119
 
Nogo provides a molecular marker for diagnosis of amyotrophic lateral sclerosis.
Dupuis L, Gonzalez de Aguilar JL, di Scala F, Rene F, de Tapia M, Pradat PF, Lacomblez L, Seihlan D, Prinjha R, Walsh FS, Meininger V, Loeffler JP
Neurobiology of disease. 2002 ; 10 (3) : 358-365.
PMID 12270696
 
Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration.
Fournier AE, GrandPre T, Strittmatter SM
Nature. 2001 ; 409 (6818) : 341-346.
PMID 11201742
 
Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein.
GrandPré T, Nakamura F, Vartanian T, Strittmatter SM
Nature. 2000 ; 403 (6768) : 439-444.
PMID 10667797
 
Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation.
He W, Lu Y, Qahwash I, Hu XY, Chang A, Yan R
Nature medicine. 2004 ; 10 (9) : 959-965.
PMID 15286784
 
Overexpression of human reticulon 3 (hRTN3) in astrocytoma.
Huang X, Yang H, Zhou Y, Liu J, Yin B, Peng X, Qiang B, Yuan J
Clinical neuropathology. 2004 ; 23 (1) : 1-7.
PMID 14986927
 
Axon regeneration in young adult mice lacking Nogo-A/B.
Kim JE, Li S, GrandPré T, Qiu D, Strittmatter SM
Neuron. 2003 ; 38 (2) : 187-199.
PMID 12718854
 
ER stress triggers apoptosis induced by Nogo-B/ASY overexpression.
Kuang E, Wan Q, Li X, Xu H, Zou T, Qi Y
Experimental cell research. 2006 ; 312 (11) : 1983-1988.
PMID 16687140
 
Link of a new type of apoptosis-inducing gene ASY/Nogo-B to human cancer.
Li Q, Qi B, Oka K, Shimakage M, Yoshioka N, Inoue H, Hakura A, Kodama K, Stanbridge EJ, Yutsudo M
Oncogene. 2001 ; 20 (30) : 3929-3936.
PMID 11494121
 
Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to produce amyloid beta-protein.
Murayama KS, Kametani F, Saito S, Kume H, Akiyama H, Araki W
The European journal of neuroscience. 2006 ; 24 (5) : 1237-1244.
PMID 16965550
 
Schizophrenia and Nogo: elevated mRNA in cortex, and high prevalence of a homozygous CAA insert.
Novak G, Kim D, Seeman P, Tallerico T
Brain research. Molecular brain research. 2002 ; 107 (2) : 183-189.
PMID 12425946
 
Nogo A, B and C expression in schizophrenia, depression and bipolar frontal cortex, and correlation of Nogo expression with CAA/TATC polymorphism in 3'-UTR.
Novak G, Tallerico T
Brain research. 2006 ; 1120 (1) : 161-171.
PMID 17022955
 
Genomic structure and functional characterisation of the promoters of human and mouse nogo/rtn4.
Oertle T, Huber C, van der Putten H, Schwab ME
Journal of molecular biology. 2003 ; 325 (2) : 299-323.
PMID 12488097
 
Nogo and its paRTNers.
Oertle T, Schwab ME
Trends in cell biology. 2003 ; 13 (4) : 187-194.
PMID 12667756
 
Inhibitor of neurite outgrowth in humans.
Prinjha R, Moore SE, Vinson M, Blake S, Morrow R, Christie G, Michalovich D, Simmons DL, Walsh FS
Nature. 2000 ; 403 (6768) : 383-384.
PMID 10667780
 
Pro-apoptotic ASY/Nogo-B protein associates with ASYIP.
Qi B, Qi Y, Watari A, Yoshioka N, Inoue H, Minemoto Y, Yamashita K, Sasagawa T, Yutsudo M
Journal of cellular physiology. 2003 ; 196 (2) : 312-318.
PMID 12811824
 
Nogo-B is a new physiological substrate for MAPKAP-K2.
Rousseau S, Peggie M, Campbell DG, Nebreda AR, Cohen P
The Biochemical journal. 2005 ; 391 (Pt 2) : 433-440.
PMID 16095439
 
The Nogo receptor complex: confining molecules to molecular mechanisms.
Schwab JM, Tuli SK, Failli V
Trends in molecular medicine. 2006 ; 12 (7) : 293-297.
PMID 16723274
 
Down-regulation of ASY/Nogo transcription associated with progression of adult T-cell leukemia/lymphoma.
Shimakage M, Inoue N, Ohshima K, Kawahara K, Oka T, Yasui K, Matsumoto K, Inoue H, Watari A, Higashiyama S, Yutsudo M
International journal of cancer. Journal international du cancer. 2006 ; 119 (7) : 1648-1653.
PMID 16646068
 
Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury.
Simonen M, Pedersen V, Weinmann O, Schnell L, Buss A, Ledermann B, Christ F, Sansig G, van der Putten H, Schwab ME
Neuron. 2003 ; 38 (2) : 201-211.
PMID 12718855
 
Mutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia.
Sinibaldi L, De Luca A, Bellacchio E, Conti E, Pasini A, Paloscia C, Spalletta G, Caltagirone C, Pizzuti A, Dallapiccola B
Human mutation. 2004 ; 24 (6) : 534-535.
PMID 15532024
 
A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity.
Tagami S, Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y
Oncogene. 2000 ; 19 (50) : 5736-5746.
PMID 11126360
 
A class of membrane proteins shaping the tubular endoplasmic reticulum.
Voeltz GK, Prinz WA, Shibata Y, Rist JM, Rapoport TA
Cell. 2006 ; 124 (3) : 573-586.
PMID 16469703
 
Multi-functional gene ASY/Nogo/RTN-X/RTN4: apoptosis, tumor suppression, and inhibition of neuronal regeneration.
Watari A, Yutsudo M
Apoptosis : an international journal on programmed cell death. 2003 ; 8 (1) : 5-9.
PMID 12510146
 
Reticulon proteins: emerging players in neurodegenerative diseases.
Yan R, Shi Q, Hu X, Zhou X
Cellular and molecular life sciences : CMLS. 2006 ; 63 (7-8) : 877-889.
PMID 16505974
 
Assignment of the human reticulon 4 gene (RTN4) to chromosome 2p14-->2p13 by radiation hybrid mapping.
Yang J, Yu L, Bi AD, Zhao SY
Cytogenetics and cell genetics. 2000 ; 88 (1-2) : 101-102.
PMID 10773680
 
Genetic deletion of the Nogo receptor does not reduce neurite inhibition in vitro or promote corticospinal tract regeneration in vivo.
Zheng B, Atwal J, Ho C, Case L, He XL, Garcia KC, Steward O, Tessier-Lavigne M
Proceedings of the National Academy of Sciences of the United States of America. 2005 ; 102 (4) : 1205-1210.
PMID 15647357
 
Lack of enhanced spinal regeneration in Nogo-deficient mice.
Zheng B, Ho C, Li S, Keirstead H, Steward O, Tessier-Lavigne M
Neuron. 2003 ; 38 (2) : 213-224.
PMID 12718856
 

Citation

This paper should be referenced as such :
Yutsudo, M
RTN4 (reticulon 4)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(2):128-130.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/RTN4ID42182ch2p16.html


External links

Nomenclature
HGNC (Hugo)RTN4   14085
Cards
AtlasRTN4ID42182ch2p16
Entrez_Gene (NCBI)RTN4  57142  reticulon 4
AliasesASY; NI220/250; NOGO; NOGO-A; 
NOGOC; NSP; NSP-CL; Nbla00271; Nbla10545; Nogo-B; Nogo-C; RTN-X; RTN4-A; RTN4-B1; RTN4-B2; RTN4-C
GeneCards (Weizmann)RTN4
Ensembl hg19 (Hinxton)ENSG00000115310 [Gene_View]  chr2:55199327-55237470 [Contig_View]  RTN4 [Vega]
Ensembl hg38 (Hinxton)ENSG00000115310 [Gene_View]  chr2:55199327-55237470 [Contig_View]  RTN4 [Vega]
ICGC DataPortalENSG00000115310
TCGA cBioPortalRTN4
AceView (NCBI)RTN4
Genatlas (Paris)RTN4
WikiGenes57142
SOURCE (Princeton)RTN4
Genomic and cartography
GoldenPath hg19 (UCSC)RTN4  -     chr2:55199327-55237470 -  2p16.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)RTN4  -     2p16.1   [Description]    (hg38-Dec_2013)
EnsemblRTN4 - 2p16.1 [CytoView hg19]  RTN4 - 2p16.1 [CytoView hg38]
Mapping of homologs : NCBIRTN4 [Mapview hg19]  RTN4 [Mapview hg38]
OMIM604475   
Gene and transcription
Genbank (Entrez)AB015639 AB020693 AB040462 AB040463 AB073351
RefSeq transcript (Entrez)NM_001321859 NM_001321860 NM_001321861 NM_001321862 NM_001321863 NM_001321904 NM_007008 NM_020532 NM_153828 NM_207520 NM_207521
RefSeq genomic (Entrez)NC_000002 NC_018913 NG_029037 NT_022184 NW_004929300
Consensus coding sequences : CCDS (NCBI)RTN4
Cluster EST : UnigeneHs.637850 [ NCBI ]
CGAP (NCI)Hs.637850
Alternative Splicing GalleryENSG00000115310
Gene ExpressionRTN4 [ NCBI-GEO ]   RTN4 [ EBI - ARRAY_EXPRESS ]   RTN4 [ SEEK ]   RTN4 [ MEM ]
Gene Expression Viewer (FireBrowse)RTN4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)57142
GTEX Portal (Tissue expression)RTN4
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9NQC3 (Uniprot)
NextProtQ9NQC3  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9NQC3
Splice isoforms : SwissVarQ9NQC3 (Swissvar)
PhosPhoSitePlusQ9NQC3
Domaine pattern : Prosite (Expaxy)RETICULON (PS50845)   
Domains : Interpro (EBI)Reticulon   
Domain families : Pfam (Sanger)Reticulon (PF02453)   
Domain families : Pfam (NCBI)pfam02453   
DMDM Disease mutations57142
Blocks (Seattle)RTN4
PDB (SRS)2G31    2JV5   
PDB (PDBSum)2G31    2JV5   
PDB (IMB)2G31    2JV5   
PDB (RSDB)2G31    2JV5   
Structural Biology KnowledgeBase2G31    2JV5   
SCOP (Structural Classification of Proteins)2G31    2JV5   
CATH (Classification of proteins structures)2G31    2JV5   
SuperfamilyQ9NQC3
Human Protein AtlasENSG00000115310
Peptide AtlasQ9NQC3
HPRD07259
IPIIPI00021766   IPI00298289   IPI00219207   IPI00477663   IPI00478442   IPI00894213   IPI00873380   IPI01011809   IPI01025160   IPI00894099   IPI00414671   
Protein Interaction databases
DIP (DOE-UCLA)Q9NQC3
IntAct (EBI)Q9NQC3
FunCoupENSG00000115310
BioGRIDRTN4
STRING (EMBL)RTN4
ZODIACRTN4
Ontologies - Pathways
QuickGOQ9NQC3
Ontology : AmiGOprotein binding  intracellular  nuclear envelope  endoplasmic reticulum  endoplasmic reticulum  endoplasmic reticulum membrane  plasma membrane  apoptotic process  axonal fasciculation  axonal fasciculation  cerebral cortex radial glia guided migration  integral component of endoplasmic reticulum membrane  negative regulation of cell growth  regulation of cell migration  negative regulation of axon extension  regulation of apoptotic process  poly(A) RNA binding  negative regulation of axonogenesis  nuclear pore complex assembly  cardiac epithelial to mesenchymal transition  extracellular exosome  endoplasmic reticulum tubular network organization  endoplasmic reticulum tubular network assembly  neuronal postsynaptic density  regulation of branching morphogenesis of a nerve  
Ontology : EGO-EBIprotein binding  intracellular  nuclear envelope  endoplasmic reticulum  endoplasmic reticulum  endoplasmic reticulum membrane  plasma membrane  apoptotic process  axonal fasciculation  axonal fasciculation  cerebral cortex radial glia guided migration  integral component of endoplasmic reticulum membrane  negative regulation of cell growth  regulation of cell migration  negative regulation of axon extension  regulation of apoptotic process  poly(A) RNA binding  negative regulation of axonogenesis  nuclear pore complex assembly  cardiac epithelial to mesenchymal transition  extracellular exosome  endoplasmic reticulum tubular network organization  endoplasmic reticulum tubular network assembly  neuronal postsynaptic density  regulation of branching morphogenesis of a nerve  
REACTOMEQ9NQC3 [protein]
REACTOME PathwaysR-HSA-193634 Axonal growth inhibition (RHOA activation) [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkRTN4
Wikipedia pathwaysRTN4
Orthology - Evolution
OrthoDB57142
GeneTree (enSembl)ENSG00000115310
Phylogenetic Trees/Animal Genes : TreeFamRTN4
Homologs : HomoloGeneRTN4
Homology/Alignments : Family Browser (UCSC)RTN4
Gene fusions - Rearrangements
Fusion : MitelmanFRMD6/RTN4 [14q22.1/2p16.1]  [t(2;14)(p16;q22)]  
Fusion : MitelmanLDAH/RTN4 [2p24.1/2p16.1]  [t(2;2)(p16;p24)]  
Fusion : MitelmanRTN4/MITD1 [2p16.1/2q11.2]  [t(2;2)(p16;q11)]  
Fusion: TCGAC2orf43 RTN4 2p16.1 SKCM
Fusion: TCGAFRMD6 14q22.1 RTN4 2p16.1 BLCA
Fusion: TCGARTN4 2p16.1 MITD1 2q11.2 LUSC
Fusion Cancer (Beijing)KARS [16q23.1]  -  RTN4 [2p16.1]  [FUSC000144]  [FUSC000144]  [FUSC000144]
Polymorphisms : SNP, variants
NCBI Variation ViewerRTN4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RTN4
dbVarRTN4
ClinVarRTN4
1000_GenomesRTN4 
Exome Variant ServerRTN4
ExAC (Exome Aggregation Consortium)RTN4 (select the gene name)
Genetic variants : HAPMAP57142
Genomic Variants (DGV)RTN4 [DGVbeta]
Mutations
ICGC Data PortalRTN4 
TCGA Data PortalRTN4 
Broad Tumor PortalRTN4
OASIS PortalRTN4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRTN4 
intOGen PortalRTN4
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch RTN4
DgiDB (Drug Gene Interaction Database)RTN4
DoCM (Curated mutations)RTN4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RTN4 (select a term)
intoGenRTN4
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)2:55199327-55237470  ENSG00000115310
CONAN: Copy Number AnalysisRTN4 
Mutations and Diseases : HGMDRTN4
OMIM604475   
MedgenRTN4
Genetic Testing Registry RTN4
NextProtQ9NQC3 [Medical]
TSGene57142
GENETestsRTN4
Huge Navigator RTN4 [HugePedia]
snp3D : Map Gene to Disease57142
BioCentury BCIQRTN4
ClinGenRTN4
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD57142
Chemical/Pharm GKB GenePA34883
Clinical trialRTN4
Miscellaneous
canSAR (ICR)RTN4 (select the gene name)
Probes
Litterature
PubMed151 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRTN4
EVEXRTN4
GoPubMedRTN4
iHOPRTN4
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Aug 10 18:46:44 CEST 2016

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