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TNN (tenascin N)

Written2008-02Martin Degen, Ruth Chiquet-Ehrismann
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland

(Note : for Links provided by Atlas : click)

Identity

Other aliasTN-W
TN-N
HGNC (Hugo) TNN
LocusID (NCBI) 63923
Atlas_Id 44209
Location 1q25.1  [Link to chromosome band 1q25]
Location_base_pair Starts at 175067858 and ends at 175148066 bp from pter ( according to hg19-Feb_2009)  [Mapping TNN.png]
Local_order tail to tail configuration next to the tenascin-R gene(TNR)
Fusion genes
(updated 2016)
TNN (1q25.1) / UBE2D1 (10q21.1)

DNA/RNA

 
  The distribution of the 19 exons is shown in the upper part, whereas the lengths of exons and introns are indicated in the lower part.
Description The tenascin-W gene consists of 19 exons spanning 80.21 kb of genomic DNA.
Transcription 5005 bp mRNA transcribed in centromeric to telomeric orientation on the forward strand; 3885 bp open reading frame.
The transcript starts with a non-coding exon followed by exon 2, which contains the start codon (ATG) for translation initiation. Exon 1 is located 9448 bp upstream of exon 2.

Protein

 
  Schematic representation of human tenascin-W is shown.
Description Tenascin-W is built up of different structural motifs arranged in a linear order, namely amino-terminal heptad repeats, 3.5 EGF-like repeats, 9 FN III domains, and a carboxyl-terminal fibrinogen globe.
The primary sequence encodes a protein of 1294 amino acids. Amino acids 1-16 represent the secretion signal, amino acids 150-254 constitute the EGF-like repeats, and amino acids 255-1054 account for the FNIII domains. FN III domain number 3 was subject to duplication as indicated by the dark boxes in the schematic representation. Tenascin-W is known to form hexameric structures called hexabrachions.
SDS-Page analysis revealed a molecular weight of 160kDa per subunit under reducing conditions.
So far, there is no evidence for alternative splicing.
Expression Initially, tenascin-W was identified in zebrafish where it was expressed in migrating cells of sclerotomal and neural crest origin. More recently, tenascin-W was characterized in mouse and chicken during embryogenesis as well as in the adult organism. These studies revealed that tenascin-W, similar to tenascin-C, shows tight regulation during development and in the adult. Immunohistochemistry showed prominent expression in the developing and adult metanephric kidney, developing and adult periosteum around ribs, and transient expression in smooth muscles of the developing gut, often but not always overlapping with tenascin-C expression. Furthermore, tenascin-W is highly expressed in the tumor stroma in different solid tumors.
Tenascin-W is most likely produced and secreted by mesenchymal cells such as fibroblasts and osteoblasts.
Known stimuli that induce tenascin-W expression include so far tumor necrosis factor alpha (TNFα) and bone morphogenetic protein 2 (BMP2).
Localisation Extracellular matrix.
Function Adhesion: Tenascin-W is an adhesive substratum for some cells (osteoblasts, fibroblasts), while others cannot attach and spread on tenascin-W.
Migration: Tenascin-W stimulates the migratory behavior of cells.
Homology Tenascin-W belongs to the tenascin family, which is a highly conserved family of large oligomeric extracellular matrix proteins. Vertebrate genomes harbor four tenascin genes, which have been termed tenascin-C, tenascin-XB (TNXB), tenascin-R, and tenascin-W.
Human tenascin-W shows high sequence conservation with mouse tenascin-W.

Implicated in

Note
  
Entity Breast cancer
Oncogenesis Tenascin-W is highly expressed in a large fraction of breast cancer patients whereas it is not detectable in normal human mammary tissue. Expression in tumors correlated with tumor grade. There is statistically significant higher mean expression of tenascin-W in low-grade tumors (Grade1/Grade2) compared to high-grade tumors (Grade3).
Tenascin-W is produced in the stromal compartment, most likely by cancer-associated fibroblasts, which are part of a tumor permissive microenvironment that facilitates tumor cell migration. In vitro, presence of tenascin-W stimulated breast cancer cell migration.
Benign tumors as well as carcinomas do express tenascin-W.
Furthermore, tenascin-W is elevated in sera of breast cancer patients compared to that of healthy volunteers.
Tenascin-W is postulated to be a marker for conversion of the normal physiological stroma to an activated stroma in breast cancer.
  
  
Entity Colorectal cancer
Oncogenesis Tenascin-W is highly expressed in colorectal cancer patients whereas it is not detectable in the normal colon mucosa. Furthermore, mean tenascin-W level in sera of colorectal cancer patients is statistically increased compared to that in sera of healthy volunteers. Follow-up studies of colorectal cancer patients revealed that 4 out of 5 patients who developed tumor recurrence after treatment showed high tenascin-W levels in their sera. Thus, tenascin-W might have prognostic value as a serum tumor marker.
  

Bibliography

Tenascin-W, a new marker of cancer stroma, is elevated in sera of colon and breast cancer patients.
Degen M, Brellier F, Schenk S, Driscoll R, Zaman K, Stupp R, Tornillo L, Terracciano L, Chiquet-Ehrismann R, Rüegg C, Seelentag W.
Int J Cancer in press.
 
Avian tenascin-W: expression in smooth muscle and bone, and effects on calvarial cell spreading and adhesion in vitro.
Meloty-Kapella C, Degen M, Chiquet-Ehrismann R, Tucker RP.
Dev Dyn. 2006 Jun;235(6):1532-42.
PMID 16534782
 
Tenascin-W is found in malignant mammry tumors, promotes alpha8 integrin-dependent motility and requires p38MAPK activity for BMP-2 and TNF alpha induced expression in vitro.
Scherberich A, Tucker RP, Degen M, Brown-Luedi M, Andres AC, Chiquet-Ehrismann R.
Oncogene. 2005 Feb 24;24(9):1525-32.
PMID 15592496
 
Phylogenetic analysis of the tenascin gene family: evidence of origin early in the chordate lineage.
Tucker RP, Drabikowski K, Hess JF, Ferralli J, Chiquet-Ehrismann R, Adams JC.
BMC Evol Biol. 2006 Aug 7;6:60.
PMID 16893461
 
Zebrafish tenascin-W, a new member of the tenascin family.
Weber P, Montag D, Schachner M.
J Neurobiol. 1998 Apr;35(1):1-16.
PMID 9552162
 

Citation

This paper should be referenced as such :
Degen, M ; Chiquet-Ehrismann, R
TNN (tenascin N)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(6):449-451.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TNNID44209ch1q25.html


External links

Nomenclature
HGNC (Hugo)TNN   22942
Cards
AtlasTNNID44209ch1q25
Entrez_Gene (NCBI)TNN  63923  tenascin N
AliasesTN-W
GeneCards (Weizmann)TNN
Ensembl hg19 (Hinxton)ENSG00000120332 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000120332 [Gene_View]  chr1:175067858-175148066 [Contig_View]  TNN [Vega]
ICGC DataPortalENSG00000120332
TCGA cBioPortalTNN
AceView (NCBI)TNN
Genatlas (Paris)TNN
WikiGenes63923
SOURCE (Princeton)TNN
Genetics Home Reference (NIH)TNN
Genomic and cartography
GoldenPath hg38 (UCSC)TNN  -     chr1:175067858-175148066 +  1q25.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TNN  -     1q25.1   [Description]    (hg19-Feb_2009)
EnsemblTNN - 1q25.1 [CytoView hg19]  TNN - 1q25.1 [CytoView hg38]
Mapping of homologs : NCBITNN [Mapview hg19]  TNN [Mapview hg38]
Gene and transcription
Genbank (Entrez)AK127044 AK127654 AL049689 BC136619 BC144305
RefSeq transcript (Entrez)NM_022093
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)TNN
Cluster EST : UnigeneHs.156369 [ NCBI ]
CGAP (NCI)Hs.156369
Alternative Splicing GalleryENSG00000120332
Gene ExpressionTNN [ NCBI-GEO ]   TNN [ EBI - ARRAY_EXPRESS ]   TNN [ SEEK ]   TNN [ MEM ]
Gene Expression Viewer (FireBrowse)TNN [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)63923
GTEX Portal (Tissue expression)TNN
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UQP3   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9UQP3  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UQP3
Splice isoforms : SwissVarQ9UQP3
PhosPhoSitePlusQ9UQP3
Domaine pattern : Prosite (Expaxy)EGF_1 (PS00022)    EGF_2 (PS01186)    FIBRINOGEN_C_1 (PS00514)    FIBRINOGEN_C_2 (PS51406)    FN3 (PS50853)   
Domains : Interpro (EBI)EGF-like_CS    EGF-like_dom    Fibrinogen_a/b/g_C_1    Fibrinogen_a/b/g_C_2    Fibrinogen_a/b/g_C_dom    Fibrinogen_CS    FN3_dom    Ig-like_fold    TNW   
Domain families : Pfam (Sanger)Fibrinogen_C (PF00147)    fn3 (PF00041)   
Domain families : Pfam (NCBI)pfam00147    pfam00041   
Domain families : Smart (EMBL)EGF (SM00181)  FBG (SM00186)  FN3 (SM00060)  
Conserved Domain (NCBI)TNN
DMDM Disease mutations63923
Blocks (Seattle)TNN
SuperfamilyQ9UQP3
Human Protein AtlasENSG00000120332
Peptide AtlasQ9UQP3
IPIIPI00010814   IPI00922500   
Protein Interaction databases
DIP (DOE-UCLA)Q9UQP3
IntAct (EBI)Q9UQP3
FunCoupENSG00000120332
BioGRIDTNN
STRING (EMBL)TNN
ZODIACTNN
Ontologies - Pathways
QuickGOQ9UQP3
Ontology : AmiGOosteoblast development  molecular_function  integrin binding  cellular_component  proteinaceous extracellular matrix  cell-matrix adhesion  axonogenesis  cell surface  cell growth  cell migration  negative regulation of osteoblast proliferation  identical protein binding  negative regulation of osteoblast differentiation  negative regulation of canonical Wnt signaling pathway involved in osteoblast differentiation  
Ontology : EGO-EBIosteoblast development  molecular_function  integrin binding  cellular_component  proteinaceous extracellular matrix  cell-matrix adhesion  axonogenesis  cell surface  cell growth  cell migration  negative regulation of osteoblast proliferation  identical protein binding  negative regulation of osteoblast differentiation  negative regulation of canonical Wnt signaling pathway involved in osteoblast differentiation  
Pathways : KEGGPI3K-Akt signaling pathway    Focal adhesion    ECM-receptor interaction    MicroRNAs in cancer   
REACTOMEQ9UQP3 [protein]
REACTOME PathwaysR-HSA-3000178 [pathway]   
NDEx NetworkTNN
Atlas of Cancer Signalling NetworkTNN
Wikipedia pathwaysTNN
Orthology - Evolution
OrthoDB63923
GeneTree (enSembl)ENSG00000120332
Phylogenetic Trees/Animal Genes : TreeFamTNN
HOVERGENQ9UQP3
HOGENOMQ9UQP3
Homologs : HomoloGeneTNN
Homology/Alignments : Family Browser (UCSC)TNN
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTNN [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TNN
dbVarTNN
ClinVarTNN
1000_GenomesTNN 
Exome Variant ServerTNN
ExAC (Exome Aggregation Consortium)TNN (select the gene name)
Genetic variants : HAPMAP63923
Genomic Variants (DGV)TNN [DGVbeta]
DECIPHERTNN [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTNN 
Mutations
ICGC Data PortalTNN 
TCGA Data PortalTNN 
Broad Tumor PortalTNN
OASIS PortalTNN [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTNN  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTNN
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 TNN
DgiDB (Drug Gene Interaction Database)TNN
DoCM (Curated mutations)TNN (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TNN (select a term)
intoGenTNN
NCG5 (London)TNN
Cancer3DTNN(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM
Orphanet
MedgenTNN
Genetic Testing Registry TNN
NextProtQ9UQP3 [Medical]
TSGene63923
GENETestsTNN
Target ValidationTNN
Huge Navigator TNN [HugePedia]
snp3D : Map Gene to Disease63923
BioCentury BCIQTNN
ClinGenTNN
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD63923
Chemical/Pharm GKB GenePA134973710
Clinical trialTNN
Miscellaneous
canSAR (ICR)TNN (select the gene name)
Probes
Litterature
PubMed12 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTNN
EVEXTNN
GoPubMedTNN
iHOPTNN
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Jun 7 12:16:52 CEST 2017

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