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TNN (tenascin N)

Identity

Other namesTN-W
TN-N
HGNC TNN
Location 1q25.1
Location_base_pair Starts at 173303617 and ends at 173383825 bp from pter ( according to hg18-Mar_2006).
Local_order tail to tail configuration next to the tenascin-R gene(TNR)

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

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.
  

External links

Nomenclature
HGNCTNN   22942
Entrez_GeneTNN  63923  tenascin N
Cards
AtlasELAVL1ID44237ch19p13
GeneCardsTNN
EnsemblENSG00000120332 [Gene_View]  TNN [Vega]
GenatlasTNN
Genomic and cartography
GoldenPathTNN  -  1q25.1   chr1:173303617-173383825 +  1q23-q24   [Description]    (hg18-Mar_2006)
EnsemblTNN - 1q23-q24 [CytoView]
NCBIMapview
HomoloGeneTNN
Gene and transcription
GenbankAK127044 [ ENTREZ ]
GenbankAK127654 [ ENTREZ ]
GenbankAL049689 [ ENTREZ ]
RefSeqNM_022093 [ SRS ]    NM_022093 [ ENTREZ ]
RefSeqAC_000044 [ SRS ]    AC_000044 [ ENTREZ ]
RefSeqAC_000133 [ SRS ]    AC_000133 [ ENTREZ ]
RefSeqNC_000001 [ SRS ]    NC_000001 [ ENTREZ ]
RefSeqNT_004487 [ SRS ]    NT_004487 [ ENTREZ ]
RefSeqNW_001838533 [ SRS ]    NW_001838533 [ ENTREZ ]
RefSeqNW_926128 [ SRS ]    NW_926128 [ ENTREZ ]
CCDSTNN CCDS - NCBI
AceViewTNN AceView - NCBI
UnigeneHs.156369 [ SRS ]    Hs.156369 [ NCBI ]
Fast-db17591 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtQ9UQP3 [ SRS]    Q9UQP3 [ EXPASY ]     Q9UQP3 [ INTERPRO ]     Q9UQP3 [ UNIPROT ] Q9UQP3 [ VarSplice FASTA ]
PrositePS00022 EGF_1 [ SRS ]    PS00022 EGF_1 [ Expasy ]
PrositePS01186 EGF_2 [ SRS ]    PS01186 EGF_2 [ Expasy ]
PrositePS50026 EGF_3 [ SRS ]    PS50026 EGF_3 [ Expasy ]
PrositePS00514 FIBRIN_AG_C_DOMAIN [ SRS ]    PS00514 FIBRIN_AG_C_DOMAIN [ Expasy ]
PrositePS50853 FN3 [ SRS ]    PS50853 FN3 [ Expasy ]
InterproIPR000742 EGF_3 [ SRS ]    IPR000742 EGF_3 [ EBI ]
InterproIPR013111 EGF_extracell [ SRS ]    IPR013111 EGF_extracell [ EBI ]
InterproIPR013032 EGF_like_reg_CS [ SRS ]    IPR013032 EGF_like_reg_CS [ EBI ]
InterproIPR002181 Fibrinogen_a/b/g_C [ SRS ]    IPR002181 Fibrinogen_a/b/g_C [ EBI ]
InterproIPR008957 Fibronectin_typ-III-like_fold [ SRS ]    IPR008957 Fibronectin_typ-III-like_fold [ EBI ]
InterproIPR003961 FN_III [ SRS ]    IPR003961 FN_III [ EBI ]
CluSTrQ9UQP3
PfamPF07974 EGF_2 [ SRS ]    PF07974 EGF_2 [ Sanger ]    pfam07974 [ NCBI-CDD ]
PfamPF00147 Fibrinogen_C [ SRS ]    PF00147 Fibrinogen_C [ Sanger ]    pfam00147 [ NCBI-CDD ]
PfamPF00041 fn3 [ SRS ]    PF00041 fn3 [ Sanger ]    pfam00041 [ NCBI-CDD ]
SmartSM00186 FBG [EMBL]
SmartSM00060 FN3 [EMBL]
BlocksQ9UQP3
Protein Interaction databases
DIPQ9UQP3
IntActQ9UQP3
Polymorphism : SNP, mutations, diseases
SNPTNN [dbSNP-NCBI]  
SNPNM_022093 [SNP-NCI]  
SNPTNN [GeneSNPs - Utah]  TNN] [HGBASE - SRS]
HAPMAPTNN [HAPMAP]  
HGMDTNN
Genetic AssociationTNN
CDC HuGETNN
General knowledge
Family BrowserTNN [UCSC Family Browser]
SOURCENM_022093
SMDHs.156369
SAGEHs.156369
GOmolecular_function [Amigo]  molecular_function
GOintegrin binding [Amigo]  integrin binding
GOcellular_component [Amigo]  cellular_component
GOproteinaceous extracellular matrix [Amigo]  proteinaceous extracellular matrix
GOcell-matrix adhesion [Amigo]  cell-matrix adhesion
GOsignal transduction [Amigo]  signal transduction
GOaxonogenesis [Amigo]  axonogenesis
GOcell surface [Amigo]  cell surface
GOcell growth [Amigo]  cell growth
GOcell migration [Amigo]  cell migration
GOidentical protein binding [Amigo]  identical protein binding
KEGGCell Communication
KEGGFocal adhesion
KEGGECM-receptor interaction
PubGeneTNN
TreeFamTNN
CTD63923 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeTNN Related clones (RZPD - Berlin)
PubMed
PubMed6 Pubmed reference(s) in Entrez

Bibliography

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
 
Murine tenascin-W: a novel mammalian tenascin expressed in kidney and at sites of bone and smooth muscle development.
Scherberich A, Tucker RP, Samandari E, Brown-Luedi M, Martin D, Chiquet-Ehrismann R.
J Cell Sci. 2004 Feb 1;117(Pt 4):571-81. Epub 2004 Jan 6.
PMID 14709716
 
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
 
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
 
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
 
Tenascin-W is a novel marker for activated tumor stroma in low-grade human breast cancer and influences cell behavior.
Degen M, Brellier F, Kain R, Ruiz C, Terracciano L, Orend G, Chiquet-Ehrismann R.
Canc Res 2007; 67: 9169-9179.
PMID 17909022
 
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.
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written02-2008Martin Degen, Ruth Chiquet-Ehrismann
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland

Citation

This paper should be referenced as such :
Degen M, Chiquet-Ehrismann R . TNN (tenascin N). Atlas Genet Cytogenet Oncol Haematol. February 2008 .
URL : http://AtlasGeneticsOncology.org/Genes/TNNID44209ch1q25.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Dec 6 18:00:18 2008


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