Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
BMC Evol Biol
2006 Aug 07;6:60. doi: 10.1186/1471-2148-6-60.
Show Gene links
Show Anatomy links
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
.
???displayArticle.abstract???
BACKGROUND: Tenascins are a family of glycoproteins found primarily in the extracellular matrix of embryos where they help to regulate cell proliferation, adhesion and migration. In order to learn more about their origins and relationships to each other, as well as to clarify the nomenclature used to describe them, the tenascin genes of the urochordate Ciona intestinalis, the pufferfish Tetraodon nigroviridis and Takifugu rubripes and the frog Xenopus tropicalis were identified and their gene organization and predicted protein products compared with the previously characterized tenascins of amniotes.
RESULTS: A single tenascin gene was identified in the genome of C. intestinalis that encodes a polypeptide with domain features common to all vertebrate tenascins. Both pufferfish genomes encode five tenascin genes: two tenascin-C paralogs, a tenascin-R with domain organization identical to mammalian and avian tenascin-R, a small tenascin-X with previously undescribed GK repeats, and a tenascin-W. Four tenascin genes corresponding to tenascin-C, tenascin-R, tenascin-X and tenascin-W were also identified in the X. tropicalis genome. Multiple sequence alignment reveals that differences in the size of tenascin-W from various vertebrate classes can be explained by duplications of specific fibronectin type III domains. The duplicated domains are encoded on single exons and contain putative integrin-binding motifs. A phylogenetic tree based on the predicted amino acid sequences of the fibrinogen-related domains demonstrates that tenascin-C and tenascin-R are the most closely related vertebrate tenascins, with the most conserved repeat and domain organization. Taking all lines of evidence together, the data show that the tenascins referred to as tenascin-Y and tenascin-N are actually members of the tenascin-X and tenascin-W gene families, respectively.
CONCLUSION: The presence of a tenascin gene in urochordates but not other invertebrate phyla suggests that tenascins may be specific to chordates. Later genomic duplication events led to the appearance of four family members in vertebrates: tenascin-C, tenascin-R, tenascin-W and tenascin-X.
Figure 1. The tenascins. Six tenascins have been described in the literature: tenascins-C, -R, -X, -W, -Y and -N. This figure shows the repeat and domain organization of a tenascin that is representative of the group belonging to the genus where it was first described. The shapes found in the diagrams at the right symbolize the N-terminal linker domain (home plate), heptad repeats (zig-zag), EGF-like repeats (diamonds and partial diamonds), FN type III domains (rectangles), and a C-terminal FReD (circle). The serine/proline-rich domains of tenascin-X and tenascin-Y are indicated by an oval.
Figure 2. Ciona intestinalis tenascin. A. The amino acid sequence of a tenascin from C. intestinalis. The N-terminal linker region is at the top, with a signal peptide shown in bold and putative heptad repeats underlined. Between amino acids 208 and 458 are 8 EGF-like repeats. These are followed by 18 FN type III domains between amino acids 459 and 2120. The tryptophan (w), leucine (l) and tyrosine (y) residues that are characteristic of these domains are highlighted and aligned, and a putative integrin-binding motif (rge) found in the third FN type III domain is shown in bold. The C-terminal FReD is composed of amino acids 2128 through 2355. B. The repeat and domain organization of the C. intestinalis tenascin shown in A. A key to the shapes symbolizing each domain can be found in the legend to Figure 1. C. A rabbit antiserum against a recombinant fragment of C. intestinalis tenascin was used to immunostain whole larvae. The antiserum recognized the tunic, a line of matrix in the tail (arrows), and faintly labelled the tail muscles (between the arrows). D. The rabbit preimmune serum inconsistently labelled the tunic but not the line of matrix in tail or the tail muscles.
Figure 3. There are two tenascin-Cs in pufferfish. A. Analysis of the genomic sequences of Tetraodon nigroviridis (T.n.) and Takifugu rubripes (T.r.) reveals that each species of pufferfish had two tenascin-C genes. The repeat and domain organization of the paralogous genes are illustrated here. All four have a putative integrin binding motifs (kgd, rgd or kge) in the third FN type III domain. B. The C-terminal FReDs (underlined in red) of the two tenascin-Cs from Tetraodon nigroviridis are highly conserved. Identical residues are boxed in blue and similar residues are boxed in yellow.
Figure 4. Tetraodon nigroviridis tenascin-X. A. The predicted amino acid sequence of T. nigroviridis tenascin-X. Putative heptad repeats (underlined) are found near the N-terminus. Between amino acids 41 and 86 are one complete are two partial EGF-like repeats. This is followed by a short (48 amino acid) linking region and 7 complete and two partial GK repeats (between amino acids 135 and 270). Between the GK repeats and amino acid 571 is a region rich in charged amino acids. Three complete and one partial FN type III domains are found between amino acids 572 and 884. There is a FReD at the C-terminus. B. The repeat and domain organization of pufferfish tenascin-X. The region between amino acids 87 and 571 is similar to the DUF612 domain of UNC-89. C. The T. nigroviridis tenascin-X gene (TNX) is found between the genes encoding cytochrome p450 21-hydroxylase (cp450), C4 complement and retinoid X receptor beta (RXRB). The same genes overlap or flank tenascin-X genes in birds and mammals.
Figure 5. Tenascin-W diversity is generated by duplications of a FN type III domain. A. The tenascin-W of Tetraodon nigroviridis is predicted to be encoded on 14 exons. The figure shows a schematic of the predicted protein's repeat and domain organization and the corresponding exons. The N-terminal linker is encoded on the first exon. The second exon encodes the heptad repeats and the EGF-like repeats. This is conserved in all of the tenascin-Ws illustrated here. FN type III domains 1, 2 and 4 are encoded on two exons, but the third FN type III domain is encoded on a single exon (shaded). The FReDs of all of the tenascin-Ws is encoded on five exons. B. The full-length predicted tenascin-W of Takifugu rubripes has five FN type III domains. The additional domain is the result of a duplication of the third FN type III domain, which is encoded on a single exon. C, D. The predicted tenascin-Ws of Danio rerio (C) and Gallus gallus (D) have 6 FN type III domains, the apparent consequence of an additional duplication of the third FN type III domain. E, F. In mouse (Mus) and man (Homo) the very large tenascin-W predicted proteins can also be explained by multiple duplications of the third FN type III domain. Note that the first FN type III domains of the pufferfish, but not the other tenascin-Ws, are encoded on two exons (black). The relative sizes of the exons and introns between the different genera are not shown to scale.
Figure 6. Alignment of the duplicated FN type III domains oftenascin-W. The third FN type III domain of Tetraodon nigroviridis tenascin-W has been duplicated one or more times in other tensacin-Ws. Alignment reveals the conservation of sequences within these domains, including putative integrin binding motifs near the N-terminus of the domain (underlined). The region where an integrin-binding RGD sequence in an exposed loop is found in chicken tenascin-C is indicated by asterisks. Several tenascin-Ws have a potentially active KGD motif in this region. At the left is a rooted phylogenetic tree generated by SATCHMO. This analysis indicates that many of the domain duplications took place after the divergence of primate and rodent lineages. Identical amino acids are shaded blue, while similar amino acids are boxed in yellow.
Figure 7. Xenopus tropicalis tenascins. Four tenascins were identified in the X. tropicalis genome. Stick diagrams of the three complete sequences are shown here. The X. tropicalis tenascin-C gene encodes 14.5 EGF-like repeats and 8 FN type III domains. There are no RGD motifs. The domain represented by an oval between the second and third FN type III domains shares sequences similarities with the DUF612 domain of pufferfish tenascin-X and the SP-domain of avian and mammalian tenascin-X. The amphibian tenascin-W contains an RGD domain in an exposed loop in the fourth FN type III domain and a KGD motif in the fifth FN type III domain; these domains appear to have undergone a recent duplication.
Figure 8. Tenascins. Stick diagrams illustrating the hypothetical repeat and domain organizations of tenascins based on genomic sequences. A key to the shapes used can be found in the legend to Figure 1. h, Homo; m, Mus; g, Gallus; t, Tetraodon; x, Xenopus.
Figure 9. A tenascin phylogenetic tree. The amino acid sequences of the FReDs from urochordate, fish, amphibian and mammalian tenascins were used to construct an unrooted molecular phlyogenetic tree. The numbers at the internal nodes are the probability that each branch point is correct. The scale represents 0.100 expected changes. The tree reveals that there are four members of the tenascin family in vertebrates: tenascin-X, tenascin-W, tenascin-C and tenascin-R.
Abi-Rached,
Evidence of en bloc duplication in vertebrate genomes.
2002, Pubmed
Abi-Rached,
Evidence of en bloc duplication in vertebrate genomes.
2002,
Pubmed
Altschul,
Basic local alignment search tool.
1990,
Pubmed
Altschul,
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
1997,
Pubmed
Becker,
Tenascin-R as a repellent guidance molecule for developing optic axons in zebrafish.
2003,
Pubmed
Berger,
Predicting coiled coils by use of pairwise residue correlations.
1995,
Pubmed
Bristow,
Tenascin-X: a novel extracellular matrix protein encoded by the human XB gene overlapping P450c21B.
1993,
Pubmed
Chiquet-Ehrismann,
Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis.
1986,
Pubmed
Chiquet-Ehrismann,
Connective tissues: signalling by tenascins.
2004,
Pubmed
Chiquet-Ehrismann,
The tenascin gene family.
1994,
Pubmed
Chiquet-Ehrismann,
Tenascins: regulation and putative functions during pathological stress.
2003,
Pubmed
Chiquet-Ehrismann,
Tenascins.
2004,
Pubmed
Dehal,
The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins.
2002,
Pubmed
Derr,
The expression of tenascin-C with the AD1 variable repeat in embryonic tissues, cell lines and tumors in various vertebrate species.
1997,
Pubmed
Dörries,
Tenascin mRNA isoforms in the developing mouse brain.
1994,
Pubmed
Edgar,
SATCHMO: sequence alignment and tree construction using hidden Markov models.
2003,
Pubmed
Erickson,
Evolution of the tenascin family--implications for function of the C-terminal fibrinogen-like domain.
1994,
Pubmed
Fischer,
Cell-adhesive responses to tenascin-C splice variants involve formation of fascin microspikes.
1997,
Pubmed
Flück,
Rapid and reciprocal regulation of tenascin-C and tenascin-Y expression by loading of skeletal muscle.
2000,
Pubmed
Ghert,
Tenascin-C splice variant adhesive/anti-adhesive effects on chondrosarcoma cell attachment to fibronectin.
2001,
Pubmed
Groenen,
A consensus linkage map of the chicken genome.
2000,
Pubmed
Gulcher,
An alternatively spliced region of the human hexabrachion contains a repeat of potential N-glycosylation sites.
1989,
Pubmed
Hagios,
Tenascin-Y, a component of distinctive connective tissues, supports muscle cell growth.
1999,
Pubmed
Hagios,
Tenascin-Y: a protein of novel domain structure is secreted by differentiated fibroblasts of muscle connective tissue.
1996,
Pubmed
Huang,
Interference of tenascin-C with syndecan-4 binding to fibronectin blocks cell adhesion and stimulates tumor cell proliferation.
2001,
Pubmed
Hughes,
Concerted evolution of exons and introns in the MHC-linked tenascin-X gene of mammals.
1999,
Pubmed
Humphries,
Mechanisms of VCAM-1 and fibronectin binding to integrin alpha 4 beta 1: implications for integrin function and rational drug design.
1995,
Pubmed
Humtsoe,
A streptococcal collagen-like protein interacts with the alpha2beta1 integrin and induces intracellular signaling.
2005,
Pubmed
Jaillon,
Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype.
2004,
Pubmed
Joester,
The structure and function of tenascins in the nervous system.
2001,
Pubmed
Jones,
A detailed structural model of cytotactin: protein homologies, alternative RNA splicing, and binding regions.
1989,
Pubmed
Jones,
The tenascin family of ECM glycoproteins: structure, function, and regulation during embryonic development and tissue remodeling.
2000,
Pubmed
Kasahara,
Genome dynamics of the major histocompatibility complex: insights from genome paralogy.
1999,
Pubmed
Kent,
BLAT--the BLAST-like alignment tool.
2002,
Pubmed
Korf,
Gene finding in novel genomes.
2004,
Pubmed
Kortschak,
EST analysis of the cnidarian Acropora millepora reveals extensive gene loss and rapid sequence divergence in the model invertebrates.
2003,
Pubmed
Leahy,
Structure of a fibronectin type III domain from tenascin phased by MAD analysis of the selenomethionyl protein.
1992,
Pubmed
Letunic,
SMART 5: domains in the context of genomes and networks.
2006,
Pubmed
Lupas,
Prediction and analysis of coiled-coil structures.
1996,
Pubmed
Mackie,
The distribution of tenascin coincides with pathways of neural crest cell migration.
1988,
Pubmed
,
Xenbase
Matsumoto,
Cluster of fibronectin type III repeats found in the human major histocompatibility complex class III region shows the highest homology with the repeats in an extracellular matrix protein, tenascin.
1992,
Pubmed
McGinnis,
BLAST: at the core of a powerful and diverse set of sequence analysis tools.
2004,
Pubmed
McLysaght,
Extensive genomic duplication during early chordate evolution.
2002,
Pubmed
Meloty-Kapella,
Avian tenascin-W: expression in smooth muscle and bone, and effects on calvarial cell spreading and adhesion in vitro.
2006,
Pubmed
Mercado,
Neurite outgrowth by the alternatively spliced region of human tenascin-C is mediated by neuronal alpha7beta1 integrin.
2004,
Pubmed
Neidhardt,
Tenascin-N: characterization of a novel member of the tenascin family that mediates neurite repulsion from hippocampal explants.
2003,
Pubmed
Olsen,
A collection of amino acid replacement matrices derived from clusters of orthologs.
2005,
Pubmed
Panopoulou,
New evidence for genome-wide duplications at the origin of vertebrates using an amphioxus gene set and completed animal genomes.
2003,
Pubmed
Pearson,
Tenascin: cDNA cloning and induction by TGF-beta.
1988,
Pubmed
Rathjen,
Restrictin: a chick neural extracellular matrix protein involved in cell attachment co-purifies with the cell recognition molecule F11.
1991,
Pubmed
Ronquist,
MrBayes 3: Bayesian phylogenetic inference under mixed models.
2003,
Pubmed
Sambrook,
Characterisation of a gene cluster in Fugu rubripes containing the complement component C4 gene.
2003,
Pubmed
Satou,
A cDNA resource from the basal chordate Ciona intestinalis.
2002,
Pubmed
Scherberich,
Murine tenascin-W: a novel mammalian tenascin expressed in kidney and at sites of bone and smooth muscle development.
2004,
Pubmed
Schultz,
SMART, a simple modular architecture research tool: identification of signaling domains.
1998,
Pubmed
Schweitzer,
Tenascin-C is involved in motor axon outgrowth in the trunk of developing zebrafish.
2005,
Pubmed
Shoguchi,
Fluorescent in situ hybridization to ascidian chromosomes.
2004,
Pubmed
Small,
Three new isoforms of Caenorhabditis elegans UNC-89 containing MLCK-like protein kinase domains.
2004,
Pubmed
Sullivan,
StellaBase: the Nematostella vectensis Genomics Database.
2006,
Pubmed
Suzuki,
Genomic approaches reveal unexpected genetic divergence within Ciona intestinalis.
2005,
Pubmed
Tucker,
Tenascin-Y in the developing and adult avian nervous system.
1999,
Pubmed
Tucker,
Tenascin-Y is concentrated in adult nerve roots and has barrier properties in vitro.
2001,
Pubmed
Weber,
Zebrafish tenascin-W, a new member of the tenascin family.
1998,
Pubmed
Yokosaki,
Identification of the ligand binding site for the integrin alpha9 beta1 in the third fibronectin type III repeat of tenascin-C.
1998,
Pubmed
