Summary: Teneurin Intracellular Region
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Teneurin Edit Wikipedia article
Teneurins are single-pass transmembrane proteins. The name refers to "ten-a" (from "tenascin-like protein, accessory") and "neurons", the primary site of teneurin expression. Ten-m refers to tenascin-like protein major are type II transmembrane glycoproteins.
Teneurins are highly conserved between Drosophila, C. elegans and vertebrates. In each species they are expressed by a subset of neurons as well as at sites of pattern formation and morphogenesis. In Drosophila, a teneurin known as ten-m or Odz is a pair-rule gene, and its expression is required for normal development. The knockdown of teneurin (ten-1) expression in C. elegans with RNAi leads to abnormal neuronal pathfinding and abnormal development of the gonads.
The intracellular domain of some, if not all, teneurins can be cleaved and transported to the cell nucleus, where it proposed to act as a transcription factor. A peptide derived from the terminus of the extracellular domain shares structural homology with certain neuropeptides.
There are four teneurin genes in vertebrates named teneurin-1 through -4. Other names found in the literature include Odz-1 through -4 and Tenm-1 through -4.
Originally discovered as ten-m and ten-a in Drosophila melanogaster, the teneurin family is conserved from Caenorhabditis elegans (ten-1) to vertebrates, in which four paralogs exist (teneurin-1 to -4 or odz-1 to -4). Their distinct protein domain architecture is highly conserved between invertebrate and vertebrate teneurins, particularly in the extracellular part. The intracellular domains of Ten-a, Ten-m/Odz and C. elegans TEN-1 are significantly different, both in size and structure, from the comparable domains of vertebrate teneurins, but the extracellular domains of all of these proteins are remarkably similar.
Teneurins translocate to the nucleus where they regulate transcriptional activity. Teneurins promote neurite outgrowth and cell adhesion. The intracellular domain interacts with the DNA-binding transcriptional repressors and also regulate the activity of transcription factors.
Additionally, they have been known to interact with the cytoskeleton adaptor protein, CAP/ponsin, suggesting cell signalling roles and regulation of actin organisation.
Ten-m1â€“4, exist as homodimers and undergo homophilic interactions in vertebrates.
C terminal domain
N terminal domain
|Teneurin Intracellular Region|
The teneurin intracellular (IC) domain (âˆ¼300â€“400 aa) is located at the N-terminus and contains a number of conserved putative tyrosine phosphorylation sites, two EF-hand-like calcium-binding motifs, and two polyproline domains. These proline-rich stretches are characteristic of SH3-binding sites. There is considerable divergence between intracellular domains of invertebrate and vertebrate teneurins as well as between different invertebrate proteins.
This domain is found in the intracellular N-terminal region of the teneurin family.
Human genes encoded teneurin domain proteins (TENM1-4) are list in the infoboxes.
- Drabikowski, Krzysztof; Trzebiatowska, Agnieszka; Chiquet-Ehrismann, Ruth (2005-06-01). "ten-1, an essential gene for germ cell development, epidermal morphogenesis, gonad migration, and neuronal pathfinding in Caenorhabditis elegans". Developmental Biology. 282 (1): 27â€“38. doi:10.1016/j.ydbio.2005.02.017. ISSN 0012-1606. PMID 15936327.
- Tucker RP, Chiquet-Ehrismann R, Chevron MP, Martin D, Hall RJ, Rubin BP (January 2001). "Teneurin-2 is expressed in tissues that regulate limb and somite pattern formation and is induced in vitro and in situ by FGF8". Dev. Dyn. 220 (1): 27â€“39. doi:10.1002/1097-0177(2000)9999:9999<::AID-DVDY1084>3.0.CO;2-B. PMID 11146505.
- Young TR, Leamey CA (2009). "Teneurins: important regulators of neural circuitry". Int J Biochem Cell Biol. 41 (5): 990â€“3. doi:10.1016/j.biocel.2008.06.014. PMID 18723111.
- Antinucci P, Nikolaou N, Meyer MP, Hindges R (2013). "Teneurin-3 specifies morphological and functional connectivity of retinal ganglion cells in the vertebrate visual system". Cell Rep. 5 (3): 582â€“92. doi:10.1016/j.celrep.2013.09.045. PMC 3898612. PMID 24183672.
- Minet AD, Rubin BP, Tucker RP, Baumgartner S, Chiquet-Ehrismann R (June 1999). "Teneurin-1, a vertebrate homologue of the Drosophila pair-rule gene ten-m, is a neuronal protein with a novel type of heparin-binding domain". J. Cell Sci. 112 (12): 2019â€“32. PMID 10341219.
- Bagutti C, Forro G, Ferralli J, Rubin B, Chiquet-Ehrismann R (July 2003). "The intracellular domain of teneurin-2 has a nuclear function and represses zic-1-mediated transcription". J. Cell Sci. 116 (Pt 14): 2957â€“66. doi:10.1242/jcs.00603. PMID 12783990.
- Tucker RP, Chiquet-Ehrismann R (February 2006). "Teneurins: a conserved family of transmembrane proteins involved in intercellular signaling during development". Dev. Biol. 290 (2): 237â€“45. doi:10.1016/j.ydbio.2005.11.038. PMID 16406038.
- Tucker RP, Kenzelmann D, Trzebiatowska A, Chiquet-Ehrismann R (2007). "Teneurins: transmembrane proteins with fundamental roles in development". Int. J. Biochem. Cell Biol. 39 (2): 292â€“7. doi:10.1016/j.biocel.2006.09.012. PMID 17095284.
- Kenzelmann D, Chiquet-Ehrismann R, Tucker RP (June 2007). "Teneurins, a transmembrane protein family involved in cell communication during neuronal development" (PDF). Cell. Mol. Life Sci. 64 (12): 1452â€“6. doi:10.1007/s00018-007-7108-9. PMID 17502993.
- Baumgartner S, Martin D, Hagios C, Chiquet-Ehrismann R (August 1994). "Tenm, a Drosophila gene related to tenascin, is a new pair-rule gene". EMBO J. 13 (16): 3728â€“40. doi:10.1002/j.1460-2075.1994.tb06682.x. PMC 395283. PMID 8070401.
- Levine A, Bashan-Ahrend A, Budai-Hadrian O, Gartenberg D, Menasherow S, Wides R (May 1994). "Odd Oz: a novel Drosophila pair rule gene". Cell. 77 (4): 587â€“98. doi:10.1016/0092-8674(94)90220-8. PMID 7514504.
- Tucker RP, Chiquet-Ehrismann R (February 2006). "Teneurins: a conserved family of transmembrane proteins involved in intercellular signaling during development". Dev. Biol. 290 (2): 237â€“45. doi:10.1016/j.ydbio.2005.11.038. PMID 16406038.
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Teneurin Intracellular Region Provide feedback
This family is found in the intracellular N-terminal region of the Teneurin family of proteins. These proteins are 'pair-rule' genes and are involved in tissue patterning, specifically probably neural patterning. The intracellular domain is cleaved in response to homophilic interaction of the extracellular domain, and translocates to the nucleus. Here it probably carries out to some transcriptional regulatory activity (). The length of this region and the conservation suggests that there may be two structural domains here (personal obs:C Yeats).
Bagutti C, Forro G, Ferralli J, Rubin B, Chiquet-Ehrismann R; , J Cell Sci 2003;116:2957-2966.: The intracellular domain of teneurin-2 has a nuclear function and represses zic-1-mediated transcription. PUBMED:12783990 EPMC:12783990
This tab holds annotation information from the InterPro database.
InterPro entry IPR009471
Teneurins are a family of phylogenetically conserved transmembrane glycoproteins expressed during pattern formation and morphogenesis [PUBMED:11146505]. Originally discovered as ten-m and ten-a in Drosophila melanogaster, the teneurin family is conserved from Caenorhabditis elegans (ten-1) to vertebrates, in which four paralogs exist (teneurin-1 to -4 or odz-1 to -4). Their distinct domain architecture is highly conserved between invertebrate and vertebrate teneurins, particularly in the extracellular part. The intracellular domains of Ten-a, Ten-m/Odz and C. elegans Ten-1 are significantly different, both in size and structure, from the comparable domains of vertebrate teneurins, but the extracellular domains of all of these proteins are remarkably similar.
The large C-terminal extracellular domain consists of eight EGF-like repeats (see PROSITEDOC), a region of conserved cysteines and unique YD-repeats. The N-terminal intracellular domain of vertebrate teneurins contains two EF-hand-like calcium-binding motifs and two polyproline regions involved in protein-protein interactions, followed by a single-span transmembrane domain. The intracellular domain is linked to the cytoskeleton through its interaction with the adaptor protein CAP/ponsin and can be cleaved near (or possibly in) the transmembrane domain and transported to the nucleus [PUBMED:12361962, PUBMED:10588872], giving teneurins the potential to act as transcription factors [PUBMED:12783990, PUBMED:12783990]. There is considerable divergence between intracellular domains of invertebrate and vertebrate teneurins as well as between different invertebrate proteins [PUBMED:10341219, PUBMED:12783990, PUBMED:16406038, PUBMED:17095284, PUBMED:17502993].
This domain is found in the intracellular N-terminal region of the Teneurin family.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||integral component of membrane (GO:0016021)|
|Biological process||signal transduction (GO:0007165)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
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We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
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- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Number in seed:||8|
|Number in full:||2037|
|Average length of the domain:||181.80 aa|
|Average identity of full alignment:||34 %|
|Average coverage of the sequence by the domain:||10.98 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||13|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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