Summary: Cache domain
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Cache domain Edit Wikipedia article
|Cache domain (type 2)|
In molecular biology, the cache domain is an extracellular protein domain that is predicted to have a role in small-molecule recognition in a wide range of proteins, including the animal dihydropyridine-sensitive voltage-gated Ca2+ channel alpha-2delta subunit, and various bacterial chemotaxis receptors. The name Cache comes from CAlcium channels and CHEmotaxis receptors. This domain consists of an N-terminal part with three predicted strands and an alpha-helix, and a C-terminal part with a strand dyad followed by a relatively unstructured region. The N-terminal portion of the (unpermuted) Cache domain contains three predicted strands that could form a sheet analogous to that present in the core of the PAS domain structure. Cache domains are particularly widespread in bacteria such as Vibrio cholerae. The animal calcium channel alpha-2delta subunits might have acquired a part of their extracellular domains from a bacterial source. The Cache domain appears to have arisen from the GAF-PAS fold despite their divergent functions.
- Anantharaman V, Aravind L (November 2000). "Cache - a signaling domain common to animal Ca(2+)-channel subunits and a class of prokaryotic chemotaxis receptors". Trends Biochem. Sci. 25 (11): 535–7. doi:10.1016/s0968-0004(00)01672-8. PMID 11084361.
- Anantharaman V, Koonin EV, Aravind L (April 2001). "Regulatory potential, phyletic distribution and evolution of ancient, intracellular small-molecule-binding domains". J. Mol. Biol. 307 (5): 1271–92. doi:10.1006/jmbi.2001.4508. PMID 11292341.
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Cache domain Provide feedback
Double cache domain 1 covers the last three strands from the membrane distal PAS-like domain, the first two strands of the membrane proximal domain, and the connecting elements between the two domains . This domain when present in chemoreceptors recognise several signals such as proteinogenic amino acids, GABA, Histamine and polyamines, decanoic acid, Autoinducer-2, purine derivatives, quaternary amines, citrate and taurine, among others. When associated with histidine kinases, it recognises C3/C4-dicarboxylic acids, Spermine, guanosine and Autoinducer-2 (Mantilla et al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1 https://doi.org/10.1093/femsre/fuab043).
Anantharaman V, Aravind L; , Trends Biochem Sci 2000;25:535-537.: Cache - a signaling domain common to animal Ca(2+)-channel subunits and a class of prokaryotic chemotaxis receptors. PUBMED:11084361 EPMC:11084361
Upadhyay AA, Fleetwood AD, Adebali O, Finn RD, Zhulin IB;, PLoS Comput Biol. 2016;12:e1004862.: Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes. PUBMED:27049771 EPMC:27049771
Internal database links
|SCOOP:||ArlS_N Cache_3-Cache_2 CHASE CHASE7 dCache_2 dCache_3 GAPES1 HAMP MCPsignal sCache_2 sCache_3_2 sCache_3_3 sCache_like|
|Similarity to PfamA using HHSearch:||dCache_2 dCache_3 sCache_like Cache_3-Cache_2 sCache_3_2|
This tab holds annotation information from the InterPro database.
InterPro entry IPR033479
Cache is an extracellular domain that is predicted to have a role in small-molecule recognition in a wide range of proteins, including the animal dihydropyridine-sensitive voltage-gated Ca2 channel alpha-2delta subunit, and various bacterial chemotaxis receptors. The name Cache comes from CAlcium channels and CHEmotaxis receptors.
The Cache domain, also known as the extracellular PAS domain, consists of an N-terminal part with three predicted strands and an alpha-helix, and a C-terminal part with a strand dyad followed by a relatively unstructured region. The N-terminal portion of the Cache domain containing the three predicted strands could form a sheet analogous to that present in the core of the PAS domain structure. Cache domains are particularly widespread in bacteria, such as Vibrio cholerae. The animal calcium channel alpha-2delta subunits might have acquired a part of their extracellular domains from a bacterial source [ PUBMED:11084361 ]. The Cache domain appears to have arisen from the GAF-PAS fold, despite their divergent functions [ PUBMED:11292341 , PUBMED:27049771 ].
This entry represents double cache domain 1, which covers the last three strands from the membrane distal PAS-like domain, the first two strands of the membrane proximal domain, and the connecting elements between the two domains [ PUBMED:27049771 ].
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:
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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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The Cache domain an extracellular domain that is thought to have a role in small-molecule recognition in a wide range of proteins, including the animal Ca(2+)-channel subunits and a class of prokaryotic chemotaxis receptors . It is homologous to, but sufficiently different from the most common intracellular sensor module, the PAS domain. Furthermore, it is suggested that it might have originated from a simpler intracellular PAS/GAF ancestor as a benefit of extracellular sensing .
The clan contains the following 23 members:2CSK_N ArlS_N Cache_3-Cache_2 CHASE CHASE4 CHASE7 CHASE8 dCache_1 dCache_2 dCache_3 Diacid_rec GAPES1 LuxQ-periplasm PhoQ_Sensor sCache_2 sCache_3_2 sCache_3_3 sCache_4 sCache_like SMP_2 Stimulus_sens_1 VGCC_alpha2 YkuI_C
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 and the UniProtKB 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.
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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.
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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.
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Curation and family details
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|Previous IDs:||Cache; Cache_1;|
|Number in seed:||107|
|Number in full:||14842|
|Average length of the domain:||237.40 aa|
|Average identity of full alignment:||12 %|
|Average coverage of the sequence by the domain:||34.85 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||21|
|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.
You can use the tree controls to manipulate how the interactive tree is displayed:
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the dCache_1 domain has been found. There are 93 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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