Summary: Ion channel regulatory protein UNC-93
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Ion channel regulatory protein UNC-93 Provide feedback
The proteins in this family are represented by UNC-93 from Caenorhabditis elegans and also includes protein unc-93 homologue A (UNC93A), protein unc-93 homologue B1 (UNC93B1), and UNC93-like protein MFSD11 (also called major facilitator superfamily domain- containing protein 11 or protein ET). UNC-93 colocalizes with SUP-10 and SUP-9 within muscle cells. UNC-93 acts as a regulatory subunit of a multi-subunit potassium channel complex that may function in coordinating muscle contraction in C. elegans . UNC93B1 controls intracellular trafficking and transport of a subset of Toll-like receptors (TLRs), including TLR3, TLR7 and TLR9, from the endoplasmic reticulum to endolysosomes where they can engage pathogen nucleotides and activate signaling cascades . MFSD11 is ubiquitously expressed in the periphery and the central nervous system of mice, where it is expressed in excitatory and inhibitory mouse brain neurons .
de la Cruz IP, Levin JZ, Cummins C, Anderson P, Horvitz HR; , J Neurosci. 2003;23:9133-9145.: sup-9, sup-10, and unc-93 may encode components of a two-pore K+ channel that coordinates muscle contraction in Caenorhabditis elegans. PUBMED:14534247 EPMC:14534247
Wang JQ, Beutler B, Goodnow CC, Horikawa K;, Blood. 2016;128:1604-1608.: Inhibiting TLR9 and other UNC93B1-dependent TLRs paradoxically increases accumulation of MYD88L265P plasmablasts in vivo. PUBMED:27458005 EPMC:27458005
Perland E, Lekholm E, Eriksson MM, Bagchi S, Arapi V, Fredriksson R;, PLoS One. 2016;11:e0156912.: The Putative SLC Transporters Mfsd5 and Mfsd11 Are Abundantly Expressed in the Mouse Brain and Have a Potential Role in Energy Homeostasis. PUBMED:27272503 EPMC:27272503
Internal database links
|SCOOP:||MFS_1 MFS_1_like MFS_2 MFS_3 OATP PUCC Sugar_tr TRI12|
|Similarity to PfamA using HHSearch:||Sugar_tr MFS_1 MFS_1|
This tab holds annotation information from the InterPro database.
InterPro entry IPR010291
The proteins in this family are represented by UNC-93 from Caenorhabditis elegans and also includes protein unc-93 homologue A (UNC93A), protein unc-93 homologue B1 (UNC93B1), and UNC93-like protein MFSD11 (also called major facilitator superfamily domain-containing protein 11 or protein ET). UNC-93 colocalizes with SUP-10 and SUP-9 within muscle cells. UNC-93 acts as a regulatory subunit of a multi-subunit potassium channel complex that may function in coordinating muscle contraction in C. elegans [ PUBMED:14534247 ]. UNC93B1 controls intracellular trafficking and transport of a subset of Toll-like receptors (TLRs), including TLR3, TLR7 and TLR9, from the endoplasmic reticulum to endolysosomes where they can engage pathogen nucleotides and activate signaling cascades [ PUBMED:27458005 ]. MFSD11 is ubiquitously expressed in the periphery and the central nervous system of mice, where it is expressed in excitatory and inhibitory mouse brain neurons [ PUBMED:27272503 ].
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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The major facilitator superfamily (MFS) is one of the two largest families of membrane transporters found on Earth . It is present ubiquitously in bacteria, archaea, and eukarya and includes members that can function by solute uniport, solute/cation symport, solute/cation antiport and/or solute/solute antiport with inwardly and/or outwardly directed polarity . All permeases of the MFS possess either 12 or 14 transmembrane helices .
The clan contains the following 26 members:Acatn ATG22 BT1 CLN3 DUF5690 Folate_carrier FPN1 LacY_symp MFS_1 MFS_1_like MFS_2 MFS_3 MFS_4 MFS_5 MFS_Mycoplasma Nodulin-like Nuc_H_symport Nucleoside_tran OATP PTR2 PUCC Sugar_tr TLC TRI12 UNC-93 UVB_sens_prot
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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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.
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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.
|Seed source:||Pfam-B_4965 (release 9.0)|
|Previous IDs:||DUF895; UNC-93_Ce;|
|Author:||Moxon SJ , Pollington J|
|Number in seed:||9|
|Number in full:||5209|
|Average length of the domain:||294.00 aa|
|Average identity of full alignment:||18 %|
|Average coverage of the sequence by the domain:||68.25 %|
|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:||19|
|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.
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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.
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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.
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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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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 UNC-93 domain has been found. There are 1 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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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.
The structural model below was generated by the Baker group with the trRosetta software using the Pfam UniProt multiple sequence alignment.
The InterPro website shows the contact map for the Pfam SEED alignment. Hovering or clicking on a contact position will highlight its connection to other residues in the alignment, as well as on the 3D structure.
- View the contact map and structural model in InterPro
- Download the model in PDB format
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