Summary: TIR domain
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TIR domain Provide feedback
This is a family of Toll-like receptors.
Internal database links
SCOOP: | DUF1863 DUF4062 Nuc_deoxyrib_tr SEFIR TIR TIR-like |
Similarity to PfamA using HHSearch: | TIR SEFIR DUF1863 TIR-like DUF4062 |
This tab holds annotation information from the InterPro database.
InterPro entry IPR000157
Toll proteins or Toll-like receptors (TLRs) and the interleukin-1 receptor (IL-1R) superfamily are both involved in innate antibacterial and antifungal immunity in insects as well as in mammals. These receptors share a conserved cytoplasmic domain of approximately 200 amino acids, known as the Toll/IL-1R homologous region (TIR). The similarity between TLRs and IL-1Rs is not restricted to sequence homology since these proteins also share a similar signaling pathway. They both induce the activation of a Rel type transcription factor via an adaptor protein and a protein kinase [PUBMED:10231569]. Interestingly, MyD88, a cytoplasmic adaptor protein found in mammals, contains a TIR domain associated to a DEATH domain [PUBMED:8621445, PUBMED:9374458, PUBMED:10679407]. Besides the mammalian and Drosophila proteins, a TIR domain is also found in a number of plant cytoplasmic proteins implicated in host defense [Van der Biezen E.A., Jones J.D., Trends Biochem. Sci. 23:454-456(1998)].
Site directed mutagenesis and deletion analysis have shown that the TIR domain is essential for Toll and IL-1R activities. Sequence analysis have revealed the presence of three highly conserved regions among the different members of the family: box 1 (FDAFISY), box 2 (GYKLC-RD-PG), and box 3 (a conserved W surrounded by basic residues). It has been proposed that boxes 1 and 2 are involved in the binding of proteins involved in signalling, whereas box 3 is primarily involved in directing localization of receptor, perhaps through interactions with cytoskeletal elements [PUBMED:10671496].
Resolution of the crystal structures of the TIR domains of human Toll-like receptors 1 and 2 has shown that they contain a central five-stranded parallel beta-sheet that is surrounded by a total of five helices on both sides [PUBMED:11081518].
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
Molecular function | protein binding (GO:0005515) |
Biological process | signal transduction (GO:0007165) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan STIR (CL0173), which has the following description:
Both members of this clan are thought to be involved in TOLL/IL1R-like pathways, by mediating protein-protein interactions between pathway components. The N-termini of SEFIR and TIR domains are similar, but the domains are more divergent towards the C-terminus [1].
The clan contains the following 6 members:
DUF1863 SEFIR TIR TIR-like TIR_2 TIR_3Alignments
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...
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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.
Seed (458) |
Full (7437) |
Representative proteomes | UniProt (22780) |
NCBI (72301) |
Meta (255) |
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RP15 (1826) |
RP35 (3984) |
RP55 (7107) |
RP75 (10857) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
— not available.
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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.
Seed (458) |
Full (7437) |
Representative proteomes | UniProt (22780) |
NCBI (72301) |
Meta (255) |
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RP15 (1826) |
RP35 (3984) |
RP55 (7107) |
RP75 (10857) |
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Raw Stockholm | |||||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
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...
Trees
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.
Curation
Seed source: | Jackhmmer:Q47BW0 |
Previous IDs: | none |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Coggill P |
Number in seed: | 458 |
Number in full: | 7437 |
Average length of the domain: | 124.70 aa |
Average identity of full alignment: | 16 % |
Average coverage of the sequence by the domain: | 20.96 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 121 | ||||||||||||
Family (HMM) version: | 7 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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Interactions
There is 1 interaction for this family. More...
TIR_2Structures
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 TIR_2 domain has been found. There are 53 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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