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1  structure 147  species 0  interactions 357  sequences 6  architectures

Family: TIR_3 (PF18567)

Summary: Toll/interleukin-1 receptor domain

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This is the Wikipedia entry entitled "Toll-Interleukin receptor". More...

Toll-Interleukin receptor Edit Wikipedia article

TIR domain
PDB 2js7 EBI.png
Structure of the MyD88 TIR domain
Identifiers
SymbolTIR
PfamPF01582
InterProIPR000157
SCOPe1fyv / SUPFAM
OPM superfamily289
OPM protein2mk9
Membranome7

The Toll/interleukin-1 receptor (TIR) homology domain is an intracellular signaling domain found in MyD88, interleukin-1 receptors, Toll receptors and many plant R proteins. It contains three highly conserved regions, and mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction components. TIR-like motifs are also found in plant proteins thought to be involved in resistance to disease. When activated, TIR domains recruit cytoplasmic adaptor proteins MyD88 (UniProt Q99836) and TOLLIP (Toll interacting protein, UniProt Q9H0E2). In turn, these associate with various kinases to set off signaling cascades.

In Drosophila melanogaster the Toll protein is involved in establishment of dorso-ventral polarity in the embryo. In addition, members of the Toll family play a key role in innate antibacterial and antifungal immunity in insects as well as in mammals. These proteins are type-I transmembrane receptors that share an intracellular 200 residue domain with the interleukin-1 receptor (IL-1R), the Toll/IL-1R homologous region (TIR). The similarity between Toll-like receptors (TLRs) and IL-1R 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.[1] MyD88, a cytoplasmic adaptor protein found in mammals, contains a TIR domain associated to a DEATH domain (see InterProIPR000488).[1][2][3] Besides the mammalian and Drosophila melanogaster proteins, a TIR domain is also found in a number of plant proteins implicated in host defense.[4] As MyD88, these proteins are cytoplasmic.

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 signaling, whereas box 3 is primarily involved in directing localization of receptor, perhaps through interactions with cytoskeletal elements.[5]

Subfamilies

Human proteins containing this domain

IL18R1; IL18RAP; IL1R1; IL1RAP; IL1RAPL1; IL1RAPL2; IL1RL1; IL1RL2; MYD88; SIGIRR; TLR1; TLR10; TLR2; TLR3; TLR4; TLR5; TLR6; TLR7; TLR8; TLR9;

References

  1. ^ a b Bonnert TP, Garka KE, Parnet P, Sims JE, Mitcham JL, Gerhart MJ, Slack JL, Gayle MA, Dower SK (1996). "T1/ST2 signaling establishes it as a member of an expanding interleukin-1 receptor family". J. Biol. Chem. 271 (10): 5777–5783. doi:10.1074/jbc.271.10.5777. PMID 8621445.
  2. ^ Dixit VM, Muzio M, Ni J, Feng P (1997). "IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling". Science. 278 (5343): 1612–1615. doi:10.1126/science.278.5343.1612. PMID 9374458.
  3. ^ Anderson KV (2000). "Toll signaling pathways in the innate immune response". Curr. Opin. Immunol. 12 (1): 13–19. doi:10.1016/s0952-7915(99)00045-x. PMID 10679407.
  4. ^ Van der Biezen EA, Jones JD (1998). "Plant disease-resistance proteins and the gene-for-gene concept". Trends Biochem. Sci. 23 (12): 454–456. doi:10.1016/s0968-0004(98)01311-5. PMID 9868361.
  5. ^ Bonnert TP, Sims JE, Schooley K, Mitcham JL, Slack JL, Dower SK, Qwarnstrom EE (2000). "Identification of two major sites in the type I interleukin-1 receptor cytoplasmic region responsible for coupling to pro-inflammatory signaling pathways". J. Biol. Chem. 275 (7): 4670–4678. doi:10.1074/jbc.275.7.4670. PMID 10671496.
This article incorporates text from the public domain Pfam and InterPro: IPR000157

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Toll/interleukin-1 receptor domain Provide feedback

This is a Toll/interleukin-1 receptor (TIR) domain found in the N-terminal region of B-cell adaptor for phosphoinositide 3-kinase (BCAP). BCAP functions in linking the B-cell receptor (BCR) and the co-receptor CD19 to the activation of PI3K via interaction with the SH2 domains on the regulatory p85 subunit. BCAP TIR associates with the MAL/TIRAP adaptor and the TIR domains of Toll-like receptors (TLRs) [1].

Literature references

  1. Halabi S, Sekine E, Verstak B, Gay NJ, Moncrieffe MC;, J Biol Chem. 2017;292:652-660.: Structure of the Toll/Interleukin-1 Receptor (TIR) Domain of the B-cell Adaptor That Links Phosphoinositide Metabolism with the Negative Regulation of the Toll-like Receptor (TLR) Signalosome. PUBMED:27909057 EPMC:27909057


This tab holds annotation information from the InterPro database.

InterPro entry IPR041340

This is a Toll/interleukin-1 receptor (TIR) domain found in the N-terminal region of B-cell adaptor for phosphoinositide 3-kinase (PIK3AP1 or BCAP). BCAP functions in linking the B-cell receptor (BCR) and the co-receptor CD19 to the activation of PI3K via interaction with the SH2 domains on the regulatory p85 subunit. BCAP TIR associates with the MAL/TIRAP adaptor and the TIR domains of Toll-like receptors (TLRs) [PUBMED:27909057].

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_3

Alignments

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
(26)
Full
(357)
Representative proteomes UniProt
(538)
NCBI
(1149)
Meta
(0)
RP15
(26)
RP35
(68)
RP55
(206)
RP75
(370)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(26)
Full
(357)
Representative proteomes UniProt
(538)
NCBI
(1149)
Meta
(0)
RP15
(26)
RP35
(68)
RP55
(206)
RP75
(370)
Alignment:
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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
(26)
Full
(357)
Representative proteomes UniProt
(538)
NCBI
(1149)
Meta
(0)
RP15
(26)
RP35
(68)
RP55
(206)
RP75
(370)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download   Download    

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.

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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 View help on the curation process

Seed source: ECOD:EUF08611
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: El-Gebali S
Number in seed: 26
Number in full: 357
Average length of the domain: 128.10 aa
Average identity of full alignment: 40 %
Average coverage of the sequence by the domain: 17.18 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.1 26.1
Trusted cut-off 26.1 29.2
Noise cut-off 25.2 25.4
Model length: 131
Family (HMM) version: 2
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence

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Structures

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_3 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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