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Toll/Interleukin receptor TIR domain superfamily

SCOP classification
Root:   SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:   Alpha and beta proteins (a/b) [ 51349] (147)
Fold:   Flavodoxin-like [ 52171] (15)
Superfamily:   Toll/Interleukin receptor TIR domain [ 52200]
Families:   Toll/Interleukin receptor TIR domain [ 52201] (2)


Superfamily statistics
Genomes (781) Uniprot 2017_06 genome PDB chains (SCOP 1.75)
Domains 9,716 25,890 4
Proteins 9,285 25,118 4


Functional annotation
General category Regulation
Detailed category Signal transduction

Document:
Function annotation of SCOP domain superfamilies

Gene Ontology (high-quality)

(show details)
GO termFDR (singleton)FDR (all)SDFO levelAnnotation (direct or inherited)
Biological Process (BP)biological regulation0.00030240Least InformativeDirect
Biological Process (BP)response to stimulus0.024630Least InformativeInherited
Biological Process (BP)immune system process0.00000062180Moderately InformativeDirect
Biological Process (BP)multi-organism process0.0027950Moderately InformativeInherited
Biological Process (BP)regulation of response to stimulus0.0014970Moderately InformativeInherited
Biological Process (BP)response to biotic stimulus0.0017690Moderately InformativeInherited
Biological Process (BP)response to external stimulus0.01320Moderately InformativeInherited
Biological Process (BP)positive regulation of immune system process0.000070080InformativeDirect
Biological Process (BP)response to bacterium0.000026090.00000005795InformativeDirect
Biological Process (BP)regulation of immune response0.0000000020260InformativeDirect

Document: GO annotation of SCOP domains

Gene Ontology (high-coverage)

(show details)
GO term FDR (all) SDFO level Annotation (direct or inherited)
Biological Process (BP) response to stimulus 0 Least Informative Direct
Biological Process (BP) biological regulation 0 Least Informative Direct
Biological Process (BP) single-organism cellular process 1 Least Informative Inherited
Biological Process (BP) multicellular organismal process 0.444 Least Informative Inherited
Biological Process (BP) macromolecule metabolic process 1 Least Informative Inherited
Biological Process (BP) primary metabolic process 1 Least Informative Inherited
Biological Process (BP) organonitrogen compound metabolic process 1 Least Informative Inherited
Biological Process (BP) immune system process 0 Moderately Informative Direct
Biological Process (BP) defense response 0 Moderately Informative Direct
Biological Process (BP) cell communication 0 Moderately Informative Direct
Biological Process (BP) response to external stimulus 0 Moderately Informative Direct
Biological Process (BP) response to biotic stimulus 0 Moderately Informative Direct
Biological Process (BP) response to organic substance 0.00000000001383 Moderately Informative Direct
Biological Process (BP) regulation of cellular biosynthetic process 0.0001488 Moderately Informative Direct
Biological Process (BP) macromolecule localization 0.000005624 Moderately Informative Direct
Biological Process (BP) single organism signaling 0 Moderately Informative Direct
Biological Process (BP) positive regulation of cellular process 0.00001613 Moderately Informative Direct
Biological Process (BP) regulation of response to stimulus 0 Moderately Informative Direct
Biological Process (BP) regulation of multicellular organismal process 0.000003054 Moderately Informative Direct
Biological Process (BP) regulation of protein metabolic process 0.000000002907 Moderately Informative Direct
Biological Process (BP) multi-organism process 0 Moderately Informative Direct
Biological Process (BP) organic substance transport 0.0004742 Moderately Informative Direct
Biological Process (BP) nitrogen compound transport 0.00001693 Moderately Informative Direct
Biological Process (BP) negative regulation of cellular process 1 Moderately Informative Inherited
Biological Process (BP) regulation of cell communication 0.05023 Moderately Informative Inherited
Biological Process (BP) regulation of signaling 0.07062 Moderately Informative Inherited
Biological Process (BP) regulation of localization 0.9993 Moderately Informative Inherited
Biological Process (BP) response to endogenous stimulus 1 Moderately Informative Inherited
Biological Process (BP) regulation of molecular function 0.5912 Moderately Informative Inherited
Biological Process (BP) response to abiotic stimulus 1 Moderately Informative Inherited
Biological Process (BP) cellular response to chemical stimulus 1 Moderately Informative Inherited
Biological Process (BP) regulation of developmental process 1 Moderately Informative Inherited
Biological Process (BP) regulation of nucleobase-containing compound metabolic process 1 Moderately Informative Inherited
Biological Process (BP) regulation of gene expression 1 Moderately Informative Inherited
Biological Process (BP) regulation of biological quality 1 Moderately Informative Inherited
Biological Process (BP) single-organism transport 0.01485 Moderately Informative Inherited
Biological Process (BP) reproduction 0.6567 Moderately Informative Inherited
Biological Process (BP) positive regulation of metabolic process 0.2553 Moderately Informative Inherited
Biological Process (BP) regulation of macromolecule biosynthetic process 0.004477 Moderately Informative Inherited
Biological Process (BP) regulation of cellular component organization 0.8372 Moderately Informative Inherited
Biological Process (BP) cellular localization 1 Moderately Informative Inherited
Biological Process (BP) response to oxygen-containing compound 0.04571 Moderately Informative Inherited
Biological Process (BP) anatomical structure morphogenesis 1 Moderately Informative Inherited
Biological Process (BP) animal organ development 0.9958 Moderately Informative Inherited
Biological Process (BP) tissue development 1 Moderately Informative Inherited
Biological Process (BP) cell differentiation 0.1807 Moderately Informative Inherited
Biological Process (BP) cellular protein modification process 1 Moderately Informative Inherited
Biological Process (BP) cell activation 0 Informative Direct
Biological Process (BP) regulation of cytokine production 0 Informative Direct
Biological Process (BP) positive regulation of immune system process 0 Informative Direct
Biological Process (BP) immune response 0 Informative Direct
Biological Process (BP) response to bacterium 0.00000005795 Informative Direct
Biological Process (BP) positive regulation of macromolecule biosynthetic process 0.00000002465 Informative Direct
Biological Process (BP) protein transport 0.00000009073 Informative Direct
Biological Process (BP) positive regulation of cellular biosynthetic process 0.000000000001621 Informative Direct
Biological Process (BP) regulation of defense response 0 Informative Direct
Biological Process (BP) regulation of protein modification process 0.00002212 Informative Direct
Biological Process (BP) secretion by cell 0.00000000004915 Informative Direct
Biological Process (BP) regulation of phosphorylation 0.000007682 Informative Direct
Biological Process (BP) regulation of cellular component biogenesis 0.00002247 Informative Direct
Biological Process (BP) regulation of immune response 0 Informative Direct
Biological Process (BP) negative regulation of transport 0.0006359 Informative Direct
Biological Process (BP) positive regulation of multicellular organismal process 0.0000001458 Informative Direct
Biological Process (BP) regulation of peptide transport 0.0005421 Informative Direct
Biological Process (BP) regulation of secretion 0.00255 Informative Inherited
Biological Process (BP) regulation of intracellular signal transduction 0.1088 Informative Inherited
Biological Process (BP) negative regulation of cell communication 0.02341 Informative Inherited
Biological Process (BP) negative regulation of signaling 0.02067 Informative Inherited
Biological Process (BP) negative regulation of response to stimulus 1 Informative Inherited
Biological Process (BP) positive regulation of phosphate metabolic process 0.2087 Informative Inherited
Biological Process (BP) positive regulation of cellular protein metabolic process 0.9455 Informative Inherited
Biological Process (BP) cellular response to oxygen-containing compound 0.003257 Informative Inherited
Biological Process (BP) epithelium development 0.7581 Informative Inherited
Biological Process (BP) positive regulation of developmental process 1 Informative Inherited
Biological Process (BP) regulation of nervous system development 0.01863 Informative Inherited
Biological Process (BP) interspecies interaction between organisms 1 Informative Inherited
Biological Process (BP) positive regulation of signal transduction 1 Informative Inherited
Biological Process (BP) response to nitrogen compound 0.1878 Informative Inherited
Biological Process (BP) response to organic cyclic compound 1 Informative Inherited
Biological Process (BP) positive regulation of transport 1 Informative Inherited
Biological Process (BP) regulation of cellular localization 0.7006 Informative Inherited
Biological Process (BP) regulation of protein localization 0.006827 Informative Inherited
Biological Process (BP) protein localization to organelle 0.08108 Informative Inherited
Biological Process (BP) regulation of cell proliferation 1 Informative Inherited
Biological Process (BP) positive regulation of cellular component organization 0.06354 Informative Inherited
Biological Process (BP) developmental process involved in reproduction 0.08707 Informative Inherited
Biological Process (BP) single organism reproductive process 0.5021 Informative Inherited
Biological Process (BP) cell development 0.3479 Informative Inherited
Biological Process (BP) multi-organism reproductive process 1 Informative Inherited
Biological Process (BP) anatomical structure formation involved in morphogenesis 0.6507 Informative Inherited
Biological Process (BP) defense response to other organism 0.003352 Informative Inherited
Biological Process (BP) regulation of catabolic process 0.34 Informative Inherited
Biological Process (BP) reproductive system development 0.09345 Informative Inherited
Biological Process (BP) cell surface receptor signaling pathway 1 Informative Inherited
Biological Process (BP) central nervous system development 0.03077 Informative Inherited
Biological Process (BP) multicellular organism reproduction 0.9387 Informative Inherited
Biological Process (BP) movement of cell or subcellular component 0.7827 Informative Inherited
Biological Process (BP) locomotion 0.8364 Informative Inherited
Biological Process (BP) localization of cell 0.778 Informative Inherited
Biological Process (BP) phosphorylation 0.3801 Informative Inherited
Biological Process (BP) positive regulation of catalytic activity 0.99 Informative Inherited
Biological Process (BP) regulation of transferase activity 0.007093 Informative Inherited
Biological Process (BP) intracellular signal transduction 1 Informative Inherited
Biological Process (BP) growth 0.5328 Informative Inherited
Biological Process (BP) regulation of cellular amide metabolic process 0.2329 Informative Inherited
Biological Process (BP) regulation of response to external stimulus 0.02003 Informative Inherited
Biological Process (BP) behavior 0.1598 Informative Inherited
Biological Process (BP) positive regulation of cytokine production 0 Highly Informative Direct
Biological Process (BP) activation of innate immune response 0.00000000000001079 Highly Informative Direct
Biological Process (BP) response to molecule of bacterial origin 0 Highly Informative Direct
Biological Process (BP) regulation of production of molecular mediator of immune response 0.0004463 Highly Informative Direct
Biological Process (BP) protein secretion 0 Highly Informative Direct
Biological Process (BP) regulation of autophagy 0.0001115 Highly Informative Direct
Biological Process (BP) regulation of toll-like receptor signaling pathway 0 Highly Informative Direct
Biological Process (BP) protein localization to nucleus 0.0008745 Highly Informative Direct
Biological Process (BP) positive regulation of cellular component biogenesis 0.00001198 Highly Informative Direct
Biological Process (BP) regulation of nucleocytoplasmic transport 0.00002379 Highly Informative Direct
Biological Process (BP) positive regulation of sequence-specific DNA binding transcription factor activity 0.0001757 Highly Informative Direct
Biological Process (BP) positive regulation of protein transport 0.00009722 Highly Informative Direct
Biological Process (BP) modification of morphology or physiology of other organism involved in symbiotic interaction 0.00005583 Highly Informative Direct
Biological Process (BP) positive regulation of leukocyte proliferation 0.0002171 Highly Informative Direct
Biological Process (BP) cellular response to biotic stimulus 0 Highly Informative Direct
Biological Process (BP) positive regulation of protein serine/threonine kinase activity 0.00003305 Highly Informative Direct
Biological Process (BP) regulation of protein localization to nucleus 0.00001578 Highly Informative Direct
Biological Process (BP) regulation of reactive oxygen species biosynthetic process 0.0000002357 Highly Informative Direct
Biological Process (BP) negative regulation of secretion by cell 0.00004922 Highly Informative Direct
Biological Process (BP) positive regulation of reactive oxygen species metabolic process 0.00009764 Highly Informative Direct
Biological Process (BP) negative regulation of intracellular signal transduction 0.46 Highly Informative Inherited
Biological Process (BP) positive regulation of cellular protein localization 0.2716 Highly Informative Inherited
Biological Process (BP) response to mechanical stimulus 0.4727 Highly Informative Inherited
Biological Process (BP) cellular response to abiotic stimulus 0.2148 Highly Informative Inherited
Biological Process (BP) morphogenesis of an epithelium 0.2518 Highly Informative Inherited
Biological Process (BP) positive regulation of nervous system development 0.9016 Highly Informative Inherited
Biological Process (BP) positive regulation of intracellular transport 0.001696 Highly Informative Inherited
Biological Process (BP) sex differentiation 0.003171 Highly Informative Inherited
Biological Process (BP) positive regulation of MAPK cascade 0.7066 Highly Informative Inherited
Biological Process (BP) regulation of cellular response to stress 0.0692 Highly Informative Inherited
Biological Process (BP) regulation of intracellular protein transport 0.09519 Highly Informative Inherited
Biological Process (BP) regulation of protein import 0.03568 Highly Informative Inherited
Biological Process (BP) negative regulation of immune system process 0.6543 Highly Informative Inherited
Biological Process (BP) germ cell development 0.3142 Highly Informative Inherited
Biological Process (BP) gliogenesis 0.02354 Highly Informative Inherited
Biological Process (BP) antimicrobial humoral response 0.06692 Highly Informative Inherited
Biological Process (BP) positive regulation of cellular catabolic process 0.134 Highly Informative Inherited
Biological Process (BP) female gamete generation 0.03312 Highly Informative Inherited
Biological Process (BP) epithelial cell differentiation 0.1118 Highly Informative Inherited
Biological Process (BP) activation of protein kinase activity 0.03404 Highly Informative Inherited
Biological Process (BP) positive regulation of immune effector process 1 Highly Informative Inherited
Biological Process (BP) developmental growth involved in morphogenesis 0.001118 Highly Informative Inherited
Biological Process (BP) regulation of humoral immune response 1 Highly Informative Inherited
Biological Process (BP) immune response-activating signal transduction 0.009106 Highly Informative Inherited
Biological Process (BP) positive regulation of response to external stimulus 0.005092 Highly Informative Inherited
Biological Process (BP) multi-organism behavior 0.1763 Highly Informative Inherited
Molecular Function (MF) binding 0.000000004392 Least Informative Direct
Molecular Function (MF) nucleic acid binding 0.001635 Moderately Informative Inherited
Molecular Function (MF) RNA binding 0.00000002339 Informative Direct
Molecular Function (MF) signal transducer activity 0 Informative Direct
Molecular Function (MF) receptor binding 0.0000001185 Informative Direct
Molecular Function (MF) amide binding 0.0001026 Informative Direct
Molecular Function (MF) molecular transducer activity 0 Informative Direct
Molecular Function (MF) DNA binding 1 Informative Inherited
Molecular Function (MF) enzyme binding 0.2829 Informative Inherited
Molecular Function (MF) kinase binding 0.000007452 Highly Informative Direct
Molecular Function (MF) peptide binding 0.0000006068 Highly Informative Direct
Molecular Function (MF) sequence-specific DNA binding 0.1366 Highly Informative Inherited
Molecular Function (MF) cytokine receptor binding 0.04667 Highly Informative Inherited
Molecular Function (MF) transmembrane signaling receptor activity 1 Highly Informative Inherited
Cellular Component (CC) membrane 0 Least Informative Direct
Cellular Component (CC) cytoplasmic part 0.00004126 Least Informative Direct
Cellular Component (CC) intracellular organelle part 1 Least Informative Inherited
Cellular Component (CC) intracellular membrane-bounded organelle 0.008373 Least Informative Inherited
Cellular Component (CC) vacuole 0.00003683 Moderately Informative Direct
Cellular Component (CC) plasma membrane 0.000008019 Moderately Informative Direct
Cellular Component (CC) endomembrane system 0 Moderately Informative Direct
Cellular Component (CC) whole membrane 0.00000004742 Moderately Informative Direct
Cellular Component (CC) intrinsic component of membrane 1 Moderately Informative Inherited
Cellular Component (CC) vesicle 0.001606 Moderately Informative Inherited
Cellular Component (CC) nuclear part 1 Moderately Informative Inherited
Cellular Component (CC) Golgi apparatus 0 Informative Direct
Cellular Component (CC) cell surface 0.00000000822 Informative Direct
Cellular Component (CC) cytoplasmic vesicle part 0.0003614 Informative Direct
Cellular Component (CC) membrane region 0.00000000000003104 Informative Direct
Cellular Component (CC) lytic vacuole 0.01277 Informative Inherited
Cellular Component (CC) endosome 0.004152 Informative Inherited
Cellular Component (CC) nuclear envelope 0.07714 Informative Inherited
Cellular Component (CC) endocytic vesicle 0.000372 Highly Informative Direct
Cellular Component (CC) nuclear membrane 0.0004924 Highly Informative Direct
Cellular Component (CC) receptor complex 0 Highly Informative Direct

Document: GO annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processImmunity0Moderately InformativeDirect
Biological processPlant defense0InformativeDirect
Biological processInflammatory response0InformativeDirect
Biological processInnate immunity0InformativeDirect
Biological processNeurogenesis0.00004658InformativeDirect
Cellular componentMembrane0Least InformativeDirect
Cellular componentCytoplasmic vesicle0Moderately InformativeDirect
Cellular componentEndosome0Moderately InformativeDirect
Cellular componentEndoplasmic reticulum0.000000001822Moderately InformativeDirect
Cellular componentGolgi apparatus0.00001625Moderately InformativeDirect
Cellular componentCell projection0.0000559Moderately InformativeDirect
Cellular componentLysosome0.00000000009591InformativeDirect
DomainTransmembrane0Least InformativeDirect
DomainRepeat0Least InformativeDirect
DomainSignal0Least InformativeDirect
DomainLeucine-rich repeat0InformativeDirect
DomainImmunoglobulin domain0InformativeDirect
Post-translational modificationReceptor0Moderately InformativeDirect
Post-translational modificationDisulfide bond0Least InformativeDirect
Post-translational modificationGlycoprotein0Least InformativeDirect

Document: KW annotation of SCOP domains

InterPro annotation
Cross references IPR000157 SSF52200 Protein matches
Abstract

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 (LTRs) 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 [PubMed8621445]. Interestingly, MyD88, a cytoplasmic adaptor protein found in mammals, contains a TIR domain associated to a DEATH domain (see ) [PubMed8621445, PubMed9374458, PubMed10679407]. Besides the mammalian and Drosophila melanogaster proteins, a TIR domain is also found in a number of plant proteins implicated in host defense [PubMed9868361]. 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 [PubMed10671496].


InterPro database


PDBeMotif information about ligands, sequence and structure motifs
Cross references PDB entries
Ligand binding statistics
Nucleic-acid binding statistics
Occurrence of secondary structure elements
Occurrence of small 3D structural motifs

PDBeMotif resource

Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Gene Ontology (high-quality) · Gene Ontology (high-coverage) · UniProtKB KeyWords (KW) ]

Internal database links

Browse genome assignments for this superfamily. The SUPERFAMILY hidden Markov model library has been used to carry out SCOP domain assignments to all genomes at the superfamily level.


Alignments of sequences to 2 models in this superfamily are available by clicking on the 'Alignments' icon above. PDB sequences less than 40% identical are shown by default, but any other sequence(s) may be aligned. Select PDB sequences, genome sequences, or paste in or upload your own sequences.


Browse and view proteins in genomes which have different domain combinations including a Toll/Interleukin receptor TIR domain domain.


Examine the distribution of domain superfamilies, or families, across the major taxonomic kingdoms or genomes within a kingdom. This gives an immediate impression of how superfamilies, or families, are restricted to certain kingdoms of life.


Explore domain occurrence network where nodes represent genomes and edges are domain architectures (shared between genomes) containing the superfamily of interest.

There are 2 hidden Markov models representing the Toll/Interleukin receptor TIR domain superfamily. Information on how the models are built, and plots showing hydrophobicity, match emmission probabilities and insertion/deletion probabilities can be inspected.


Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Gene Ontology (high-quality) · Gene Ontology (high-coverage) · UniProtKB KeyWords (KW) · Internal database links ]