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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 2018_03 genome PDB chains (SCOP 1.75)
Domains 9,716 31,743 4
Proteins 9,285 30,843 4

Functional annotation
General category Regulation
Detailed category Signal transduction

Function annotation of SCOP domain superfamilies

Disease Ontology (DO)

(show details)
DO termFDR (all)SDDO levelAnnotation (direct or inherited)
Disease Ontology (DO)nervous system disease0.9126Least InformativeInherited
Disease Ontology (DO)organ system cancer0.9736Least InformativeInherited
Disease Ontology (DO)disease by infectious agent0.0000005699Moderately InformativeDirect
Disease Ontology (DO)gastrointestinal system disease0.005071Moderately InformativeInherited
Disease Ontology (DO)skin disease0.005577Moderately InformativeInherited
Disease Ontology (DO)syndrome0.01977Moderately InformativeInherited
Disease Ontology (DO)hematologic cancer0.181Moderately InformativeInherited
Disease Ontology (DO)connective tissue disease0.3364Moderately InformativeInherited
Disease Ontology (DO)lower respiratory tract disease0.6509Moderately InformativeInherited
Disease Ontology (DO)asthma0.000000000003305InformativeDirect
Disease Ontology (DO)allergic rhinitis0.000009113InformativeDirect
Disease Ontology (DO)liver disease0.00007379InformativeDirect
Disease Ontology (DO)inflammatory bowel disease0.000257InformativeDirect
Disease Ontology (DO)primary bacterial infectious disease0.0006049InformativeDirect
Disease Ontology (DO)muscle tissue disease0.005906InformativeInherited
Disease Ontology (DO)lymphoma0.01516InformativeInherited
Disease Ontology (DO)hypersensitivity reaction type IV disease0.01722InformativeInherited
Disease Ontology (DO)interstitial lung disease0.2213InformativeInherited
Disease Ontology (DO)parasitic protozoa infectious disease0.4462InformativeInherited
Disease Ontology (DO)opportunistic mycosis0.00000000001432Highly InformativeDirect
Disease Ontology (DO)filariasis0.00000000002272Highly InformativeDirect
Disease Ontology (DO)dermatomyositis0.00000277Highly InformativeDirect
Disease Ontology (DO)Chagas disease0.000005504Highly InformativeDirect
Disease Ontology (DO)mycosis fungoides0.00006164Highly InformativeDirect
Disease Ontology (DO)sarcoidosis0.00007722Highly InformativeDirect
Disease Ontology (DO)meningitis0.00009627Highly InformativeDirect
Disease Ontology (DO)atopic dermatitis0.0006452Highly InformativeDirect
Disease Ontology (DO)irritable bowel syndrome0.0006532Highly InformativeDirect

Document: DO annotation of SCOP domains

Mouse Phenotype (MP)

(show details)
MP termFDR (all)SDMP levelAnnotation (direct or inherited)
Mammalian Phenotype (MP)immune system phenotype0.000000006158Least InformativeDirect
Mammalian Phenotype (MP)hematopoietic system phenotype0.000002623Least InformativeDirect
Mammalian Phenotype (MP)cardiovascular system phenotype0.3198Least InformativeInherited
Mammalian Phenotype (MP)abnormal homeostasis0.3316Least InformativeInherited
Mammalian Phenotype (MP)cellular phenotype0.4363Least InformativeInherited
Mammalian Phenotype (MP)nervous system phenotype0.6217Least InformativeInherited
Mammalian Phenotype (MP)mortality/aging0.7254Least InformativeInherited
Mammalian Phenotype (MP)abnormal immune serum protein physiology0.000005625Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal protein level0.00001942Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal induced morbidity/mortality0.00005602Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal renal/urinary system physiology0.003327Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hematopoietic cell number0.0136Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal professional antigen presenting cell physiology0.02977Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal cardiovascular system physiology0.06363Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal nervous system physiology0.1341Moderately InformativeInherited
Mammalian Phenotype (MP)respiratory system phenotype0.162Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal leukocyte physiology0.2509Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal eye morphology0.4571Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal inflammatory response0.4612Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal mononuclear cell morphology0.7197Moderately InformativeInherited
Mammalian Phenotype (MP)increased susceptibility to infection0.0000000000717InformativeDirect
Mammalian Phenotype (MP)abnormal intestine physiology0.00003182InformativeDirect
Mammalian Phenotype (MP)autoimmune response0.0001877InformativeDirect
Mammalian Phenotype (MP)abnormal kidney physiology0.0001877InformativeDirect
Mammalian Phenotype (MP)abnormal macrophage physiology0.0002585InformativeDirect
Mammalian Phenotype (MP)abnormal circulating cytokine level0.0007583InformativeDirect
Mammalian Phenotype (MP)abnormal response to injury0.001941InformativeInherited
Mammalian Phenotype (MP)abnormal humoral immune response0.02491InformativeInherited
Mammalian Phenotype (MP)abnormal gas homeostasis0.03205InformativeInherited
Mammalian Phenotype (MP)abnormal eye development0.03829InformativeInherited
Mammalian Phenotype (MP)abnormal respiratory function0.09274InformativeInherited
Mammalian Phenotype (MP)joint inflammation0.1173InformativeInherited
Mammalian Phenotype (MP)abnormal mature B cell morphology0.1321InformativeInherited
Mammalian Phenotype (MP)hemorrhage0.1809InformativeInherited
Mammalian Phenotype (MP)abnormal interferon level0.1899InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin secretion0.1963InformativeInherited
Mammalian Phenotype (MP)abnormal blood vessel physiology0.2917InformativeInherited
Mammalian Phenotype (MP)decreased cell proliferation0.4002InformativeInherited
Mammalian Phenotype (MP)increased leukocyte cell number0.4596InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin level0.4633InformativeInherited
Mammalian Phenotype (MP)abnormal T cell physiology0.6506InformativeInherited
Mammalian Phenotype (MP)abnormal natural killer cell mediated cytotoxicity0.7556InformativeInherited
Mammalian Phenotype (MP)abnormal interferon secretion0.9187InformativeInherited
Mammalian Phenotype (MP)abnormal B cell proliferation0.9725InformativeInherited
Mammalian Phenotype (MP)decreased interleukin-12b secretion0Highly InformativeDirect
Mammalian Phenotype (MP)decreased macrophage cytokine production0.00000000003936Highly InformativeDirect
Mammalian Phenotype (MP)decreased immunoglobulin level0.000000001149Highly InformativeDirect
Mammalian Phenotype (MP)abnormal interleukin-1 beta secretion0.000004313Highly InformativeDirect
Mammalian Phenotype (MP)abnormal glial cell physiology0.00003352Highly InformativeDirect
Mammalian Phenotype (MP)abnormal airway responsiveness0.0002305Highly InformativeDirect
Mammalian Phenotype (MP)abnormal B-1 B cell number0.0003105Highly InformativeDirect
Mammalian Phenotype (MP)decreased B cell proliferation0.0003225Highly InformativeDirect
Mammalian Phenotype (MP)decreased interleukin-10 secretion0.0003485Highly InformativeDirect
Mammalian Phenotype (MP)altered susceptibility to kidney reperfusion injury0.000498Highly InformativeDirect
Mammalian Phenotype (MP)abnormal dendritic cell physiology0.0005246Highly InformativeDirect
Mammalian Phenotype (MP)abnormal enterocyte physiology0.0007759Highly InformativeDirect
Mammalian Phenotype (MP)abnormal vascular wound healing0.0008136Highly InformativeDirect
Mammalian Phenotype (MP)gastrointestinal hemorrhage0.002517Highly InformativeInherited
Mammalian Phenotype (MP)abnormal nitric oxide homeostasis0.003665Highly InformativeInherited
Mammalian Phenotype (MP)decreased inflammatory response0.005619Highly InformativeInherited
Mammalian Phenotype (MP)increased B cell number0.01465Highly InformativeInherited
Mammalian Phenotype (MP)decreased susceptibility to injury0.02867Highly InformativeInherited
Mammalian Phenotype (MP)abnormal tumor necrosis factor secretion0.03506Highly InformativeInherited
Mammalian Phenotype (MP)abnormal fat cell morphology0.05216Highly InformativeInherited
Mammalian Phenotype (MP)abnormal immune organ physiology0.1127Highly InformativeInherited
Mammalian Phenotype (MP)abnormal acute inflammation0.2632Highly InformativeInherited

Document: MP annotation of SCOP domains

Fly Phenotype (FP)

(show details) Document: FP annotation of SCOP domains

Fly Anatomy (FA)

(show details)
FA termFDR (all)SDFA levelAnnotation (direct or inherited)
Fly Anatomy (FA)larva0Least InformativeDirect
Fly Anatomy (FA)multi-tissue structure0.09088Least InformativeInherited
Fly Anatomy (FA)organ system subdivision0.182Least InformativeInherited
Fly Anatomy (FA)nervous system0.2999Least InformativeInherited
Fly Anatomy (FA)ganglion0.02392Moderately InformativeInherited
Fly Anatomy (FA)central nervous system0.04733Moderately InformativeInherited
Fly Anatomy (FA)ventral nerve cord0.0007379InformativeDirect

Document: FA annotation of SCOP domains

Xenopus Anatomy (XA)

(show details) Document: XA annotation of SCOP domains

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEC levelAnnotation (direct or inherited)
Enzyme Commission (EC)Hydrolases0Least InformativeDirect
Enzyme Commission (EC)Glycosylases0Moderately InformativeDirect
Enzyme Commission (EC)Hydrolyzing N-glycosyl compounds0InformativeDirect
Enzyme Commission (EC)ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase0Highly InformativeDirect

Document: EC annotation of SCOP domains

InterPro annotation
Cross references IPR000157 SSF52200 Protein matches

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 · Disease Ontology (DO) · Mouse Phenotype (MP) · Fly Phenotype (FP) · Fly Anatomy (FA) · Xenopus Anatomy (XA) · Enzyme Commission (EC) ]

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 4 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 4 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 · Disease Ontology (DO) · Mouse Phenotype (MP) · Fly Phenotype (FP) · Fly Anatomy (FA) · Xenopus Anatomy (XA) · Enzyme Commission (EC) · Internal database links ]