UniProtKB - P58753 (TIRAP_HUMAN)
Toll/interleukin-1 receptor domain-containing adapter protein
TIRAP
Functioni
Adapter involved in TLR2 and TLR4 signaling pathways in the innate immune response. Acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B, MAPK1, MAPK3 and JNK, and resulting in cytokine secretion and the inflammatory response. Positively regulates the production of TNF-alpha and interleukin-6.
2 PublicationsCaution
GO - Molecular functioni
- identical protein binding Source: IntAct
- NAD+ nucleosidase activity Source: InterPro
- phosphatidylinositol-4,5-bisphosphate binding Source: BHF-UCL
- protein kinase C binding Source: BHF-UCL
- protein-macromolecule adaptor activity Source: BHF-UCL
- Toll-like receptor 2 binding Source: BHF-UCL
- Toll-like receptor 4 binding Source: BHF-UCL
GO - Biological processi
- 3'-UTR-mediated mRNA stabilization Source: BHF-UCL
- activation of NF-kappaB-inducing kinase activity Source: AgBase
- cell surface receptor signaling pathway Source: BHF-UCL
- cellular response to bacterial lipopeptide Source: BHF-UCL
- cellular response to lipoteichoic acid Source: BHF-UCL
- defense response to Gram-positive bacterium Source: BHF-UCL
- I-kappaB kinase/NF-kappaB signaling Source: GO_Central
- inflammatory response Source: UniProtKB-KW
- innate immune response Source: UniProtKB-KW
- MyD88-dependent toll-like receptor signaling pathway Source: BHF-UCL
- myeloid cell differentiation Source: BHF-UCL
- positive regulation of B cell proliferation Source: BHF-UCL
- positive regulation of chemokine (C-X-C motif) ligand 1 production Source: BHF-UCL
- positive regulation of chemokine (C-X-C motif) ligand 2 production Source: BHF-UCL
- positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: BHF-UCL
- positive regulation of innate immune response Source: GO_Central
- positive regulation of interleukin-12 production Source: BHF-UCL
- positive regulation of interleukin-15 production Source: BHF-UCL
- positive regulation of interleukin-6 production Source: BHF-UCL
- positive regulation of interleukin-8 production Source: BHF-UCL
- positive regulation of JNK cascade Source: BHF-UCL
- positive regulation of neutrophil chemotaxis Source: BHF-UCL
- positive regulation of NF-kappaB transcription factor activity Source: BHF-UCL
- positive regulation of protein-containing complex assembly Source: BHF-UCL
- positive regulation of toll-like receptor 2 signaling pathway Source: BHF-UCL
- positive regulation of toll-like receptor 3 signaling pathway Source: BHF-UCL
- positive regulation of toll-like receptor 4 signaling pathway Source: BHF-UCL
- positive regulation of tumor necrosis factor production Source: BHF-UCL
- regulation of innate immune response Source: BHF-UCL
- regulation of interferon-beta production Source: BHF-UCL
- regulation of stress-activated MAPK cascade Source: GO_Central
- response to lipopolysaccharide Source: BHF-UCL
- TIRAP-dependent toll-like receptor 4 signaling pathway Source: BHF-UCL
Keywordsi
Biological process | Immunity, Inflammatory response, Innate immunity |
Enzyme and pathway databases
PathwayCommonsi | P58753 |
Reactomei | R-HSA-1236974, ER-Phagosome pathway R-HSA-166058, MyD88:MAL(TIRAP) cascade initiated on plasma membrane R-HSA-5602498, MyD88 deficiency (TLR2/4) R-HSA-5603041, IRAK4 deficiency (TLR2/4) |
SignaLinki | P58753 |
SIGNORi | P58753 |
Protein family/group databases
TCDBi | 8.A.43.1.22, the neat-domain containing methaemoglobin heme sequestration (n-mhs) family |
Names & Taxonomyi
Protein namesi | Recommended name: Toll/interleukin-1 receptor domain-containing adapter proteinShort name: TIR domain-containing adapter protein Alternative name(s): Adaptor protein Wyatt MyD88 adapter-like protein Short name: MyD88-2 |
Gene namesi | Name:TIRAP Synonyms:MAL |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:17192, TIRAP |
MIMi | 606252, gene |
neXtProti | NX_P58753 |
VEuPathDBi | HostDB:ENSG00000150455 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Other locations
- Membrane 1 Publication
Note: Colocalizes with DAB2IP at the plasma membrane.
Cytosol
- cytosol Source: Reactome
Plasma Membrane
- plasma membrane Source: UniProtKB
- ruffle membrane Source: BHF-UCL
Other locations
- cytoplasm Source: UniProtKB
- endocytic vesicle Source: BHF-UCL
Keywords - Cellular componenti
Cell membrane, Cytoplasm, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 125 | P → H: Abolishes NF-kappa-B activation. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 114609 |
MalaCardsi | TIRAP |
MIMi | 607948, phenotype 611162, phenotype 614382, phenotype |
OpenTargetsi | ENSG00000150455 |
PharmGKBi | PA134972842 |
Miscellaneous databases
Pharosi | P58753, Tbio |
Genetic variation databases
BioMutai | TIRAP |
DMDMi | 50403750 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000072547 | 1 – 221 | Toll/interleukin-1 receptor domain-containing adapter proteinAdd BLAST | 221 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 89 ↔ 134 | 1 Publication | ||
Disulfide bondi | 142 ↔ 174 | 1 Publication |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | P58753 |
MassIVEi | P58753 |
PaxDbi | P58753 |
PeptideAtlasi | P58753 |
PRIDEi | P58753 |
ProteomicsDBi | 57101 [P58753-1] 57102 [P58753-2] 57103 [P58753-3] |
PTM databases
GlyGeni | P58753, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P58753 |
PhosphoSitePlusi | P58753 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000150455, Expressed in monocyte and 140 other tissues |
ExpressionAtlasi | P58753, baseline and differential |
Genevisiblei | P58753, HS |
Organism-specific databases
HPAi | ENSG00000150455, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer. Also forms heterodimers with MYD88. May interact with PIK3AP1 (By similarity).
Interacts with TLR4 and IRAK2 via their respective TIR domains.
Interacts with BMX and TBK1.
Interacts with EIF2AK2. Does not interact with IRAK1, nor TLR9.
By similarity6 Publications(Microbial infection) In case of infection, interacts with Brucella protein BtpA.
1 PublicationBinary interactionsi
P58753
Isoform 2 [P58753-2]
With | #Exp. | IntAct |
---|---|---|
CASP1 [P29466] | 5 | EBI-528654,EBI-516667 |
GO - Molecular functioni
- identical protein binding Source: IntAct
- protein kinase C binding Source: BHF-UCL
- Toll-like receptor 2 binding Source: BHF-UCL
- Toll-like receptor 4 binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 125325, 44 interactors |
DIPi | DIP-33489N |
IntActi | P58753, 43 interactors |
MINTi | P58753 |
STRINGi | 9606.ENSP00000376445 |
Miscellaneous databases
RNActi | P58753, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P58753 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 84 – 213 | TIRPROSITE-ProRule annotationAdd BLAST | 130 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 82 | DisorderedSequence analysisAdd BLAST | 82 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 40 – 82 | Polar residuesSequence analysisAdd BLAST | 43 |
Phylogenomic databases
eggNOGi | ENOG502S07Q, Eukaryota |
GeneTreei | ENSGT00510000048428 |
HOGENOMi | CLU_091033_1_0_1 |
InParanoidi | P58753 |
OMAi | FVQDDWC |
OrthoDBi | 1327598at2759 |
PhylomeDBi | P58753 |
TreeFami | TF330734 |
Family and domain databases
DisProti | DP01768 |
Gene3Di | 3.40.50.10140, 1 hit |
InterProi | View protein in InterPro IPR000157, TIR_dom IPR017279, Tol-interleuk_rcpt_adapt_Tirap IPR035897, Toll_tir_struct_dom_sf |
PANTHERi | PTHR22662, PTHR22662, 1 hit |
Pfami | View protein in Pfam PF13676, TIR_2, 1 hit |
PIRSFi | PIRSF037750, TIR_Tirap, 1 hit |
SUPFAMi | SSF52200, SSF52200, 1 hit |
PROSITEi | View protein in PROSITE PS50104, TIR, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MASSTSLPAP GSRPKKPLGK MADWFRQTLL KKPKKRPNSP ESTSSDASQP
60 70 80 90 100
TSQDSPLPPS LSSVTSPSLP PTHASDSGSS RWSKDYDVCV CHSEEDLVAA
110 120 130 140 150
QDLVSYLEGS TASLRCFLQL RDATPGGAIV SELCQALSSS HCRVLLITPG
160 170 180 190 200
FLQDPWCKYQ MLQALTEAPG AEGCTIPLLS GLSRAAYPPE LRFMYYVDGR
210 220
GPDGGFRQVK EAVMRYLQTL S
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketF5H2K1 | F5H2K1_HUMAN | Toll/interleukin-1 receptor domain-... | TIRAP | 49 | Annotation score: |
Polymorphismi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_019143 | 9 | A → P Does not affect NF-kappa-B activation and TNF-alpha production. 2 PublicationsCorresponds to variant dbSNP:rs8177369Ensembl. | 1 | |
Natural variantiVAR_019144 | 13 | R → W Does not affect NF-kappa-B activation and TNF-alpha production. 2 PublicationsCorresponds to variant dbSNP:rs8177399Ensembl. | 1 | |
Natural variantiVAR_036691 | 55 | S → N Does not affect NF-kappa-B activation and TNF-alpha production. 2 PublicationsCorresponds to variant dbSNP:rs3802813Ensembl. | 1 | |
Natural variantiVAR_019145 | 96 | D → N Hypomorphic variant resulting in impaired NF-kappa-B activation and TNF-alpha production; cannot bind MYD88. 2 PublicationsCorresponds to variant dbSNP:rs8177400Ensembl. | 1 | |
Natural variantiVAR_019146 | 180 | S → L At heterozygosity it protects against invasive pneumococcal disease, malaria, bacteremia and tuberculosis; does not affect NF-kappa-B activation and TNF-alpha production; attenuates TLR2 signal transduction. 4 PublicationsCorresponds to variant dbSNP:rs8177374EnsemblClinVar. | 1 | |
Natural variantiVAR_061713 | 197 | V → I Does not affect NF-kappa-B activation and TNF-alpha production. 1 PublicationCorresponds to variant dbSNP:rs7932976Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_010765 | 216 – 221 | YLQTLS → CKLLQEGEGERDSATVSDLL in isoform 2. 4 Publications | 6 | |
Alternative sequenceiVSP_017239 | 221 | S → WHLLYHGTPEIGVKLETENP CRASDSHKCDKRYRE in isoform 3. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF406652 mRNA Translation: AAL01160.1 AF378129 mRNA Translation: AAL05627.1 AF410783 mRNA Translation: AAL05036.1 AY576785 mRNA Translation: AAT90417.1 AY576786 mRNA Translation: AAT90418.1 AY576787 mRNA Translation: AAT90419.1 AB446477 mRNA Translation: BAG55254.1 AK124298 mRNA Translation: BAG54027.1 AK313147 mRNA Translation: BAG35965.1 AY282416 Genomic DNA Translation: AAP31973.1 AP001318 Genomic DNA No translation available. CH471065 Genomic DNA Translation: EAW67687.1 CH471065 Genomic DNA Translation: EAW67689.1 BC032474 mRNA Translation: AAH32474.1 |
CCDSi | CCDS41731.1 [P58753-2] CCDS8472.1 [P58753-1] |
RefSeqi | NP_001034750.1, NM_001039661.1 [P58753-1] NP_001305705.1, NM_001318776.1 [P58753-2] NP_001305706.1, NM_001318777.1 [P58753-1] NP_683708.1, NM_148910.2 [P58753-2] XP_005271456.2, XM_005271399.3 XP_011540878.1, XM_011542576.2 XP_016872651.1, XM_017017162.1 |
Genome annotation databases
Ensembli | ENST00000392678; ENSP00000376445; ENSG00000150455 [P58753-2] ENST00000392679; ENSP00000376446; ENSG00000150455 ENST00000392680; ENSP00000376447; ENSG00000150455 ENST00000479770; ENSP00000436967; ENSG00000150455 |
GeneIDi | 114609 |
KEGGi | hsa:114609 |
MANE-Selecti | ENST00000392679.6; ENSP00000376446.1; NM_001318777.2; NP_001305706.1 |
UCSCi | uc001qdl.2, human [P58753-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
SeattleSNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF406652 mRNA Translation: AAL01160.1 AF378129 mRNA Translation: AAL05627.1 AF410783 mRNA Translation: AAL05036.1 AY576785 mRNA Translation: AAT90417.1 AY576786 mRNA Translation: AAT90418.1 AY576787 mRNA Translation: AAT90419.1 AB446477 mRNA Translation: BAG55254.1 AK124298 mRNA Translation: BAG54027.1 AK313147 mRNA Translation: BAG35965.1 AY282416 Genomic DNA Translation: AAP31973.1 AP001318 Genomic DNA No translation available. CH471065 Genomic DNA Translation: EAW67687.1 CH471065 Genomic DNA Translation: EAW67689.1 BC032474 mRNA Translation: AAH32474.1 |
CCDSi | CCDS41731.1 [P58753-2] CCDS8472.1 [P58753-1] |
RefSeqi | NP_001034750.1, NM_001039661.1 [P58753-1] NP_001305705.1, NM_001318776.1 [P58753-2] NP_001305706.1, NM_001318777.1 [P58753-1] NP_683708.1, NM_148910.2 [P58753-2] XP_005271456.2, XM_005271399.3 XP_011540878.1, XM_011542576.2 XP_016872651.1, XM_017017162.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2NDH | NMR | - | A | 79-221 | [»] | |
2Y92 | X-ray | 3.01 | A | 79-221 | [»] | |
3UB2 | X-ray | 2.40 | A | 78-221 | [»] | |
3UB3 | X-ray | 2.75 | A | 78-221 | [»] | |
3UB4 | X-ray | 3.10 | A | 78-221 | [»] | |
4FZ5 | X-ray | 3.60 | A/B | 72-221 | [»] | |
4LQD | X-ray | 2.45 | A | 81-221 | [»] | |
5T7Q | NMR | - | A | 15-35 | [»] | |
5UZB | electron microscopy | 7.00 | A/B/C/D/E/F/G/H/I/J/K/L/M/N | 79-221 | [»] | |
SMRi | P58753 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 125325, 44 interactors |
DIPi | DIP-33489N |
IntActi | P58753, 43 interactors |
MINTi | P58753 |
STRINGi | 9606.ENSP00000376445 |
Protein family/group databases
TCDBi | 8.A.43.1.22, the neat-domain containing methaemoglobin heme sequestration (n-mhs) family |
PTM databases
GlyGeni | P58753, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P58753 |
PhosphoSitePlusi | P58753 |
Genetic variation databases
BioMutai | TIRAP |
DMDMi | 50403750 |
Proteomic databases
jPOSTi | P58753 |
MassIVEi | P58753 |
PaxDbi | P58753 |
PeptideAtlasi | P58753 |
PRIDEi | P58753 |
ProteomicsDBi | 57101 [P58753-1] 57102 [P58753-2] 57103 [P58753-3] |
Protocols and materials databases
Antibodypediai | 19148, 528 antibodies from 39 providers |
DNASUi | 114609 |
Genome annotation databases
Ensembli | ENST00000392678; ENSP00000376445; ENSG00000150455 [P58753-2] ENST00000392679; ENSP00000376446; ENSG00000150455 ENST00000392680; ENSP00000376447; ENSG00000150455 ENST00000479770; ENSP00000436967; ENSG00000150455 |
GeneIDi | 114609 |
KEGGi | hsa:114609 |
MANE-Selecti | ENST00000392679.6; ENSP00000376446.1; NM_001318777.2; NP_001305706.1 |
UCSCi | uc001qdl.2, human [P58753-1] |
Organism-specific databases
CTDi | 114609 |
DisGeNETi | 114609 |
GeneCardsi | TIRAP |
HGNCi | HGNC:17192, TIRAP |
HPAi | ENSG00000150455, Low tissue specificity |
MalaCardsi | TIRAP |
MIMi | 606252, gene 607948, phenotype 611162, phenotype 614382, phenotype |
neXtProti | NX_P58753 |
OpenTargetsi | ENSG00000150455 |
PharmGKBi | PA134972842 |
VEuPathDBi | HostDB:ENSG00000150455 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S07Q, Eukaryota |
GeneTreei | ENSGT00510000048428 |
HOGENOMi | CLU_091033_1_0_1 |
InParanoidi | P58753 |
OMAi | FVQDDWC |
OrthoDBi | 1327598at2759 |
PhylomeDBi | P58753 |
TreeFami | TF330734 |
Enzyme and pathway databases
PathwayCommonsi | P58753 |
Reactomei | R-HSA-1236974, ER-Phagosome pathway R-HSA-166058, MyD88:MAL(TIRAP) cascade initiated on plasma membrane R-HSA-5602498, MyD88 deficiency (TLR2/4) R-HSA-5603041, IRAK4 deficiency (TLR2/4) |
SignaLinki | P58753 |
SIGNORi | P58753 |
Miscellaneous databases
BioGRID-ORCSi | 114609, 11 hits in 1047 CRISPR screens |
ChiTaRSi | TIRAP, human |
GenomeRNAii | 114609 |
Pharosi | P58753, Tbio |
PROi | PR:P58753 |
RNActi | P58753, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000150455, Expressed in monocyte and 140 other tissues |
ExpressionAtlasi | P58753, baseline and differential |
Genevisiblei | P58753, HS |
Family and domain databases
DisProti | DP01768 |
Gene3Di | 3.40.50.10140, 1 hit |
InterProi | View protein in InterPro IPR000157, TIR_dom IPR017279, Tol-interleuk_rcpt_adapt_Tirap IPR035897, Toll_tir_struct_dom_sf |
PANTHERi | PTHR22662, PTHR22662, 1 hit |
Pfami | View protein in Pfam PF13676, TIR_2, 1 hit |
PIRSFi | PIRSF037750, TIR_Tirap, 1 hit |
SUPFAMi | SSF52200, SSF52200, 1 hit |
PROSITEi | View protein in PROSITE PS50104, TIR, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TIRAP_HUMAN | |
Accessioni | P58753Primary (citable) accession number: P58753 Secondary accession number(s): B3KW65 Q8N5E5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 27, 2002 |
Last sequence update: | July 19, 2004 | |
Last modified: | February 23, 2022 | |
This is version 178 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references