Recombinant Human Toll/interleukin-1 receptor domain-containing adapter protein(TIRAP)

Code CSB-EP023570HU
Size US$1726
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.

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Product Details

Purity Greater than 90% as determined by SDS-PAGE.
Target Names TIRAP
Uniprot No. P58753
Research Area Immunology
Alternative Names TIRAP; MAL; Toll/interleukin-1 receptor domain-containing adapter protein; TIR domain-containing adapter protein; Adaptor protein Wyatt; MyD88 adapter-like protein; MyD88-2
Species Homo sapiens (Human)
Source E.coli
Expression Region 1-221aa
Target Protein Sequence MASSTSLPAPGSRPKKPLGKMADWFRQTLLKKPKKRPNSPESTSSDASQPTSQDSPLPPSLSSVTSPSLPPTHASDSGSSRWSKDYDVCVCHSEEDLVAAQDLVSYLEGSTASLRCFLQLRDATPGGAIVSELCQALSSSHCRVLLITPGFLQDPWCKYQMLQALTEAPGAEGCTIPLLSGLSRAAYPPELRFMYYVDGRGPDGGFRQVKEAVMRYLQTLS
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight 50.9kDa
Protein Length Full Length
Tag Info N-terminal GST-tagged
Form Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting
and FAQs
Protein FAQs
Storage Condition Store at -20°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Notes Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA Please contact us to get it.

Target Data

Function 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.
Gene References into Functions
  1. TIRAP is phosphorylated at Thr28 within its phosphoinositide (PI)-binding motif (PBM), which leads to its ubiquitination and degradation. The authors demonstrate that phosphorylation distorts the helical structure of TIRAP PBM, reducing PI interactions and cell membrane targeting. PMID: 28225045
  2. MAL is not disulfide-bonded and requires glutathionylation of C91 for signaling. PMID: 28739909
  3. The Mal-Toll/interleukin-1 receptor (TIR) domains AB loop is capable of mediating direct binding to the TIR domains of TLR4 and MyD88 simultaneously. PMID: 22485159
  4. MAL is multifunctional and integral for the molecular control of bacterial infections as well as inflammatory diseases. [Review] PMID: 23983209
  5. Data indicate that TcpB (Q8YF5, BtpA/Btp1) interacts with MAL, MyD88, and TLR4 but interferes only with the MAL-TLR4 interaction. PMID: 24265315
  6. Docking and physicochemical studies indicated that BTK was involved in close contact with Tyr86 and Tyr106 of MAL, whereas PKCdelta may phosphorylate Tyr106 only. PMID: 24840642
  7. Results show that MAL protein binds to and regulates MYD88. PMID: 26876098
  8. Here the authors show that MAL TIR domains spontaneously and reversibly form filaments in vitro. They also form cofilaments with TLR4 TIR domains and induce formation of MyD88 assemblies. PMID: 28759049
  9. The major allele A of rs2511521 located in DRD2 and the minor allele T of rs625413 located in TIRAP are significantly associated with increased risk of food addiction in overweight/obese subjects with low/zero food addiction symptoms. PMID: 28115213
  10. Combined targeting of UBAP1 and toll-like receptor adaptors TIRAP and MyD88 by Pseudomonas aeruginosa PumA impedes both cytokine and toll-like receptor signalling, highlighting a novel strategy for innate immune evasion. PMID: 28483816
  11. Epistatic interaction between MyD88 and TIRAP against Helicobacter pylori. PMID: 27296467
  12. Presence of at least one copy of the TIRAP (2054C > T) variant may be associated with severity of bronchopulmonary dysplasia among preterm neonates. PMID: 27457283
  13. Chances of malaria caused by Plasmodium falciparum were low in CC genotype carriers in comparison to other genotypes PMID: 26614847
  14. TIRAP polymorphisms are associated with progression and survival of patients with symptomatic myeloma. PMID: 26564000
  15. This present meta-analysis suggests TIRAP C539T polymorphism is significantly correlated with reduced risk of TB infection, with stronger effect in European. PMID: 25003251
  16. Evaluated the possible association between TIRAP rs1893352 and rs8177374 (S180L) gene polymorphisms and pulmonary tuberculosis in a sample of Iranian population. PMID: 25066393
  17. CCL2rs2530797A/A and TIRAPrs8177376A/A were associated to an increase susceptibility to Chagas disease cardiomyopathy. PMID: 24330528
  18. TIRAP rs81777374 is associated with resistance to pulmonary tuberculosis. PMID: 24067789
  19. Data indicate that TcpB (NP_540591) may mimic the function of TIRAP through their similar TIR domain structures. PMID: 24275656
  20. PSP has an immunoregulatory effect through regulation of the TLR4-TIRAP/MAL-MyD88 signaling pathway. PMID: 23802631
  21. the results of our study suggest that there is a defect of TIRAP and MyD88 proteins in B-CLL lymphocytes. PMID: 23419703
  22. TIRAP S180L polymorphism is not increased in Behcet's disease patients in Italian or Turkish populations. PMID: 24064014
  23. In our study, a TLR pathway adapter variant (TIRAP (rs8177374)) protected against preterm birht<32 weeks, supporting our hypothesis that genetic variation in the innate immune signaling pathway contributes to altered risk of PTB. PMID: 23047423
  24. MyD88 exerts antiapoptotic functions in colon cancer cells via the Ras/Erk, but not the NF-kappaB, pathway. MyD88 inhibition leads to defective ERCC1-dependent DNA repair and to accumulation of DNA damage, resulting in cancer cell death via p53. PMID: 23766530
  25. Identification of binding sites for myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 in MyD88 adapter-like (Mal). PMID: 23460645
  26. PIP5Kalpha promotes TLR4-associated microglial inflammation by mediating PIP(2)-dependent recruitment of TIRAP to the plasma membrane PMID: 23297396
  27. Compared to white women, African American women with clinically suspected pelvic inflammatory disease were more likely to carry variants in the TLR1, TLR2, and TIRAP genes. PMID: 23255565
  28. induction of both IL-6 and IL-8 is associated with elevated TIRAP and reduced TRAM mRNA expression PMID: 22970235
  29. Data suggest a protection effect of the Mal/TIRAP S180L SNP against serious infections in HIV-1 infected individuals with low CD4 cell counts. PMID: 22683004
  30. Data indicate that MyD88 works together with the IL-1/IL-18 receptors, can interact with two distinct sorting adaptors, TRAM and Mal, in a conserved manner. PMID: 22685567
  31. Poxviral protein A46 inhibits TLR4 signaling and interacts with Toll-IL-1 receptor (TIR) domain-containing proteins of the receptor complex. PMID: 22593572
  32. TIRAP S180L polymorphism is unlikely to substantially contribute to tuberculosis susceptibility (Meta-analysis) PMID: 21419702
  33. Blocking of the function of TIRAP and MyD88 largely abrogated intracellular signaling from ligand-activated RAGE PMID: 21829704
  34. TIRAP G286A (D96N) polymorphism is associated with susceptibility to tuberculosis. PMID: 21218381
  35. TIRAP 180Leu was significantly associated with Behcet's disease in UK, but not Middle Eastern, patients. PMID: 21705416
  36. a molecular and structural basis for the role of MAL in TLR signaling and disease protection. PMID: 21873236
  37. RA synovium showed abundant expression of TLR. RA synovitis tissue seems to be responsive to TLR ligands. PMID: 21324962
  38. Comparison of the tirap S180L genotypes between patients with mild malaria and those healthy individuals showed that the frequency of heterozygosity was significantly higher in infected than non-infected individuals. PMID: 21457584
  39. Data demonstrate a key role for Mal in mediating TLR2 and TLR4 activation of CREB and induction of CREB-responsive genes including Il-10. PMID: 21398611
  40. Genetic variations in MyD88 adaptor-like are associated with atopic dermatitis PMID: 21399862
  41. TIRAP gene might be associated with susceptibility to sepsis-associated acute lung injury in the Han Chinese population. PMID: 21118491
  42. Patients simultaneously carrying polymorphisms in TIRAP/Mal and TLR4 and patients homozygous for the TIRAP/Mal SNP had a significantly higher risk of severe infections after surgery PMID: 20525286
  43. The recessive homozygous genotype for a single-nucleotide polymorphisms in the TIRAP (also known as MAL) gene (rs1893352) was strongly associated with nonmeningitis cases of haemophilus influenzae serotype b vaccine failure. PMID: 20804371
  44. An Asp96Asn single nucleotide polymorphism prevents Mal from recruiting its signaling partner MyD88 to the plasma membrane and fails to induce NF-kappa B signaling in human tumor line Huh-7 hepatocytes. PMID: 20164415
  45. Data show that AIP1 is a novel GTPase-activating protein for Arf6, a small GTPase regulating cellular PIP(2) production and formation of the TLR4-TIRAP-MyD88 complex. PMID: 19948740
  46. A TIR domain variant of MyD88 adapter-like (Mal)/TIRAP results in loss of MyD88 binding and reduced TLR2/TLR4 signaling. PMID: 19509286
  47. Polymorphisms in TIRAP do not appear to be involved in childhood tuberculosis susceptibility in South Africa, but may play a role in determining occurrence of tubercular meningitis PMID: 19693265
  48. MyD88 and Mal/TIRAP are essential for LPS-induced I kappa B alpha phosphorylation, NF-kappa B activation, and interleukin 6 (IL-6) or IL-8 production in fibroblasts and endothelial cells in a pathway that also requires IKK2. PMID: 14630816
  49. involvement of a previously uncharacterized, evolutionarily conserved TIR domain protein in innate immunity that is functionally distinct from other known TIR domain signaling adapters PMID: 15123841
  50. activation of Rac1 leads to HIV-LTR trans-activation, mediated through TIRAP. Rac1 and TIRAP are important in TLR4 activation of HIV replication PMID: 15187145
  51. role for Mal in TLR-mediated signaling in regulating NF-kappaB-dependent gene transcription via its interaction with TRAF6 PMID: 15247281
  52. Mal phosphorylation has an effect on tyrosine during signaling by TLR2 and TLR4 and Btk is the kinase involved PMID: 16439361
  53. TIRAP contains a PIP2 binding domain, which mediates TIRAP recruitment to the plasma membrane. TIRAP then functions to facilitate MyD88 delivery to activated TLR4 to initiate signal transduction. PMID: 16751103
  54. These results suggest that PKCdelta binding to TIRAP/Mal promotes TLR signaling events. PMID: 17161867
  55. Mal S180L variant attenuated TLR2 signal transduction and confers a protective effect against infectious diseases. PMID: 17322885
  56. analysis offers additional evidence that the TLR4 pathway - in this case, TLR4 and its signaling molecule TIRAP - plays a role in susceptibility to inflammatory bowel diseases PMID: 17538633
  57. A polymorphism modulating innate immunity signal transduction has recently been shown to influence human susceptibility to many different infections. PMID: 17610834
  58. tyrosine phosphorylation of Mal is required for adapter signaling, regulates Mal interactions with TLR4 and receptor signaling, and is inhibited in endotoxin tolerance PMID: 18070880
  59. The Mal S180L and TLR4 G299D polymorphisms do not contribute to RA susceptibility or severity either individually or in combination. PMID: 18180278
  60. In fibroblast-like synoviocytes of rheumatoid arthritis patients, T-cell maturation-associated protein MAL is implicated in the cross-talk between focal adhesion kinase (FAK) and myeloid differentiation factor 88 (MyD88) pathways. PMID: 18292575
  61. Analysis of association of the TIRAP (MAL) S180L variant and tuberculosis in three populations. PMID: 18305471
  62. the TIRAP Leu180 allele was found to be a protective factor against developing tuberculosis and systemic lupus erythematosus PMID: 18417424
  63. single nucleotide polymorphism, C558T, influences susceptibility to both meningeal and pulmonary tuberculosis PMID: 19120490
  64. Chagas disease patients who are heterozygous for the TIRAP S180L variant that leads to a decrease in signal transduction upon ligation of TLR2 or TLR4 to their respective ligand may have a lower risk of developing chronic Chagas cardiomyopathy. PMID: 19456234
  65. individuals bearing the TIRAP 180L allele display an increased, innate immune response to TLR4 and TLR2 ligands, but not to TLR9 stimulation. PMID: 19509334
  66. Mal specifically connects TLR2/6 to PI3K activation, PIP(3) generation and macrophage polarization. PMID: 19574958
  67. the novel role for Mal in facilitating the direct recruitment of TRAF6 to the plasma membrane, which is necessary for TLR2- and TLR4-induced transactivation of NF-kappaB and regulation of the subsequent pro-inflammatory response. PMID: 19592497
  68. A broad protective effect of TIRAP S180L against infectious diseases per se is not discernible PMID: 19602285
  69. a role for TIRAP in mediating LPS-induced NF-kappaB activation and apoptosis in human endothelial cells PMID: 12083783

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Subcellular Location Cytoplasm, Cell membrane, Membrane
Tissue Specificity Highly expressed in liver, kidney, spleen, skeletal muscle and heart. Also detected in peripheral blood leukocytes, lung, placenta, small intestine, thymus, colon and brain.
Database Links

HGNC: 17192

OMIM: 606252

KEGG: hsa:114609

STRING: 9606.ENSP00000376445

UniGene: Hs.537126

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