产品: Phospho-IRAK1 (Thr387) 抗体
货号: AF8009
来源: Rabbit
应用: WB, IHC, ELISA(peptide)
反应: Human, Mouse, Rat
预测: Pig, Zebrafish, Bovine, Horse, Sheep, Rabbit, Dog
分子量: 77kD; 77kD(Calculated).
蛋白号: P51617
RRID: AB_2840072

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   规格 价格 库存
 100ul ¥2800 现货
 200ul ¥3800 现货

货期: 当天发货

产品描述

来源:
Rabbit
应用:
WB 1:1000-3000, IHC 1:50-1:200, ELISA(peptide) 1:20000-1:40000
*The optimal dilutions should be determined by the end user.
*Tips:

WB: 适用于变性蛋白样本的免疫印迹检测. IHC: 适用于组织样本的石蜡(IHC-p)或冰冻(IHC-f)切片样本的免疫组化/荧光检测. IF/ICC: 适用于细胞样本的荧光检测. ELISA(peptide): 适用于抗原肽的ELISA检测.

反应:
Human,Mouse,Rat
预测:
Pig(91%), Zebrafish(100%), Bovine(91%), Horse(91%), Sheep(91%), Rabbit(91%), Dog(91%)
克隆:
Polyclonal
特异性:
Phospho-IRAK1 (Thr387) Antibody detects endogenous levels of IRAK1 only when phosphorylated at Thr387.
RRID:
AB_2840072
引用格式: Affinity Biosciences Cat# AF8009, RRID:AB_2840072.
纯化:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
保存:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
别名:

展开/折叠

AA48924; Il1rak; Interleukin 1 receptor associated kinase 1; Interleukin-1 receptor-associated kinase 1; IRAK; IRAK-1; Irak1; IRAK1-S; IRAK1_HUMAN; mPLK; OTTHUMP00000026014; OTTHUMP00000026015; OTTHUMP00000026020; OTTHUMP00000180621; Pelle; Pelle homolog; Pelle-like protein kinase; Plpk;

抗原和靶标

免疫原:
Uniprot:
基因/基因ID:
表达特异性:
P51617 IRAK1_HUMAN:

Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2.

蛋白序列:
MAGGPGPGEPAAPGAQHFLYEVPPWVMCRFYKVMDALEPADWCQFAALIVRDQTELRLCERSGQRTASVLWPWINRNARVADLVHILTHLQLLRARDIITAWHPPAPLPSPGTTAPRPSSIPAPAEAEAWSPRKLPSSASTFLSPAFPGSQTHSGPELGLVPSPASLWPPPPSPAPSSTKPGPESSVSLLQGARPFPFCWPLCEISRGTHNFSEELKIGEGGFGCVYRAVMRNTVYAVKRLKENADLEWTAVKQSFLTEVEQLSRFRHPNIVDFAGYCAQNGFYCLVYGFLPNGSLEDRLHCQTQACPPLSWPQRLDILLGTARAIQFLHQDSPSLIHGDIKSSNVLLDERLTPKLGDFGLARFSRFAGSSPSQSSMVARTQTVRGTLAYLPEEYIKTGRLAVDTDTFSFGVVVLETLAGQRAVKTHGARTKYLKDLVEEEAEEAGVALRSTQSTLQAGLAADAWAAPIAMQIYKKHLDPRPGPCPPELGLGLGQLACCCLHRRAKRRPPMTQVYERLEKLQAVVAGVPGHSEAASCIPPSPQENSYVSSTGRAHSGAAPWQPLAAPSGASAQAAEQLQRGPNQPVESDESLGGLSAALRSWHLTPSCPLDPAPLREAGCPQGDTAGESSWGSGPGSRPTAVEGLALGSSASSSSEPPQIIINPARQKMVQKLALYEDGALDSLQLLSSSSLPGLGLEQDRQGPEESDEFQS

种属预测

种属预测:

score>80的预测可信度较高,可尝试用于WB检测。*预测模型主要基于免疫原序列比对,结果仅作参考,不作为质保凭据。

Species
Results
Score
Zebrafish
100
Pig
91
Horse
91
Bovine
91
Sheep
91
Dog
91
Rabbit
91
Xenopus
0
Chicken
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

翻译修饰 - P51617 作为底物

Site PTM Type Enzyme
T66 Phosphorylation P41743 (PRKCI)
T100 Phosphorylation P31749 (AKT1)
S110 Phosphorylation
R117 Methylation
S131 Phosphorylation
K134 Ubiquitination
T141 Phosphorylation
S144 Phosphorylation
S163 Phosphorylation
S173 Phosphorylation
K180 Ubiquitination
T209 Phosphorylation P51617 (IRAK1)
K239 Acetylation
K242 Ubiquitination
K253 Ubiquitination
K342 Ubiquitination
K355 Ubiquitination
S371 Phosphorylation
S373 Phosphorylation
S375 Phosphorylation
S376 Phosphorylation Q9NWZ3 (IRAK4)
T381 Phosphorylation
T387 Phosphorylation P51617 (IRAK1) , Q9NWZ3 (IRAK4)
K397 Ubiquitination
K435 Ubiquitination
Y515 Phosphorylation
S556 Phosphorylation
S568 Phosphorylation
S591 Phosphorylation
S601 Phosphorylation
T605 Phosphorylation
S650 Phosphorylation
S653 Phosphorylation

翻译修饰 - P51617 作为激酶

Substrate Site Source
P40763 (STAT3) S727 Uniprot
P51617-2 (IRAK1) T66 Uniprot
P51617 (IRAK1) T209 Uniprot
P51617-4 (IRAK1) S376 Uniprot
P51617 (IRAK1) T387 Uniprot
P58753 (TIRAP) T28 Uniprot
Q96FA3 (PELI1) S70 Uniprot
Q96FA3 (PELI1) S76 Uniprot
Q96FA3 (PELI1) S78 Uniprot
Q96FA3 (PELI1) T80 Uniprot
Q96FA3 (PELI1) S82 Uniprot
Q96FA3 (PELI1) T86 Uniprot
Q96FA3 (PELI1) S125 Uniprot
Q96FA3 (PELI1) T127 Uniprot
Q96FA3 (PELI1) T288 Uniprot
Q96FA3 (PELI1) S293 Uniprot
Q9H4G4 (GLIPR2) S58 Uniprot
Q9HAT8 (PELI2) T290 Uniprot

研究背景

功能:

Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3.

翻译修饰:

Following recruitment on the activated receptor complex, phosphorylated on Thr-209, probably by IRAK4, resulting in a conformational change of the kinase domain, allowing further phosphorylations to take place. Thr-387 phosphorylation in the activation loop is required to achieve full enzymatic activity.

Polyubiquitinated by TRAF6 after cell stimulation with IL-1-beta by PELI1, PELI2 and PELI3. Polyubiquitination occurs with polyubiquitin chains linked through 'Lys-63'. Ubiquitination promotes interaction with NEMO/IKBKG. Also sumoylated; leading to nuclear translocation.

细胞定位:

Cytoplasm. Nucleus. Lipid droplet.
Note: Translocates to the nucleus when sumoylated. RSAD2/viperin recruits it to the lipid droplet (By similarity).

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
组织特异性:

Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2.

亚基结构:

Homodimer (By similarity). Forms a complex with TRAF6, PELI1, IRAK4 and MYD88. Direct binding of SMAD6 to PELI1 prevents complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression. The TRAF6-PELI1-IRAK4-MYD88 complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation. Interaction with MYD88 recruits IRAK1 to the stimulated receptor complex. Interacts with TOLLIP; this interaction occurs in the cytosol prior to receptor activation. Interacts with IL1RL1. Interacts with PELI1 and TRAF6. Interacts (when polyubiquitinated) with IKBKG/NEMO. Interacts with RSAD2/viperin (By similarity). Interacts with IRAK1BP1 (By similarity). Interacts with PELI2 (By similarity). Interacts with ZC3H12A; this interaction increases the interaction between ZC3H12A and IKBKB/IKKB (By similarity). Interacts with IRAK4. Interacts with PELI3. Interacts with INAVA; the interaction takes place upon PRR stimulation. Interacts (via C-terminus) with NFATC4 (via N-terminus).

(Microbial infection) Interacts with mumps virus protein SH; this interaction inhibits downstream NF-kappa-B pathway activation.

蛋白家族:

The ProST region is composed of many proline and serine residues (more than 20 of each) and some threonines. This region is the site of IRAK-1 hyperphosphorylation.

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.

研究领域

· Environmental Information Processing > Signal transduction > MAPK signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > NF-kappa B signaling pathway.   (View pathway)

· Human Diseases > Infectious diseases: Bacterial > Pertussis.

· Human Diseases > Infectious diseases: Parasitic > Leishmaniasis.

· Human Diseases > Infectious diseases: Parasitic > Chagas disease (American trypanosomiasis).

· Human Diseases > Infectious diseases: Parasitic > Toxoplasmosis.

· Human Diseases > Infectious diseases: Bacterial > Tuberculosis.

· Human Diseases > Infectious diseases: Viral > Measles.

· Human Diseases > Infectious diseases: Viral > Epstein-Barr virus infection.

· Organismal Systems > Immune system > Toll-like receptor signaling pathway.   (View pathway)

· Organismal Systems > Nervous system > Neurotrophin signaling pathway.   (View pathway)

文献引用

1). Meng DF et al. S100A14 suppresses metastasis of nasopharyngeal carcinoma by inhibition of NF-kB signaling through degradation of IRAK1. Oncogene 2020 Jun 17. (PubMed: 32555330) [IF=8.756]

Application: WB    Species: Human    Sample: nasopharyngeal mucosa and nasopharyngeal carcinoma

Fig. 5 S100A14 promotes ubiquitin–proteasome-mediated degradation of IRAK1. a Immunoblotting analysis of P-IRAK1 (T387) and IRAK1 protein levels in the S100A14 overexpressing cells and S100A14 knocked-down cells.

2). Yang YF et al. Ficolin-A/2, acting as a new regulator of macrophage polarization, mediates the inflammatory response in experimental mouse colitis. Immunology 2017 Aug;151(4):433-450 (PubMed: 28380665) [IF=7.215]

Application: WB    Species: mouse    Sample:

Figure 7. FCN-A promoted the M1 polarization of BMDMs through a TLR4/MyD88-dependent pathway in vitro. (a) The protein expressions of the purified GST-FCN-A and GST were determined by SDS-PAGE. (b) The extracted membrane proteins from RAW264.7 cells were incubated with the purified GST-FCN-A or GST proteins. Co-IP analysis of the interaction between TLR4 of macrophage and GST-FCN-A was performed by using anti-TLR4. Rabbit IgG was used as a negative control in co-IP. (c, e) BMDMs, isolated from WT, TLR4-/- or MyD88-/- mice, were stimulated with FCN-A (10g/mL) for 24 h, then the expressions of iNOS and Arg-1 from BMDMs were examined by Western blot analysis. (d, f) The levels of pro-inflammatory cytokines IL-1in cell lysates, and secreted IL-6, TNF- were detected by ELISA. (g, h) Western blot analysis of p-IRAK1, p-p65, p-ERK1/2, and p-JNK in the BMDM lysates of TLR4-/-, MyD88-/- or WT after stimulation with FCN-A for 0-45 min. In d and f, values are mean ± [SEM] from three independent experiments.

3). Zheng Q et al. Isorhynchophylline ameliorates paraquat-induced acute kidney injury by attenuating oxidative stress and mitochondrial damage via regulating toll-interacting expression. Toxicol Appl Pharmacol 2021 Apr 8;420:115521. (PubMed: 33838153) [IF=4.460]

Application: WB    Species: Rat    Sample: kidney tissues

Fig. 4. Effects of INR on Tollip expression and mitochondrial damage in kidney tissues of PQ-intoxicated rats. (A) Tollip expression in kidney tissues was detected by immunohistochemistry. Scale bars: 200 μm (100× magnification) and 50 μm (400× magnification). (B, C) Western blot showed the expression of Tollip, p-IRAK1 and IRAK1 in kidney tissues. (D, E) Western blot evaluated the release of Cytochrome C from mitochondria into cytosol. ###p < 0.001 vs. PQ.

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