产品: 磷酸化 TAK1 (Thr187) 抗体
货号: AF3019
描述: Rabbit polyclonal antibody to Phospho-TAK1 (Thr187)
应用: WB IHC IF/ICC
反应: Human, Mouse, Rat
预测: Zebrafish, Bovine, Horse, Sheep, Rabbit, Dog, Chicken, Xenopus
分子量: 70kDa; 67kD(Calculated).
蛋白号: O43318
RRID: AB_2832996

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产品描述

来源:
Rabbit
应用:
WB 1:500-1:2000, IHC 1:50-1:500, IF/ICC 1:100-1:500
*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:
Zebrafish(100%), Bovine(100%), Horse(100%), Sheep(100%), Rabbit(100%), Dog(100%), Chicken(100%), Xenopus(100%)
克隆:
Polyclonal
特异性:
Phospho-TAK1 (Thr187) Antibody detects endogenous levels of TAK1 only when phosphorylated at Threonine 187.
RRID:
AB_2832996
引用格式: Affinity Biosciences Cat# AF3019, RRID:AB_2832996.
偶联:
Unconjugated.
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

M3K7_HUMAN; MAP3K 7; Map3k7; MEKK7; Mitogen activated protein kinase kinase kinase 7; Mitogen-activated protein kinase kinase kinase 7; TAK1; TGF beta activated kinase 1; TGF-beta-activated kinase 1; TGF1a; Transforming growth factor beta activated kinase 1; Transforming growth factor-beta-activated kinase 1;

抗原和靶标

免疫原:
Uniprot:
基因/基因ID:
表达:
O43318 M3K7_HUMAN:

Isoform 1A is the most abundant in ovary, skeletal muscle, spleen and blood mononuclear cells. Isoform 1B is highly expressed in brain, kidney and small intestine. Isoform 1C is the major form in prostate. Isoform 1D is the less abundant form.

描述:
AK1 a protein kinase of the MLK family. Mediates signal transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B.
序列:
MSTASAASSSSSSSAGEMIEAPSQVLNFEEIDYKEIEVEEVVGRGAFGVVCKAKWRAKDVAIKQIESESERKAFIVELRQLSRVNHPNIVKLYGACLNPVCLVMEYAEGGSLYNVLHGAEPLPYYTAAHAMSWCLQCSQGVAYLHSMQPKALIHRDLKPPNLLLVAGGTVLKICDFGTACDIQTHMTNNKGSAAWMAPEVFEGSNYSEKCDVFSWGIILWEVITRRKPFDEIGGPAFRIMWAVHNGTRPPLIKNLPKPIESLMTRCWSKDPSQRPSMEEIVKIMTHLMRYFPGADEPLQYPCQYSDEGQSNSATSTGSFMDIASTNTSNKSDTNMEQVPATNDTIKRLESKLLKNQAKQQSESGRLSLGASRGSSVESLPPTSEGKRMSADMSEIEARIAATTAYSKPKRGHRKTASFGNILDVPEIVISGNGQPRRRSIQDLTVTGTEPGQVSSRSSSPSVRMITTSGPTSEKPTRSHPWTPDDSTDTNGSDNSIPMAYLTLDHQLQPLAPCPNSKESMAVFEQHCKMAQEYMKVQTEIALLLQRKQELVAELDQDEKDQQNTSRLVQEHKKLLDENKSLSTYYQQCKKQLEVIRSQQQKRQGTS

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

翻译修饰 - O43318 作为底物

Site PTM Type Enzyme
Phosphorylation
Ubiquitination
K34 Ubiquitination
K63 Ubiquitination
K72 Ubiquitination
K158 Ubiquitination
T178 Phosphorylation O43318 (MAP3K7)
T184 Phosphorylation O43318 (MAP3K7)
T187 Phosphorylation O43318 (MAP3K7)
S192 Phosphorylation O43318 (MAP3K7)
K209 Ubiquitination
S268 Phosphorylation
K269 Ubiquitination
T333 Phosphorylation
T344 Phosphorylation
K346 Ubiquitination
K351 Ubiquitination
K354 Ubiquitination
S361 Phosphorylation
S367 Phosphorylation
S371 Phosphorylation
S375 Phosphorylation
K386 Acetylation
S389 Phosphorylation
S393 Phosphorylation
Y405 Phosphorylation
S406 Phosphorylation
T415 Phosphorylation
S417 Phosphorylation
S439 Phosphorylation
T444 Phosphorylation
T448 Phosphorylation
S454 Phosphorylation
S455 Phosphorylation
S458 Phosphorylation
S459 Phosphorylation
T471 Phosphorylation
S472 Phosphorylation
K474 Ubiquitination
T538 Phosphorylation
K547 Ubiquitination
K573 Acetylation
K579 Ubiquitination
Y584 Phosphorylation
Y585 Phosphorylation
K590 Ubiquitination

翻译修饰 - O43318 作为激酶

Substrate Site Source
O14920 (IKBKB) S177 Uniprot
O14920-1 (IKBKB) S181 Uniprot
O43318 (MAP3K7) T178 Uniprot
O43318-3 (MAP3K7) T184 Uniprot
O43318 (MAP3K7) T187 Uniprot
O43318-1 (MAP3K7) S192 Uniprot
P26045 (PTPN3) S359 Uniprot
P52564 (MAP2K6) S207 Uniprot
P52564 (MAP2K6) T211 Uniprot
P54646 (PRKAA2) T172 Uniprot
P56524 (HDAC4) S246 Uniprot
P84022-1 (SMAD3) S422 Uniprot
P84022-1 (SMAD3) S423 Uniprot
P84022-1 (SMAD3) S425 Uniprot
Q01094 (E2F1) S337 Uniprot
Q15750 (TAB1) S452 Uniprot
Q15750 (TAB1) S453 Uniprot
Q15750 (TAB1) S456 Uniprot
Q15750 (TAB1) S457 Uniprot
Q8IVT5 (KSR1) S406 Uniprot
Q8WUI4 (HDAC7) S155 Uniprot
Q9UQL6 (HDAC5) S259 Uniprot

研究背景

功能:

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity. Phosphorylates RIPK1 at 'Ser-321' which positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (By similarity).

翻译修饰:

Association with TAB1/MAP3K7IP1 promotes autophosphorylation at Ser-192 and subsequent activation. Association with TAB2/MAP3K7IP2, itself associated with free unanchored Lys-63 polyubiquitin chain, promotes autophosphorylation and subsequent activation of MAP3K7. Dephosphorylation at Ser-192 by PPM1B/PP2CB and at Thr-187 by PP2A and PPP6C leads to inactivation.

'Lys-48'-linked polyubiquitination at Lys-72 is induced by TNFalpha, and leads to proteasomal degradation. Undergoes 'Lys-48'-linked polyubiquitination catalyzed by ITCH (By similarity). Requires 'Lys-63'-linked polyubiquitination for autophosphorylation and subsequent activation. 'Lys-63'-linked ubiquitination does not lead to proteasomal degradation. Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin chains. Deubiquitinated by Y.enterocolitica YopP.

(Microbial infection) Cleaved and inactivated by the proteases 3C of coxsackievirus A16 and human enterovirus D68, allowing the virus to disrupt TRAF6-triggered NF-kappa-B induction.

细胞定位:

Cytoplasm. Cell membrane>Peripheral membrane protein>Cytoplasmic side.
Note: Although the majority of MAP3K7/TAK1 is found in the cytosol, when complexed with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2, it is also localized at the cell membrane.

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 1A is the most abundant in ovary, skeletal muscle, spleen and blood mononuclear cells. Isoform 1B is highly expressed in brain, kidney and small intestine. Isoform 1C is the major form in prostate. Isoform 1D is the less abundant form.

亚基结构:

Can form homodimer. Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with TAB1/MAP3K7IP1, TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3. Identified in the TRIKA2 complex composed of MAP3K7/TAK1, TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2. Interacts with PPM1L and PPM1B/PP2CB. Interaction with PP2A and PPP6C leads to its repressed activity. Interacts with TRAF6 and TAB1/MAP3K7IP1; during IL-1 signaling. Interacts with TAOK1 and TAOK2; interaction with TAOK2 interferes with MAP3K7 interaction with IKKA, thus preventing NF-kappa-B activation. Interacts with WDR34 (via WD domains). Interacts with CYLD and RBCK1. Interacts with TGFBR1; induces MAP3K7/TAK1 activation by TRAF6. Interacts with MAPK8IP1 and SMAD6 (By similarity). Interacts with isoform 1 of VRK2. Interacts with DAB2; the interaction is induced by TGF-beta stimulation and may mediate TGF-beta stimulated JNK activation. Interacts with TRIM5. Part of a complex containing ITCH, NDFIP1 and MAP3K7 (By similarity). Interacts with IFIT5; the interaction synergizes the recruitment of IKK to MAP3K7 and enhances IKK phosphorylation. Interacts with PLEKHM1 (via N- and C-terminus) (By similarity). Interacts with TRIM8. Found in a complex with SH3RF1, RAC2, MAP2K7/MKK7, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2 (By similarity). Interacts with SASH1. Interacts with RIPK1 (By similarity).

(Microbial infection) Interacts with herpes simplex virus 2 protein US2; this interaction induces MAP3K7 phosphorylation and subsequent activation.

蛋白家族:

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.

研究领域

· Cellular Processes > Transport and catabolism > Autophagy - animal.   (View pathway)

· Cellular Processes > Cellular community - eukaryotes > Adherens junction.   (View pathway)

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

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

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

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

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

· Human Diseases > Infectious diseases: Parasitic > Leishmaniasis.

· Human Diseases > Infectious diseases: Parasitic > Toxoplasmosis.

· Human Diseases > Infectious diseases: Viral > Measles.

· Human Diseases > Infectious diseases: Viral > Herpes simplex infection.

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

· Organismal Systems > Development > Osteoclast differentiation.   (View pathway)

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

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

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

· Organismal Systems > Immune system > IL-17 signaling pathway.   (View pathway)

· Organismal Systems > Immune system > T cell receptor signaling pathway.   (View pathway)

文献引用

1). TRAF3 mediates neuronal apoptosis in early brain injury following subarachnoid hemorrhage via targeting TAK1-dependent MAPKs and NF-κB pathways. Cell Death & Disease, 2021 (PubMed: 33414375) [IF=9.0]

Application: WB    Species: Human    Sample: neural cells

Fig. 7 TRAF3–TAK1 interaction and phosphorylation of TAK1 are required for TRAF3-dependent neuronal apoptosis in SAH. Western blot analysis revealed that TRAF3 siRNA reduced the phosphorylation of TAK1 after SAH both in vivo (A, B) and in vitro (C, D). N = 6 mice or wells per group. *p 

2). Kongensin a attenuates intervertebral disc degeneration by inhibiting TAK1-mediated PANoptosis of nucleus pulposus cells. International immunopharmacology, 2024 (PubMed: 38359662) [IF=5.6]

Application: WB    Species: Rat    Sample: NPCs

Fig. 3. Biobehavioral differences induced by KA treatment of NPCs. a Volcano plot presenting 20 upregulated and 78 downregulated DEGs in RNA-seq analysis. b-d GO enrichment results showed that most DEGs were involved in response to oxidative stress, ROS and regeneration. e KEGG enrichment analysis was used to study pathways that may be involved in the treatment process. f, g Effects of KA on TAK1 and p-TAK1 expression (n = 3).

3). SHP-1 suppresses endotoxin-induced uveitis by inhibiting the TAK1/JNK pathway. Journal of Cellular and Molecular Medicine, 2021 (PubMed: 33207073) [IF=5.3]

Application: WB    Species: Rat    Sample: rMC‐1 cells

FIGURE 7 SHP‐1 negatively regulates kinase phosphorylation in LPS‐treated rMC‐1 cells. A, Effects of SHP‐1 overexpression on inflammatory signalling pathways. Blank‐rLV‐ and SHP‐1‐rLV‐ transfected rMC‐1 cells were exposed to 10 μg/mL LPS for 0, 15 or 30 min, and Western blotting was performed to determine the phosphorylation status of TAK1, JNK and NF‐κB and the total protein levels of JNK and NF‐κB. B‐D, Quantitative analysis of pTAK1/β‐actin (B), pJNK/JNK (C) and pNF‐κB/NF‐κB (D). E, Effects of SHP‐1 knockdown on inflammatory signalling pathways. Blank‐rLV‐ and shRNA‐SHP‐1‐rLV‐transfected rMC‐1 cells were exposed to 10 μg/mL LPS for 0, 15, or 30 min, and Western blotting was performed to determine the phosphorylation status of TAK1, JNK and NF‐κB and the total protein levels of JNK and NF‐κB. F‐H, Quantitative analysis of pTAK1/β‐actin (F), pJNK/JNK (G) and pNF‐κB/NF‐κB (H). Two‐way ANOVA followed by Dunnett's test was used. n = 3 per group. *P < .05 and **P < .01

4). TAK1 Reduces Surgery-induced Overactivation of RIPK1 to Relieve Neuroinflammation and Cognitive Dysfunction in Aged Rats. Neurochemical Research, 2023 (PubMed: 37329446) [IF=4.4]

Application: WB    Species: Rat    Sample: hippocampal

Fig. 3 TAK1 inhibition exacerbated neuroinflammation and cognitive dysfunction in young rats after surgery, which were reversed by a RIPK1 inhibitor. (a-b) Comparison of the total distance travelled by the rats in the OFT at different time points. (c) The percentage of freezing time at 72 h after surgery. (d-e) Representative western blots and analysis of TAK1, pTAK1, RIPK1 and pRIPK1 expression at 72 h after surgery. (f-i) Representative western blots and analysis of TNF-α, pro-IL-1β, AP-1 and NF-κB p65 expression in hippocampal samples 72 h after surgery. (j) Quantification of GFAP and Iba1 fluorescence in the hippocampal CA1 region 72 h after surgery. (k) Representative images of GFAP and Iba1 fluorescence in the hippocampal CA1 region 72 h after surgery. The data are presented as the mean ± SD (n = 10).

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