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  4. Recombinant Human Mixed lineage kinase domain-like protein (MLKL)

Recombinant Human Mixed lineage kinase domain-like protein (MLKL)

In Stock
  • 货号：
    CSB-EP850851HUa0
  • 规格：
    ￥1836
  • 图片：
    • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
  • 其他：

产品详情

  • 纯度：
    Greater than 85% as determined by SDS-PAGE.
  • 基因名：
  • Uniprot No.：
  • 别名：
    9130019I15Rik; FLJ34389; hMLKL; Mixed lineage kinase domain like; Mixed lineage kinase domain like protein; Mixed lineage kinase domain like pseudokinase; Mixed lineage kinase domain-like protein; Mlkl; MLKL_HUMAN
  • 种属：
    Homo sapiens (Human)
  • 蛋白长度：
    Full Length
  • 来源：
    E.coli
  • 分子量：
    58.5 kDa
  • 表达区域：
    1-471aa
  • 氨基酸序列
    MENLKHIITLGQVIHKRCEEMKYCKKQCRRLGHRVLGLIKPLEMLQDQGKRSVPSEKLTTAMNRFKAALEEANGEIEKFSNRSNICRFLTASQDKILFKDVNRKLSDVWKELSLLLQVEQRMPVSPISQGASWAQEDQQDADEDRRAFQMLRRDNEKIEASLRRLEINMKEIKETLRQYLPPKCMQEIPQEQIKEIKKEQLSGSPWILLRENEVSTLYKGEYHRAPVAIKVFKKLQAGSIAIVRQTFNKEIKTMKKFESPNILRIFGICIDETVTPPQFSIVMEYCELGTLRELLDREKDLTLGKRMVLVLGAARGLYRLHHSEAPELHGKIRSSNFLVTQGYQVKLAGFELRKTQTSMSLGTTREKTDRVKSTAYLSPQELEDVFYQYDVKSEIYSFGIVLWEIATGDIPFQGCNSEKIRKLVAVKRQQEPLGEDCPSELREIIDECRAHDPSVRPSVDEILKKLSTFSK
    Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
  • 蛋白标签：
    N-terminal 6xHis-tagged
  • 产品提供形式：
    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.
  • 缓冲液：
    Tris-based buffer,50% glycerol
  • 储存条件：
    Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
  • 保质期：
    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.
  • 货期：
    3-7 business days
  • 注意事项：
    Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
  • 产品描述：
        MLKL属于蛋白激酶超家族，包含一个蛋白激酶样结构域，但是蛋白激酶结构域无催化活性。MLKL在TNF诱导的程序性细胞坏死过程中起关键作用。MLKL介导坏死信号，并以受体相互作用蛋白激酶3 (RIPK3)依赖的方式触发细胞死亡2。在肝细胞癌免疫逃逸中，MLKL的RIPK3非依赖性作用通过抑制PARP-1依赖性细胞死亡促进肝细胞癌的免疫逃避。此外，MLKL还在脑缺血中发挥重要作用。在脑缺血后，MLKL作为受体相互作用蛋白3的底物，经过聚集和磷酸化，从细胞质中转移到细胞膜，引起线粒体分裂和细胞死亡。总的来说，MLKL在细胞死亡和炎症等病理过程中起着关键作用，与神经系统、免疫系统、肿瘤等疾病密切相关。
        j9九游会登录入口首页生物提供大肠杆菌表达系统制备的全长MLKL重组蛋白，助您进行相关科研工作。
  • Datasheet & COA：
    Please contact us to get it.

产品评价

靶点详情

  • 功能：
    Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process. Does not have protein kinase activity. Activated following phosphorylation by RIPK3, leading to homotrimerization, localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage. In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following activation by ZBP1, MLKL is phosphorylated by RIPK3 in the nucleus, triggering disruption of the nuclear envelope and leakage of cellular DNA into the cytosol.following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol. Binds to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which is essential for its necroptotic function.
  • 基因功能参考文献：
    1. Following activation, toggling within the MLKL pseudokinase domain promotes 4HB domain disengagement from the pseudokinase domain alphaC helix and pseudocatalytic loop, to enable formation of a necroptosis-inducing tetramer. PMID: 29930286
    2. Data show that phosphatidylinositol transfer protein alpha (PITPalpha) is involved in the function of mixed lineage kinase domain-like protein (MLKL) in necroptosis. PMID: 29104146
    3. MLKL expression alters APP metabolism and loss-of-function mutation might contribute to late-onset ApoE varepsilon4-negative AD in the Hong Kong Chinese population. PMID: 29656768
    4. Results demonstrate that MLKL concentrations measured after three days of ICU treatment in critically ill patients predict prognosis during intensive care unit treatment. These data not only suggest a previously unrecognized function of MLKL as a biomarker in critical illness and sepsis but also highlight the clinical relevance of MLKL in the pathophysiology of inflammatory and infectious diseases. PMID: 29606984
    5. Thus, activation of MLKL determines cell lysis with release of proinflammatory mediators. We found that pMLKL, the activated form of MLKL, is significantly increased in intestinal epithelial cells expressing RIP3 as well as in bioptic inflamed ileal and colonic tissues from CD and UC patients. PMID: 28844856
    6. Biological events and molecular signaling following MLKL activation during necroptosis have been reported. PMID: 28854080
    7. Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival in all patient-group with resected colon cancer. PMID: 27432118
    8. Phosphorylated MLKL leads to a conformational change, exposure of the N-terminal domain, results in MLKL membrane localization, oligomerization and membrane permeabilization. PMID: 26868910
    9. adhesion-induced eosinophil cytolysis takes place through RIPK3-MLKL-dependent necroptosis, which can be counterregulated by autophagy PMID: 28412393
    10. MLKL forms cation channels that are permeable preferentially to Mg(2+) rather than Ca(2+) in the presence of Na(+) and K(+). PMID: 27033670
    11. RIPK3 is a key factor in protection against OLs death and abnormal myelin development via its interaction with MLKL. PMID: 28230861
    12. these findings demonstrate that Trx1 is a critical regulator of necroptosis that suppresses cell death by maintaining MLKL in a reduced inactive state. PMID: 28878015
    13. this study shows that release of phosphorylated MLKL within extracellular vesicles serves as a mechanism for self-restricting the necroptotic activity of this protein PMID: 28666573
    14. this study shows that MLKL is an endogenous activator of the NLRP3 inflammasome, and that MLKL activation provides a mechanism for concurrent processing and release of IL-1beta independently of gasdermin-D PMID: 28130493
    15. Data suggest that necroptotic cells externalize phosphatidylserine (PS) after translocation of phosphorylated MLKL to cell membrane; necroptotic cells with exposed PS release extracellular vesicles containing MLKL; inhibition of MLKL after PS exposure can reverse process of necroptosis and restore cell viability. PMID: 28650960
    16. results reveal a pathway for MLKL-dependent programmed necrosis that is executed in the absence of RIPK3 and potentially drives the pathogenesis of severe liver diseases. PMID: 27756058
    17. MLKL octamer formation depends on alpha-helices 4 and 5. PMID: 27920255
    18. Necroptosis signaling is modulated by the kinase RIPK1 and requires the kinase RIPK3 and the pseudokinase MLKL. (Review) PMID: 26865533
    19. In AML, MLKL expression is reduced in specific subsets. This is linked to its function in activating the ASC inflammasome. PMID: 27411587
    20. Downregulated expression of MLKL is associated with gastric caner. PMID: 27473085
    21. Results from interaction proteomics identified MLKL as a novel HSP90 client protein in HT-29 cells. PMID: 26933192
    22. coexpression of Hsp90 increases MLKL oligomerization and plasma membrane translocation and enhances MLKL-mediated necroptosis. Findings demonstrate that an efficient necrotic response requires a functional Hsp90. PMID: 26866270
    23. MLKL was a prognostic biomarker for cervical squamous cell carcinoma PMID: 26823841
    24. Modelling predicts that a C-terminal helix constrains the activity of MLKL1, but not MLKL2 PMID: 26704887
    25. Results show that upon activation, MLKL undergoes oligomerization mediated by the brace domain, being recruited to the plasma membrane through avidity of N-terminal helix bundle for phosphatidylinositol phosphate (PIP). PMID: 26853145
    26. MLKL structure determined by nuclear magnetic resonance spectroscopy reveals how different structural elements of the MLKL N-terminal region contribute to MLKL function and membrane permeation. PMID: 25220470
    27. MLKL upregulation in SPARC overexpressed cells treated with Ara-C, indicates necrosis as a possible cell death process for the SKM-1 cells under these stringent conditions PMID: 26165695
    28. in the absence of caspase-8 activity, 24(S)-Hydroxycholesterol induces a necroptosis-like cell death which is RIPK1-dependent but MLKL-independent. PMID: 25697054
    29. These data reveal a potential role for RIPK3 as a suppressor of MLKL activation and indicate that phosphorylation can fine-tune the ability of MLKL to induce necroptosis. PMID: 26283547
    30. a novel non-enzymatic function of AChE-R is to stimulate RIPK1/MLKL-dependent regulated necrosis (necroptosis). The latter complements a cholinergic system in the ovary, which determines life and death of ovarian cells. PMID: 25766324
    31. High expression of RIP3 in keratinocytes from toxic epidermal necrolysis patients potentiates MLKL phosphorylation/activation and necrotic cell death. PMID: 25748555
    32. s demonstrate that the full four-helical bundle domain (4HBD) in the N-terminal region of MLKL is required and sufficient to induce its oligomerization and trigger cell death. PMID: 24813885
    33. MLKL binding to phosphatidylinositol phosphates is required for plasma membrane rupture PMID: 24813885
    34. Report role of MLKL/RIP3 pathway in necrotic membrane disruption. PMID: 24703947
    35. MLKL protein expression is significantly upregulated in children, diagnosed with inflammatory bowel disease. PMID: 24322838
    36. Data suggest that nucleotide- (ATP-) binding residues of human MLKL have divergently evolved from mouse Mlkl and conventional protein kinases; studies include small-angle X-ray scattering, thermal shift of nucleotide binding, and sequence alignment. PMID: 24219132
    37. This study reveals a crucial mechanism of MLKL-mediated TNF-induced necroptosis. PMID: 24316671
    38. Low expression of MLKL is associated with decreased OS in patients with resected PAC and decreased RFS and OS in the subset of patients with resected PAC who receive adjuvant chemotherapy. PMID: 23720157
    39. the importance of the RIP3-MLKL interaction in the formation of functional necrosomes and suggest that translocation of necrosomes to mitochondria-associated membranes is essential for necroptosis signaling. PMID: 23612963
    40. study suggests that MLKL is a key RIP3 downstream component of TNF-induced necrotic cell death PMID: 22421439
    41. Findings implicate MLKL as a key mediator of necrosis signaling downstream of the kinase RIP3. PMID: 22265413

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  • 亚细胞定位：
    Cytoplasm. Cell membrane. Nucleus.
  • 蛋白家族：
    Protein kinase superfamily
  • 数据库链接：

    HGNC: 26617

    OMIM: 615153

    KEGG: hsa:197259

    STRING: 9606.ENSP00000308351

    UniGene: Hs.119878