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Mouse Anti-MLKL (Phosphorylated S358) Recombinant Antibody (6B4) (PTM-CBMAB-0438LY)


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Summary

Host Animal
Mouse
Specificity
Human
Clone
6B4
Antibody Isotype
IgG
Application
IHC-P

Basic Information

Specificity
Human
Antibody Isotype
IgG
Clonality
Monoclonal
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Formulations & Storage [For reference only, actual COA shall prevail!]

Format
Liquid
Buffer
PBS (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol
Purity
> 95% Purity determined by SDS-PAGE.
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.

Target

Full Name
Mixed Lineage Kinase Domain Like Pseudokinase
Introduction
This gene belongs to the protein kinase superfamily. The encoded protein contains a protein kinase-like domain; however, is thought to be inactive because it lacks several residues required for activity. This protein plays a critical role in tumor necrosis factor (TNF)-induced necroptosis, a programmed cell death process, via interaction with receptor-interacting protein 3 (RIP3), which is a key signaling molecule in necroptosis pathway. Inhibitor studies and knockdown of this gene inhibited TNF-induced necrosis. High levels of this protein and RIP3 are associated with inflammatory bowel disease in children. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2015]
Entrez Gene ID
197259
UniProt ID
Q8NB16
Alternative Names
Mixed Lineage Kinase Domain Like Pseudokinase; HMLKL; Mixed Lineage Kinase Domain-Like Protein; Mixed Lineage Kinase Domain-Like;
Function
Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671).

Does not have protein kinase activity (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671).

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 (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671).

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 (By similarity).

Binds to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which is essential for its necroptotic function (PubMed:29883610).
Biological Process
Cell surface receptor signaling pathway Source: InterPro
Defense response to virus Source: UniProtKB
Execution phase of necroptosis Source: UniProtKB
Necroptotic process Source: UniProtKB
Necroptotic signaling pathway Source: UniProtKB
Protein homotrimerization Source: UniProtKB
Cellular Location
Cytoplasm
Nucleus
Plasma membrane
Cell membrane
Note: Localizes to the cytoplasm and translocates to the plasma membrane on necroptosis induction (PubMed:24316671). Localizes to the nucleus in response to orthomyxoviruses infection (By similarity).
PTM
Phosphorylation by RIPK3 induces a conformational switch that is required for necroptosis (PubMed:22265413). It also induces homotrimerization and localization to the plasma membrane (PubMed:22265413).
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For research use only. Not intended for any clinical use.

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