Details of the BTS

General Information of Binding Target of SBP (BTS) (ID: ST00207)
BTS Name
Mixed lineage kinase domain-like protein
Synonyms
hMLKL
BTS Type
Protein
Family
Protein kinase superfamily
Gene Name
MLKL
Organism
Homo sapiens (Human)
Function
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 (By similarity). Binds to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which is essential for its necroptotic function
UniProt ID
Q8NB16
UniProt Entry
MLKL_HUMAN
PFam
PF07714
Gene ID
197259
Sequence
MENLKHIITLGQVIHKRCEEMKYCKKQCRRLGHRVLGLIKPLEMLQDQGKRSVPSEKLTT
AMNRFKAALEEANGEIEKFSNRSNICRFLTASQDKILFKDVNRKLSDVWKELSLLLQVEQ
RMPVSPISQGASWAQEDQQDADEDRRAFQMLRRDNEKIEASLRRLEINMKEIKETLRQYL
PPKCMQEIPQEQIKEIKKEQLSGSPWILLRENEVSTLYKGEYHRAPVAIKVFKKLQAGSI
AIVRQTFNKEIKTMKKFESPNILRIFGICIDETVTPPQFSIVMEYCELGTLRELLDREKD
LTLGKRMVLVLGAARGLYRLHHSEAPELHGKIRSSNFLVTQGYQVKLAGFELRKTQTSMS
LGTTREKTDRVKSTAYLSPQELEDVFYQYDVKSEIYSFGIVLWEIATGDIPFQGCNSEKI
RKLVAVKRQQEPLGEDCPSELREIIDECRAHDPSVRPSVDEILKKLSTFSK
Sequence Length
471
Synthetic Binding Protein (SBP) Targeting This BTS
SBP Name Highest Status Mechanism Affinity Application Details Ref
Monobody anti-MLKL clone 26 Research Binder Kd: 176 nM Tools for inducing necroptotic cell death
SBP Info
 		[1]
Monobody anti-MLKL clone 27 Research Binder Kd: 75 nM Tools for inducing necroptotic cell death
SBP Info
 		[1]
Monobody anti-MLKL clone 32 Research Blocker Kd: 37.1 nM Tools for identification of MLKL membrane translocation as a checkpoint in necroptotic cell death
SBP Info
 		[2]
Monobody anti-MLKL clone 33 Research Blocker Kd: 141 nM Tools for identification of MLKL membrane translocation as a checkpoint in necroptotic cell death
SBP Info
 		[2]
Monobody anti-MLKL clone 37 Research Blocker Kd: 170 nM Tools for identification of MLKL membrane translocation as a checkpoint in necroptotic cell death
SBP Info
 		[2]
References
1 Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis. Nat Commun. 2021 Apr 13;12(1):2211.
2 Identification of MLKL membrane translocation as a checkpoint in necroptotic cell death using Monobodies. Proc Natl Acad Sci U S A. 2020 Apr 14;117(15):8468-8475.