Skip to main content
  •   Home
  •   Download
  •   Manual
  •   Contact

Molecule Details

General Information of the Molecule
Name
Mixed lineage kinase domain-like protein (MLKL)
Synonyms
Hmlkl
Gene Name
MLKL
Gene ID
197259
Sequence
MENLKHIITLGQVIHKRCEEMKYCKKQCRRLGHRVLGLIKPLEMLQDQGKRSVPSEKLTT
AMNRFKAALEEANGEIEKFSNRSNICRFLTASQDKILFKDVNRKLSDVWKELSLLLQVEQ
RMPVSPISQGASWAQEDQQDADEDRRAFQMLRRDNEKIEASLRRLEINMKEIKETLRQYL
PPKCMQEIPQEQIKEIKKEQLSGSPWILLRENEVSTLYKGEYHRAPVAIKVFKKLQAGSI
AIVRQTFNKEIKTMKKFESPNILRIFGICIDETVTPPQFSIVMEYCELGTLRELLDREKD
LTLGKRMVLVLGAARGLYRLHHSEAPELHGKIRSSNFLVTQGYQVKLAGFELRKTQTSMS
LGTTREKTDRVKSTAYLSPQELEDVFYQYDVKSEIYSFGIVLWEIATGDIPFQGCNSEKI
RKLVAVKRQQEPLGEDCPSELREIIDECRAHDPSVRPSVDEILKKLSTFSK
    Click to Show/Hide
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.
    Click to Show/Hide
Uniprot ID
MLKL_HUMAN
TC Number
TC: 1.A.105.1.1
Pfam
PF07714
KEGG ID
hsa197259
A List of Drug Combination(s) Able to Regulate This Molecule
          Phosphorylation Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Phosphorylation of This Molecule [1]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Berberine   NP Info  + Cisplatin   Drug Info 
                    Structure +
References
Reference 1 Berberine in combination with cisplatin induces necroptosis and apoptosis in ovarian cancer cells. Biol Res. 2019 Jul 18;52(1):37.
Cite NPCDR
Visitor Map
Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China