Overview
| Uniprot ID | Q8NB16 |
|---|
| Protein Name | Mixed lineage kinase domain-like protein |
|---|
| Gene Name | MLKL |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 157 |
MLRRDNEKIEASLRR |
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)
Protein Sequence
10
MENLKHIITL
20
GQVIHKRCEE
30
MKYCKKQCRR
40
LGHRVLGLIK
50
PLEMLQDQGK
60
RSVPSEKLTT
70
AMNRFKAALE
80
EANGEIEKFS
90
NRSNICRFLT
100
ASQDKILFKD
110
VNRKLSDVWK
120
ELSLLLQVEQ
130
RMPVSPISQG
140
ASWAQEDQQD
150
ADEDRRAFQM
160
LRRDNEKIEA
170
SLRRLEINMK
180
EIKETLRQYL
190
PPKCMQEIPQ
200
EQIKEIKKEQ
210
LSGSPWILLR
220
ENEVSTLYKG
230
EYHRAPVAIK
240
VFKKLQAGSI
250
AIVRQTFNKE
260
IKTMKKFESP
270
NILRIFGICI
280
DETVTPPQFS
290
IVMEYCELGT
300
LRELLDREKD
310
LTLGKRMVLV
320
LGAARGLYRL
330
HHSEAPELHG
340
KIRSSNFLVT
350
QGYQVKLAGF
360
ELRKTQTSMS
370
LGTTREKTDR
380
VKSTAYLSPQ
390
ELEDVFYQYD
400
VKSEIYSFGI
410
VLWEIATGDI
420
PFQGCNSEKI
430
RKLVAVKRQQ
440
EPLGEDCPSE
450
LREIIDECRA
460
HDPSVRPSVD
470
EILKKLSTFS
K
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0030054 |
cell junction |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0042802 |
identical protein binding |
| Molecular Function |
GO:0019901 |
protein kinase binding |
| Molecular Function |
GO:0044877 |
protein-containing complex binding |
| Biological Process |
GO:0007166 |
cell surface receptor signaling pathway |
| Biological Process |
GO:0051607 |
defense response to virus |
| Biological Process |
GO:0097528 |
execution phase of necroptosis |
| Biological Process |
GO:0070266 |
necroptotic process |
| Biological Process |
GO:0097527 |
necroptotic signaling pathway |
| Biological Process |
GO:0070207 |
protein homotrimerization |
Reference
[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.