MLKL
Summary: 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].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| mixed lineage kinase domain like pseudokinase | MIM:615153 | Ensembl:ENSG00000168404 | HGNC:HGNC:26617 | PA142671349 | 16q23.1 |
GO terms in MLKL
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| CC | IDA | GO:0005737 | cytoplasm |
| CC | TAS | GO:0005829 | cytosol |
| CC | IDA | GO:0005886 | plasma membrane |
| BP | IBA | GO:0000165 | MAPK cascade |
| BP | IEA | GO:0007166 | cell surface receptor signaling pathway |
| BP | IBA | GO:0007257 | activation of JUN kinase activity |
| BP | IDA | GO:0070207 | protein homotrimerization |
| BP | IMP | GO:0070266 | necroptotic process |
| BP | TAS | GO:0070266 | necroptotic process |
| MF | ISS | GO:0004672 | protein kinase activity |
| MF | IBA | GO:0004674 | protein serine/threonine kinase activity |
| MF | IBA | GO:0004706 | JUN kinase kinase kinase activity |
| MF | IPI | GO:0005515 | protein binding |
| MF | IDA | GO:0005524 | ATP binding |
| MF | IEA | GO:0019901 | protein kinase binding |
| MF | IDA | GO:0044877 | protein-containing complex binding |
Gene expression in normal tissue: MLKL
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in MLKL
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| kegg | hsa04217 | Necroptosis - Homo sapiens (human) |
| kegg | hsa04668 | TNF signaling pathway - Homo sapiens (human) |
| wikipathways | WP710 | DNA Damage Response (only ATM dependent) |
| reactome | R-HSA-2672351 | Stimuli-sensing channels |
| reactome | R-HSA-3295583 | TRP channels |
| reactome | R-HSA-382551 | Transport of small molecules |
| reactome | R-HSA-5213460 | RIPK1-mediated regulated necrosis |
| reactome | R-HSA-5218859 | Regulated Necrosis |
| reactome | R-HSA-5357801 | Programmed Cell Death |
| reactome | R-HSA-983712 | Ion channel transport |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD512 | nutlin 3 | 6 |
| iGMDRD599 | Salermide | 3 |
| iGMDRD84 | Lovastatin acid | 2 |
| iGMDRD126 | Tipifarnib | 2 |
| iGMDRD532 | Olaparib | 2 |
| iGMDRD116 | CD437 | 2 |
| iGMDRD424 | Tamatinib | 2 |
| iGMDRD427 | ABT737 | 4 |
| iGMDRD314 | Tanespimycin | 2 |
| iGMDRD639 | YK 4-279 | 2 |
| iGMDRD901 | ELCPK | 2 |
| iGMDRD280 | CYTOCHALASIN B | 1 |
| iGMDRD158 | NSC141540 | 2 |
| iGMDRD267 | Oligomycin A | 1 |
| iGMDRD309 | 17AAG | 2 |
| iGMDRD782 | DC-45-A2 | 2 |
| iGMDRD562 | Navitoclax | 4 |
| iGMDRD398 | Sepantronium | 7 |
| iGMDRD871 | BRD6368 | 2 |
| iGMDRD367 | Ro 28-1675 | 2 |
| iGMDRD74 | Idarubicin | 2 |
| iGMDRD730 | Kahalalide F | 2 |
| iGMDRD23 | Gossypol | 2 |
| iGMDRD353 | PD0325901 | 2 |
| iGMDRD444 | Tivantinib | 2 |
| iGMDRD300 | Tozasertib | 2 |
| iGMDRD246 | NPC26 | 2 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in MLKL
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