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Mlkl mixed lineage kinase domain-like [ Mus musculus (house mouse) ]

Gene ID: 74568, updated on 18-Apr-2024

Summary

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Official Symbol
Mlklprovided by MGI
Official Full Name
mixed lineage kinase domain-likeprovided by MGI
Primary source
MGI:MGI:1921818
See related
Ensembl:ENSMUSG00000012519 AllianceGenome:MGI:1921818
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as
9130019I15Rik
Summary
This gene belongs to the protein kinase superfamily. The encoded protein contains a protein kinase-like domain; however, is thought to lack protein kinase 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. Knockout of this gene in mice showed that it is essential for necroptosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]
Expression
Broad expression in bladder adult (RPKM 2.9), liver E18 (RPKM 1.8) and 21 other tissues See more
Orthologs
human all
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Genomic context

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Location:
8 E1; 8 57.98 cM
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 8 NC_000074.7 (112037879..112065081, complement)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 8 NC_000074.6 (111311255..111338479, complement)

Chromosome 8 - NC_000074.7Genomic Context describing neighboring genes Neighboring gene ring finger and WD repeat domain 3 Neighboring gene STARR-seq mESC enhancer starr_22693 Neighboring gene ubiquitin-40S ribosomal protein S27a pseudogene Neighboring gene STARR-positive B cell enhancer ABC_E6684 Neighboring gene fatty acid 2-hydroxylase Neighboring gene predicted gene, 24793

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. MLKL deficiency protects against low-grade, sterile inflammation in aged mice. Tovey Crutchfield EC, et al. Cell Death Differ, 2023 Apr. PMID 36755069, Free PMC Article
  2. MLKL-mediated necroptosis is a target for cardiac protection in mouse models of type-1 diabetes. Cao T, et al. Cardiovasc Diabetol, 2022 Aug 27. PMID 36030201, Free PMC Article
  3. Loss of MLKL ameliorates liver fibrosis by inhibiting hepatocyte necroptosis and hepatic stellate cell activation. Guo R, et al. Theranostics, 2022. PMID 35836819, Free PMC Article
  4. Blockage of MLKL prevents myelin damage in experimental diabetic neuropathy. Guo J, et al. Proc Natl Acad Sci U S A, 2022 Apr 5. PMID 35344427, Free PMC Article
  5. The role of MLKL in Hepatic Ischemia-Reperfusion Injury of Alcoholic Steatotic Livers. Chen H, et al. Int J Biol Sci, 2022. PMID 35173541, Free PMC Article

See all (207) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. MLKL overexpression leads to Ca[2+] and metabolic dyshomeostasis in a neuronal cell model.
    Title: MLKL overexpression leads to Ca(2+) and metabolic dyshomeostasis in a neuronal cell model.
  2. MLKL Protects Pulmonary Endothelial Cells in Acute Lung Injury.
    Title: MLKL Protects Pulmonary Endothelial Cells in Acute Lung Injury.
  3. Non-Necroptotic Roles of MLKL in Diet-Induced Obesity, Liver Pathology, and Insulin Sensitivity: Insights from a High-Fat, High-Fructose, High-Cholesterol Diet Mouse Model.
    Title: Non-Necroptotic Roles of MLKL in Diet-Induced Obesity, Liver Pathology, and Insulin Sensitivity: Insights from a High-Fat, High-Fructose, High-Cholesterol Diet Mouse Model.
  4. The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formation.
    Title: The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formation.
  5. MLKL deficiency alleviates neuroinflammation and motor deficits in the alpha-synuclein transgenic mouse model of Parkinson's disease.
    Title: MLKL deficiency alleviates neuroinflammation and motor deficits in the α-synuclein transgenic mouse model of Parkinson's disease.
  6. A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation.
    Title: A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation.
  7. RIP3/MLKL regulates necroptosis via activating 4EBP1-eIF4E pathway.
    Title: RIP3/MLKL regulates necroptosis via activating 4EBP1-eIF4E pathway.
  8. MLKL deficiency protects against low-grade, sterile inflammation in aged mice.
    Title: MLKL deficiency protects against low-grade, sterile inflammation in aged mice.
  9. Resistance To Poxvirus Lethality Does Not Require the Necroptosis Proteins RIPK3 or MLKL.
    Title: Resistance To Poxvirus Lethality Does Not Require the Necroptosis Proteins RIPK3 or MLKL.
  10. MLKL signaling regulates macrophage polarization in acute pancreatitis through CXCL10.
    Title: MLKL signaling regulates macrophage polarization in acute pancreatitis through CXCL10.
Submit: New GeneRIF Correction See all GeneRIFs (80)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Gene trapped (1) 
  • Targeted (3)  1 citation
  • Endonuclease-mediated (20)  1 citation
  • Chemically induced (ENU) (4) 

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables ATP binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables ATP binding ISO
Inferred from Sequence Orthology
more info
  
enables identical protein binding ISO
Inferred from Sequence Orthology
more info
  
enables nucleotide binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
NOT enables protein kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein kinase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
NOT enables protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein-containing complex binding ISO
Inferred from Sequence Orthology
more info
  
Process Evidence Code Pubs
involved_in cell surface receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in defense response to virus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in defense response to virus IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in execution phase of necroptosis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in execution phase of necroptosis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in execution phase of necroptosis ISO
Inferred from Sequence Orthology
more info
  
involved_in necroptotic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in necroptotic process ISO
Inferred from Sequence Orthology
more info
  
involved_in necroptotic signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in necroptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in necroptotic signaling pathway ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within programmed cell death IEA
Inferred from Electronic Annotation
more info
  
involved_in protein homotrimerization ISO
Inferred from Sequence Orthology
more info
  
involved_in protein phosphorylation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cell junction ISO
Inferred from Sequence Orthology
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm ISO
Inferred from Sequence Orthology
more info
  
located_in cytosol ISO
Inferred from Sequence Orthology
more info
  
located_in membrane IEA
Inferred from Electronic Annotation
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane ISO
Inferred from Sequence Orthology
more info
  

General protein information

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Preferred Names
mixed lineage kinase domain-like protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001310613.1 → NP_001297542.1  mixed lineage kinase domain-like protein isoform 1

    See identical proteins and their annotated locations for NP_001297542.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC163625, AK018636, BY467591, BY740989
    Consensus CDS
    CCDS80932.1
    UniProtKB/Swiss-Prot
    Q8CIJ5, Q9D2Y4
    Related
    ENSMUSP00000055521.8, ENSMUST00000056157.14
    Conserved Domains (1) summary
    PHA02988
    Location:198 → 446
    PHA02988; hypothetical protein; Provisional

  2. NM_029005.3 → NP_083281.1  mixed lineage kinase domain-like protein isoform 2

    See identical proteins and their annotated locations for NP_083281.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region compared to variant 1. It encodes isoform 2, which is shorter than isoform 1.
    Source sequence(s)
    AC163625, AK018636, BY467591, BY740989
    Consensus CDS
    CCDS52671.1
    UniProtKB/Swiss-Prot
    Q9D2Y4
    Related
    ENSMUSP00000113718.2, ENSMUST00000120432.3
    Conserved Domains (1) summary
    PHA02988
    Location:198 → 454
    PHA02988; hypothetical protein; Provisional

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000074.7 Reference GRCm39 C57BL/6J

    Range
    112037879..112065081 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_036154342.1 → XP_036010235.1  mixed lineage kinase domain-like protein isoform X3

    Conserved Domains (2) summary
    cd21037
    Location:5 → 143
    MLKL_NTD; N-terminal domain of mixed lineage kinase domain-like protein (MLKL) and similar proteins
    cl21453
    Location:238 → 368
    PKc_like; Protein Kinases, catalytic domain

  2. XM_006531442.4 → XP_006531505.1  mixed lineage kinase domain-like protein isoform X1

    See identical proteins and their annotated locations for XP_006531505.1

    UniProtKB/Swiss-Prot
    Q8CIJ5, Q9D2Y4
    Conserved Domains (1) summary
    PHA02988
    Location:198 → 446
    PHA02988; hypothetical protein; Provisional

  3. XM_030243820.2 → XP_030099680.1  mixed lineage kinase domain-like protein isoform X2

    Conserved Domains (1) summary
    PHA02988
    Location:198 → 454
    PHA02988; hypothetical protein; Provisional

  4. XM_006531443.5 → XP_006531506.1  mixed lineage kinase domain-like protein isoform X4

    Conserved Domains (1) summary
    PHA02988
    Location:198 → 385
    PHA02988; hypothetical protein; Provisional

RNA

  1. XR_004934892.1 RNA Sequence

Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9D2Y4.1 GenPept UniProtKB/Swiss-Prot:Q9D2Y4

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