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

Summary

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

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_000074.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

MLKL promotes hepatocarcinogenesis through inhibition of AMPK-mediated autophagy.
Title: MLKL promotes hepatocarcinogenesis through inhibition of AMPK-mediated autophagy.
Deletion of Mixed Lineage Kinase Domain Like Pseudokinase Aggravates Chronic Alcohol-Induced Liver Injury via Increasing Apoptosis.
Title: Deletion of Mixed Lineage Kinase Domain Like Pseudokinase Aggravates Chronic Alcohol-Induced Liver Injury via Increasing Apoptosis.
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.
MLKL Protects Pulmonary Endothelial Cells in Acute Lung Injury.
Title: MLKL Protects Pulmonary Endothelial Cells in Acute Lung Injury.
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.
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.
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.
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.
RIP3/MLKL regulates necroptosis via activating 4EBP1-eIF4E pathway.
Title: RIP3/MLKL regulates necroptosis via activating 4EBP1-eIF4E pathway.
MLKL deficiency protects against low-grade, sterile inflammation in aged mice.
Title: MLKL deficiency protects against low-grade, sterile inflammation in aged mice.

Submit: New GeneRIF Correction See all GeneRIFs (82)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (4)
Endonuclease-mediated (21) 1 citation
Gene trapped (1)
Targeted (3) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

C81326 (e-PCR)
- UniSTS:159818

RH127055 (e-PCR)
- UniSTS:167566

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 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	IEA Inferred from Electronic Annotation 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
involved_in protein homotrimerization	ISO Inferred from Sequence Orthology more info
involved_in protein homotrimerization	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cell junction	IEA Inferred from Electronic Annotation more info
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 cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology 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
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity 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)

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
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

NC_000074.7 Reference GRCm39 C57BL/6J

Range

112037879..112065081 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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