Map3k11 mitogen-activated protein kinase kinase kinase 11 [Mus musculus (house mouse) ]

Gene ID: 26403, updated on 8-Mar-2025

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Gene Sequences (FASTA)

Transcript sequences (FASTA)

Protein sequences(FASTA)

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Summary

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Official Symbol: Map3k11provided byMGI
Official Full Name: mitogen-activated protein kinase kinase kinase 11provided byMGI
Primary source: MGI:MGI:1346880
See related: Ensembl:ENSMUSG00000004054 AllianceGenome:MGI:1346880
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Mlk3; PTK1; SPRK; 2610017K16Rik
Summary: Predicted to enable several functions, including ATP binding activity; JUN kinase kinase kinase activity; and enzyme binding activity. Predicted to be involved in several processes, including JNK cascade; cell cycle G1/S phase transition; and positive regulation of MAPK cascade. Predicted to be located in microtubule. Predicted to be active in centrosome and cytoplasm. Is expressed in blood vessel; brain; and embryo. Orthologous to human MAP3K11 (mitogen-activated protein kinase kinase kinase 11). [provided by Alliance of Genome Resources, Mar 2025]
Expression: Ubiquitous expression in lung adult (RPKM 55.6), duodenum adult (RPKM 45.6) and 28 other tissuesSee more
Orthologs: human all
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Genomic context

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See Map3k11 inGenome Data Viewer

Location:: 19 A; 19 4.34 cM

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	19	NC_000085.7 (5738764..5752893)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	19	NC_000085.6 (5688411..5702865)

Chromosome 19 - NC_000085.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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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?

MLK3 Regulates Inflammatory Response via Activation of AP-1 Pathway in HEK293 and RAW264.7 Cells.
Title: MLK3 Regulates Inflammatory Response via Activation of AP-1 Pathway in HEK293 and RAW264.7 Cells.
Mixed lineage kinase 3 requires a functional CRIB domain for regulation of blood pressure, cardiac hypertrophy, and left ventricular function.
Title: Mixed lineage kinase 3 requires a functional CRIB domain for regulation of blood pressure, cardiac hypertrophy, and left ventricular function.
Silence of MLK3 alleviates lipopolysaccharide-induced lung epithelial cell injury via inhibiting p53-mediated ferroptosis.
Title: Silence of MLK3 alleviates lipopolysaccharide-induced lung epithelial cell injury via inhibiting p53-mediated ferroptosis.
MLK3 mediates impact of PKG1alpha on cardiac function and controls blood pressure through separate mechanisms.
Title: MLK3 mediates impact of PKG1α on cardiac function and controls blood pressure through separate mechanisms.
Anthocyanins attenuate neuroinflammation through the suppression of MLK3 activation in a mouse model of perioperative neurocognitive disorders.
Title: Anthocyanins attenuate neuroinflammation through the suppression of MLK3 activation in a mouse model of perioperative neurocognitive disorders.
Pyroptosis and ferroptosis induced by mixed lineage kinase 3 (MLK3) signaling in cardiomyocytes are essential for myocardial fibrosis in response to pressure overload.
Title: Pyroptosis and ferroptosis induced by mixed lineage kinase 3 (MLK3) signaling in cardiomyocytes are essential for myocardial fibrosis in response to pressure overload.
Study identified that genetic loss/inhibition of a MLK3, increases CD8+ T cell cytotoxicity via inhibition of a prolyl isomerase, Ppia, and nuclear translocation of NFATc1. The MLK3 inhibitor increased the tumor infiltration of cytotoxic T cells in an immune-competent mouse model of breast cancer and increased the cytotoxic T cell population in pan T cells isolated from breast cancer patients with metastatic disease.
Title: Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity.
This study is the first to identify GNAI2 as a promising target for prevention of hepatic I/R-induced injury and related liver diseases
Title: Guanine nucleotide-binding protein G(i)α2 aggravates hepatic ischemia-reperfusion injury in mice by regulating MLK3 signaling.
MLK3-/- mice exhibited baseline cardiac hypertrophy with preserved cardiac function. MLK3-/- mice subjected to chronic left ventricular pressure overload developed worsened cardiac dysfunction.
Title: Mixed lineage kinase-3 prevents cardiac dysfunction and structural remodeling with pressure overload.
In lipotoxic hepatocytes, MLK3 activates a MAPK signaling cascade, resulting in the activating phosphorylation of STAT1, and CXCL10 transcriptional upregulation.
Title: Mixed Lineage Kinase 3 Mediates the Induction of CXCL10 by a STAT1-Dependent Mechanism During Hepatocyte Lipotoxicity.

Submit:New GeneRIF Correction See all GeneRIFs (29)

Variation

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Alleles

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

Spontaneous (1)
Targeted (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI502630 (e-PCR)
- UniSTS:261724

PMC87148P2 (e-PCR)
- UniSTS:273583

PMC114715P1 (e-PCR)
- UniSTS:270276

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP binding	ISO Inferred from Sequence Orthology more info
enables JUN kinase kinase kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables JUN kinase kinase kinase activity	IEA Inferred from Electronic Annotation more info
enables JUN kinase kinase kinase activity	ISO Inferred from Sequence Orthology more info
enables MAP kinase kinase kinase activity	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables mitogen-activated protein kinase kinase binding	IEA Inferred from Electronic Annotation more info
enables mitogen-activated protein kinase kinase binding	ISO Inferred from Sequence Orthology more info
enables mitogen-activated protein kinase kinase kinase binding	IEA Inferred from Electronic Annotation more info
enables mitogen-activated protein kinase kinase kinase binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
enables small GTPase binding	IEA Inferred from Electronic Annotation more info
enables small GTPase binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in JNK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in JNK cascade	IEA Inferred from Electronic Annotation more info
involved_in JNK cascade	ISO Inferred from Sequence Orthology more info
involved_in MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in cell cycle G1/S phase transition	IEA Inferred from Electronic Annotation more info
involved_in cell cycle G1/S phase transition	ISO Inferred from Sequence Orthology more info
involved_in microtubule-based process	IBA Inferred from Biological aspect of Ancestor more info
involved_in microtubule-based process	IEA Inferred from Electronic Annotation more info
involved_in microtubule-based process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of JNK cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of JNK cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of JUN kinase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neuron apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in protein autophosphorylation	ISO Inferred from Sequence Orthology more info
involved_in protein phosphorylation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in centrosome	IBA Inferred from Biological aspect of Ancestor more info
located_in centrosome	IEA Inferred from Electronic Annotation more info
located_in centrosome	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in microtubule	IEA Inferred from Electronic Annotation more info
located_in microtubule	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: mitogen-activated protein kinase kinase kinase 11

Names: mixed lineage kinase 3

NP_001405272.1

EC2.7.11.25

NP_001405273.1

EC2.7.11.25

NP_001405274.1

EC2.7.11.25

NP_071295.2

EC2.7.11.25

XP_030106811.1

EC2.7.11.25

XP_030106812.1

EC2.7.11.25

XP_036017492.1

EC2.7.11.25

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 inGenomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001418343.1 →NP_001405272.1 mitogen-activated protein kinase kinase kinase 11 isoform 1
Status: VALIDATED
Source sequence(s)
AC134563
UniProtKB/Swiss-Prot
Q80XI6,Q8K0M8,Q9JJ15
NM_001418344.1 →NP_001405273.1 mitogen-activated protein kinase kinase kinase 11 isoform 1
Status: VALIDATED
Source sequence(s)
AC134563
UniProtKB/Swiss-Prot
Q80XI6,Q8K0M8,Q9JJ15
NM_001418345.1 →NP_001405274.1 mitogen-activated protein kinase kinase kinase 11 isoform 2
Status: VALIDATED
Source sequence(s)
AC134563
NM_022012.4 →NP_071295.2 mitogen-activated protein kinase kinase kinase 11 isoform 1
See identical proteins and their annotated locations for NP_071295.2
Status: VALIDATED
Source sequence(s)
AC134563
Consensus CDS
CCDS29476.1
UniProtKB/Swiss-Prot
Q80XI6,Q8K0M8,Q9JJ15
Related
ENSMUSP00000004156.9,ENSMUST00000004156.10
Conserved Domains (2)summary
cd12059
Location:46 →103
SH3_MLK1-3; Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3
cd14147
Location:114 →380
STKc_MLK3; Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

This section includes genomic Reference Sequences (RefSeqs) from all assemblies on which this gene is annotated, such as RefSeqs for chromosomes and scaffolds (contigs) from both reference and alternate assemblies. Model RNAs and proteins are also reported here.

Reference GRCm39 C57BL/6J

Genomic

NC_000085.7 Reference GRCm39 C57BL/6J
Range
5738764..5752893
Download
GenBank,FASTA,Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030250951.2 →XP_030106811.1 mitogen-activated protein kinase kinase kinase 11 isoform X1
UniProtKB/Swiss-Prot
Q80XI6,Q8K0M8,Q9JJ15
Conserved Domains (2)summary
cd12059
Location:46 →103
SH3_MLK1-3; Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3
cd14147
Location:114 →380
STKc_MLK3; Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3
XM_030250952.1 →XP_030106812.1 mitogen-activated protein kinase kinase kinase 11 isoform X1
UniProtKB/Swiss-Prot
Q80XI6,Q8K0M8,Q9JJ15
Conserved Domains (2)summary
cd12059
Location:46 →103
SH3_MLK1-3; Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3
cd14147
Location:114 →380
STKc_MLK3; Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3
XM_036161599.1 →XP_036017492.1 mitogen-activated protein kinase kinase kinase 11 isoform X1
UniProtKB/Swiss-Prot
Q80XI6,Q8K0M8,Q9JJ15
Conserved Domains (2)summary
cd12059
Location:46 →103
SH3_MLK1-3; Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3
cd14147
Location:114 →380
STKc_MLK3; Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3