Map3k12 mitogen-activated protein kinase kinase kinase 12 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Map3k12provided by MGI
Official Full Name: mitogen-activated protein kinase kinase kinase 12provided by MGI
Primary source: MGI:MGI:1346881
See related: Ensembl:ENSMUSG00000023050 AllianceGenome:MGI:1346881
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: DLK; MUK; Zpk
Summary: Enables protein homodimerization activity; protein serine/threonine kinase activator activity; and protein serine/threonine kinase activity. Involved in several processes, including JNK cascade; positive regulation of JUN kinase activity; and protein phosphorylation. Acts upstream of or within negative regulation of motor neuron apoptotic process. Located in cytosol; growth cone; and plasma membrane. Is expressed in several structures, including alimentary system; genitourinary system; integumental system; nervous system; and sensory organ. Orthologous to human MAP3K12 (mitogen-activated protein kinase kinase kinase 12). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in cerebellum adult (RPKM 25.4), CNS E18 (RPKM 18.8) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 15 F3; 15 57.63 cM

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	15	NC_000081.7 (102406079..102425311, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	15	NC_000081.6 (102497647..102517004, complement)

Chromosome 15 - NC_000081.7 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?

MiR-191-5p alleviates microglial cell injury by targeting Map3k12 (mitogen-activated protein kinase kinase kinase 12) to inhibit the MAPK (mitogen-activated protein kinase) signaling pathway in Alzheimer's disease.
Title: MiR-191-5p alleviates microglial cell injury by targeting Map3k12 (mitogen-activated protein kinase kinase kinase 12) to inhibit the MAPK (mitogen-activated protein kinase) signaling pathway in Alzheimer's disease.
Activation of MAP3K DLK and LZK in Purkinje cells causes rapid and slow degeneration depending on signaling strength.
Title: Activation of MAP3K DLK and LZK in Purkinje cells causes rapid and slow degeneration depending on signaling strength.
Dual Leucine Zipper Kinase Is Constitutively Active in the Adult Mouse Brain and Has Both Stress-Induced and Homeostatic Functions.
Title: Dual Leucine Zipper Kinase Is Constitutively Active in the Adult Mouse Brain and Has Both Stress-Induced and Homeostatic Functions.
Study shows that dual leucine zipper kinase inhibition preserves neuronal network connectivity.
Title: High-throughput microscopy exposes a pharmacological window in which dual leucine zipper kinase inhibition preserves neuronal network connectivity.
Using a sensory neuron-conditional DLK knockout mouse model, we show a time course for the dependency of gene expression changes on the DLK pathway after sciatic nerve injury.
Title: DLK regulates a distinctive transcriptional regeneration program after peripheral nerve injury.
DLK is required for mechanical allodynia and microgliosis after nerve injury by controling a transcriptional program in somatosensory neurons regulating the expression of numerous genes implicated in pain pathogenesis, including Csf1.
Title: Dual leucine zipper kinase is required for mechanical allodynia and microgliosis after nerve injury.
These findings demonstrate that pathological activation of DLK is a conserved mechanism that regulates neurodegeneration.
Title: Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease.
These findings identify DLK as a central regulator of not only JNK but also PERK stress signaling in neurons, with both pathways contributing to neurodegeneration.
Title: Dual leucine zipper kinase-dependent PERK activation contributes to neuronal degeneration following insult.
Results provide the first evidence that axon guidance genes are downstream targets of the dual leucine zipper kinase (DLK) signaling pathway, which through their regulation probably modulates neuronal cell development, structure and function.
Title: Dual leucine zipper kinase regulates expression of axon guidance genes in mouse neuronal cells.
LZK cooperates with DLK to promote retinal ganglion cell death in response to axon injury.
Title: Enhanced Functional Genomic Screening Identifies Novel Mediators of Dual Leucine Zipper Kinase-Dependent Injury Signaling in Neurons.

Submit: New GeneRIF Correction See all GeneRIFs (28)

Variation

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Alleles

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

Endonuclease-mediated (2)
Gene trapped (1) 1 citation
Targeted (8) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AW412548 (e-PCR)
- UniSTS:180842

Map3k12 (e-PCR), detects polymorphism
- UniSTS:507045

PMC87148P1 (e-PCR)
- UniSTS:273582

AA924752 (e-PCR)
- UniSTS:261821

RH127097 (e-PCR)
- UniSTS:209150

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables JUN kinase kinase kinase activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase binding	IEA Inferred from Electronic Annotation more info
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activator activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in JNK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in JNK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of motor neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-serine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-threonine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of ERK1 and ERK2 cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of ERK1 and ERK2 cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of JUN kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in post-translational protein modification	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in axon	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in growth cone	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: mitogen-activated protein kinase kinase kinase 12

Names: MAPK-upstream kinase; dual leucine zipper bearing kinase; leucine-zipper protein kinase; mixed lineage kinase; zipper (leucine) protein kinase

NP_001157115.1

EC 2.7.11.25

NP_001345773.1

EC 2.7.11.25

NP_001398789.1

EC 2.7.11.25

NP_001398790.1

EC 2.7.11.25

NP_033608.3

EC 2.7.11.25

XP_006521076.1

EC 2.7.11.25

XP_017172113.1

EC 2.7.11.25

XP_017172114.1

EC 2.7.11.25

XP_030104450.1

EC 2.7.11.25

XP_030104451.1

EC 2.7.11.25

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 in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001163643.2 → NP_001157115.1 mitogen-activated protein kinase kinase kinase 12

See identical proteins and their annotated locations for NP_001157115.1

Status: VALIDATED

Source sequence(s)

AC137156

Consensus CDS

CCDS27885.1

UniProtKB/Swiss-Prot

P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6

Related

ENSMUSP00000133209.2, ENSMUST00000169377.8

Conserved Domains (1) summary

cd14059
Location:164 → 400

STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13
NM_001358844.2 → NP_001345773.1 mitogen-activated protein kinase kinase kinase 12

Status: VALIDATED

Source sequence(s)

AC137156

Consensus CDS

CCDS27885.1

UniProtKB/Swiss-Prot

P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6

Related

ENSMUSP00000127629.2, ENSMUST00000171565.8

Conserved Domains (1) summary

cd14059
Location:164 → 400

STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13
NM_001411860.1 → NP_001398789.1 mitogen-activated protein kinase kinase kinase 12

Status: VALIDATED

Source sequence(s)

AC137156

UniProtKB/Swiss-Prot

P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6
NM_001411861.1 → NP_001398790.1 mitogen-activated protein kinase kinase kinase 12

Status: VALIDATED

Source sequence(s)

AC137156

UniProtKB/Swiss-Prot

P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6
NM_009582.5 → NP_033608.3 mitogen-activated protein kinase kinase kinase 12

See identical proteins and their annotated locations for NP_033608.3

Status: VALIDATED

Source sequence(s)

AC137156

Consensus CDS

CCDS27885.1

UniProtKB/Swiss-Prot

P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6

Related

ENSMUSP00000023812.3, ENSMUST00000023812.10

Conserved Domains (1) summary

cd14059
Location:164 → 400

STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13

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_000081.7 Reference GRCm39 C57BL/6J

Range

102406079..102425311 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030248590.2 → XP_030104450.1 mitogen-activated protein kinase kinase kinase 12 isoform X2
XM_017316624.2 → XP_017172113.1 mitogen-activated protein kinase kinase kinase 12 isoform X1

UniProtKB/Swiss-Prot

P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6

Conserved Domains (1) summary

cd14059
Location:164 → 400

STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13
XM_030248591.2 → XP_030104451.1 mitogen-activated protein kinase kinase kinase 12 isoform X2
XM_017316625.3 → XP_017172114.1 mitogen-activated protein kinase kinase kinase 12 isoform X1

UniProtKB/Swiss-Prot

P70286, Q3TLL7, Q60700, Q8C4N7, Q8CBX3, Q8CDL6

Conserved Domains (1) summary

cd14059
Location:164 → 400

STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13
XM_006521013.4 → XP_006521076.1 mitogen-activated protein kinase kinase kinase 12 isoform X2