Map2k6 mitogen-activated protein kinase kinase 6 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Map2k6provided by MGI
Official Full Name: mitogen-activated protein kinase kinase 6provided by MGI
Primary source: MGI:MGI:1346870
See related: Ensembl:ENSMUSG00000020623 AllianceGenome:MGI:1346870
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: MEK6; MKK6; MAPKK6; Prkmk6; SAPKK3; MAPKK 6
Summary: Enables MAP kinase kinase activity. Involved in bone development; negative regulation of cold-induced thermogenesis; and osteoblast differentiation. Acts upstream of or within several processes, including MAPK cascade; cardiac muscle contraction; and positive regulation of MAP kinase activity. Predicted to be located in cytosol and nucleoplasm. Is expressed in several structures, including alimentary system; brain; early conceptus; genitourinary system; and sensory organ. Human ortholog(s) of this gene implicated in Pick's disease; cervical cancer; ovarian carcinoma; progressive supranuclear palsy; and restrictive cardiomyopathy. Orthologous to human MAP2K6 (mitogen-activated protein kinase kinase 6). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Broad expression in CNS E11.5 (RPKM 3.9), CNS E14 (RPKM 3.3) and 23 other tissues See more
Orthologs: human all
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Genomic context

Location:: 11 E1- E2; 11 73.6 cM

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	11	NC_000077.7 (110289928..110416348)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	11	NC_000077.6 (110399102..110525522)

Chromosome 11 - NC_000077.7 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?

MKK6 deficiency promotes cardiac dysfunction through MKK3-p38gamma/delta-mTOR hyperactivation.
Title: MKK6 deficiency promotes cardiac dysfunction through MKK3-p38γ/δ-mTOR hyperactivation.
MicroRNA-370 carried by M2 macrophage-derived exosomes alleviates asthma progression through inhibiting the FGF1/MAPK/STAT1 axis.
Title: MicroRNA-370 carried by M2 macrophage-derived exosomes alleviates asthma progression through inhibiting the FGF1/MAPK/STAT1 axis.
MEK6 Overexpression Exacerbates Fat Accumulation and Inflammatory Cytokines in High-Fat Diet-Induced Obesity.
Title: MEK6 Overexpression Exacerbates Fat Accumulation and Inflammatory Cytokines in High-Fat Diet-Induced Obesity.
Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis.
Title: Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis.
Elevated miR-10a-5p facilitates cell cycle and restrains adipogenic differentiation via targeting Map2k6 and Fasn, respectively.
Title: Elevated miR-10a-5p facilitates cell cycle and restrains adipogenic differentiation via targeting Map2k6 and Fasn, respectively.
Optical control of MAP kinase kinase 6 (MKK6) reveals that it has divergent roles in pro-apoptotic and anti-proliferative signaling.
Title: Optical control of MAP kinase kinase 6 (MKK6) reveals that it has divergent roles in pro-apoptotic and anti-proliferative signaling.
Circ_016719 plays a critical role in neuron cell apoptosis induced by I/R via targeting miR-29c/Map2k6.
Title: Circ_016719 plays a critical role in neuron cell apoptosis induced by I/R via targeting miR-29c/Map2k6.
acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditure
Title: MKK6 controls T3-mediated browning of white adipose tissue.
MAP2K6 functions in mouse testis determination, via positive effects on Sry, and a minor role for MAP2K3.
Title: Genetic Analyses Reveal Functions for MAP2K3 and MAP2K6 in Mouse Testis Determination.
MKK3 and MKK6 differentially regulate bone loss due to estrogen withdrawal. MKK3 directly mediates osteoclastogenesis while MKK6 likely contributes to pro-inflammatory cytokine production that promotes osteoclast formation.
Title: Differential roles of MAPK kinases MKK3 and MKK6 in osteoclastogenesis and bone loss.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Variation

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Alleles

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

Endonuclease-mediated (2)
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

D11Mit300 (e-PCR), detects polymorphism
- UniSTS:126510

UniSTS:224328 (e-PCR)
- UniSTS:224328

Map2k6 (e-PCR), detects polymorphism
- UniSTS:507044

Map2k6 (e-PCR), detects polymorphism
- UniSTS:143819

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables JUN kinase kinase activity	IEA Inferred from Electronic Annotation more info
enables MAP kinase kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables MAP kinase kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables MAP kinase kinase activity	ISO Inferred from Sequence Orthology more info
enables MAP kinase kinase activity	TAS Traceable Author Statement more info
enables histone H2AXY142 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3Y41 kinase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction 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 activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in JNK cascade	IEA Inferred from Electronic Annotation more info
involved_in MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within MAPK cascade	IPI Inferred from Physical Interaction more info	PubMed
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in bone development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cardiac muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to sorbitol	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cold-induced thermogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in osteoblast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ovulation cycle process	IEA Inferred from Electronic Annotation more info
involved_in p38MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in p38MAPK cascade	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of MAP kinase activity	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of MAPK cascade	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of prostaglandin secretion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of prostaglandin secretion	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein phosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in response to ischemia	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in stress-activated MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in stress-activated MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in stress-activated protein kinase signaling cascade	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
is_active_in cytosol	ISO Inferred from Sequence Orthology more info	PubMed
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: dual specificity mitogen-activated protein kinase kinase 6

Names: MAP kinase kinase 6; MAPK/ERK kinase 6; protein kinase, mitogen activated, kinase 6

NP_001343274.1

EC 2.7.12.2

NP_001343275.1

EC 2.7.12.2

NP_001343276.1

EC 2.7.12.2

NP_001343281.1

EC 2.7.12.2

NP_001343282.1

EC 2.7.12.2

NP_036073.1

EC 2.7.12.2

XP_011247336.2

EC 2.7.12.2

XP_011247337.1

EC 2.7.12.2

XP_036012601.1

EC 2.7.12.2

XP_036012602.1

EC 2.7.12.2

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_001356345.1 → NP_001343274.1 dual specificity mitogen-activated protein kinase kinase 6 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) includes a different 3' exon structure, compared to variant 1. It encodes isoform 2, which is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AK086722, AK162671, BY280286

Consensus CDS

CCDS88279.1

UniProtKB/TrEMBL

A2AGS2, Q8C371

Related

ENSMUSP00000097831.2, ENSMUST00000100260.2

Conserved Domains (1) summary

cd06617
Location:51 → 293

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
NM_001356346.1 → NP_001343275.1 dual specificity mitogen-activated protein kinase kinase 6 isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and the 5' CDS and uses a downstream start codon, compared to variant 1. It encodes isoform 3, which has a shorter N-terminus, compared to isoform 1. Variants 3, 4 and 5 encode the same isoform (3).

Source sequence(s)

AI429449, AK162671, BY284275

Conserved Domains (1) summary

cd06617
Location:1 → 264

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
NM_001356347.1 → NP_001343276.1 dual specificity mitogen-activated protein kinase kinase 6 isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and the 5' CDS and uses a downstream start codon, compared to variant 1. It encodes isoform 3, which has a shorter N-terminus, compared to isoform 1. Variants 3, 4 and 5 encode the same isoform (3).

Source sequence(s)

AA389344, AI429449, AK162671, AL691461, BY284275

Conserved Domains (1) summary

cd06617
Location:1 → 264

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
NM_001356352.1 → NP_001343281.1 dual specificity mitogen-activated protein kinase kinase 6 isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and the 5' CDS and uses a downstream start codon, compared to variant 1. It encodes isoform 3, which has a shorter N-terminus, compared to isoform 1. Variants 3, 4 and 5 encode the same isoform (3).

Source sequence(s)

AI429449, AK140289, BY280286

Conserved Domains (1) summary

cd06617
Location:1 → 264

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
NM_001356353.1 → NP_001343282.1 dual specificity mitogen-activated protein kinase kinase 6 isoform 4

Status: VALIDATED

Description

Transcript Variant: This variant (6) differs in the 5' UTR and the 5' CDS and uses a downstream start codon, compared to variant 1. It encodes isoform 4, which has a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AI429449, AK140289, AK141708, BB202796, BE859531, BU695367, BY280286

UniProtKB/TrEMBL

Q60521

Related

ENSMUST00000146084.8

Conserved Domains (1) summary

cl21453
Location:1 → 236

PKc_like; Protein Kinases, catalytic domain
NM_011943.3 → NP_036073.1 dual specificity mitogen-activated protein kinase kinase 6 isoform 1

See identical proteins and their annotated locations for NP_036073.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AI429449, AK043482, BY280286

Consensus CDS

CCDS25592.1

UniProtKB/Swiss-Prot

P70236

UniProtKB/TrEMBL

Q543Z5, Q8BP44

Related

ENSMUSP00000020949.6, ENSMUST00000020949.12

Conserved Domains (1) summary

cd06617
Location:51 → 333

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6

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_000077.7 Reference GRCm39 C57BL/6J

Range

110289928..110416348

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011249034.4 → XP_011247336.2 dual specificity mitogen-activated protein kinase kinase 6 isoform X1

Conserved Domains (1) summary

cd06617
Location:1 → 264

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
XM_036156708.1 → XP_036012601.1 dual specificity mitogen-activated protein kinase kinase 6 isoform X2

UniProtKB/TrEMBL

Q8BP44

Conserved Domains (1) summary

cd06617
Location:64 → 346

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
XM_011249035.3 → XP_011247337.1 dual specificity mitogen-activated protein kinase kinase 6 isoform X1

See identical proteins and their annotated locations for XP_011247337.1

Conserved Domains (1) summary

cd06617
Location:1 → 264

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6
XM_036156709.1 → XP_036012602.1 dual specificity mitogen-activated protein kinase kinase 6 isoform X1

Conserved Domains (1) summary

cd06617
Location:1 → 264

PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6