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

Gene ID: 26399, updated on 5-Mar-2024

Summary

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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; phosphatase activator activity; and protein serine/threonine kinase activator 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, Apr 2022]
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

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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_000077.7Genomic Context describing neighboring genes Neighboring gene STARR-positive B cell enhancer mm9_chr11:110133108-110133408 Neighboring gene STARR-seq mESC enhancer starr_31036 Neighboring gene ATP-binding cassette, sub-family A member 5 Neighboring gene predicted gene, 39445 Neighboring gene STARR-seq mESC enhancer starr_31038 Neighboring gene CapStarr-seq enhancer MGSCv37_chr11:110260179-110260474 Neighboring gene STARR-positive B cell enhancer ABC_E8466 Neighboring gene STARR-positive B cell enhancer ABC_E8467 Neighboring gene STARR-positive B cell enhancer mm9_chr11:110309701-110310002 Neighboring gene STARR-positive B cell enhancer mm9_chr11:110344566-110344867 Neighboring gene predicted gene, 39446 Neighboring gene predicted gene, 30009 Neighboring gene predicted gene 11682

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. MEK6 Overexpression Exacerbates Fat Accumulation and Inflammatory Cytokines in High-Fat Diet-Induced Obesity. Lee S, et al. Int J Mol Sci, 2021 Dec 17. PMID 34948353, Free PMC Article
  2. Optical control of MAP kinase kinase 6 (MKK6) reveals that it has divergent roles in pro-apoptotic and anti-proliferative signaling. Rahman SMT, et al. J Biol Chem, 2020 Jun 19. PMID 32371393, Free PMC Article
  3. MKK6 phosphorylation regulates production of superoxide by enhancing Rac GTPase activity. Harraz MM, et al. Antioxid Redox Signal, 2007 Nov. PMID 17854274, Free PMC Article
  4. Alterations in oxidative phosphorylation complex proteins in the hearts of transgenic mice that overexpress the p38 MAP kinase activator, MAP kinase kinase 6. Wall JA, et al. Am J Physiol Heart Circ Physiol, 2006 Nov. PMID 16766635
  5. Involvement of MKK6 in TCRalphabeta(int)CD69lo: a target population for apoptotic cell death in thymocytes. Suzuki H, et al. FASEB J, 2003 Aug. PMID 12824301

See all (78) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. MKK6 deficiency promotes cardiac dysfunction through MKK3-p38gamma/delta-mTOR hyperactivation.
    Title: MKK6 deficiency promotes cardiac dysfunction through MKK3-p38γ/δ-mTOR hyperactivation.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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)
  • Targeted (3)  1 citation
  • Endonuclease-mediated (2) 

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 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 identical protein binding ISO
Inferred from Sequence Orthology
more info
  
enables kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables nucleotide binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein kinase binding ISO
Inferred from Sequence Orthology
more info
  
enables protein serine/threonine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein tyrosine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables transferase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
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 MAPK cascade ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within 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 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 p38MAPK cascade ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within phosphorylation IEA
Inferred from Electronic Annotation
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 ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of nitric-oxide synthase biosynthetic process ISO
Inferred from Sequence Orthology
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 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 cytoplasm IEA
Inferred from Electronic Annotation
more info
  
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 ISO
Inferred from Sequence Orthology
more info
  
located_in nucleus IEA
Inferred from Electronic Annotation
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
NP_001343275.1
NP_001343276.1
NP_001343281.1
NP_001343282.1
NP_036073.1
XP_011247336.2
XP_011247337.1
XP_036012601.1
XP_036012602.1

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_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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  1. NC_000077.7 Reference GRCm39 C57BL/6J

    Range
    110289928..110416348
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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

  3. 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

  4. 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
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P70236.1 GenPept UniProtKB/Swiss-Prot:P70236

Gene LinkOut

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