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MAP2K6 mitogen-activated protein kinase kinase 6 [ Homo sapiens (human) ]

Gene ID: 5608, updated on 3-Apr-2024

Summary

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Official Symbol
MAP2K6provided by HGNC
Official Full Name
mitogen-activated protein kinase kinase 6provided by HGNC
Primary source
HGNC:HGNC:6846
See related
Ensembl:ENSG00000108984 MIM:601254; AllianceGenome:HGNC:6846
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
MEK6; MKK6; MAPKK6; PRKMK6; SAPKK3; SAPKK-3
Summary
This gene encodes a member of the dual specificity protein kinase family, which functions as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein phosphorylates and activates p38 MAP kinase in response to inflammatory cytokines or environmental stress. As an essential component of p38 MAP kinase mediated signal transduction pathway, this gene is involved in many cellular processes such as stress induced cell cycle arrest, transcription activation and apoptosis. [provided by RefSeq, Jul 2008]
Expression
Broad expression in colon (RPKM 5.8), small intestine (RPKM 1.8) and 22 other tissues See more
Orthologs
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Genomic context

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See MAP2K6 in Genome Data Viewer
Location:
17q24.3
Exon count:
18
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (69414697..69553865)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (70291653..70430810)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (67410838..67550006)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371878 Neighboring gene uncharacterized LOC124900401 Neighboring gene uncharacterized LOC105371879 Neighboring gene Sharpr-MPRA regulatory region 9140 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:67425744-67426560 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12654 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:67443780-67444760 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:67444761-67445742 Neighboring gene uncharacterized LOC105371880 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12655 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12656 Neighboring gene NANOG hESC enhancer GRCh37_chr17:67502478-67502979 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12657 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12658 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:67565237-67565738 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr17:67603079-67604278 Neighboring gene long intergenic non-protein coding RNA 1483 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr17:67757718-67758917 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:67797333-67798295 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:67798296-67799257 Neighboring gene MPRA-validated peak2972 silencer Neighboring gene MPRA-validated peak2973 silencer Neighboring gene long intergenic non-protein coding RNA 1497

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Monocytic cell differentiation from band-stage neutrophils under inflammatory conditions via MKK6 activation. Köffel R, et al. Blood, 2014 Oct 23. PMID 25214442, Free PMC Article
  2. MKK6 is upregulated in human esophageal, stomach, and colon cancers. Parray AA, et al. Cancer Invest, 2014 Oct. PMID 25019214
  3. Crystal structure of non-phosphorylated MAP2K6 in a putative auto-inhibition state. Matsumoto T, et al. J Biochem, 2012 May. PMID 22383536
  4. MKK6 increases the melanocyte dendricity through the regulation of Rho family GTPases. Kim MY, et al. J Dermatol Sci, 2010 Nov. PMID 20869211
  5. [Effect of mitogen-activated protein kinase kinase 6-p38 alpha signal pathway on receptor for advanced glycation end-product expression in alveolar epithelial cells induced by mechanical stretch]. Ding N, et al. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 2009 Oct. PMID 19846005

See all (150) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. PPM1G promotes the progression of lung adenocarcinoma by inhibiting p38 activation via dephosphorylation of MEK6.
    Title: PPM1G promotes the progression of lung adenocarcinoma by inhibiting p38 activation via dephosphorylation of MEK6.
  2. Circ_0005925 Promotes Granulosa Cell Growth by Targeting MiR-324-3p to Upregulate MAP2K6 in Polycystic Ovary Syndrome.
    Title: Circ_0005925 Promotes Granulosa Cell Growth by Targeting MiR-324-3p to Upregulate MAP2K6 in Polycystic Ovary Syndrome.
  3. APEX1 promotes the oncogenicity of hepatocellular carcinoma via regulation of MAP2K6.
    Title: APEX1 promotes the oncogenicity of hepatocellular carcinoma via regulation of MAP2K6.
  4. MiR-1298-5p level downregulation induced by Helicobacter pylori infection inhibits autophagy and promotes gastric cancer development by targeting MAP2K6.
    Title: MiR-1298-5p level downregulation induced by Helicobacter pylori infection inhibits autophagy and promotes gastric cancer development by targeting MAP2K6.
  5. A novel tumour suppressor protein encoded by circMAPK14 inhibits progression and metastasis of colorectal cancer by competitively binding to MKK6.
    Title: A novel tumour suppressor protein encoded by circMAPK14 inhibits progression and metastasis of colorectal cancer by competitively binding to MKK6.
  6. The interaction of p38 with its upstream kinase MKK6.
    Title: The interaction of p38 with its upstream kinase MKK6.
  7. Based on the experimentally determined models and parameters, dynamics of the p38alpha-MKK6-MKP5 system were explored, demonstrating for the first time that bistability can arise with this model at biologically feasible parameter values
    Title: Kinetic and mechanistic studies of p38α MAP kinase phosphorylation by MKK6.
  8. The loss of MKK6 protein diminishes p38 activation, leading to further degradation of the remaining TRIM9 in glioblastoma cells. The disruption of the TRIM9s-MKK6 mutual stabilization loop ultimately leads to the inactivation of p38 signaling and promotes tumor progression.
    Title: Mutual Stabilization between TRIM9 Short Isoform and MKK6 Potentiates p38 Signaling to Synergistically Suppress Glioblastoma Progression.
  9. Data suggest that mitogen-activated protein kinase kinase 6 (MAP2K6) might be an important regulator of leukemia inhibitory factor receptor (LIFR)-induced radioresistance in nasopharyngeal carcinoma cells (NPC).
    Title: Quantitative proteome analysis identifies MAP2K6 as potential regulator of LIFR-induced radioresistance in nasopharyngeal carcinoma cells.
  10. USP22 could interact directly with MKK6 promoter. Down-regulation of USP22 led to the decreased MKK6 mRNA expression
    Title: [Ubiquitin specific peptidase 22 regulates the transcription activity of mitogen-activated protein kinase kinase 6 gene].
Submit: New GeneRIF Correction See all GeneRIFs (51)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384.
EBI GWAS Catalog
Investigation of single nucleotide polymorphisms and biological pathways associated with response to TNFα inhibitors in patients with rheumatoid arthritis.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat The interaction of HIV-1 Tat with cellular transcription factors CDK9 and Sp1 is required for Tat activation of MAP2K3-, MAP2K6-, and IRF7-mediated luciferase transcription PubMed
tat The association of HIV-1 Tat with MAP2K6 promoter leads to the activation of this kinase in immature dendritic cells and in monocyte-derived macrophages PubMed
tat MAP2K6 and IRF7 induce HIV-1 Tat-mediated cellular gene modulation through the p38 MAPK/STAT1 pathway in immature dendritic cells and in monocyte-derived macrophages PubMed
tat SiRNA-mediated inhibition of MAP2K6 and MAP2K3 reduces HIV-1 Tat-induced modulation of interferon (IFN)-stimulated genes in immature dendritic cells and in monocyte-derived macrophages PubMed

Go to the HIV-1, Human Interaction Database

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 GOA

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 IDA
Inferred from Direct Assay
more info
 PubMed 
enables MAP kinase kinase activity TAS
Traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
  
enables protein tyrosine kinase 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 IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in bone development IEA
Inferred from Electronic Annotation
more info
  
involved_in cardiac muscle contraction IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to sorbitol IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular senescence TAS
Traceable Author Statement
more info
  
involved_in negative regulation of cold-induced thermogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway TAS
Traceable Author Statement
more info
  
involved_in osteoblast differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in ovulation cycle process IEA
Inferred from Electronic Annotation
more info
  
involved_in p38MAPK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in p38MAPK cascade TAS
Traceable Author Statement
more info
  
involved_in phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of nitric-oxide synthase biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of prostaglandin secretion IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of protein phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of cell cycle TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of signal transduction by p53 class mediator TAS
Traceable Author Statement
more info
  
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 signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in signal transduction in response to DNA damage TAS
Traceable Author Statement
more info
 PubMed 
involved_in stress-activated MAPK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in stress-activated protein kinase signaling cascade IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm TAS
Traceable Author Statement
more info
 PubMed 
located_in cytoskeleton IEA
Inferred from Electronic Annotation
more info
  
is_active_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
dual specificity mitogen-activated protein kinase kinase 6
Names
MAPK/ERK kinase 6
MAPKK 6
MEK 6
SAPK kinase 3
protein kinase, mitogen-activated, kinase 6 (MAP kinase kinase 6)
stress-activated protein kinase kinase 3
NP_001317379.1
NP_002749.2
XP_005257573.1
XP_006722038.1
XP_011523329.1
XP_047292366.1
XP_047292367.1
XP_054172660.1
XP_054172661.1
XP_054172662.1
XP_054172663.1
XP_054172664.1

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.

Genomic

  1. NG_029437.2 RefSeqGene

    Range
    5001..144169
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001330450.2 → NP_001317379.1  dual specificity mitogen-activated protein kinase kinase 6 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC002546, BC037328
    Consensus CDS
    CCDS82194.1
    UniProtKB/TrEMBL
    B5BU16
    Related
    ENSP00000467213.1, ENST00000589647.5
    Conserved Domains (1) summary
    cd06617
    Location:1 → 277
    PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6

  2. NM_002758.4 → NP_002749.2  dual specificity mitogen-activated protein kinase kinase 6 isoform 1

    See identical proteins and their annotated locations for NP_002749.2

    Status: REVIEWED

    Source sequence(s)
    AA932919, AC002546, BC012009, DB111443
    Consensus CDS
    CCDS11686.1
    UniProtKB/Swiss-Prot
    P52564
    UniProtKB/TrEMBL
    A8K3Y2, B5BU16
    Related
    ENSP00000468348.1, ENST00000590474.7
    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_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    69414697..69553865
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047436411.1 → XP_047292367.1  dual specificity mitogen-activated protein kinase kinase 6 isoform X2

  2. XM_011525027.4 → XP_011523329.1  dual specificity mitogen-activated protein kinase kinase 6 isoform X2

    See identical proteins and their annotated locations for XP_011523329.1

    UniProtKB/TrEMBL
    B5BU16
    Conserved Domains (1) summary
    cd06617
    Location:1 → 277
    PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6

  3. XM_047436410.1 → XP_047292366.1  dual specificity mitogen-activated protein kinase kinase 6 isoform X1

  4. XM_005257516.3 → XP_005257573.1  dual specificity mitogen-activated protein kinase kinase 6 isoform X2

    See identical proteins and their annotated locations for XP_005257573.1

    UniProtKB/TrEMBL
    B5BU16
    Conserved Domains (1) summary
    cd06617
    Location:1 → 277
    PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6

  5. XM_006721975.4 → XP_006722038.1  dual specificity mitogen-activated protein kinase kinase 6 isoform X2

    See identical proteins and their annotated locations for XP_006722038.1

    UniProtKB/TrEMBL
    B5BU16
    Conserved Domains (1) summary
    cd06617
    Location:1 → 277
    PKc_MKK3_6; Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    70291653..70430810
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054316686.1 → XP_054172661.1  dual specificity mitogen-activated protein kinase kinase 6 isoform X2

  2. XM_054316687.1 → XP_054172662.1  dual specificity mitogen-activated protein kinase kinase 6 isoform X2

  3. XM_054316685.1 → XP_054172660.1  dual specificity mitogen-activated protein kinase kinase 6 isoform X1

  4. XM_054316689.1 → XP_054172664.1  dual specificity mitogen-activated protein kinase kinase 6 isoform X2

  5. XM_054316688.1 → XP_054172663.1  dual specificity mitogen-activated protein kinase kinase 6 isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_031988.1: Suppressed sequence

    Description
    NM_031988.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P52564.1 GenPept UniProtKB/Swiss-Prot:P52564

Gene LinkOut

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