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

Summary

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: mouse all
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Genomic context

Location:: 17q24.3

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (69414697..69553865)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (70291653..70430810)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (67410838..67550006)

Chromosome 17 - NC_000017.11 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: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
APEX1 promotes the oncogenicity of hepatocellular carcinoma via regulation of MAP2K6.
Title: APEX1 promotes the oncogenicity of hepatocellular carcinoma via regulation of MAP2K6.
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.
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.
The interaction of p38 with its upstream kinase MKK6.
Title: The interaction of p38 with its upstream kinase MKK6.
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.
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.
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.
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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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 EBI GWAS CatalogPubMed
Investigation of single nucleotide polymorphisms and biological pathways associated with response to TNF&#x003b1; inhibitors in patients with rheumatoid arthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

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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

MARC_24286-24287:1044369540:1 (e-PCR)
- UniSTS:268873

D17S1526 (e-PCR)
- UniSTS:12639

D17S1471E (e-PCR)
- UniSTS:151679

G20292 (e-PCR)
- UniSTS:17318

A005K40 (e-PCR)
- UniSTS:17319

D17S1786 (e-PCR)
- UniSTS:43983

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 identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
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 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 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

EC 2.7.12.2

NP_002749.2

EC 2.7.12.2

XP_005257573.1

EC 2.7.12.2

XP_006722038.1

EC 2.7.12.2

XP_011523329.1

EC 2.7.12.2

XP_047292366.1

EC 2.7.12.2

XP_047292367.1

EC 2.7.12.2

XP_054172660.1

EC 2.7.12.2

XP_054172661.1

EC 2.7.12.2

XP_054172662.1

EC 2.7.12.2

XP_054172663.1

EC 2.7.12.2

XP_054172664.1

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.

Genomic

NG_029437.2 RefSeqGene

Range

5001..144169

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

69414697..69553865

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047436411.1 → XP_047292367.1 dual specificity mitogen-activated protein kinase kinase 6 isoform X2
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
XM_047436410.1 → XP_047292366.1 dual specificity mitogen-activated protein kinase kinase 6 isoform X1
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
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

NC_060941.1 Alternate T2T-CHM13v2.0

Range

70291653..70430810

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054316686.1 → XP_054172661.1 dual specificity mitogen-activated protein kinase kinase 6 isoform X2
XM_054316687.1 → XP_054172662.1 dual specificity mitogen-activated protein kinase kinase 6 isoform X2
XM_054316685.1 → XP_054172660.1 dual specificity mitogen-activated protein kinase kinase 6 isoform X1
XM_054316689.1 → XP_054172664.1 dual specificity mitogen-activated protein kinase kinase 6 isoform X2
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

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.