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MAP2K7 mitogen-activated protein kinase kinase 7 [ Homo sapiens (human) ]

Gene ID: 5609, updated on 22-Apr-2024

Summary

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Official Symbol
MAP2K7provided by HGNC
Official Full Name
mitogen-activated protein kinase kinase 7provided by HGNC
Primary source
HGNC:HGNC:6847
See related
Ensembl:ENSG00000076984 MIM:603014; AllianceGenome:HGNC:6847
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
MEK; MKK7; JNKK2; MEK 7; MAPKK7; PRKMK7; SAPKK4; SAPKK-4
Summary
The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically activates MAPK8/JNK1 and MAPK9/JNK2, and this kinase itself is phosphorylated and activated by MAP kinase kinase kinases including MAP3K1/MEKK1, MAP3K2/MEKK2,MAP3K3/MEKK5, and MAP4K2/GCK. This kinase is involved in the signal transduction mediating the cell responses to proinflammatory cytokines, and environmental stresses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
Expression
Ubiquitous expression in testis (RPKM 9.3), spleen (RPKM 8.9) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
19p13.2
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (7903877..7914478)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (7904832..7915433)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (7968762..7979363)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:7953152-7953850 Neighboring gene RNA, 5S ribosomal pseudogene 463 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:7954740-7955240 Neighboring gene leucine rich repeat containing 8 VRAC subunit E Neighboring gene uncharacterized LOC124904630 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:7968039-7968616 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:7969265-7969804 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:7980702-7981202 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9996 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:7981823-7982699 Neighboring gene transforming growth factor beta receptor 3 like Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:7982700-7983575 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:7984251-7984750 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10000 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10001 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:7986451-7987053 Neighboring gene small nuclear RNA activating complex polypeptide 2

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. High-resolution structure discloses the potential for allosteric regulation of mitogen-activated protein kinase kinase 7. Kinoshita T, et al. Biochem Biophys Res Commun, 2017 Nov 4. PMID 28890347
  2. Rare variant of MAP2K7 is associated with increased risk of COPD in southern and eastern Chinese. Qiu F, et al. Respirology, 2017 May. PMID 28120412
  3. A crucial role of Cys218 in configuring an unprecedented auto-inhibition form of MAP2K7. Sogabe Y, et al. Biochem Biophys Res Commun, 2016 Apr 29. PMID 26987717
  4. Involvement of oxidative stress in taxol-induced apoptosis in chronic myelogenous leukemia K562 cells. Meshkini A, et al. Exp Toxicol Pathol, 2012 May. PMID 21074392
  5. Cloning and expression of human mitogen-activated protein kinase kinase 7gamma1. Michael L, et al. Biochem Biophys Res Commun, 2006 Mar 17. PMID 16442502

See all (157) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Inhibition of MEK Signaling Attenuates Cancer Stem Cell Activity in Anaplastic Thyroid Cancer.
    Title: Inhibition of MEK Signaling Attenuates Cancer Stem Cell Activity in Anaplastic Thyroid Cancer.
  2. Combined PDE4+MEK inhibition shows antiproliferative effects in NRASQ61 mutated melanoma preclinical models.
    Title: Combined PDE4+MEK inhibition shows antiproliferative effects in NRASQ61 mutated melanoma preclinical models.
  3. IL-17 promotes IL-18 production via the MEK/ERK/miR-4492 axis in osteoarthritis synovial fibroblasts.
    Title: IL-17 promotes IL-18 production via the MEK/ERK/miR-4492 axis in osteoarthritis synovial fibroblasts.
  4. Transcription factor ZNF488 accelerates cervical cancer progression through regulating the MEK/ERK signaling pathway.
    Title: Transcription factor ZNF488 accelerates cervical cancer progression through regulating the MEK/ERK signaling pathway.
  5. FOXM1, MEK, and CDK4/6: New Targets for Malignant Peripheral Nerve Sheath Tumor Therapy.
    Title: FOXM1, MEK, and CDK4/6: New Targets for Malignant Peripheral Nerve Sheath Tumor Therapy.
  6. Lymphatic disorders caused by mosaic, activating KRAS variants respond to MEK inhibition.
    Title: Lymphatic disorders caused by mosaic, activating KRAS variants respond to MEK inhibition.
  7. Low expression of PGC-1beta and other mitochondrial biogenesis modulators in melanoma is associated with growth arrest and the induction of an immunosuppressive gene expression program dependent on MEK and IRF-1.
    Title: Low expression of PGC-1β and other mitochondrial biogenesis modulators in melanoma is associated with growth arrest and the induction of an immunosuppressive gene expression program dependent on MEK and IRF-1.
  8. Excellent Response to MEK Inhibition in an AGK-BRAF Gene Fusion Driven Carcinoma: Case Report and Literature Review.
    Title: Excellent Response to MEK Inhibition in an AGK-BRAF Gene Fusion Driven Carcinoma: Case Report and Literature Review.
  9. A Phase Ib/II Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAF(V600E/K) -mutant Solid Tumors.
    Title: A Phase Ib/II Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAF(V600E/K) -mutant Solid Tumors.
  10. A tumor-associated splice-isoform of MAP2K7 drives dedifferentiation in MBNL1-low cancers via JNK activation.
    Title: A tumor-associated splice-isoform of MAP2K7 drives dedifferentiation in MBNL1-low cancers via JNK activation.
Submit: New GeneRIF Correction See all GeneRIFs (60)

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

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
Vpr vpr Activation of TAK1 by HIV-1 Vpr leads to increased levels of phosphorylated IKK-beta and MKK7 in cells PubMed
vpr Synthetic HIV-1 Vpr protein activates AP-1 (Jun/Fos), c-Jun N-terminal kinase (JNK), NF-kappaB, and MKK7 in both U937 cells and primary 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 JUN kinase kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables JUN kinase kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables JUN kinase kinase activity TAS
Traceable Author Statement
more info
  
enables MAP kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables MAP kinase kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables enzyme binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables magnesium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables molecular function activator activity EXP
Inferred from Experiment
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 phosphatase binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein tyrosine kinase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in Fc-epsilon receptor signaling pathway TAS
Traceable Author Statement
more info
  
involved_in JNK cascade ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in JNK cascade TAS
Traceable Author Statement
more info
  
involved_in apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to interleukin-1 IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to lipopolysaccharide IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular senescence TAS
Traceable Author Statement
more info
  
involved_in phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of DNA-templated transcription IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of ERK1 and ERK2 cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of JNK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of JUN kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of telomerase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of telomere capping IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of telomere maintenance via telomerase IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of motor neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in response to UV IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to heat IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to osmotic stress IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to tumor necrosis factor IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to wounding IEA
Inferred from Electronic Annotation
more info
  
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in stress-activated MAPK cascade IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in stress-activated MAPK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in nucleus ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
dual specificity mitogen-activated protein kinase kinase 7
Names
JNK-activating kinase 2
MAP kinase kinase 7
MAPK/ERK kinase 7
SAPK kinase 4
c-Jun N-terminal kinase kinase 2
stress-activated protein kinase kinase 4
NP_001284484.1
NP_001284485.1
NP_660186.1
XP_006722863.1
XP_054177441.1

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_029438.2 RefSeqGene

    Range
    4998..15599
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001297555.2 → NP_001284484.1  dual specificity mitogen-activated protein kinase kinase 7 isoform 1

    See identical proteins and their annotated locations for NP_001284484.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AK098807, AK300988, BC038295, BF445461, DQ445915, HY063492
    Consensus CDS
    CCDS74277.1
    UniProtKB/TrEMBL
    B4DV95
    Related
    ENSP00000381070.2, ENST00000397983.7
    Conserved Domains (1) summary
    cd06618
    Location:120 → 416
    PKc_MKK7; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7

  2. NM_001297556.2 → NP_001284485.1  dual specificity mitogen-activated protein kinase kinase 7 isoform 2

    See identical proteins and their annotated locations for NP_001284485.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. It encodes isoform 2, which is shorter than isoform 1.
    Source sequence(s)
    AK098807, AK300988, BC038295, BF445461, HY063492
    Consensus CDS
    CCDS74278.1
    UniProtKB/TrEMBL
    B4DV95
    Related
    ENSP00000381068.3, ENST00000397981.7
    Conserved Domains (1) summary
    cd06618
    Location:104 → 407
    PKc_MKK7; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7

  3. NM_145185.4 → NP_660186.1  dual specificity mitogen-activated protein kinase kinase 7 isoform 3

    See identical proteins and their annotated locations for NP_660186.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. It encodes isoform 3, which lacks an internal segment and is shorter, compared to isoform 1.
    Source sequence(s)
    AF022805, AK098807, BC038295, BF445461, HY063492
    Consensus CDS
    CCDS42491.1
    UniProtKB/Swiss-Prot
    B2R9S5, D6W659, O14648, O14733, O14816, O60452, O60453, Q1PG43, Q8IY10
    UniProtKB/TrEMBL
    B4DV95
    Related
    ENSP00000381066.3, ENST00000397979.4
    Conserved Domains (1) summary
    cd06618
    Location:104 → 400
    PKc_MKK7; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7

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_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    7903877..7914478
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006722800.3 → XP_006722863.1  dual specificity mitogen-activated protein kinase kinase 7 isoform X1

    See identical proteins and their annotated locations for XP_006722863.1

    UniProtKB/TrEMBL
    B4DV95
    Conserved Domains (1) summary
    cd06618
    Location:120 → 423
    PKc_MKK7; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    7904832..7915433
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054321466.1 → XP_054177441.1  dual specificity mitogen-activated protein kinase kinase 7 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O14733.2 GenPept UniProtKB/Swiss-Prot:O14733

Gene LinkOut

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