Free for academic non-profit institutions. Other users need a Commercial license

Aliases for MAP2K4 Gene

Aliases for MAP2K4 Gene

  • Mitogen-Activated Protein Kinase Kinase 4 2 3 5
  • Stress-Activated Protein Kinase Kinase 1 3 4
  • C-Jun N-Terminal Kinase Kinase 1 3 4
  • JNK-Activating Kinase 1 3 4
  • MAP Kinase Kinase 4 3 4
  • MAPK/ERK Kinase 4 3 4
  • SAPK/ERK Kinase 1 3 4
  • EC 2.7.12.2 4 63
  • MAPKK 4 3 4
  • SAPKK-1 3 4
  • PRKMK4 3 4
  • SAPKK1 3 4
  • MEK 4 3 4
  • SERK1 3 4
  • JNKK1 3 4
  • JNKK 3 4
  • MEK4 3 4
  • MKK4 3 4
  • SEK1 3 4
  • SKK1 3 4
  • JNK-Activated Kinase 1 3
  • SAPK Kinase 1 4
  • MAPKK4 3

External Ids for MAP2K4 Gene

Previous HGNC Symbols for MAP2K4 Gene

  • SERK1

Previous GeneCards Identifiers for MAP2K4 Gene

  • GC17P012290
  • GC17P013039
  • GC17P011868
  • GC17P012124
  • GC17P011864

Summaries for MAP2K4 Gene

Entrez Gene Summary for MAP2K4 Gene

  • This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

GeneCards Summary for MAP2K4 Gene

MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4) is a Protein Coding gene. Diseases associated with MAP2K4 include ovarian serous carcinoma. Among its related pathways are Sertoli-Sertoli Cell Junction Dynamics and IL6-mediated signaling events. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is MAP2K2.

UniProtKB/Swiss-Prot for MAP2K4 Gene

  • Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.

Gene Wiki entry for MAP2K4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MAP2K4 Gene

Genomics for MAP2K4 Gene

Regulatory Elements for MAP2K4 Gene

Promoters for MAP2K4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around MAP2K4 on UCSC Golden Path with GeneCards custom track

Genomic Location for MAP2K4 Gene

Chromosome:
17
Start:
12,020,818 bp from pter
End:
12,143,831 bp from pter
Size:
123,014 bases
Orientation:
Plus strand

Genomic View for MAP2K4 Gene

Genes around MAP2K4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP2K4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MAP2K4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP2K4 Gene

Proteins for MAP2K4 Gene

  • Protein details for MAP2K4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P45985-MP2K4_HUMAN
    Recommended name:
    Dual specificity mitogen-activated protein kinase kinase 4
    Protein Accession:
    P45985
    Secondary Accessions:
    • B2R7N7
    • B3KYB2
    • D3DTS5
    • Q5U0B8
    • Q6FHX4
    • Q6P9H2
    • Q6PIE6

    Protein attributes for MAP2K4 Gene

    Size:
    399 amino acids
    Molecular mass:
    44288 Da
    Quaternary structure:
    • Interacts with SPAG9 (By similarity). Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2, MAPK10/JNK3, MAPK11 and MAPK14. Interacts (via its DVD domain) with MAP3Ks activators like MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with ARRB1, ARRB2 and MAPK8IP3/JIP3.

    Three dimensional structures from OCA and Proteopedia for MAP2K4 Gene

    Alternative splice isoforms for MAP2K4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP2K4 Gene

Proteomics data for MAP2K4 Gene at MOPED

Selected DME Specific Peptides for MAP2K4 Gene

Post-translational modifications for MAP2K4 Gene

  • Activated by phosphorylation on Ser-257 and Thr-261 by MAP kinase kinase kinases (MAP3Ks).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for MAP2K4 (MKK4)

Domains & Families for MAP2K4 Gene

Graphical View of Domain Structure for InterPro Entry

P45985

UniProtKB/Swiss-Prot:

MP2K4_HUMAN :
  • The DVD domain (residues 364-387) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
Domain:
  • The DVD domain (residues 364-387) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.
  • The D domain (residues 34-52) contains a conserved docking site and is required for the binding to MAPK substrates.
  • Contains 1 protein kinase domain.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
genes like me logo Genes that share domains with MAP2K4: view

Function for MAP2K4 Gene

Molecular function for MAP2K4 Gene

GENATLAS Biochemistry:
mitogen-activated protein kinase kinase 4,binding to JUN transactivation domain and phosphorylating it,involved in signal transduction,also involved in Ras pathway and hepatogenesis
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated in response to a variety of cellular stresses, including UV and gamma-irradiation, heat shock, hyperosmolarity, T-cell receptor stimulation, peroxide and inflammatory cytokines. Also activated by developmental cues. MAP2K4/MKK4 is activated by the majority of MKKKs, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K7/TAK1, MAP3K10/MLK2, MAP3K11/MLK3, MAP3K12/DLK and MAP3K13/LZK.
UniProtKB/Swiss-Prot Function:
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.

Enzyme Numbers (IUBMB) for MAP2K4 Gene

Gene Ontology (GO) - Molecular Function for MAP2K4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IEA,TAS 7716521
GO:0004713 protein tyrosine kinase activity IEA --
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with MAP2K4: view
genes like me logo Genes that share phenotypes with MAP2K4: view

Animal Models for MAP2K4 Gene

MGI Knock Outs for MAP2K4:

Animal Model Products

CRISPR Products

miRNA for MAP2K4 Gene

miRTarBase miRNAs that target MAP2K4

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MAP2K4 Gene

Localization for MAP2K4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP2K4 Gene

Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MAP2K4 Gene COMPARTMENTS Subcellular localization image for MAP2K4 gene
Compartment Confidence
cytosol 5
nucleus 5
mitochondrion 2
cytoskeleton 1
extracellular 1
plasma membrane 1

No data available for Gene Ontology (GO) - Cellular Components for MAP2K4 Gene

Pathways & Interactions for MAP2K4 Gene

SuperPathways for MAP2K4 Gene

Superpath Contained pathways
1 MyD88 cascade initiated on plasma membrane
2 IL-2 Pathway
3 4-1BB Pathway
4 Toll-Like receptor Signaling Pathways
5 Toll-like receptor signaling pathway
genes like me logo Genes that share pathways with MAP2K4: view

Pathways by source for MAP2K4 Gene

SIGNOR curated interactions for MAP2K4 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for MAP2K4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002224 toll-like receptor signaling pathway TAS --
GO:0002755 MyD88-dependent toll-like receptor signaling pathway TAS --
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS --
GO:0006468 protein phosphorylation IEA --
GO:0006915 apoptotic process IEA --
genes like me logo Genes that share ontologies with MAP2K4: view

Drugs & Compounds for MAP2K4 Gene

(38) Drugs for MAP2K4 Gene - From: Novoseek, DGIdb, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Dabrafenib Approved Pharma Inhibition, inhibitor BRAF kinase inhibitor, Kinase Inhibitors, Mutant BRAF Kinase 70
Trametinib Approved Pharma inhibitor, Biomarker MEK 1/2 inhibitor, MEK Inhibitors, Kinase Inhibitors, Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors 111
Adenosine triphosphate Approved Nutra 0
AZD6244 Pharma Inhibition, inhibitor 0
BAY86-9766 Pharma Inhibition, inhibitor MEK inhibitor, MEK Inhibitors 0

(11) Additional Compounds for MAP2K4 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
genes like me logo Genes that share compounds with MAP2K4: view

Transcripts for MAP2K4 Gene

Unigene Clusters for MAP2K4 Gene

Mitogen-activated protein kinase kinase 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for MAP2K4 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13a · 13b · 13c
SP1: - - -
SP2: - - - -
SP3: - -
SP4: - - - -
SP5:
SP6:

Relevant External Links for MAP2K4 Gene

GeneLoc Exon Structure for
MAP2K4
ECgene alternative splicing isoforms for
MAP2K4

Expression for MAP2K4 Gene

mRNA expression in normal human tissues for MAP2K4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MAP2K4 Gene

This gene is overexpressed in Frontal cortex (9.5) and Brain (8.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for MAP2K4 Gene



SOURCE GeneReport for Unigene cluster for MAP2K4 Gene Hs.514681

mRNA Expression by UniProt/SwissProt for MAP2K4 Gene

P45985-MP2K4_HUMAN
Tissue specificity: Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues.
genes like me logo Genes that share expression patterns with MAP2K4: view

Protein tissue co-expression partners for MAP2K4 Gene

- Elite partner

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for MAP2K4 Gene

Orthologs for MAP2K4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for MAP2K4 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia MAP2K4 35
  • 94.29 (n)
  • 99.74 (a)
MAP2K4 36
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MAP2K4 35
  • 95.49 (n)
  • 98.67 (a)
MAP2K4 36
  • 96 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Map2k4 35
  • 95.21 (n)
  • 98.4 (a)
Map2k4 16
Map2k4 36
  • 98 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia MAP2K4 35
  • 99.59 (n)
  • 99.51 (a)
MAP2K4 36
  • 97 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Map2k4 35
  • 94.41 (n)
  • 98.4 (a)
oppossum
(Monodelphis domestica)
Mammalia -- 36
  • 77 (a)
OneToMany
-- 36
  • 96 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia MAP2K4 36
  • 49 (a)
OneToOne
chicken
(Gallus gallus)
Aves MAP2K4 35
  • 89.18 (n)
  • 96.54 (a)
MAP2K4 36
  • 93 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MAP2K4 36
  • 76 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia map2k4 35
  • 80.39 (n)
  • 92.82 (a)
African clawed frog
(Xenopus laevis)
Amphibia Xl.13308 35
zebrafish
(Danio rerio)
Actinopterygii Dr.10451 35
map2k4a 35
  • 77.78 (n)
  • 90.55 (a)
map2k4a 36
  • 85 (a)
OneToMany
map2k4b 36
  • 81 (a)
OneToMany
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4083 35
fruit fly
(Drosophila melanogaster)
Insecta lic 37
  • 52 (a)
Mkk4 37
  • 67 (a)
Mkk4 35
  • 57.38 (n)
  • 63.79 (a)
Mkk4 36
  • 53 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003365 35
  • 59.33 (n)
  • 67.92 (a)
worm
(Caenorhabditis elegans)
Secernentea F35C8.1 37
  • 39 (a)
jkk-1 37
  • 39 (a)
sek-1 37
  • 51 (a)
VZC374L.1 37
  • 48 (a)
mkk-4 36
  • 46 (a)
OneToMany
sek-3 36
  • 37 (a)
OneToMany
sek-6 36
  • 40 (a)
OneToMany
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes wis1 35
  • 52.56 (n)
  • 44 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 53 (a)
OneToOne
Species with no ortholog for MAP2K4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MAP2K4 Gene

ENSEMBL:
Gene Tree for MAP2K4 (if available)
TreeFam:
Gene Tree for MAP2K4 (if available)

Paralogs for MAP2K4 Gene

Paralogs for MAP2K4 Gene

(9) SIMAP similar genes for MAP2K4 Gene using alignment to 5 proteins:

Pseudogenes.org Pseudogenes for MAP2K4 Gene

genes like me logo Genes that share paralogs with MAP2K4: view

Variants for MAP2K4 Gene

Sequence variations from dbSNP and Humsavar for MAP2K4 Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type
VAR_040818 A lung squamous cell carcinoma sample
VAR_040819 A colorectal adenocarcinoma sample
VAR_040820 An ovarian serous carcinoma sample
VAR_040821 A metastatic melanoma sample
VAR_040822 A colorectal adenocarcinoma sample

Structural Variations from Database of Genomic Variants (DGV) for MAP2K4 Gene

Variant ID Type Subtype PubMed ID
esv25918 CNV Loss 19812545
esv991595 CNV Gain 20482838
nsv1983 CNV Insertion 18451855
dgv3060n71 CNV Gain 21882294

Variation tolerance for MAP2K4 Gene

Residual Variation Intolerance Score: 25.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.42; 9.23% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for MAP2K4 Gene

HapMap Linkage Disequilibrium report
MAP2K4
Human Gene Mutation Database (HGMD)
MAP2K4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP2K4 Gene

Disorders for MAP2K4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for MAP2K4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
ovarian serous carcinoma
  • ovarian serous adenocarcinoma
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for MAP2K4

Genetic Association Database (GAD)
MAP2K4
Human Genome Epidemiology (HuGE) Navigator
MAP2K4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
MAP2K4
genes like me logo Genes that share disorders with MAP2K4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MAP2K4 Gene

Publications for MAP2K4 Gene

  1. Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. (PMID: 7716521) Lin A. … Karin M. (Science 1995) 2 3 4 67
  2. Filamin associates with stress signalling kinases MKK7 and MKK4 and regulates JNK activation. (PMID: 20156194) Nakagawa K. … Nishina H. (Biochem. J. 2010) 3 23
  3. Cardiac-specific deletion of mkk4 reveals its role in pathological hypertrophic remodeling but not in physiological cardiac growth. (PMID: 19265040) Liu W. … Wang X. (Circ. Res. 2009) 3 23
  4. Overexpression of mitogen-activated protein kinase kinase 4 and nuclear factor-kappaB in laryngeal squamous cell carcinoma: a potential indicator for poor prognosis. (PMID: 19513509) Huang C. … Chen H.Y. (Oncol. Rep. 2009) 3 23
  5. The association between -1304T>G polymorphism in the promoter of MKK4 gene and the risk of sporadic colorectal cancer in southern Chinese population. (PMID: 19610067) Wei Y. … Wang J. (Int. J. Cancer 2009) 3 23

Products for MAP2K4 Gene

Sources for MAP2K4 Gene

Back to Top

Content