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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]
MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4) is a Protein Coding gene. Diseases associated with MAP2K4 include Ovarian Serous Carcinoma and Cardiomyopathy, Familial Hypertrophic, 25. Among its related pathways are MAPK Signaling: Oxidative Stress Pathway and Beta-Adrenergic Signaling. Gene Ontology (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 MAP2K7.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | TAS | 7716521 |
GO:0004674 | protein serine/threonine kinase activity | IEA | -- |
GO:0004708 | MAP kinase kinase activity | IBA | 21873635 |
GO:0004713 | protein tyrosine kinase activity | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005634 | nucleus | IEA | -- |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005829 | cytosol | TAS | -- |
GO:0030424 | axon | IEA | -- |
GO:0032839 | dendrite cytoplasm | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Activated TLR4 signalling | ||
2 | IL-2 Pathway |
ErbB4 Pathway
.59
Prolactin Signaling
.54
Thrombopoietin Pathway
.51
ErbB2-ErbB3 Heterodimers
.49
IL-2 Pathway
.48
|
LPS Stimulated MAPK Signaling
.47
TREM1 Pathway
.43
PACAP Signaling
.37
HMGB1 Pathway
.36
IL-4 Pathway
.34
|
3 | TNFR1 Pathway |
TNFR1 Pathway
.56
TNF Signaling
.55
Apoptosis and survival TNFR1 signaling pathway
.52
Apoptosis through Death Receptors
.42
|
Fas Signaling
.35
|
4 | Toll-Like receptor Signaling Pathways |
Mucin expression in CF via TLRs, EGFR signaling pathways
.42
Immune response IL-1 signaling pathway
.41
|
|
5 | 4-1BB Pathway |
4-1BB Pathway
.54
CD40 Signaling
.54
CD27 Pathway
.48
|
NF-KappaB Activation by EBV
.42
PKR Pathway
.36
SUMO Pathway
.30
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | IEA | -- |
GO:0000187 | activation of MAPK activity | IBA | 21873635 |
GO:0001934 | positive regulation of protein phosphorylation | IEA | -- |
GO:0006468 | protein phosphorylation | IEA | -- |
GO:0006915 | apoptotic process | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Ethanol | Approved | Pharma | 3481 | |||
Dabrafenib | Approved, Investigational | Pharma | Inhibition, inhibitor | BRAF kinase inhibitor, Kinase Inhibitors, Mutant BRAF Kinase | 133 | |
Selumetinib | Approved, Investigational | Pharma | inhibitor, Biomarker | MEK inhibitor, MEK Inhibitors, Kinase Inhibitors, Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors | 0 | |
Trametinib | Approved | Pharma | inhibitor, Biomarker | MEK 1/2 inhibitor, MEK Inhibitors, Kinase Inhibitors, Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors | 212 | |
ATP | Investigational | Nutra | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
58-64-0 |
|
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: |
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | MAP2K4 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | -- 31 |
|
OneToMany | |
-- 31 |
|
OneToMany | |||
Dog (Canis familiaris) |
Mammalia | MAP2K4 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Map2k4 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Map2k4 30 |
|
||
Cow (Bos Taurus) |
Mammalia | MAP2K4 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | MAP2K4 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | MAP2K4 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | MAP2K4 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | map2k4 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.13308 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | map2k4b 31 |
|
OneToMany | |
map2k4a 30 31 |
|
OneToMany | |||
Dr.10451 30 |
|
||||
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.4083 30 |
|
||
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP003365 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | Mkk4 30 31 32 |
|
OneToOne | |
lic 32 |
|
|
|||
Worm (Caenorhabditis elegans) |
Secernentea | sek-1 32 |
|
|
|
VZC374L.1 32 |
|
|
|||
mkk-4 31 |
|
OneToMany | |||
sek-6 31 |
|
OneToMany | |||
jkk-1 32 |
|
|
|||
F35C8.1 32 |
|
|
|||
sek-3 31 |
|
OneToMany | |||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToOne | |
Fission Yeast (Schizosaccharomyces pombe) |
Schizosaccharomycetes | wis1 30 |
|
SNP ID | Clinical significance and condition | Chr 17 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
rs1555550018 | Other: Neuroblastoma | 12,107,814(+) |
C/G NM_003010.4(MAP2K4):c.538C>G (p.Leu180Val) |
MISSENSE | |
rs1567657403 | A colorectal adenocarcinoma sample |
p.Arg154Trp |
|||
rs753665559 | A colorectal adenocarcinoma sample |
p.Ala279Thr |
|||
VAR_040818 | A lung squamous cell carcinoma sample |
p.Gln142Leu |
|||
VAR_040820 | An ovarian serous carcinoma sample |
p.Asn234Ile |
Disorder | Aliases | PubMed IDs |
---|---|---|
ovarian serous carcinoma |
|
|
cardiomyopathy, familial hypertrophic, 25 |
|
|
anthrax disease |
|
|
breast mucoepidermoid carcinoma |
|
|
pancreatic cancer |
|
|