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The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts 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 kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]
MAP2K1 is a dual-specificity kinase known for it's involvement in the ERK pathway by activation of ERK1 and ERK2. MAP2K1 activating mutations have been observed in a number of cancers including ovarian, melanoma and lung. These activating mutations are generally found in the N-terminal negative regulatory region or the ATP-binding region of the N-terminal lobe. Inhibitors of MEK genes have been shown to inhibit tumor growth in these cases.
MAP2K1 (Mitogen-Activated Protein Kinase Kinase 1) is a Protein Coding gene. Diseases associated with MAP2K1 include Cardiofaciocutaneous Syndrome 3 and Cardiofaciocutaneous Syndrome 1. Among its related pathways are Association Between Physico-Chemical Features and Toxicity Associated Pathways and Common Cytokine Receptor Gamma-Chain Family Signaling Pathways. 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 MAP2K2.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA,TAS | 10570282 |
GO:0004674 | protein serine/threonine kinase activity | TAS | -- |
GO:0004708 | MAP kinase kinase activity | IBA,IDA | 8388392 |
GO:0004712 | protein serine/threonine/tyrosine kinase activity | TAS | 19565474 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005634 | nucleus | TAS | 19565474 |
GO:0005737 | cytoplasm | IBA | -- |
GO:0005739 | mitochondrion | TAS | 19565474 |
GO:0005769 | early endosome | TAS | 19565474 |
GO:0005770 | late endosome | TAS | 19565474 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Activated TLR4 signalling | ||
3 | IL-2 Pathway |
ErbB Family Pathway
.59
ErbB4 Pathway
.59
Prolactin Signaling
.54
Thrombopoietin Pathway
.51
ErbB2-ErbB3 Heterodimers
.49
IL-2 Pathway
.48
LPS Stimulated MAPK Signaling
.47
|
UVC-Induced MAPK Signaling
.44
TREM1 Pathway
.43
PACAP Signaling
.37
HMGB1 Pathway
.36
PI3K Signaling in B-Lymphocyte
.35
IL-4 Pathway
.34
|
4 | Regulation of lipid metabolism Insulin signaling-generic cascades |
Regulation of lipid metabolism Insulin signaling-generic cascades
.59
Translation Insulin regulation of translation
.59
Transcription Receptor-mediated HIF regulation
.51
Translation Regulation of EIF2 activity
.47
Translation Regulation of EIF4F activity
.44
Development CNTF receptor signaling
.43
|
Cell adhesion PLAU signaling
.35
Development Growth hormone signaling via PI3K/AKT and MAPK cascades
.34
|
5 | Common Cytokine Receptor Gamma-Chain Family Signaling Pathways |
Immune response IL-9 signaling pathway
.42
Development Thrombopoietin-regulated cell processes
.38
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0000187 | activation of MAPK activity | IDA,TAS | 19565474 |
GO:0006468 | protein phosphorylation | IEA,IDA | 28166211 |
GO:0006935 | chemotaxis | TAS | 10570282 |
GO:0007050 | cell cycle arrest | IMP | 9765203 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
cobimetinib | Approved, Investigational | Pharma | Target, inhibitor | Selective MEK inhibitor | 0 | |
Selumetinib | Approved, Investigational | Pharma | Target, inhibitor, Biomarker | MEK inhibitor, MEK Inhibitors, Kinase Inhibitors, Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors | 0 | |
Trametinib | Approved | Pharma | Target, antagonist, inhibitor, Biomarker | MEK 1/2 inhibitor, MEK Inhibitors, Kinase Inhibitors, Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors | 194 | |
bosutinib | Approved | Pharma | Target, inhibitor | Kinase Inhibitors, SRC/BCR-ABL tyrosine kinase inhibitors | 0 | |
Dabrafenib | Approved, Investigational | Pharma | Inhibition, inhibitor | BRAF kinase inhibitor, Kinase Inhibitors, Mutant BRAF Kinase | 116 |
Compound | Action | Cas Number |
---|---|---|
10Z-Hymenialdisine | Pan kinase inhibitor; potently inhibits MEK1 | 82005-12-7 |
BIX 02189 | Selective MEK5 and ERK5 inhibitor | 1265916-41-3 |
Compound | Action | Cas Number |
---|---|---|
10Z-Hymenialdisine | 82005-12-7 | |
Arctigenin | Anti-inflammatory, antiproliferative | 7770-78-7 |
AZD6244 (Selumetinib) | MEK inhibitor | 606143-52-6 |
AZD8330 | MEK 1/2 inhibitor | 869357-68-6 |
BI-847325 | dual inhibitor of MEK and Aurora kinases | 1207293-36-4 |
BIX 02188 | MEK5 inhibitor,potent and selective | 1094614-84-2 |
BIX 02189 | Selective MEK5 inhibitor | 1094614-85-3 |
Cobimetinib | Selective MEK inhibitor | 934660-93-2 |
Cobimetinib (racemate) | Selective MEK inhibitor | 934662-91-6 |
Cobimetinib (R-enantiomer) | Selective MEK inhibitor | 934660-94-3 |
FR 180204 | ERK inhibitor | 865362-74-9 |
GDC-0623 | MEK1 inhibitor, potent and ATP-uncompetitive | 1168091-68-6 |
GDC-0994 | ERK1/2 inhibitor | 1453848-26-4 |
MEK inhibitor | Potent MEK inhibitor, Antitumor agent | 334951-92-7 |
MEK Inhibitor Set | For phosphorylation and dephosphorylation applications | |
MEK162 (ARRY-162, ARRY-438162) | MEK1/2 inhibitor,potent and selective | 606143-89-9 |
PD 198306 | MEK inhibitor | 212631-61-3 |
PD 334581 | 548756-68-9 | |
PD0325901 | MEK inhibitor | 391210-10-9 |
PD184352 (CI-1040) | Selective MEK inhibitor | 212631-79-3 |
PD318088 | Allosteric MEK1/2 inhibitor, non-ATP competitive | 391210-00-7 |
PD98059 | MEK inhibitor,selective and reversible | 167869-21-8 |
Pimasertib (AS-703026) | MEK1/2 inhibitor | 1236699-92-5 |
Refametinib | MEK 1/ MEK 2 inhibitor | 923032-37-5 |
RO4987655 | MEK inhibitor | 874101-00-5 |
RO5126766(CH5126766) | Raf/MEK dual inhibitor | 946128-88-7 |
SCH772984 | ERK1 and ERK2 inhibitor | 942183-80-4 |
SCH772984 HCl | ||
SCH772984 TFA | ||
SL-327 | Selective MEK1/2 inhibitor | 305350-87-2 |
TAK-733 | MEK allosteric site inhibitor | 1035555-63-5 |
Trametinib (GSK1120212) | MEK1 and MEK2 inhibitor, potent and selective | 871700-17-3 |
Trametinib DMSO solvate | Allosteric MEK1/MEK2 kinase inhibitor | 1187431-43-1 |
U0124 | 108923-79-1 | |
U0126-EtOH | MEK1/2 inhibitor | 1173097-76-1 |
Vemurafenib (PLX4032, RG7204) | BRAF kinase inhibitor | 918504-65-1 |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | MAP2K1 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | MAP2K1 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | MAP2K1 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | MAP2K1 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Map2k1 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Map2k1 30 17 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | MAP2K1 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | MAP2K1 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | -- 31 |
|
ManyToMany | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | map2k1 30 |
|
||
Str.10686 30 |
|
||||
African clawed frog (Xenopus laevis) |
Amphibia | mek-2-prov 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | map2k1 30 31 |
|
OneToOne | |
Dr.25154 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | Dsor1 30 31 32 |
|
OneToMany |