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The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. Mutations in this gene cause cardiofaciocutaneous syndrome (CFC syndrome), a disease characterized by heart defects, cognitive disability, and distinctive facial features similar to those found in Noonan syndrome. The inhibition or degradation of this kinase is also found to be involved in the pathogenesis of Yersinia and anthrax. A pseudogene, which is located on chromosome 7, has been identified for this gene. [provided by RefSeq, Jul 2008]
MAP2K2 (Mitogen-Activated Protein Kinase Kinase 2) is a Protein Coding gene. Diseases associated with MAP2K2 include Cardiofaciocutaneous Syndrome 4 and Cardiofaciocutaneous Syndrome 1. Among its related pathways are MAPK Signaling: Oxidative Stress Pathway and Bladder cancer. 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 ENSG00000230626.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
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:0005576 | extracellular region | NAS | 8388392 |
GO:0005634 | nucleus | TAS | 19565474 |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005739 | mitochondrion | TAS | 19565474 |
GO:0005769 | early endosome | TAS | 19565474 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | 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
|
3 | 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
|
4 | Common Cytokine Receptor Gamma-Chain Family Signaling Pathways |
Immune response IL-9 signaling pathway
.42
|
|
5 | Endometrial cancer |
Signal transduction PTEN pathway
.44
|
.36
.32
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0000187 | activation of MAPK activity | TAS | 19565474 |
GO:0006468 | protein phosphorylation | IEA | -- |
GO:0010629 | negative regulation of gene expression | IGI | 23626836 |
GO:0016310 | phosphorylation | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
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 | 212 | |
cobimetinib | Approved, Investigational | Pharma | inhibitor | Selective MEK inhibitor | 0 | |
binimetinib | Approved, Investigational | Pharma | Target, inhibitor | 0 | ||
bosutinib | Approved | Pharma | Target, inhibitor | Kinase Inhibitors, SRC/BCR-ABL tyrosine kinase inhibitors | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
58-64-0 |
|
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 |
---|---|---|
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 |
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 |
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 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 |
ExUns: | 1 | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5a | · | 5b | ^ | 6 | ^ | 7 | ^ | 8a | · | 8b | · | 8c | · | 8d | ^ | 9 | ^ | 10 | ^ | 11 | ^ | 12a | · | 12b | ^ | 13a | · | 13b | ^ | 14 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||
SP2: | - | - | - | - | |||||||||||||||||||||||||||||||||||
SP3: | - | ||||||||||||||||||||||||||||||||||||||
SP4: | |||||||||||||||||||||||||||||||||||||||
SP5: | - | ||||||||||||||||||||||||||||||||||||||
SP6: | - | ||||||||||||||||||||||||||||||||||||||
SP7: | |||||||||||||||||||||||||||||||||||||||
SP8: |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | MAP2K2 31 |
|
OneToOne | |
LOC100611792 30 |
|
||||
Platypus (Ornithorhynchus anatinus) |
Mammalia | MAP2K2 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | MAP2K2 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | MAP2K2 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | MAP2K2 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Map2k2 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Map2k2 30 |
|
||
Chicken (Gallus gallus) |
Aves | MAP2K2 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | MAP2K2 31 |
|
OneToOne | |
Zebrafish (Danio rerio) |
Actinopterygii | map2k2b 31 |
|
OneToMany | |
map2k2a 30 31 |
|
OneToMany | |||
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.3525 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | Dsor1 31 32 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | mek-2 31 32 |
|
OneToMany | |
A. gosspyii yeast (Eremothecium gossypii) |
Saccharomycetes | AGOS_ACR196C 30 |
|
||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | STE7 30 |
|
||
PBS2 31 33 |
|
OneToMany | |||
K. Lactis Yeast (Kluyveromyces lactis) |
Saccharomycetes | KLLA0C16577g 30 |
|
||
Thale Cress (Arabidopsis thaliana) |
eudicotyledons | MKK6 30 |
|
||
Rice (Oryza sativa) |
Liliopsida | Os01g0510100 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.8484 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 19 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
40812 | Uncertain Significance: Rasopathy | 4,101,120(-) |
C/T NM_030662.3(MAP2K2):c.604G>A (p.Val202Met) |
MISSENSE | |
837134 | Uncertain Significance: Rasopathy | 4,101,256(-) |
G/A NM_030662.4(MAP2K2):c.553C>T (p.Arg185Ter) |
NONSENSE | |
837201 | Likely Pathogenic: Rasopathy | 4,110,624(-) |
C/A NM_030662.4(MAP2K2):c.335G>T (p.Arg112Leu) |
MISSENSE | |
837895 | Uncertain Significance: Rasopathy; not specified | 4,090,624(-) |
C/T NM_030662.4(MAP2K2):c.1177G>A (p.Gly393Ser) |
MISSENSE | |
843844 | Uncertain Significance: Rasopathy | 4,101,042(-) |
C/G NM_030662.4(MAP2K2):c.682G>C (p.Val228Leu) |
MISSENSE |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv1694n106 | CNV | deletion | 24896259 |
esv1448615 | CNV | insertion | 17803354 |
esv2717979 | CNV | deletion | 23290073 |
esv3555894 | CNV | deletion | 23714750 |
nsv1072846 | CNV | deletion | 25765185 |
nsv2393 | CNV | insertion | 18451855 |
nsv470115 | CNV | loss | 18288195 |
nsv578435 | CNV | loss | 21841781 |
nsv833716 | CNV | loss | 17160897 |
Disorder | Aliases | PubMed IDs |
---|---|---|
cardiofaciocutaneous syndrome 4 |
|
|
cardiofaciocutaneous syndrome 1 |
|
|
tafro syndrome |
|
|
rasopathy |
|
|
neurofibromatosis-noonan syndrome |
|
|