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The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Several alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, May 2014]
MAP3K4 (Mitogen-Activated Protein Kinase Kinase Kinase 4) is a Protein Coding gene. Among its related pathways are NGF Pathway and Integrin Pathway. 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 MAP3K2.
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 | IBA | -- |
GO:0004709 | MAP kinase kinase kinase activity | IEA,IDA | 9305639 |
GO:0005515 | protein binding | IPI | 12052864 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005737 | cytoplasm | IBA,IDA | 9827804 |
GO:0048471 | perinuclear region of cytoplasm | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Development Endothelin-1/EDNRA signaling |
Development Endothelin-1/EDNRA signaling
.41
|
|
2 | MAPK signaling pathway | ||
3 | B Cell Receptor Signaling Pathway (sino) | ||
4 | TNFR1 Pathway |
TNF Signaling
.55
|
Apoptosis through Death Receptors
.42
|
5 | 4-1BB Pathway |
CD27 Pathway
.48
|
TNFR2 Pathway
.37
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | IEA | -- |
GO:0000186 | activation of MAPKK activity | IDA | 9305639 |
GO:0001890 | placenta development | IEA | -- |
GO:0006468 | protein phosphorylation | IEA | -- |
GO:0007346 | regulation of mitotic cell cycle | IBA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
fostamatinib | Approved, Investigational | Pharma | Target, inhibitor | Kinase Inhibitors | 0 | |
Magnesium | Approved, Experimental, Investigational | Pharma | 0 | |||
ATP | Investigational | Nutra | Agonist, Activator, Partial agonist, Antagonist, Full agonist, Gating inhibitor, Pore Blocker, Potentiation | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
ExUns: | 1 | ^ | 2a | · | 2b | ^ | 3a | · | 3b | ^ | 4a | · | 4b | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10 | ^ | 11 | ^ | 12a | · | 12b | · | 12c | ^ | 13a | · | 13b | ^ | 14 | ^ | 15a | · | 15b | ^ | 16a | · | 16b | ^ | 17 | ^ | 18 | ^ |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||
SP2: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP3: | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||||
SP4: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP5: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP6: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP7: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP8: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP9: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP10: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP11: | - | - |
ExUns: | 19a | · | 19b | ^ | 20 | ^ | 21 | ^ | 22 | ^ | 23 | ^ | 24 | ^ | 25 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | |||||||||||||
SP2: | - | - | |||||||||||||
SP3: | |||||||||||||||
SP4: | |||||||||||||||
SP5: | |||||||||||||||
SP6: | - | ||||||||||||||
SP7: | |||||||||||||||
SP8: | |||||||||||||||
SP9: | |||||||||||||||
SP10: | |||||||||||||||
SP11: |
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | MAP3K4 30 |
|
||
Dog (Canis familiaris) |
Mammalia | MAP3K4 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | MAP3K4 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | MAP3K4 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | MAP3K4 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Map3k4 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Map3k4 30 17 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | MAP3K4 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | MAP3K4 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | map3k4 30 |
|
||
Str.625 30 |
|
||||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.15863 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | map3k4 30 31 |
|
OneToOne | |
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP002371 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | Mekk1 30 31 32 |
|
OneToOne | |
Worm (Caenorhabditis elegans) |
Secernentea | mtk-1 32 |
|
|
|
F18F11.5 31 |
|
OneToOne | |||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | SSK22 31 |
|
OneToMany | |
SSK2 31 33 |
|
OneToMany | |||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 06 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
713468 | Benign: not provided | 161,108,866(+) | C/T | INTRON_VARIANT | |
759692 | Likely Benign: not provided | 161,092,006(+) | A/C | INTRON_VARIANT | |
790732 | Benign: not provided | 161,091,414(+) | T/A | MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT | |
VAR_040691 | An ovarian serous carcinoma sample | p.Glu1413Gln | |||
rs34018542 | - | p.Gln584His |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv1009798 | CNV | deletion | 20482838 |
esv1022211 | CNV | deletion | 17803354 |
esv2287098 | CNV | deletion | 18987734 |
esv2422347 | CNV | duplication | 17116639 |
esv2733067 | CNV | deletion | 23290073 |
esv2733068 | CNV | deletion | 23290073 |
esv2733069 | CNV | deletion | 23290073 |
esv2733070 | CNV | deletion | 23290073 |
esv2733071 | CNV | deletion | 23290073 |
esv3576242 | CNV | gain | 25503493 |
esv3611453 | CNV | gain | 21293372 |
esv5229 | CNV | loss | 18987735 |
nsv1026543 | CNV | gain | 25217958 |
nsv1030045 | CNV | gain | 25217958 |
nsv1030852 | CNV | gain | 25217958 |
nsv1074442 | CNV | deletion | 25765185 |
nsv1074443 | CNV | deletion | 25765185 |
nsv1130850 | CNV | deletion | 24896259 |
nsv1137172 | CNV | deletion | 24896259 |
nsv1137559 | CNV | deletion | 24896259 |
nsv1143327 | CNV | deletion | 24896259 |
nsv1146290 | CNV | deletion | 26484159 |
nsv1148627 | CNV | deletion | 26484159 |
nsv949883 | CNV | duplication | 24416366 |
No disorders were found for MAP3K4 Gene.