ID:M3K4_HUMAN DESCRIPTION: RecName: Full=Mitogen-activated protein kinase kinase kinase 4; EC=2.7.11.25; AltName: Full=MAP three kinase 1; AltName: Full=MAPK/ERK kinase kinase 4; Short=MEK kinase 4; Short=MEKK 4; FUNCTION: Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. ENZYME REGULATION: N-terminal autoinhibitory domain interacts with the C-terminal kinase domain, inhibiting kinase activity, and preventing interaction with its substrate, MAP2K6. The GADD45 proteins activate the kinase by binding to the N-terminal domain. Activated by phosphorylation on Thr-1505. SUBUNIT: Monomer and homodimer. Homodimerization enhances kinase activity. Interacts with TRAF4; this promotes homodimerization (By similarity). Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with AXIN1 and DIXDC1; interaction with DIXDC1 prevents interaction with AXIN1. SUBCELLULAR LOCATION: Cytoplasm, perinuclear region (By similarity). Note=Localized in perinuclear vesicular-like structures, probably Golgi-associated vesicles (By similarity). TISSUE SPECIFICITY: Expressed at high levels in heart, placenta, skeletal muscle and pancreas, and at lower levels in other tissues. SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=BAA13204.2; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAC12766.2; Type=Erroneous gene model prediction; Sequence=CAH70639.1; Type=Erroneous gene model prediction; Sequence=CAH70640.1; Type=Erroneous gene model prediction; Sequence=CAI20815.1; Type=Erroneous gene model prediction; Sequence=CAI20816.1; Type=Erroneous gene model prediction; Sequence=CAI21477.1; Type=Erroneous gene model prediction; Sequence=CAI41309.1; Type=Erroneous gene model prediction; Sequence=CAI41310.1; Type=Erroneous gene model prediction;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9Y6R4
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000165 MAPK cascade GO:0000186 activation of MAPKK activity GO:0001890 placenta development GO:0006468 protein phosphorylation GO:0007346 regulation of mitotic cell cycle GO:0010225 response to UV-C GO:0010468 regulation of gene expression GO:0016310 phosphorylation GO:0019100 male germ-line sex determination GO:0032212 positive regulation of telomere maintenance via telomerase GO:0035556 intracellular signal transduction GO:0042981 regulation of apoptotic process GO:0043507 positive regulation of JUN kinase activity GO:0051973 positive regulation of telomerase activity GO:0060718 chorionic trophoblast cell differentiation GO:1900745 positive regulation of p38MAPK cascade GO:1904355 positive regulation of telomere capping
Cellular Component: GO:0005737 cytoplasm GO:0048471 perinuclear region of cytoplasm
Descriptions from all associated GenBank mRNAs
D86968 - Homo sapiens mRNA for KIAA0213 gene. BC146770 - Homo sapiens mitogen-activated protein kinase kinase kinase 4, mRNA (cDNA clone MGC:166846 IMAGE:9007216), complete cds. AF002715 - Homo sapiens MAP kinase kinase kinase (MTK1) mRNA, complete cds. BC143735 - Homo sapiens mitogen-activated protein kinase kinase kinase 4, mRNA (cDNA clone MGC:177266 IMAGE:9052249), complete cds. BC136276 - Homo sapiens mitogen-activated protein kinase kinase kinase 4, mRNA (cDNA clone MGC:167886 IMAGE:9020263), complete cds. BC143743 - Homo sapiens cDNA clone IMAGE:9052257. BC143750 - Homo sapiens cDNA clone IMAGE:9052264. AK307866 - Homo sapiens cDNA, FLJ97814. JD423233 - Sequence 404257 from Patent EP1572962. JD479651 - Sequence 460675 from Patent EP1572962. JD271279 - Sequence 252303 from Patent EP1572962. JD458430 - Sequence 439454 from Patent EP1572962. JD056223 - Sequence 37247 from Patent EP1572962. JD128940 - Sequence 109964 from Patent EP1572962. JD056226 - Sequence 37250 from Patent EP1572962. JD458471 - Sequence 439495 from Patent EP1572962. AF116604 - Homo sapiens PRO0412 mRNA, complete cds. AK124430 - Homo sapiens cDNA FLJ42439 fis, clone BLADE2007935, highly similar to MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 4 (EC 2.7.1.-). JD534290 - Sequence 515314 from Patent EP1572962. JD088223 - Sequence 69247 from Patent EP1572962. JD272310 - Sequence 253334 from Patent EP1572962. JD137162 - Sequence 118186 from Patent EP1572962. JD488804 - Sequence 469828 from Patent EP1572962. JD048169 - Sequence 29193 from Patent EP1572962. JD534930 - Sequence 515954 from Patent EP1572962. JD403637 - Sequence 384661 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_mapkPathway - MAPKinase Signaling Pathway
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
