ID:M3K11_HUMAN DESCRIPTION: RecName: Full=Mitogen-activated protein kinase kinase kinase 11; EC=2.7.11.25; AltName: Full=Mixed lineage kinase 3; AltName: Full=Src-homology 3 domain-containing proline-rich kinase; FUNCTION: Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium (By similarity). ENZYME REGULATION: Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation. SUBUNIT: Homodimer; undergoes dimerization during activation. Interacts with MAP2K4/MKK4. Interacts with MAP2K7/MKK7 (By similarity). INTERACTION: P60953:CDC42; NbExp=2; IntAct=EBI-49961, EBI-81752; P35240:NF2; NbExp=4; IntAct=EBI-49961, EBI-1014472; SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, centrosome. Note=Location is cell cycle dependent. TISSUE SPECIFICITY: Expressed in a wide variety of normal and neoplastic tissues including fetal lung, liver, heart and kidney, and adult lung, liver, heart, kidney, placenta, skeletal muscle, pancreas and brain. PTM: Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation. Thr-277 is likely to be the main autophosphorylation site. Phosphorylation of Ser-555 and Ser-556 is induced by CDC42. SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SH3 domain. SEQUENCE CAUTION: Sequence=BAD92892.1; Type=Erroneous initiation;
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.
Pfam Domains: PF00018 - SH3 domain PF00069 - Protein kinase domain PF07653 - Variant SH3 domain PF07714 - Protein tyrosine and serine/threonine kinase PF14604 - Variant SH3 domain
SCOP Domains: 50044 - SH3-domain 56112 - Protein kinase-like (PK-like)
ModBase Predicted Comparative 3D Structure on Q16584
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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.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000166 nucleotide binding GO:0004672 protein kinase activity GO:0004674 protein serine/threonine kinase activity GO:0004706 JUN kinase kinase kinase activity GO:0004709 MAP kinase kinase kinase activity GO:0005515 protein binding GO:0005524 ATP binding GO:0016301 kinase activity GO:0016740 transferase activity GO:0031434 mitogen-activated protein kinase kinase binding GO:0031435 mitogen-activated protein kinase kinase kinase binding GO:0042802 identical protein binding GO:0042803 protein homodimerization activity GO:0048365 Rac GTPase binding
Biological Process: GO:0000187 activation of MAPK activity GO:0006468 protein phosphorylation GO:0007017 microtubule-based process GO:0007254 JNK cascade GO:0007256 activation of JNKK activity GO:0007257 activation of JUN kinase activity GO:0008219 cell death GO:0008283 cell proliferation GO:0016310 phosphorylation GO:0043065 positive regulation of apoptotic process GO:0043507 positive regulation of JUN kinase activity GO:0043525 positive regulation of neuron apoptotic process GO:0046330 positive regulation of JNK cascade GO:0046777 protein autophosphorylation