Mitogen-activated protein kinase kinase kinase 1

Function

Component of a protein kinase signal transduction cascade. Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4. May phosphorylate the MAPK8/JNK1 kinase. Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway.

Classification

Family (Pfam)

PF00069 Pkinase, PF04434 SWIM, PF28295 TOG_MAP3K1

InterPro

ARM-like, ARM-type_fold, Kinase-like_dom_sf, MAP_kinase_kinase_kinase, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS, Znf_RING, Znf_RING/FYVE/PHD, Znf_SWIM

Functional cluster

RNA Polymerase II Transcription Factors

Experimental structures · PDB · 1

• 6WHB X-ray 1.90A

A predicted model is available from AlphaFold.

Gene Ontology · 14

• GO:0005829 cytosol
• GO:0070160 tight junction
• GO:0005524 ATP binding
• GO:0004709 MAP kinase kinase kinase activity
• GO:0004672 protein kinase activity
• GO:0019901 protein kinase binding
• GO:0106310 protein serine kinase activity
• GO:0004674 protein serine/threonine kinase activity
• GO:0061630 ubiquitin protein ligase activity
• GO:0008270 zinc ion binding
• GO:0071260 cellular response to mechanical stimulus
• GO:0038095 Fc-epsilon receptor signaling pathway
• GO:0000165 MAPK cascade
• GO:0006468 protein phosphorylation

Disease associations

• 46,XY sex reversal 6 MONDO:0013410

Drugs targeting this protein · 1

• E-6201 inhibitor

Related proteins · sequence + function similarity

• Mitogen-activated protein kinase kinase kinase 1 0.96
• Mitogen-activated protein kinase kinase kinase 1 0.95
• BTB/POZ domain-containing protein KCTD8 0.64
• BTB/POZ domain-containing protein KCTD8 0.63
• Inner nuclear membrane protein Man1 0.60
• Histone-lysine N-methyltransferase SETD5 0.59
• Breakpoint cluster region protein 0.59
• Histone-lysine N-methyltransferase SETD5 0.59
• Breakpoint cluster region protein 0.59
• Breakpoint cluster region protein 0.58
• FERM domain-containing protein 4A 0.58
• RAB11-binding protein RELCH homolog 0.58

Co-cited proteins · studied together in the literature

• Mitogen-activated protein kinase kinase kinase 2 1 shared papers
• Serine/threonine-protein kinase 38 1 shared papers
• Mitogen-activated protein kinase kinase kinase 1 2 shared papers
• Dixin 1 shared papers
• GRIP1-associated protein 1 1 shared papers
• Mitogen-activated protein kinase kinase kinase 1 1 shared papers
• Axin-1 2 shared papers
• GRIP1-associated protein 1 1 shared papers
• E3 SUMO-protein ligase PIAS4 1 shared papers
• Dixin 1 shared papers
• Mitogen-activated protein kinase kinase kinase 4 1 shared papers
• Mitogen-activated protein kinase kinase kinase 4 1 shared papers

Literature · 17 cited papers

• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination. Am. J. Hum. Genet. · 2010
• Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J. Proteome Res. · 2008
• Negative regulation of MEKK1/2 signaling by serine-threonine kinase 38 (STK38). Oncogene · 2008
• GRASP-1 is a neuronal scaffold protein for the JNK signaling pathway. FEBS Lett. · 2007
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• MEKK1 mediates the ubiquitination and degradation of c-Jun in response to osmotic stress. Mol. Cell. Biol. · 2007
• The DNA sequence and comparative analysis of human chromosome 5. Nature · 2004
• … and 5 more in the literature graph