Mitogen-activated protein kinase kinase kinase 12

Function

Part of a non-canonical MAPK signaling pathway. Activated by APOE, enhances the AP-1-mediated transcription of APP, via a MAP kinase signal transduction pathway composed of MAP2K7 and MAPK1/ERK2 and MAPK3/ERK1. May be an activator of the JNK/SAPK pathway.

Classification

Family (Pfam)

PF07714 PK_Tyr_Ser-Thr

InterPro

Kinase-like_dom_sf, MAP3K12_MAP3K13, MAPKKK12, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ser/Thr_kinase_AS, Ser/Thr_Kinases-Pseudokinases

Functional cluster

Eukaryotic Transcription Factors & related

Experimental structures · PDB · 12

• 5CEN X-ray 1.70A
• 5CEO X-ray 2.28A
• 5CEP X-ray 1.99A
• 5CEQ X-ray 1.91A
• 5VO1 X-ray 2.45A
• 5VO2 X-ray 2.96A
• 8DEG X-ray 2.79A
• 8OUR X-ray 1.95A
• 8OUS X-ray 2.20A
• 8OUT X-ray 1.94A
• 9CDX X-ray 2.38A
• 9CDY X-ray 1.50A

A predicted model is available from AlphaFold.

Gene Ontology · 20

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0030426 growth cone
• GO:0016020 membrane
• GO:0005886 plasma membrane
• GO:0005524 ATP binding
• GO:0004709 MAP kinase kinase kinase activity
• GO:0042803 protein homodimerization activity
• GO:0004672 protein kinase activity
• GO:0019901 protein kinase binding
• GO:0106310 protein serine kinase activity
• GO:0043539 protein serine/threonine kinase activator activity
• GO:0004674 protein serine/threonine kinase activity
• GO:0035556 intracellular signal transduction
• GO:0007254 JNK cascade
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0070374 positive regulation of ERK1 and ERK2 cascade
• GO:0043687 post-translational protein modification
• GO:0046777 protein autophosphorylation
• GO:0006468 protein phosphorylation

Drugs targeting this protein · 1

• CEP-1347 inhibitor

Related proteins · sequence + function similarity

• Mitogen-activated protein kinase kinase kinase 12 0.99
• Mitogen-activated protein kinase kinase kinase 12 0.99
• Mitogen-activated protein kinase kinase kinase 10 0.86
• Mitogen-activated protein kinase kinase kinase 10 0.86
• Mitogen-activated protein kinase kinase kinase 10 0.86
• Mitogen-activated protein kinase kinase kinase 9 0.85
• Mitogen-activated protein kinase kinase kinase 11 0.85
• Mitogen-activated protein kinase kinase kinase 11 0.85
• Mitogen-activated protein kinase kinase kinase 11 0.84
• Dual specificity testis-specific protein kinase 1 0.84
• Dual specificity testis-specific protein kinase 1 0.83
• Dual specificity testis-specific protein kinase 1 0.83

Co-cited proteins · studied together in the literature

• MAP3K12-binding inhibitory protein 1 1 shared papers
• Mitogen-activated protein kinase kinase kinase 12 1 shared papers
• Dual specificity mitogen-activated protein kinase kinase 7 1 shared papers
• Dual specificity mitogen-activated protein kinase kinase 7 1 shared papers
• Apolipoprotein E 1 shared papers

Literature · 10 cited papers

• ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and Abeta Secretion. Cell · 2017
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• The finished DNA sequence of human chromosome 12. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• SP3 acts as a positive regulator on the core promoter of human ZPK gene. Biochem. Biophys. Res. Commun. · 2004
• MAPK upstream kinase (MUK)-binding inhibitory protein, a negative regulator of MUK/Dual leucine zipper-bearing kinase/leucine zipper protein kinase. J. Biol. Chem. · 2000
• Cloning of a novel putative protein kinase having a leucine zipper domain from human brain. Biochem. Biophys. Res. Commun. · 1994