CATH Classification

Domain Context

CATH Clusters

Superfamily Phosphorylase Kinase; domain 1
Functional Family Mitogen-activated protein kinase kinase kinase 5

Enzyme Information

2.7.11.25
Mitogen-activated protein kinase kinase kinase.
based on mapping to UniProt Q99683
ATP + a protein = ADP + a phosphoprotein.
-!- This enzyme phosphorylates and activates its downstream protein kinase, EC 2.7.12.2, but requires MAPKKKK for activation. -!- Some members of this family can be activated by p21-activated kinases (PAK/STE20) or Ras. -!- While c-Raf and c-Mos activate the classical MAPK/ERK pathway, MEKK1 and MEKK2 preferentially activate the c-Jun N-terminal protein kinase(JNK)/stress-activated protein kinase (SAPK) pathway. -!- Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. -!- Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumor necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischemeic injury. -!- Formerly EC 2.7.1.37.

UniProtKB Entries (1)

Q99683
M3K5_HUMAN
Homo sapiens
Mitogen-activated protein kinase kinase kinase 5

PDB Structure

PDB 5VIO
External Links
Method X-RAY DIFFRACTION
Organism
Primary Citation
Rational approach to highly potent and selective apoptosis signal-regulating kinase 1 (ASK1) inhibitors.
Lovering, F., Morgan, P., Allais, C., Aulabaugh, A., Brodfuehrer, J., Chang, J., Coe, J., Ding, W., Dowty, H., Fleming, M., Frisbie, R., Guzova, J., Hepworth, D., Jasti, J., Kortum, S., Kurumbail, R., Mohan, S., Papaioannou, N., Strohbach, J.W., Vincent, F., Lee, K., Zapf, C.W.
Eur J Med Chem