CATH Domain 5u6iA02

CATH Classification

Level	CATH Code	Description
	1	Mainly Alpha
	1.10	Orthogonal Bundle
	1.10.510	Transferase(Phosphotransferase); domain 1
	1.10.510.10	Transferase(Phosphotransferase) domain 1

Domain Context

CATH Clusters

Superfamily	Transferase(Phosphotransferase) domain 1
Functional Family	Mitogen-activated protein kinase 1

Enzyme Information

2.7.11.24

Mitogen-activated protein kinase.

based on mapping to UniProt P63086

ATP + a protein = ADP + a phosphoprotein.

-!- Phosphorylation of specific tyrosine and threonine residues in the activation loop of this enzyme by EC 2.7.12.2 is necessary for enzyme activation. -!- Once activated, the enzyme phosphorylates target substrates on serine or threonine residues followed by a proline. -!- A distinguishing feature of all MAPKs is the conserved sequence Thr- Xaa-Tyr (TXY). -!- 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)

P63086

MK01_RAT

Rattus norvegicus

Mitogen-activated protein kinase 1

PDB Structure

PDB	5U6I
External Links	PDBSum Proteopedia
Method	X-RAY DIFFRACTION
Organism
Primary Citation	Discovery of a 3-(4-Pyrimidinyl) Indazole (MLi-2), an Orally Available and Selective Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitor that Reduces Brain Kinase Activity. Scott, J.D., DeMong, D.E., Greshock, T.J., Basu, K., Dai, X., Harris, J., Hruza, A., Li, S.W., Lin, S.I., Liu, H., Macala, M.K., Hu, Z., Mei, H., Zhang, H., Walsh, P., Poirier, M., Shi, Z.C., Xiao, L., Agnihotri, G., Baptista, M.A., Columbus, J., Fell, M.J., Hyde, L.A., Kuvelkar, R., Lin, Y., Mirescu, C., Morrow, J.A., Yin, Z., Zhang, X., Zhou, X., Chang, R.K., Embrey, M.W., Sanders, J.M., Tiscia, H.E., Drolet, R.E., Kern, J.T., Sur, S.M., Renger, J.J., Bilodeau, M.T., Kennedy, M.E., Parker, E.M., Stamford, A.W., Nargund, R., McCauley, J.A., Miller, M.W. J. Med. Chem.