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Overview for MACiE Entry M0282

Version history

General Information

EC Number: 2.7.12.2 (A member of the Transferases, Transferring phosphorus-containing groups, Dual-specificity kinases (those acting on Ser/Thr and Tyr residues))

Enzyme Name: mitogen-activated protein kinase kinase

Biological Species: Homo sapiens (Human)

Catalytic Chain UniprotKB Accession Codes:

  • P36507 - Dual specificity mitogen-activated protein kinase kinase 2

Representative PDB Code: 1s9i - X-RAY STRUCTURE OF THE HUMAN MITOGEN-ACTIVATED PROTEINKINASE KINASE 2 (MEK2)IN A COMPLEX WITH LIGAND AND MGATP (Resolution = 3.20 Å).

Catalytic CATH Codes:

"Other" CATH Codes:

Display structure information

Overall Reaction:

Image of serine protein

Image of ATP

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Image of phosphorylated serine protein

Image of ADP

serine protein
C02189
CHEBI:29999
ATP
C00002
CHEBI:30616
phosphorylated serine protein
X00134
CHEBI:61975
ADP
C00008
CHEBI:456216

Overall Comment: The enzyme phosphorylates mitogen-activated protein kinase substrates at serine, tyrosine or threonine residues.

The enzyme does not return to a state in which it can catalyse another reaction


View similar reactions


Stepwise Description of the Reaction

Step 1The serine residue of the protein substrate attacks the terminal, pentavalent phosphorous of ATP.
Step 2Asp194 abstracts a proton from the phospho-serine residue.
Step 3Asp194 relays the proton to ADP, regenerating the active site.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Asp 194 A Side Chain
Asp 221 A Side Chain

Metal Cofactors for M0282

Type Het group Number Chain
magnesium MG 536 A Overview

References

  1. J. F. Ohren et al. (2004), Nat. Struct. Mol. Biol., 11, 1192-1197. Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition.
    Medline: 15543157
  2. K. Gopalbhai et al. (2003), J. Biol. Chem., 7, 8118-8125. Negative regulation of MAPKK by phosphorylation of a conserved serine residue equivalent to Ser212 of MEK1.
    Medline: 12506122
  3. J. Zheng et al. (1993), Acta Crystallogr. D Biol. Crystallogr., 49, 362-365. 2.2 A refined crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MnATP and a peptide inhibitor.
    Medline: 15299527
  4. V. E. Anderson et al. (2006), Chem. Rev., 106, 3236-3251. Activation of Oxygen Nucleophiles in Enzyme Catalysis.
    Medline: 16895326
  5. J. A. Adams (2001), Chem. Rev., 101, 2271-2290. Kinetic and catalytic mechanisms of protein kinases.
    Medline: 11749373
  6. S. K. Hanks et al. (1995), FASEB J., 9, 576-596. Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification.
    Medline: 7768349

Homologue information for M0282 (1s9i)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)



Entries with at least one Catalytic CATH code in common (different mechanisms):

MACiE Entry Enzyme Name
EC Number
PDB code CATH code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0246 receptor protein-tyrosine kinase
2.7.10.1
1ir3 1.10.510.10
3.30.200.20
0.40.4849Compare
M0035 phosphorylase kinase
2.7.11.19
2phk 1.10.510.10
3.30.200.20
0.70.3792Compare

View a comparison of the other reactions in MACiE with the CATH domain 1.10.510.10

View a comparison of the other reactions in MACiE with the CATH domain 3.30.200.20


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ

GOA logo
MAPK cascade (biological process)
nucleotide binding (molecular function)
activation of MAPKK activity (biological process)
activation of MAPK activity (biological process)
toll-like receptor signaling pathway (biological process)
MyD88-dependent toll-like receptor signaling pathway (biological process)
MyD88-independent toll-like receptor signaling pathway (biological process)
protein kinase activity (molecular function)
protein serine/threonine kinase activity (molecular function)
MAP kinase kinase activity (molecular function)
protein tyrosine kinase activity (molecular function)
protein binding (molecular function)
ATP binding (molecular function)
extracellular region (cellular component)
soluble fraction (cellular component)
cytosol (cellular component)
cell cortex (cellular component)
protein phosphorylation (biological process)
epidermal growth factor receptor signaling pathway (biological process)
small GTPase mediated signal transduction (biological process)
Ras protein signal transduction (biological process)
axon guidance (biological process)
Toll signaling pathway (biological process)
insulin receptor signaling pathway (biological process)
toll-like receptor 1 signaling pathway (biological process)
toll-like receptor 2 signaling pathway (biological process)
toll-like receptor 3 signaling pathway (biological process)
toll-like receptor 4 signaling pathway (biological process)
innate immune response (biological process)
neurotrophin TRK receptor signaling pathway (biological process)
stress-activated MAPK cascade (biological process)
ERK1 and ERK2 cascade (biological process)
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