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mitogen-activated protein kinase kinase kinase 1 (MAP3K1, MAPK/ERK kinase kinase 1, MEKK1, MAPKKK1, MEKK)
Function:
- component of a protein kinase signal transduction cascade
- activates the ERK & JNK kinase pathways by phosphorylation of MAP2K1 & MAP2K4
- activates CHUK & IKBKB, the central protein kinases of the NF-kappa-B pathway
- binds both upstream activators & downstream substrates in multimolecular complexes through its N-terminus
- oligomerizes after binding MAP4K2 or TRAF2
- interacts with AXIN1
- activated by autophosphorylation on Thr-1402 & Thr-1414 following oligomerization
- autophosphorylated (putative)
ATP + a protein ADP + a phosphoprotein
Cofactor: Mg+2
Structure:
- belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
- contains 1 protein kinase domain
- contains 1 RING-type Zn+2 finger
- contains 1 SWIM-type Zn+2 finger
Interactions
molecular events
General
mitogen-activated protein kinase kinase kinase (MAP3K) or MEK kinase (MEKK)
ring finger protein
Properties
SIZE: entity length = 1514 aa
MW = 165 kD
MOTIF: alanine-rich region {2-5}
MOTIF: alanine residue (SEVERAL)
glycine-rich region {25-29}
alanine-rich region {36-41}
MOTIF: alanine residue (SEVERAL)
Zinc finger
NAME: Zinc finger
SITE: 338-366
EFFECTOR-BOUND: Zn+2
serine-rich region {422-431}
MOTIF: serine residue (SEVERAL)
RING-finger {443-492}
EFFECTOR-BOUND: Zn+2
FOR-BINDING-OF: DNA motif
serine-rich region {842-847}
MOTIF: serine residue (SEVERAL)
threonine-rich region {944-951}
MOTIF: threonine residue (SEVERAL)
glutamate-rich region {1184-1189}
MOTIF: glutamate residue (SEVERAL)
kinase domain
SITE: 1245-1510
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 1251-1259
ATP-binding site
NAME: ATP-binding site
SITE: 1274-1274
aspartate residue {D1371}
Thr phosphorylation site {T1402}
Thr phosphorylation site {T1414}
STATE: active state
References
UniProt :accession Q13233
Databases & Figures
OMIM 600982
UniProt Q13233
PFAM correlations
Entrez Gene 4214
Kegg hsa/hsa04210
ENZYME 2.7.11.25
MAP kinase pathways