InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MAP2K4

Summary

InnateDB Protein

IDBP-369000.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MAP2K4

Protein Name

mitogen-activated protein kinase kinase 4

Synonyms

JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4; SAPKK-1; SAPKK1; SEK1; SERK1; SKK1;

Species

Homo sapiens

Ensembl Protein

ENSP00000410402

InnateDB Gene

IDBG-31021 (MAP2K4)

Protein Structure

UniProt Annotation

Function

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. {ECO:0000269PubMed:7716521}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.

Disease Associations

Tissue Specificity

Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 69 experimentally validated interaction(s) in this database.
They are also associated with 12 interaction(s) predicted by orthology.

Experimentally validated
Total	69 [view]
Protein-Protein	65 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	4 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	12 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004708	MAP kinase kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008545	JUN kinase kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0031435	mitogen-activated protein kinase kinase kinase binding

Biological Process

GO:0000165	MAPK cascade
GO:0001934	positive regulation of protein phosphorylation
GO:0002224	toll-like receptor signaling pathway
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007165	signal transduction
GO:0007254	JNK cascade
GO:0007257	activation of JUN kinase activity
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034146	toll-like receptor 5 signaling pathway
GO:0034162	toll-like receptor 9 signaling pathway
GO:0034166	toll-like receptor 10 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
GO:0043065	positive regulation of apoptotic process
GO:0043525	positive regulation of neuron apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0045740	positive regulation of DNA replication
GO:0051403	stress-activated MAPK cascade
GO:0051770	positive regulation of nitric-oxide synthase biosynthetic process
GO:0061049	cell growth involved in cardiac muscle cell development
GO:0071260	cellular response to mechanical stimulus
GO:0072709	cellular response to sorbitol

Cellular Component

GO:0005634	nucleus
GO:0005829	cytosol
GO:0030424	axon
GO:0032839	dendrite cytoplasm
GO:0043204	perikaryon

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt