InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Map2k4

Summary

InnateDB Protein

IDBP-186474.6

Last Modified

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

Gene Symbol

Map2k4

Protein Name

mitogen-activated protein kinase kinase 4

Synonyms

JNKK1; MEK4; MKK4; PRKMK4; Sek1; Serk1;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000041282

InnateDB Gene

IDBG-186472 (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:11390361, ECO:0000269PubMed:12624093, ECO:0000269PubMed:7997269, ECO:0000269PubMed:9620683, ECO:0000269PubMed:9891090}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:9891090}. Nucleus {ECO:0000269PubMed:9891090}.

Disease Associations

Tissue Specificity

Strong expression is detected in most of the central nervous system and in liver and thymus during early stages of development. While expression in nervous system increases over time, expression in fetal liver and thymus gradually decreases as embryogenesis proceeds. High level of expression in the central nervous system persists throughout postnatal development and remained at a stable level in adult brain. {ECO:0000269PubMed:10095085}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 20 experimentally validated interaction(s) in this database.
They are also associated with 46 interaction(s) predicted by orthology.

Experimentally validated
Total	20 [view]
Protein-Protein	19 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	1 [view]
DNA-RNA	0

Predicted by orthology
Total	46 [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:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007254	JNK cascade
GO:0007257	activation of JUN kinase activity
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0043065	positive regulation of apoptotic process
GO:0043525	positive regulation of neuron apoptotic process
GO:0045740	positive regulation of DNA replication
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

MGI:1346869

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