InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Map2k6

Summary

InnateDB Protein

IDBP-213981.6

Last Modified

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

Gene Symbol

Map2k6

Protein Name

mitogen-activated protein kinase kinase 6

Synonyms

MEK6; MKK6; Prkmk6; SAPKK3;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000020949

InnateDB Gene

IDBG-213977 (Map2k6)

Protein Structure

UniProt Annotation

Function

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG- dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases. {ECO:0000269PubMed:12151339, ECO:0000269PubMed:12824301, ECO:0000269PubMed:12893778, ECO:0000269PubMed:15644321, ECO:0000269PubMed:16387856, ECO:0000269PubMed:16498455, ECO:0000269PubMed:20004242}.

Subcellular Localization

Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Note=Binds to microtubules. {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 4 experimentally validated interaction(s) in this database.
They are also associated with 23 interaction(s) predicted by orthology.

Experimentally validated
Total	4 [view]
Protein-Protein	3 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	23 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004702	receptor signaling 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:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019901	protein kinase binding

Biological Process

GO:0000165	MAPK cascade
GO:0000187	activation of MAPK activity
GO:0001934	positive regulation of protein phosphorylation
GO:0002931	response to ischemia
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0022602	ovulation cycle process
GO:0032308	positive regulation of prostaglandin secretion
GO:0042493	response to drug
GO:0043065	positive regulation of apoptotic process
GO:0051770	positive regulation of nitric-oxide synthase biosynthetic process
GO:0060048	cardiac muscle contraction
GO:0072709	cellular response to sorbitol

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005856	cytoskeleton

Protein Structure and Domains

PDB ID

MGI:1346870

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