InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Map3k8

Summary

InnateDB Protein

IDBP-127809.6

Last Modified

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

Gene Symbol

Map3k8

Protein Name

mitogen-activated protein kinase kinase kinase 8

Synonyms

c-COT; Cot; Cot/Tpl2; Est; Estf; Tpl-2; Tpl2;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000025078

InnateDB Gene

IDBG-127807 (Map3k8)

Protein Structure

UniProt Annotation

Function

Required for lipopolysaccharide (LPS)-induced, TLR4- mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF- alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B- cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. {ECO:0000269PubMed:11163183, ECO:0000269PubMed:12667451, ECO:0000269PubMed:12881420, ECO:0000269PubMed:15833743, ECO:0000269PubMed:19001140, ECO:0000269PubMed:19808894, ECO:0000269PubMed:23842752}.

Subcellular Localization

Cytoplasm.

Disease Associations

Tissue Specificity

Expressed in bone marrow-derived macrophages, peritoneal macrophages, splenocytes and 3T3-L1 fibroblasts and differentiated adipocytes (at protein level). Highly expressed in adult submandibular gland, thymus, spleen and newborn digestive tract. {ECO:0000269PubMed:12667451, ECO:0000269PubMed:19808894}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 8 experimentally validated interaction(s) in this database.
They are also associated with 35 interaction(s) predicted by orthology.

Experimentally validated
Total	8 [view]
Protein-Protein	8 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	35 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004709	MAP kinase 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

Biological Process

GO:0000165	MAPK cascade
GO:0000186	activation of MAPKK activity
GO:0002376	immune system process
GO:0006468	protein phosphorylation
GO:0007049	cell cycle
GO:0035556	intracellular signal transduction
GO:0045087	innate immune response (InnateDB)

Cellular Component

GO:0005737

cytoplasm

Protein Structure and Domains

PDB ID

MGI:1346878

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