InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MAP3K8

Summary

InnateDB Protein

IDBP-584780.3

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; EST; ESTF; MEKK8; Tpl-2; TPL2;

Species

Homo sapiens

Ensembl Protein

ENSP00000443610

InnateDB Gene

IDBG-66703 (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. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant. {ECO:0000269PubMed:11342626, ECO:0000269PubMed:12667451, ECO:0000269PubMed:15169888, ECO:0000269PubMed:16371247, ECO:0000269PubMed:1833717, ECO:0000269PubMed:19001140, ECO:0000269PubMed:19754427, ECO:0000269PubMed:19808894}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:1833717, ECO:0000269PubMed:8226782}.

Disease Associations

Tissue Specificity

Expressed in several normal tissues and human tumor-derived cell lines.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 32 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	32 [view]
Protein-Protein	31 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine 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:0006468	protein phosphorylation
GO:0007049	cell cycle
GO:0031295	T cell costimulation
GO:0045087	innate immune response (InnateDB)

Cellular Component

GO:0005737	cytoplasm
GO:0005829	cytosol

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