InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MAP4K2

Summary

InnateDB Protein

IDBP-55187.6

Last Modified

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

Gene Symbol

MAP4K2

Protein Name

mitogen-activated protein kinase kinase kinase kinase 2

Synonyms

BL44; GCK; RAB8IP;

Species

Homo sapiens

Ensembl Protein

ENSP00000294066

InnateDB Gene

IDBG-55181 (MAP4K2)

Protein Structure

UniProt Annotation

Function

Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extend of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. {ECO:0000269PubMed:11784851, ECO:0000269PubMed:15456887, ECO:0000269PubMed:17584736, ECO:0000269PubMed:7477268, ECO:0000269PubMed:7515885, ECO:0000269PubMed:9712898}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Basolateral cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Golgi apparatus membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.

Disease Associations

Tissue Specificity

Highly expressed in germinal center but not mantle zone B-cells. Also expressed in lung, brain and placenta and at lower levels in other tissues examined. {ECO:0000269PubMed:7515885}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 27 experimentally validated interaction(s) in this database.

Experimentally validated
Total	27 [view]
Protein-Protein	27 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005083	small GTPase regulator activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0031435	mitogen-activated protein kinase kinase kinase binding

Biological Process

GO:0000185	activation of MAPKKK activity
GO:0006468	protein phosphorylation
GO:0006903	vesicle targeting
GO:0006955	immune response
GO:0007254	JNK cascade
GO:0007257	activation of JUN kinase activity
GO:0035556	intracellular signal transduction
GO:0045087	innate immune response
GO:0046330	positive regulation of JNK cascade

Cellular Component

GO:0000139	Golgi membrane
GO:0016323	basolateral plasma membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001180 Citron-like
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
PF00780
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00036
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt