InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MAP3K5

Summary

InnateDB Protein

IDBP-96938.5

Last Modified

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

Gene Symbol

MAP3K5

Protein Name

mitogen-activated protein kinase kinase kinase 5

Synonyms

ASK1; MAPKKK5; MEKK5;

Species

Homo sapiens

Ensembl Protein

ENSP00000351908

InnateDB Gene

IDBG-96934 (MAP3K5)

Protein Structure

UniProt Annotation

Function

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1). {ECO:0000269PubMed:10411906, ECO:0000269PubMed:10688666, ECO:0000269PubMed:10849426, ECO:0000269PubMed:11029458, ECO:0000269PubMed:11154276, ECO:0000269PubMed:11689443, ECO:0000269PubMed:11920685, ECO:0000269PubMed:12697749, ECO:0000269PubMed:14688258, ECO:0000269PubMed:14749717, ECO:0000269PubMed:15023544, ECO:0000269PubMed:16129676, ECO:0000269PubMed:17220297, ECO:0000269PubMed:23102700, ECO:0000269PubMed:8940179, ECO:0000269PubMed:8974401, ECO:0000269PubMed:9564042, ECO:0000269PubMed:9774977}.

Subcellular Localization

Cytoplasm. Endoplasmic reticulum. Note=Interaction with 14-3-3 proteins alters the distribution of MAP3K5/ASK1 and restricts it to the perinuclear endoplasmic reticulum region.

Disease Associations

Tissue Specificity

Abundantly expressed in heart and pancreas.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 137 experimentally validated interaction(s) in this database.
They are also associated with 11 interaction(s) predicted by orthology.

Experimentally validated
Total	137 [view]
Protein-Protein	132 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	11 [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:0008656	cysteine-type endopeptidase activator activity involved in apoptotic process
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019901	protein kinase binding
GO:0019903	protein phosphatase binding
GO:0042803	protein homodimerization activity

Biological Process

GO:0000165	MAPK cascade
GO:0000186	activation of MAPKK activity
GO:0000187	activation of MAPK activity
GO:0001934	positive regulation of protein phosphorylation
GO:0002931	response to ischemia
GO:0006468	protein phosphorylation
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0007254	JNK cascade
GO:0007257	activation of JUN kinase activity
GO:0008631	intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0010941	regulation of cell death
GO:0016032	viral process
GO:0043065	positive regulation of apoptotic process
GO:0043280	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0070301	cellular response to hydrogen peroxide
GO:0097190	apoptotic signaling pathway
GO:0097300	programmed necrotic cell death
GO:1901216	positive regulation of neuron death
GO:1902170	cellular response to reactive nitrogen species

Cellular Component

GO:0005783	endoplasmic reticulum
GO:0005829	cytosol
GO:1902911	protein kinase complex

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
IPR013761 Sterile alpha motif/pointed domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt