InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Mapkapk5

Summary

InnateDB Protein

IDBP-197367.6

Last Modified

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

Gene Symbol

Mapkapk5

Protein Name

MAP kinase-activated protein kinase 5

Synonyms

MK5; PRAK;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000031410

InnateDB Gene

IDBG-197365 (Mapkapk5)

Protein Structure

UniProt Annotation

Function

Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras- induced senescence and phosphorylating p53/TP53. Involved in post- transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement. {ECO:0000269PubMed:15538386, ECO:0000269PubMed:15577943, ECO:0000269PubMed:16973613, ECO:0000269PubMed:17254968, ECO:0000269PubMed:21336308, ECO:0000269PubMed:21575178}.

Subcellular Localization

Cytoplasm. Nucleus. Note=Translocates to the cytoplasm following phosphorylation and activation. Interaction with ERK3/MAPK6 or ERK4/MAPK4 and phosphorylation at Thr-182, activates the protein kinase activity, followed by translocation to the cytoplasm. Phosphorylation by PKA/PRKACA at Ser-115 also induces nuclear export.

Disease Associations

Tissue Specificity

Expressed ubiquitously. {ECO:0000269PubMed:9480836}.

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 21 interaction(s) predicted by orthology.

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

Predicted by orthology
Total	21 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002039	p53 binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine 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:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0051019	mitogen-activated protein kinase binding

Biological Process

GO:0006417	regulation of translation
GO:0006468	protein phosphorylation
GO:0007265	Ras protein signal transduction
GO:0009103	lipopolysaccharide biosynthetic process
GO:0032007	negative regulation of TOR signaling
GO:0046777	protein autophosphorylation
GO:0090400	stress-induced premature senescence

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0016020	membrane

Protein Structure and Domains

PDB ID

MGI:1333110

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR010440 Lipopolysaccharide kinase
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF06293

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt