Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

MAPKAPK5 (Q8IW41) - Overview - Molecular Target Synopsis

Protein


MAPKAPK5, MAP kinase-activated protein kinase 5
Enzyme Classification 2.7.11.1
UniProt Q8IW41

Also Known as MAPK5_HUMAN, MAPKAPK5, PRAK

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. Interacts with ERK3/MAPK6 and ERK4/MAPK4 (via FRIEDE motif); the interaction is direct (By similarity). Interacts with YWHAE; the interaction prevents phosphorylation of HSP27/HSPB1 leading to disrupt F-actin polymerization. Interacts with SQSTM1.

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: MAPKAPK5 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: MAPKAPK5 is active in the following subcellular-locations: cytoplasm, cytosol, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MAPKAPK5 has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 1005 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: KM12, HL_60, K_562

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: RCM-1, LS1034, SK-N-FI

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: K562, SK-N-SH, MCF-7

(see details)

RNA Interference


MAPKAPK5 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: HCH1, HCC202. (see details)

3D Structures


At greater than 35% identity similarity to MAPKAPK5 there are:
45 structures (122 chains) solved
37 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MAPKAPK5 has been screened with 1123 compounds (1842 bioactivities), 16 compounds have bioactivities that show binding affinity of <= 500nM (24 bioactivities). (see details)