MAP kinase-activated protein kinase 5

UniProt Q8IW41 Organism Homo sapiens Gene MAPKAPK5, PRAK EC 2.7.11.1

Also known as: MAPKAPK5, PRAK

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.

Classification

Family (Pfam): PF00069 Pkinase
InterPro: CDPK_Ser/Thr_kinases, Kinase-like_dom_sf, MAPKAPK_C, Prot_kinase_dom, Ser/Thr_kinase_AS
Functional cluster: Protein Serine/Threonine Kinases

Gene Ontology · 25

Disease associations

neurocardiofaciodigital syndrome MONDO:0859247

Drugs targeting this protein · 1

GLPG-0259 inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Heat shock protein beta-1 1 shared papers
Forkhead box protein O3 1 shared papers
Sequestosome-1 1 shared papers
MAP kinase-activated protein kinase 5 1 shared papers
Cellular tumor antigen p53 1 shared papers
Cellular tumor antigen p53 1 shared papers

Literature · 17 cited papers

Biallelic truncating variants in MAPKAPK5 cause a new developmental disorder involving neurological, cardiac, and facial anomalies combined with synpolydactyly. Genet. Med. · 2021
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
The MK5/PRAK kinase and Myc form a negative feedback loop that is disrupted during colorectal tumorigenesis. Mol. Cell · 2011
Mitogen-activated protein kinase p38 and MK2, MK3 and MK5: menage a trois or menage a quatre? Cell. Signal. · 2010
Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
PKA-induced F-actin rearrangement requires phosphorylation of Hsp27 by the MAPKAP kinase MK5. Cell. Signal. · 2009
A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
The full-ORF clone resource of the German cDNA consortium. BMC Genomics · 2007
14-3-3epsilon inhibits MK5-mediated cell migration by disrupting F-actin polymerization. Cell. Signal. · 2007
Patterns of somatic mutation in human cancer genomes. Nature · 2007
PRAK is essential for ras-induced senescence and tumor suppression. Cell · 2007
… and 5 more in the literature graph

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