TARGETID

T29754

FORMERID

TTDI02542

UNIPROID

MAPK5_HUMAN

TARGNAME

MAPK-activated protein kinase 5 (MAPKAPK5)

GENENAME

MAPKAPK5

TARGTYPE

Discontinued target

SYNONYMS

p38regulated/activated protein kinase; p38-regulated/activated protein kinase; PRAK; MK5; MK-5; MAPKactivated protein kinase 5; MAPKAPK-5; MAPKAP-K5; MAPKAP kinase 5; MAP kinaseactivated protein kinase 5; MAP kinase-activated protein kinase 5

FUNCTION

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. Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation.

BIOCLASS

Kinase

ECNUMBER

EC 2.7.11.1

SEQUENCE

MSEESDMDKAIKETSILEEYSINWTQKLGAGISGPVRVCVKKSTQERFALKILLDRPKARNEVRLHMMCATHPNIVQIIEVFANSVQFPHESSPRARLLIVMEMMEGGELFHRISQHRHFTEKQASQVTKQIALALRHCHLLNIAHRDLKPENLLFKDNSLDAPVKLCDFGFAKIDQGDLMTPQFTPYYVAPQVLEAQRRHQKEKSGIIPTSPTPYTYNKSCDLWSLGVIIYVMLCGYPPFYSKHHSRTIPKDMRRKIMTGSFEFPEEEWSQISEMAKDVVRKLLKVKPEERLTIEGVLDHPWLNSTEALDNVLPSAQLMMDKAVVAGIQQAHAEQLANMRIQDLKVSLKPLHSVNNPILRKRKLLGTKPKDSVYIHDHENGAEDSNVALEKLRDVIAQCILPQAGKGENEDEKLNEVMQEAWKYNRECKLLRDTLQSFSWNGRGFTDKVDRLKLAEIVKQVIEEQTTSHESQ

DRUGINFO

GLPG-0259

DRUGINFO

PMID17480064C16

WIKIPATH

WP382:MAPK Signaling Pathway

WIKIPATH

WP400:p38 MAPK Signaling Pathway

REACPATH

R-HSA-2559580:Oxidative Stress Induced Senescence

REACPATH

R-HSA-5687128:MAPK6/MAPK4 signaling

INTEPATH

p38alphabetadownstreampathway:Signaling mediated by p38-alpha and p38-beta