Mapkapk5
entrez
17165
canonical
uniprot
O54992
canonical
ensembl
ENSMUSG00000029454
resolver
ensp
ENSMUSP00000031410
resolver
genesymbol
Mapkapk5
resolver
uniprot
E9QQ45
resolver
uniprot
Q6QME4
resolver
uniprot
Q6QME5
resolver
uniprot
Q6QME6
resolver
uniprot
Q6QME7
resolver
uniprot_entry
MAPK5_MOUSE
resolver
uniprot_sec
E9QQ45
resolver
uniprot_sec
Q6QME4
resolver
uniprot_sec
Q6QME5
resolver
uniprot_sec
Q6QME6
resolver
uniprot_sec
Q6QME7
resolver
activity_regulation
ACTIVITY REGULATION: Activated following phosphorylation at Thr-182 by p38-alpha/MAPK14, p38-beta/MAPK11, ERK2/MAPK1, ERK3/MAPK6, and ERK4/MAPK4. Activated by stress-related extracellular stimuli; such as H(2)O(2), arsenite, anisomycin TNF alpha and also PMA and the calcium ionophore A23187; but to a lesser extent. In vitro, activated by SQSTM1. Inhibited by diterpenoid alkaloid noroxoaconitine. {ECO:0000269|PubMed:20640477, ECO:0000269|PubMed:9480836}.
uniprot
proteins
amino_acid_sequence
MSEDSDMEKAIKETSILEEYSINWTQKLGAGISGPVRVCVKKSTQERFALKILLDRPKARNEVRLHMMCATHPNIVQIIEVFANSVQFPHESSPRARLLIVMEMMEGGELFHRISQHRHFTEKQASQVTKQIALALQHCHLLNIAHRDLKPENLLFKDNSLDAPVKLCDFGFAKVDQGDLMTPQFTPYYVAPQVLEAQRRHQKEKSGIIPTSPTPYTYNKSCDLWSLGVIIYVMLCGYPPFYSKHHSRTIPKDMRKKIMTGSFEFPEEEWSQISEMAKDVVRKLLKVKPEERLTIEGVLDHPWLNSTEALDNVLPSAQLMMDKAVVAGIQQAHAEQLANMRIQDLKVSLKPLHSVNNPILRKRKLLGTKPKDGIYIHDHENGTEDSNVALEKLRDVIAQCILPQAGKGENEDEKLNEVMQEAWKYNRECKLLRDALQSFSWNGRGFTDKVDRLKLAEVVKQVIEEQTLPHEPQ
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
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:0000269|PubMed:15538386, ECO:0000269|PubMed:15577943, ECO:0000269|PubMed:16973613, ECO:0000269|PubMed:17254968, ECO:0000269|PubMed:21336308, ECO:0000269|PubMed:21575178}.
uniprot
proteins
mass_dalton
54152
uniprot
proteins
mutagenesis
MUTAGEN 51; /note="K->E: No p38-alpha/MAPK14-, p38-beta/MAPK11-, ERK3/MAPK6-, ERK4/MAPK4-induced activation."; /evidence="ECO:0000269|PubMed:15538386, ECO:0000269|PubMed:17254968, ECO:0000269|PubMed:21336308, ECO:0000269|PubMed:9480836"; MUTAGEN 51; /note="K->R,M: Kinase defective mutant, abolishes activity."; /evidence="ECO:0000269|PubMed:15538386, ECO:0000269|PubMed:17254968, ECO:0000269|PubMed:21336308, ECO:0000269|PubMed:9480836"; MUTAGEN 115; /note="S->A: Impairs shuttling to the cytoplasm."; /evidence="ECO:0000269|PubMed:20734105"; MUTAGEN 115; /note="S->D: Mimicks phosphorylation state, leading to localization to the cytoplasm."; /evidence="ECO:0000269|PubMed:20734105"; MUTAGEN 182; /note="T->A: Impairs protein kinase activity and shuttling to the cytoplasm."; /evidence="ECO:0000269|PubMed:15538386, ECO:0000269|PubMed:15577943, ECO:0000269|PubMed:17254968, ECO:0000269|PubMed:20640477"; MUTAGEN 337; /note="L->A: Constitutive active mutant. In a knockin model, mouse display increased amounts of head dips and open arm time on the maze, compared to littermate controls. In addition, they also explore further into the open arm on the elevated plus maze and are less active in the closed arm compared to littermate controls. Male knockin mice display no differences in anxiety, but their locomotor activity increases compared to non-transgenic littermates."; /evidence="ECO:0000269|PubMed:17997833
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on Thr-182 ERK3/MAPK6 or ERK4/MAPK4; which is the regulatory phosphorylation site and is located on the T-loop/loop 12, leading to activation. Phosphorylation at Thr-182 by p38-alpha/MAPK14, p38-beta/MAPK11 is subject to debate. Phosphorylated at Ser-115 by PKA/PRKACA, leading to localization to the cytoplasm. Autophosphorylated. {ECO:0000269|PubMed:15538386, ECO:0000269|PubMed:15577943, ECO:0000269|PubMed:20734105, ECO:0000269|PubMed:9480836}.
uniprot
proteins
protein_family
CAMK Ser/Thr protein kinase family
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
14560018
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15538386
uniprot
proteins
pubmed
15577943
uniprot
proteins
pubmed
16973613
uniprot
proteins
pubmed
17254968
uniprot
proteins
pubmed
17947239
uniprot
proteins
pubmed
17997833
uniprot
proteins
pubmed
18248330
uniprot
proteins
pubmed
18268017
uniprot
proteins
pubmed
18720373
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
19473979
uniprot
proteins
pubmed
20640477
uniprot
proteins
pubmed
20734105
uniprot
proteins
pubmed
21336308
uniprot
proteins
pubmed
21575178
uniprot
proteins
pubmed
9480836
uniprot
proteins
sequence_length
473
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: 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.
uniprot
proteins