MAPKAPK5
entrez
8550
canonical
uniprot
Q8IW41
canonical
ensembl
ENSG00000089022
resolver
ensp
ENSP00000449381
resolver
ensp
ENSP00000449667
resolver
ensp
ENSP00000662789
resolver
ensp
ENSP00000662790
resolver
ensp
ENSP00000662791
resolver
ensp
ENSP00000662792
resolver
ensp
ENSP00000700603
resolver
ensp
ENSP00000700608
resolver
ensp
ENSP00000700610
resolver
ensp
ENSP00000792926
resolver
genesymbol
MAPKAPK5
resolver
genesymbol_syn
PRAK
resolver
hgnc
HGNC:6889
resolver
uniprot
B3KVA5
resolver
uniprot
O60491
resolver
uniprot
Q86X46
resolver
uniprot
Q9BVX9
resolver
uniprot
Q9UG86
resolver
uniprot_entry
MAPK5_HUMAN
resolver
uniprot_sec
B3KVA5
resolver
uniprot_sec
O60491
resolver
uniprot_sec
Q86X46
resolver
uniprot_sec
Q9BVX9
resolver
uniprot_sec
Q9UG86
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:10708586, ECO:0000269|PubMed:9628874}.
uniprot
proteins
amino_acid_sequence
MSEESDMDKAIKETSILEEYSINWTQKLGAGISGPVRVCVKKSTQERFALKILLDRPKARNEVRLHMMCATHPNIVQIIEVFANSVQFPHESSPRARLLIVMEMMEGGELFHRISQHRHFTEKQASQVTKQIALALRHCHLLNIAHRDLKPENLLFKDNSLDAPVKLCDFGFAKIDQGDLMTPQFTPYYVAPQVLEAQRRHQKEKSGIIPTSPTPYTYNKSCDLWSLGVIIYVMLCGYPPFYSKHHSRTIPKDMRRKIMTGSFEFPEEEWSQISEMAKDVVRKLLKVKPEERLTIEGVLDHPWLNSTEALDNVLPSAQLMMDKAVVAGIQQAHAEQLANMRIQDLKVSLKPLHSVNNPILRKRKLLGTKPKDSVYIHDHENGAEDSNVALEKLRDVIAQCILPQAGKGENEDEKLNEVMQEAWKYNRECKLLRDTLQSFSWNGRGFTDKVDRLKLAEIVKQVIEEQTTSHESQ
uniprot
proteins
disease_involvement
DISEASE: Neurocardiofaciodigital syndrome (NCFD) [MIM:619869]: An autosomal recessive syndrome characterized by severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with a supernumerary hypoplastic digit between the fourth and fifth digits of the hands and/or feet. Other features include eye abnormalities, hearing impairment, and electroencephalogram anomalies. {ECO:0000269|PubMed:33442026}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:17254968, ECO:0000269|PubMed:17728103, ECO:0000269|PubMed:19166925, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:9628874}.
uniprot
proteins
mass_dalton
54220
uniprot
proteins
mutagenesis
MUTAGEN 51; /note="K->M: Kinase defective mutant, abolishes activity."; /evidence="ECO:0000269|PubMed:12808055"; MUTAGEN 182; /note="T->A: No p38-beta/MAPK11-induced activation."; /evidence="ECO:0000269|PubMed:12808055, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:9628874"; MUTAGEN 182; /note="T->D: Mimicks phosphorylation state and induces constitutive protein kinase activity."; /evidence="ECO:0000269|PubMed:12808055, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:9628874"; MUTAGEN 212; /note="S->D: Mimicks phosphorylation state and displays a slightly higher protein kinase activity."; /evidence="ECO:0000269|PubMed:12808055"; MUTAGEN 337; /note="L->G: Induces constitutive protein kinase activity."; /evidence="ECO:0000269|PubMed:21329882
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 (By similarity). {ECO:0000250}.
uniprot
proteins
protein_family
CAMK Ser/Thr protein kinase family
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10708586
uniprot
proteins
pubmed
12808055
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17254968
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17728103
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19166925
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20227494
uniprot
proteins
pubmed
21329882
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
33442026
uniprot
proteins
pubmed
9628874
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