MAPK15
entrez
225689
canonical
uniprot
Q8TD08
canonical
ensembl
ENSG00000181085
resolver
ensembl
ENSG00000274205
resolver
ensp
ENSP00000337691
resolver
ensp
ENSP00000553285
resolver
genesymbol
MAPK15
resolver
genesymbol_syn
ERK7
resolver
genesymbol_syn
ERK8
resolver
hgnc
HGNC:24667
resolver
uniprot
Q2TCF9
resolver
uniprot
Q8N362
resolver
uniprot_entry
MK15_HUMAN
resolver
uniprot_sec
Q2TCF9
resolver
uniprot_sec
Q8N362
resolver
activity_regulation
ACTIVITY REGULATION: Activated by threonine and tyrosine phosphorylation (PubMed:11875070, PubMed:16336213, PubMed:19166846). Inhibited by dual specificity phosphatases, such as DUSP1 (By similarity). Phosphorylation and activation in response to DNA damaging agents, serum stimulation (PubMed:11875070, PubMed:16336213, PubMed:19166846). Constitutively activated when phosphorylated on Tyr-177. Activity depends on the relative rates of MAPK15 autophosphorylation and dephosphorylation by PTPN1 (PubMed:16336213). {ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16336213, ECO:0000269|PubMed:19166846}.
uniprot
proteins
amino_acid_sequence
MCTVVDPRIVRRYLLRRQLGQGAYGIVWKAVDRRTGEVVAIKKIFDAFRDKTDAQRTFREITLLQEFGDHPNIISLLDVIRAENDRDIYLVFEFMDTDLNAVIRKGGLLQDVHVRSIFYQLLRATRFLHSGHVVHRDQKPSNVLLDANCTVKLCDFGLARSLGDLPEGPEDQAVTEYVATRWYRAPEVLLSSHRYTLGVDMWSLGCILGEMLRGRPLFPGTSTLHQLELILETIPPPSEEDLLALGSGCRASVLHQLGSRPRQTLDALLPPDTSPEALDLLRRLLVFAPDKRLSATQALQHPYVQRFHCPSDEWAREADVRPRAHEGVQLSVPEYRSRVYQMILECGGSSGTSREKGPEGVSPSQAHLHKPRADPQLPSRTPVQGPRPRPQSSPGHDPAEHESPRAAKNVPRQNSAPLLQTALLGNGERPPGAKEAPPLTLSLVKPSGRGAAPSLTSQAAAQVANQALIRGDWNRGGGVRVASVQQVPPRLPPEARPGRRMFSTSALQGAQGGARALLGGYSQAYGTVCHSALGHLPLLEGHHV
uniprot
proteins
ec_number
2.7.11.24
uniprot
proteins
function
FUNCTION: Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner (PubMed:20733054, PubMed:21847093, PubMed:22948227, PubMed:24618899, PubMed:29021280). Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation (PubMed:22948227). Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling (PubMed:29021280). Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins (PubMed:24618899). Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion (PubMed:21847093). Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA (PubMed:20733054). Regulates DA transporter (DAT) activity and protein expression via activation of RhoA (PubMed:28842414). In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression (PubMed:26595526). Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP (PubMed:11875070, PubMed:16484222, PubMed:19166846, PubMed:20638370). During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (By similarity). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity (PubMed:21190936). {ECO:0000250|UniProtKB:Q80Y86, ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16484222, ECO:0000269|PubMed:19166846, ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:20733054, ECO:0000269|PubMed:21190936, ECO:0000269|PubMed:21847093, ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:24618899, ECO:0000269|PubMed:26595526, ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280}.
uniprot
proteins
mass_dalton
59832
uniprot
proteins
mutagenesis
MUTAGEN 42; /note="K->A: Not phosphorylated at Thr-175 and Tyr-177."; /evidence="ECO:0000269|PubMed:16336213"; MUTAGEN 42; /note="K->R: Loss of autophosphorylation and activity. Does not increase dopamine transporter activity. Impairs kinase activity. Does not rescue cilium assembly in MAPK15-depleted cells."; /evidence="ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280"; MUTAGEN 59; /note="R->Q: Does not increase dopamine transporter activity. Impairs kinase activity."; /evidence="ECO:0000269|PubMed:28842414"; MUTAGEN 155; /note="D->A: Unable to induce the formation of autophagosomal structures. Is able to bind to MAP1LC3B and to colocalize with this protein to autophagosomal structures. Does not induce phosphorylation by methyl methanesulfonate. Loas of phosphorylation. Dominant negative mutant. Not phosphorylated at Thr-175 and Tyr-177."; /evidence="ECO:0000269|PubMed:16336213, ECO:0000269|PubMed:19166846, ECO:0000269|PubMed:22948227"; MUTAGEN 175; /note="T->A: Loss of autophosphorylation and activity. Still heavily phosphorylated at Tyr-177. Does not rescues inhibition of O-glycosylation in MAPK15-depleted cells; when associated with F-177."; /evidence="ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16336213, ECO:0000269|PubMed:24618899"; MUTAGEN 177; /note="Y->A: Loss of autophosphorylation and activity. Heavily phosphorylated at Thr-175."; /evidence="ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16336213"; MUTAGEN 177; /note="Y->F: Does not rescue inhibition of O-glycosylation in MAPK15-depleted cells; when associated with A-175."; /evidence="ECO:0000269|PubMed:24618899"; MUTAGEN 265..269; /note="LDALL->ADAAA: Markedly decreases interaction with ESRRA. Impairs interaction with ESRRA; when associated with A-281 and 284-A--A-285. Loses the ability to re-localize ESRRA to the cytoplasm. Does not affect subcellular location in cytoplasm in presence of ESRRA. Loses the ability to repress ESRRA transcriptional activity."; /evidence="ECO:0000269|PubMed:21190936"; MUTAGEN 281..285; /note="LRRLL->ARRAA: Markedly decreases interaction with ESRRA. Impairs interaction with ESRRA; when associated with A-265 and 268-A--A-269. Loses the ability to re-localize ESRRA to the cytoplasm. Does not affect subcellular location in cytoplasm in presence of ESRRA.Loses the ability to repress ESRRA transcriptional activity."; /evidence="ECO:0000269|PubMed:21190936"; MUTAGEN 300; /note="Q->A: Impairs interaction with PCNA. Associates with chromatin."; /evidence="ECO:0000269|PubMed:20733054"; MUTAGEN 340..343; /note="YQMI->AQMA: Impairs interaction with GABARAP and MAP1LC3B. Affects subcellular localization in autophagosome. Does not induce autophagy."; /evidence="ECO:0000269|PubMed:22948227"; MUTAGEN 390; /note="P->A: Impairs chromatin binding; when associated with A-398. Increases kinase activity; when associated with A-398."; /evidence="ECO:0000269|PubMed:20733054"; MUTAGEN 398; /note="P->A: Impairs chromatin binding; when associated with A-390. Increases kinase activity; when associated with A-390."; /evidence="ECO:0000269|PubMed:20733054
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated on Thr-175 and Tyr-177; activates the enzyme. {ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16336213, ECO:0000269|PubMed:19166846}.; PTM: Ubiquitinated (PubMed:19166846). Ubiquitination may allow its tight kinase activity regulation and rapid turnover. May be ubiquitinated by a SCF E3 ligase (By similarity). {ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:19166846}.
uniprot
proteins
protein_family
CMGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
MAP kinase subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
11875070
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16336213
uniprot
proteins
pubmed
16484222
uniprot
proteins
pubmed
16624805
uniprot
proteins
pubmed
19166846
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
20638370
uniprot
proteins
pubmed
20733054
uniprot
proteins
pubmed
21190936
uniprot
proteins
pubmed
21847093
uniprot
proteins
pubmed
22948227
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24618899
uniprot
proteins
pubmed
26595526
uniprot
proteins
pubmed
28842414
uniprot
proteins
pubmed
29021280
uniprot
proteins
sequence_length
544
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body {ECO:0000269|PubMed:29021280}. Cell junction, tight junction {ECO:0000269|PubMed:29021280}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole {ECO:0000269|PubMed:29021280}. Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:22948227}. Golgi apparatus {ECO:0000269|PubMed:24618899}. Nucleus {ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:21190936}. Cytoplasm {ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:21190936}. Cytoplasm, cytoskeleton, spindle {ECO:0000250|UniProtKB:Q80Y86}. Note=Co-localizes to the cytoplasm only in presence of ESRRA (PubMed:21190936). Translocates to the nucleus upon activation (PubMed:20638370). At prometaphase I, metaphase I (MI), anaphase I, telophase I, and metaphase II (MII) stages, is stably detected at the spindle (By similarity). {ECO:0000250|UniProtKB:Q80Y86, ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:21190936}.
uniprot
proteins