MAPK8
entrez
5599
canonical
uniprot
P45983
canonical
ensembl
ENSG00000107643
resolver
ensp
ENSP00000353483
resolver
ensp
ENSP00000363294
resolver
ensp
ENSP00000363297
resolver
ensp
ENSP00000363304
resolver
ensp
ENSP00000378974
resolver
ensp
ENSP00000530662
resolver
genesymbol
MAPK8
resolver
genesymbol_syn
JNK1
resolver
genesymbol_syn
PRKM8
resolver
genesymbol_syn
SAPK1
resolver
genesymbol_syn
SAPK1C
resolver
hgnc
HGNC:6881
resolver
uniprot
A1L4K2
resolver
uniprot
B5BTZ5
resolver
uniprot
B7ZLV4
resolver
uniprot
D3DX88
resolver
uniprot
D3DX92
resolver
uniprot
Q15709
resolver
uniprot
Q15712
resolver
uniprot
Q15713
resolver
uniprot
Q308M2
resolver
uniprot_entry
A1L4K2_HUMAN
resolver
uniprot_entry
MK08_HUMAN
resolver
uniprot_sec
B5BTZ5
resolver
uniprot_sec
B7ZLV4
resolver
uniprot_sec
D3DX88
resolver
uniprot_sec
D3DX92
resolver
uniprot_sec
Q15709
resolver
uniprot_sec
Q15712
resolver
uniprot_sec
Q15713
resolver
uniprot_sec
Q308M2
resolver
activity_regulation
ACTIVITY REGULATION: Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by SERPINB3. {ECO:0000269|PubMed:19166818}.
uniprot
proteins
amino_acid_sequence
MSRSKRDNNFYSVEIGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGYKENVDLWSVGCIMGEMVCHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTVRTYVENRPKYAGYSFEKLFPDVLFPADSEHNKLKASQARDLLSKMLVIDASKRISVDEALQHPYINVWYDPSEAEAPPPKIPDKQLDEREHTIEEWKELIYKEVMDLEERTKNGVIRGQPSPLGAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR
uniprot
proteins
ec_number
2.7.11.24
uniprot
proteins
function
FUNCTION: Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway (PubMed:28943315). In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:18307971). Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins (PubMed:21856198). Loss of this interaction abrogates the acetylation required for replication initiation (PubMed:21856198). Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1 (PubMed:21364637). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation (PubMed:21095239). Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy (PubMed:18570871). Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons (By similarity). In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (By similarity). Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH (PubMed:16581800, PubMed:17296730, PubMed:20027304). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity). Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly (PubMed:22966201). Phosphorylates SIRT6 in response to oxidative stress, stimulating its mono-ADP-ribosyltransferase activity (PubMed:27568560). Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome (PubMed:28943315). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (PubMed:34048572). {ECO:0000250|UniProtKB:P49185, ECO:0000250|UniProtKB:Q91Y86, ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:18307971, ECO:0000269|PubMed:18570871, ECO:0000269|PubMed:20027304, ECO:0000269|PubMed:21095239, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:22966201, ECO:0000269|PubMed:27568560, ECO:0000269|PubMed:28943315, ECO:0000269|PubMed:34048572}.; FUNCTION: JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.
uniprot
proteins
mass_dalton
48296
uniprot
proteins
mutagenesis
MUTAGEN 55; /note="K->D: Abolished protein kinase activity."; /evidence="ECO:0000269|PubMed:22966201, ECO:0000269|PubMed:28943315"; MUTAGEN 183; /note="T->A: Phosphorylation blocked."; /evidence="ECO:0000269|PubMed:7839144"; MUTAGEN 185; /note="Y->F: Phosphorylation blocked."; /evidence="ECO:0000269|PubMed:7839144
uniprot
proteins
post_translational_modification
PTM: Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme (PubMed:11062067). Phosphorylated by TAOK2 (PubMed:17158878). May be phosphorylated at Thr-183 and Tyr-185 by MAP3K1/MEKK1 (PubMed:17761173). Phosphorylated form is more concentrated at synapses than none-phosphorylated (By similarity). {ECO:0000250|UniProtKB:P49185, ECO:0000269|PubMed:11062067, ECO:0000269|PubMed:17158878, ECO:0000269|PubMed:17761173}.
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
10747973
uniprot
proteins
pubmed
10856240
uniprot
proteins
pubmed
11062067
uniprot
proteins
pubmed
12514174
uniprot
proteins
pubmed
15141161
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15693750
uniprot
proteins
pubmed
16581800
uniprot
proteins
pubmed
17158878
uniprot
proteins
pubmed
17296730
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17761173
uniprot
proteins
pubmed
17875713
uniprot
proteins
pubmed
18307971
uniprot
proteins
pubmed
18570871
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19054851
uniprot
proteins
pubmed
19166818
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
20027304
uniprot
proteins
pubmed
21095239
uniprot
proteins
pubmed
21148294
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21364637
uniprot
proteins
pubmed
21660049
uniprot
proteins
pubmed
21856198
uniprot
proteins
pubmed
22327296
uniprot
proteins
pubmed
22441692
uniprot
proteins
pubmed
22966201
uniprot
proteins
pubmed
27568560
uniprot
proteins
pubmed
28943315
uniprot
proteins
pubmed
30878395
uniprot
proteins
pubmed
34048572
uniprot
proteins
pubmed
7839144
uniprot
proteins
pubmed
8137421
uniprot
proteins
pubmed
8654373
uniprot
proteins
sequence_length
427
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21148294}. Nucleus {ECO:0000269|PubMed:21148294, ECO:0000269|PubMed:30878395}. Synapse {ECO:0000250|UniProtKB:P49185}. Note=In the cortical neurons, predominantly cytoplasmic and associated with the Golgi apparatus and endosomal fraction. Increased neuronal activity increases phosphorylated form at synapses (By similarity). Colocalizes with POU5F1 in the nucleus. {ECO:0000250|UniProtKB:P49185, ECO:0000250|UniProtKB:Q91Y86}.
uniprot
proteins