Names & Taxonomy

Uniprot ID:
P45983
Entry Name:
MK08_HUMAN
Status:
reviewed
Protein Names:
Mitogen-activated protein kinase 8 (MAP kinase 8) (MAPK 8) (EC 2.7.11.24) (JNK-46) (Stress-activated protein kinase 1c) (SAPK1c) (Stress-activated protein kinase JNK1) (c-Jun N-terminal kinase 1)
Gene Names:
MAPK8 JNK1 PRKM8 SAPK1 SAPK1C
Gene Names Primary:
MAPK8
Organism:
Homo sapiens (Human)

Structure

Length:
427
Sequence:
MSRSKRDNNFYSVEIGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGYKENVDLWSVGCIMGEMVCHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTVRTYVENRPKYAGYSFEKLFPDVLFPADSEHNKLKASQARDLLSKMLVIDASKRISVDEALQHPYINVWYDPSEAEAPPPKIPDKQLDEREHTIEEWKELIYKEVMDLEERTKNGVIRGQPSPLGAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm

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 proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. 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. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. 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. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. 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. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692).
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.
Cofactor:
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme Regulation:
ENZYME 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.
Active Site:
ACT_SITE 151 151 Proton acceptor.
Gene Ontology Go:
cytosol
mitochondrion
nucleoplasm
nucleus
ATP binding
enzyme binding
histone deacetylase binding
histone deacetylase regulator activity
JUN kinase activity
protein serine/threonine kinase activity
apoptotic process
apoptotic signaling pathway
cellular response to lipopolysaccharide
cellular response to mechanical stimulus
DNA repair
double-strand break repair
Fc-epsilon receptor signaling pathway
innate immune response
intrinsic apoptotic signaling pathway
JNK cascade
JUN phosphorylation
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of apoptotic process
negative regulation of protein binding
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
positive regulation of apoptotic process
positive regulation of cyclase activity
positive regulation of deacetylase activity
positive regulation of gene expression
positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
positive regulation of protein metabolic process
programmed cell death
protein phosphorylation
regulation of circadian rhythm
regulation of histone deacetylation
regulation of macroautophagy
regulation of protein localization
regulation of sequence-specific DNA binding transcription factor activity
response to stress
response to UV
rhythmic process
stress-activated MAPK cascade
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
TRIF-dependent toll-like receptor signaling pathway
Gene Ontology Biological Process:
apoptotic process
apoptotic signaling pathway
cellular response to lipopolysaccharide
cellular response to mechanical stimulus
DNA repair
double-strand break repair
Fc-epsilon receptor signaling pathway
innate immune response
intrinsic apoptotic signaling pathway
JNK cascade
JUN phosphorylation
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of apoptotic process
negative regulation of protein binding
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
positive regulation of apoptotic process
positive regulation of cyclase activity
positive regulation of deacetylase activity
positive regulation of gene expression
positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
positive regulation of protein metabolic process
programmed cell death
protein phosphorylation
regulation of circadian rhythm
regulation of histone deacetylation
regulation of macroautophagy
regulation of protein localization
regulation of sequence-specific DNA binding transcription factor activity
response to stress
response to UV
rhythmic process
stress-activated MAPK cascade
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
TRIF-dependent toll-like receptor signaling pathway
Gene Ontology Molecular Function:
ATP binding
enzyme binding
histone deacetylase binding
histone deacetylase regulator activity
JUN kinase activity
protein serine/threonine kinase activity
Gene Ontology Cellular Component:
cytosol
mitochondrion
nucleoplasm
nucleus
Keywords:
3D-structure
ATP-binding
Alternative splicing
Biological rhythms
Complete proteome
Cytoplasm
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
S-nitrosylation
Serine/threonine-protein kinase
Transferase
Interacts With:
Q92934; P22681; P60953; P46108; P05412; O14733; O14733-2; Q9UQF2; Q9WVI9-1; P27986

Publication

PubMed ID:
8137421 8654373 15164054 19054851 15489334 7839144 11062067 10856240 12514174 15693750 16581800 17875713 17158878 17296730 18307971 18570871 18691976 18669648 19166818 19369195 20027304 21364637 21269460 21660049 22441692 21095239 21148294 21856198 15141161 17344846