Mitogen-activated protein kinase 8

NameMitogen-activated protein kinase 8
Synonyms
  • 2.7.11.24
  • c-Jun N-terminal kinase 1
  • JNK-46
  • JNK1
  • MAP kinase 8
  • PRKM8
  • SAPK1
  • SAPK1C
  • Stress-activated protein kinase 1c
  • Stress-activated protein kinase JNK1
Gene NameMAPK8
OrganismHuman
Amino acid sequence
>lcl|BSEQ0007270|Mitogen-activated protein kinase 8
MSRSKRDNNFYSVEIGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRP
FQNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQ
MELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSF
MMTPYVVTRYYRAPEVILGMGYKENVDLWSVGCIMGEMVCHKILFPGRDYIDQWNKVIEQ
LGTPCPEFMKKLQPTVRTYVENRPKYAGYSFEKLFPDVLFPADSEHNKLKASQARDLLSK
MLVIDASKRISVDEALQHPYINVWYDPSEAEAPPPKIPDKQLDEREHTIEEWKELIYKEV
MDLEERTKNGVIRGQPSPLGAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAA
GPLGCCR
Number of residues427
Molecular Weight48295.14
Theoretical pI6.89
GO Classification
Functions
  • enzyme binding
  • histone deacetylase binding
  • histone deacetylase regulator activity
  • ATP binding
  • JUN kinase activity
  • protein serine/threonine kinase activity
Processes
  • peptidyl-threonine phosphorylation
  • response to stress
  • toll-like receptor 5 signaling pathway
  • apoptotic signaling pathway
  • toll-like receptor 9 signaling pathway
  • intrinsic apoptotic signaling pathway
  • toll-like receptor signaling pathway
  • peptidyl-serine phosphorylation
  • toll-like receptor TLR1
  • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
  • double-strand break repair
  • toll-like receptor TLR6
  • regulation of circadian rhythm
  • innate immune response
  • TRIF-dependent toll-like receptor signaling pathway
  • negative regulation of protein binding
  • response to UV
  • positive regulation of apoptotic process
  • regulation of protein localization
  • Fc-epsilon receptor signaling pathway
  • positive regulation of deacetylase activity
  • MyD88-dependent toll-like receptor signaling pathway
  • cellular response to mechanical stimulus
  • positive regulation of protein metabolic process
  • MyD88-independent toll-like receptor signaling pathway
  • apoptotic process
  • negative regulation of apoptotic process
  • regulation of sequence-specific DNA binding transcription factor activity
  • neurotrophin TRK receptor signaling pathway
  • stress-activated MAPK cascade
  • protein phosphorylation
  • JUN phosphorylation
  • toll-like receptor 10 signaling pathway
  • cellular response to lipopolysaccharide
  • positive regulation of cyclase activity
  • DNA repair
  • toll-like receptor 2 signaling pathway
  • JNK cascade
  • regulation of histone deacetylation
  • programmed cell death
  • toll-like receptor 3 signaling pathway
  • positive regulation of gene expression
  • rhythmic process
  • toll-like receptor 4 signaling pathway
Components
  • cytosol
  • nucleoplasm
  • nucleus
General FunctionProtein serine/threonine kinase activity
Specific FunctionSerine/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).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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID474901
UniProtKB IDP45983
UniProtKB Entry NameMK08_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0017225|Mitogen-activated protein kinase 8 (MAPK8)
ATGAGCAGAAGCAAGCGTGACAACAATTTTTATAGTGTAGAGATTGGAGATTCTACATTC
ACAGTCCTGAAACGATATCAGAATTTAAAACCTATAGGCTCAGGAGCTCAAGGAATAGTA
TGCGCAGCTTATGATGCCATTCTTGAAAGAAATGTTGCAATCAAGAAGCTAAGCCGACCA
TTTCAGAATCAGACTCATGCCAAGCGGGCCTACAGAGAGCTAGTTCTTATGAAATGTGTT
AATCACAAAAATATAATTGGCCTTTTGAATGTTTTCACACCACAGAAATCCCTAGAAGAA
TTTCAAGATGTTTACATAGTCATGGAGCTCATGGATGCAAATCTTTGCCAAGTGATTCAG
ATGGAGCTAGATCATGAAAGAATGTCCTACCTTCTCTATCAGATGCTGTGTGGAATCAAG
CACCTTCATTCTGCTGGAATTATTCATCGGGACTTAAAGCCCAGTAATATAGTAGTAAAA
TCTGATTGCACTTTGAAGATTCTTGACTTCGGTCTGGCCAGGACTGCAGGAACGAGTTTT
ATGATGACGCCTTATGTAGTGACTCGCTACTACAGAGCACCCGAGGTCATCCTTGGCATG
GGCTACAAGGAAAACGTTGACATTTGGTCAGTTGGGTGCATCATGGGAGAAATGATCAAA
GGTGGTGTTTTGTTCCCAGGTACAGATCATATTGATCAGTGGAATAAAGTTATTGAACAG
CTTGGAACACCATGTCCTGAATTCATGAAGAAACTGCAACCAACAGTAAGGACTTACGTT
GAAAACAGACCTAAATATGCTGGATATAGCTTTGAGAAACTCTTCCCTGATGTCCTTTTC
CCAGCTGACTCAGAACACAACAAACTTAAAGCCAGTCAGGCAAGGGATTTGTTATCCAAA
ATGCTGGTAATAGATGCATCTAAAAGGATCTCTGTAGATGAAGCTCTCCAACACCCGTAC
ATCAATGTCTGGTATGATCCTTCTGAAGCAGAAGCTCCACCACCAAAGATCCCTGACAAG
CAGTTAGATGAAAGGGAACACACAATAGAAGAGTGGAAAGAATTGATATATAAGGAAGTT
ATGGACTTGGAGGAGAGAACCAAGAATGGAGTTATACGGGGGCAGCCCTCTCCTTTAGGT
GCAGCAGTGATCAATGGCTCTCAGCATCCATCATCATCGTCGTCTGTCAATGATGTGTCT
TCAATGTCAACAGATCCGACTTTGGCCTCTGATACAGACAGCAGTCTAGAAGCAGCAGCT
GGGCCTCTGGGCTGCTGTAGATGA
GenBank Gene IDL26318
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:6881
Chromosome Location10
Locus10q11.22
References
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