Mitogen-activated protein kinase 8
| Name | Mitogen-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 Name | MAPK8 |
| Organism | Human |
| Amino acid sequence | >lcl|BSEQ0007270|Mitogen-activated protein kinase 8 MSRSKRDNNFYSVEIGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRP FQNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQ MELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSF MMTPYVVTRYYRAPEVILGMGYKENVDLWSVGCIMGEMVCHKILFPGRDYIDQWNKVIEQ LGTPCPEFMKKLQPTVRTYVENRPKYAGYSFEKLFPDVLFPADSEHNKLKASQARDLLSK MLVIDASKRISVDEALQHPYINVWYDPSEAEAPPPKIPDKQLDEREHTIEEWKELIYKEV MDLEERTKNGVIRGQPSPLGAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAA GPLGCCR |
| Number of residues | 427 |
| Molecular Weight | 48295.14 |
| Theoretical pI | 6.89 |
| GO Classification |
Functions
enzyme binding ATP binding protein serine/threonine kinase activity histone deacetylase binding histone deacetylase regulator activity JUN kinase activity Processes
response to UV toll-like receptor 9 signaling pathway protein phosphorylation JUN phosphorylation regulation of protein localization toll-like receptor signaling pathway cellular response to lipopolysaccharide positive regulation of cyclase activity MyD88-dependent toll-like receptor signaling pathway toll-like receptor TLR1 JNK cascade regulation of histone deacetylation MyD88-independent toll-like receptor signaling pathway double-strand break repair toll-like receptor TLR6 positive regulation of gene expression regulation of sequence-specific DNA binding transcription factor activity innate immune response TRIF-dependent toll-like receptor signaling pathway peptidyl-threonine phosphorylation stress-activated MAPK cascade positive regulation of apoptotic process negative regulation of protein binding apoptotic signaling pathway toll-like receptor 10 signaling pathway Fc-epsilon receptor signaling pathway intrinsic apoptotic signaling pathway toll-like receptor 2 signaling pathway DNA repair cellular response to mechanical stimulus positive regulation of deacetylase activity peptidyl-serine phosphorylation toll-like receptor 3 signaling pathway programmed cell death apoptotic process positive regulation of protein metabolic process positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway rhythmic process toll-like receptor 4 signaling pathway negative regulation of apoptotic process regulation of circadian rhythm response to stress toll-like receptor 5 signaling pathway neurotrophin TRK receptor signaling pathway Components
cytosol nucleoplasm nucleus |
| General Function | Protein serine/threonine kinase activity |
| Specific 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).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. |
| Transmembrane Regions | |
| GenBank Protein ID | 474901 |
| UniProtKB ID | P45983 |
| UniProtKB Entry Name | MK08_HUMAN |
| Cellular Location | Cytoplasm |
| 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 ID | L26318 |
| GeneCard ID | None |
| GenAtlas ID | |
| HGNC ID | HGNC:6881 |
| Chromosome Location | 10 |
| Locus | 10q11.22 |
| References |
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Related FRC
| FRCD ID | Name | Exact Mass | Structure |
|---|---|---|---|
Cadmium |
112.414 |