Mitogen-activated protein kinase 8
Details
- Name
- Mitogen-activated protein kinase 8
- Synonyms
- 2.7.11.24
- c-Jun N-terminal kinase 1
- JNK-46
- JNK1
- MAP kinase 8
- MAPK 8
- PRKM8
- SAPK1
- SAPK1C
- Stress-activated protein kinase 1c
- Stress-activated protein kinase JNK1
- Gene Name
- MAPK8
- UniProtKB Entry
- P45983Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- 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
- Functionsprotein phosphatase binding / protein serine kinase activity / protein serine/threonine kinase bindingProcessescellular response to amino acid starvation / cellular response to cadmium ion / cellular response to oxidative stress / cellular response to reactive oxygen species / cellular senescence / energy homeostasis / positive regulation of cell killing / positive regulation of establishment of protein localization to mitochondrion / positive regulation of NLRP3 inflammasome complex assembly / regulation of macroautophagy / response to mechanical stimulus / response to oxidative stressComponentsaxon / basal dendrite / cytoplasm / synapse
- General 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)
- Specific Function
- ATP binding
- Pfam Domain Function
- Pkinase (PF00069)
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- 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
- Chromosome Location
- 10
- Locus
- 10q11.22
- External Identifiers
Resource Link UniProtKB ID P45983 UniProtKB Entry Name MK08_HUMAN GenBank Protein ID 474901 GenBank Gene ID L26318 GeneCard ID MAPK8 HGNC ID HGNC:6881 PDB ID(s) 1UKH, 1UKI, 2G01, 2GMX, 2H96, 2NO3, 2XRW, 2XS0, 3ELJ, 3O17, 3O2M, 3PZE, 3V3V, 3VUD, 3VUG, 3VUH, 3VUI, 3VUK, 3VUL, 3VUM, 4AWI, 4E73, 4G1W, 4HYS, 4HYU, 4IZY, 4L7F, 4QTD, 4UX9, 4YR8, 5LW1, 6F5E, 6ZR5, 8X5M KEGG ID hsa:5599 IUPHAR/Guide To Pharmacology ID 1496 NCBI Gene ID 5599 - General References
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Associated Data
- Bio-Entities
Bio-Entity Type Mitogen-activated protein kinase 8 (Humans) protein primaryMitogen-activated Protein Kinases (Humans) protein c-Jun N-terminal kinases (Humans) protein - Drug Relations