Details of Protein

General Information of Protein (ID: PRT01154)
Name Stress-activated protein kinase JNK1 (JNK1)
Synonyms   Click to Show/Hide Synonyms of This Protein
MAP kinase 8; MAPK 8; JNK-46; Stress-activated protein kinase 1c; SAPK1c; Stress-activated protein kinase JNK1; c-Jun N-terminal kinase 1; MAPK8; JNK1; PRKM8; SAPK1; SAPK1C
Gene Name MAPK8 Gene ID
5599
UniProt ID
P45983
Family Transferases (EC 2)
EC Number   EC: 2.7.11.24  (Click to Show/Hide the Complete EC Tree)
Transferase
Kinase
Protein-serine/threonine kinases
EC: 2.7.11.24
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MSRSKRDNNFYSVEIGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRP
FQNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQ
MELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSF
MMTPYVVTRYYRAPEVILGMGYKENVDLWSVGCIMGEMVCHKILFPGRDYIDQWNKVIEQ
LGTPCPEFMKKLQPTVRTYVENRPKYAGYSFEKLFPDVLFPADSEHNKLKASQARDLLSK
MLVIDASKRISVDEALQHPYINVWYDPSEAEAPPPKIPDKQLDEREHTIEEWKELIYKEV
MDLEERTKNGVIRGQPSPLGAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAA
GPLGCCR
Structure
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
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. Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity. Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation. Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1. In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses. Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly.; 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.
Regulatory Network
Full List of Metabolite(s) Regulating This Protein
      Lipids and lipid-like molecules
            (2E,4E)-9-Hydroxyoctadeca-2,4-dienoic acid Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation (2E,4E)-9-Hydroxyoctadeca-2,4-dienoic acid addition (0.17 hours)
                      Induced Change MAPK8 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Atherosclerosis [ICD-11: BD40]
                      Details It is reported that (2E,4E)-9-hydroxyoctadeca-2,4-dienoic acid addition causes the increase of MAPK8 protein phosphorylation compared with control group.
      Organic acids and derivatives
            Leucine Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Leucine addition (5 hours)
                      Induced Change MAPK8 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that leucine addition causes the increase of MAPK8 protein phosphorylation compared with control group.
References
1 Identification of 9-hydroxyoctadecadienoic acid and other oxidized free fatty acids as ligands of the G protein-coupled receptor G2A. J Biol Chem. 2005 Dec 9;280(49):40676-83.
2 Influence of leucine on protein metabolism, phosphokinase expression, and cell proliferation in human duodenum1,3. Am J Clin Nutr. 2011 Jun;93(6):1255-62.

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