ID:MK08_HUMAN DESCRIPTION: RecName: Full=Mitogen-activated protein kinase 8; Short=MAP kinase 8; Short=MAPK 8; EC=2.7.11.24; AltName: Full=JNK-46; AltName: Full=Stress-activated protein kinase 1c; Short=SAPK1c; AltName: Full=Stress-activated protein kinase JNK1; AltName: Full=c-Jun N-terminal kinase 1; 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. FUNCTION: 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. 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. SUBUNIT: Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway. Interacts with TP53 and WWOX. Interacts with JAMP. Forms a complex with MAPK8IP1 and ARHGEF28 (By similarity). Interacts (phosphorylated form) with NFE2; the interaction phosphorylates NFE2 in undifferentiated cells (By similarity). Interacts with NFATC4. Interacts with MECOM; regulates JNK signaling. Interacts with PIN1; this interaction mediates MAPK8 conformational changes leading to the binding of MAPK8 to its substrates. INTERACTION: P05412:JUN; NbExp=2; IntAct=EBI-286483, EBI-852823; O14733-2:MAP2K7; NbExp=3; IntAct=EBI-286483, EBI-492627; Q9WVI9-1:Mapk8ip1 (xeno); NbExp=2; IntAct=EBI-286483, EBI-288461; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. DOMAIN: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. PTM: Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme. Phosphorylated by TAOK2. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/JNK1ID196.html"; WEB RESOURCE: Name=Wikipedia; Note=C-Jun N-terminal kinases entry; URL="http://en.wikipedia.org/wiki/C-Jun_N-terminal_kinases";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P45983
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006468 protein phosphorylation GO:0007254 JNK cascade GO:0007258 JUN phosphorylation GO:0009411 response to UV GO:0010628 positive regulation of gene expression GO:0016241 regulation of macroautophagy GO:0016310 phosphorylation GO:0018105 peptidyl-serine phosphorylation GO:0018107 peptidyl-threonine phosphorylation GO:0031063 regulation of histone deacetylation GO:0031281 positive regulation of cyclase activity GO:0032091 negative regulation of protein binding GO:0032880 regulation of protein localization GO:0034198 cellular response to amino acid starvation GO:0034614 cellular response to reactive oxygen species GO:0038095 Fc-epsilon receptor signaling pathway GO:0042752 regulation of circadian rhythm GO:0043065 positive regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0048511 rhythmic process GO:0048666 neuron development GO:0051247 positive regulation of protein metabolic process GO:0051403 stress-activated MAPK cascade GO:0071222 cellular response to lipopolysaccharide GO:0071260 cellular response to mechanical stimulus GO:0071276 cellular response to cadmium ion GO:0071345 cellular response to cytokine stimulus GO:0090045 positive regulation of deacetylase activity GO:1900740 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway GO:1902595 regulation of DNA replication origin binding
AK292523 - Homo sapiens cDNA FLJ77387 complete cds, highly similar to Homo sapiens mitogen-activated protein kinase 8 (MAPK8), transcript variant 4, mRNA. BC130570 - Homo sapiens mitogen-activated protein kinase 8, mRNA (cDNA clone MGC:163442 IMAGE:40146601), complete cds. BC130572 - Homo sapiens mitogen-activated protein kinase 8, mRNA (cDNA clone MGC:163444 IMAGE:40146603), complete cds. BC144063 - Homo sapiens mitogen-activated protein kinase 8, mRNA (cDNA clone MGC:177600 IMAGE:9052583), complete cds. U35004 - Human JNK1 beta1 protein kinase (JNK1B1) mRNA, complete cds. HH837089 - Sequence 16 from Patent EP2231168. HH837090 - Sequence 17 from Patent EP2231168. HH837091 - Sequence 18 from Patent EP2231168. HH837092 - Sequence 19 from Patent EP2231168. HI214730 - Sequence 16 from Patent EP2076526. HI214731 - Sequence 17 from Patent EP2076526. HI214732 - Sequence 18 from Patent EP2076526. HI214733 - Sequence 19 from Patent EP2076526. HV601532 - JP 2011500003-A/16: Novel siRNA Structures. HV601533 - JP 2011500003-A/17: Novel siRNA Structures. HV601534 - JP 2011500003-A/18: Novel siRNA Structures. HV601535 - JP 2011500003-A/19: Novel siRNA Structures. HV856605 - JP 2010507387-A/16: Novel siRNAs and Methods of Use Thereof. HV856606 - JP 2010507387-A/17: Novel siRNAs and Methods of Use Thereof. HV856607 - JP 2010507387-A/18: Novel siRNAs and Methods of Use Thereof. HV856608 - JP 2010507387-A/19: Novel siRNAs and Methods of Use Thereof. HW061143 - JP 2012529430-A/18: METHODS FOR TREATING CHRONIC KIDNEY DISEASE. HW061144 - JP 2012529430-A/19: METHODS FOR TREATING CHRONIC KIDNEY DISEASE. HW061145 - JP 2012529430-A/20: METHODS FOR TREATING CHRONIC KIDNEY DISEASE. HW061146 - JP 2012529430-A/21: METHODS FOR TREATING CHRONIC KIDNEY DISEASE. HW165092 - JP 2013102767-A/16: Novel siRNA's and Use Thereof. HW165093 - JP 2013102767-A/17: Novel siRNA's and Use Thereof. HW165094 - JP 2013102767-A/18: Novel siRNA's and Use Thereof. HW165095 - JP 2013102767-A/19: Novel siRNA's and Use Thereof. HW675600 - JP 2014210789-A/16: Novel siRNA Structures. HW675601 - JP 2014210789-A/17: Novel siRNA Structures. HW675602 - JP 2014210789-A/18: Novel siRNA Structures. HW675603 - JP 2014210789-A/19: Novel siRNA Structures. HW835288 - JP 2015051004-A/16: Novel siRNA's and Use Thereof. HW835289 - JP 2015051004-A/17: Novel siRNA's and Use Thereof. HW835290 - JP 2015051004-A/18: Novel siRNA's and Use Thereof. HW835291 - JP 2015051004-A/19: Novel siRNA's and Use Thereof. JA482098 - Sequence 81 from Patent WO2011072091. JA482099 - Sequence 82 from Patent WO2011072091. JA482100 - Sequence 83 from Patent WO2011072091. JA482101 - Sequence 84 from Patent WO2011072091. JA538131 - Sequence 16 from Patent EP2371958. JA538132 - Sequence 17 from Patent EP2371958. JA538133 - Sequence 18 from Patent EP2371958. JA538134 - Sequence 19 from Patent EP2371958. JB251951 - Sequence 18 from Patent EP2440214. JB251952 - Sequence 19 from Patent EP2440214. JB251953 - Sequence 20 from Patent EP2440214. JB251954 - Sequence 21 from Patent EP2440214. JE980390 - Sequence 81 from Patent EP2862929. JE980391 - Sequence 82 from Patent EP2862929. JE980392 - Sequence 83 from Patent EP2862929. JE980393 - Sequence 84 from Patent EP2862929. L26318 - Human protein kinase (JNK1) mRNA, complete cds. LP764850 - Sequence 18 from Patent EP3276004. LP764851 - Sequence 19 from Patent EP3276004. LP764852 - Sequence 20 from Patent EP3276004. LP764853 - Sequence 21 from Patent EP3276004. U35005 - Human JNK1 beta2 protein kinase (JNK1B2) mRNA, complete cds. U34822 - Human JNK1 alpha2 protein kinase (JNK1A2) mRNA, complete cds. HQ258413 - Synthetic construct Homo sapiens clone IMAGE:100072842 mitogen-activated protein kinase 8 (MAPK8), transcript variant JNK1-b2 (MAPK8) gene, encodes complete protein. KJ891893 - Synthetic construct Homo sapiens clone ccsbBroadEn_01287 MAPK8 gene, encodes complete protein. AB527605 - Synthetic construct DNA, clone: pF1KB6687, Homo sapiens MAPK8 gene for mitogen-activated protein kinase 8, without stop codon, in Flexi system. AB451354 - Homo sapiens MAPK8 mRNA for mitogen-activated protein kinase 8 isoform JNK1 alpha1, partial cds, clone: FLJ08021AAAF. AB451231 - Homo sapiens MAPK8 mRNA for mitogen-activated protein kinase 8 isoform JNK1 alpha1, complete cds, clone: FLJ08021AAAN. DQ234352 - Homo sapiens mitogen-activated protein kinase 8 transcript variant 2 mRNA, complete cds, alternatively spliced. AB451398 - Homo sapiens MAPK8 mRNA for mitogen-activated protein kinase 8 isoform JNK1 beta2, partial cds, clone: FLJ08098AAAF. AB451271 - Homo sapiens MAPK8 mRNA for mitogen-activated protein kinase 8 isoform JNK1 beta2, complete cds, clone: FLJ08098AAAN. AL137667 - Homo sapiens mRNA; cDNA DKFZp434B231 (from clone DKFZp434B231). AK094000 - Homo sapiens cDNA FLJ36681 fis, clone UTERU2006547. AX748405 - Sequence 1930 from Patent EP1308459. JD069093 - Sequence 50117 from Patent EP1572962. JD316726 - Sequence 297750 from Patent EP1572962. JD267188 - Sequence 248212 from Patent EP1572962. AK125150 - Homo sapiens cDNA FLJ43160 fis, clone FCBBF2000199. AB074280 - Homo sapiens primary neuroblastoma cDNA, clone:Nbla11051, full insert sequence.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_arenrf2Pathway - Oxidative Stress Induced Gene Expression Via Nrf2 h_dspPathway - Regulation of MAP Kinase Pathways Through Dual Specificity Phosphatases h_epoPathway - EPO Signaling Pathway h_il1rPathway - Signal transduction through IL1R h_insulinPathway - Insulin Signaling Pathway h_keratinocytePathway - Keratinocyte Differentiation h_malPathway - Role of MAL in Rho-Mediated Activation of SRF h_mapkPathway - MAPKinase Signaling Pathway h_tollPathway - Toll-Like Receptor Pathway h_IL12Pathway - IL12 and Stat4 Dependent Signaling Pathway in Th1 Development h_ngfPathway - Nerve growth factor pathway (NGF) h_pyk2Pathway - Links between Pyk2 and Map Kinases h_ranklPathway - Bone Remodelling h_tnfr1Pathway - TNFR1 Signaling Pathway h_41bbPathway - The 4-1BB-dependent immune response h_atmPathway - ATM Signaling Pathway h_egfPathway - EGF Signaling Pathway h_fasPathway - FAS signaling pathway ( CD95 ) h_tall1Pathway - TACI and BCMA stimulation of B cell immune responses. h_tcrPathway - T Cell Receptor Signaling Pathway h_p53hypoxiaPathway - Hypoxia and p53 in the Cardiovascular system h_agrPathway - Agrin in Postsynaptic Differentiation h_ceramidePathway - Ceramide Signaling Pathway h_fcer1Pathway - Fc Epsilon Receptor I Signaling in Mast Cells h_metPathway - Signaling of Hepatocyte Growth Factor Receptor h_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart) h_pdgfPathway - PDGF Signaling Pathway h_At1rPathway - Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling h_Ccr5Pathway - Pertussis toxin-insensitive CCR5 Signaling in Macrophage h_bcrPathway - BCR Signaling Pathway h_il2Pathway - IL 2 signaling pathway h_stressPathway - TNF/Stress Related Signaling h_HivnefPathway - HIV-I Nef: negative effector of Fas and TNF h_biopeptidesPathway - Bioactive Peptide Induced Signaling Pathway h_gleevecpathway - Inhibition of Cellular Proliferation by Gleevec h_igf1Pathway - IGF-1 Signaling Pathway h_integrinPathway - Integrin Signaling Pathway
Reactome (by CSHL, EBI, and GO)
Protein P45983 (Reactome details) participates in the following event(s):
R-HSA-204949 NRIF and TRAF6 may activate JNK R-HSA-205132 NRAGE activates JNK R-HSA-205136 GTP-bound RAC contributes to JNK activation R-HSA-451347 Activation of JNK by DSCAM R-HSA-193666 Active JNK moves to the nucleus and phosphorylates different transcription factors R-HSA-5683986 APBB1 and MAPK8 bind diphosphorylated H2AFX R-HSA-168162 Phosphorylation of human JNKs by activated MKK4/MKK7 R-HSA-139908 Phosphorylation of DLC2 by MAPK8 R-HSA-139918 Phosphorylation of BIM by JNK R-HSA-450348 Activated human JNKs migrate to nucleoplasm R-HSA-205075 JNK phosphorylates BIM, BAD and other targets R-HSA-168136 Activated JNKs phosphorylate c-JUN R-HSA-168053 Phosphorylated MAPKs phosphorylate ATF-2 R-HSA-205043 NRIF signals cell death from the nucleus R-HSA-193648 NRAGE signals death through JNK R-HSA-376172 DSCAM interactions R-HSA-9007892 Interleukin-38 signaling R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 R-HSA-2559580 Oxidative Stress Induced Senescence R-HSA-2871796 FCERI mediated MAPK activation R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE R-HSA-373752 Netrin-1 signaling R-HSA-446652 Interleukin-1 family signaling R-HSA-139910 Activation of BMF and translocation to mitochondria R-HSA-111446 Activation of BIM and translocation to mitochondria R-HSA-5693606 DNA Double Strand Break Response R-HSA-450294 MAP kinase activation R-HSA-2559583 Cellular Senescence R-HSA-2454202 Fc epsilon receptor (FCERI) signaling R-HSA-193704 p75 NTR receptor-mediated signalling R-HSA-422475 Axon guidance R-HSA-449147 Signaling by Interleukins R-HSA-114452 Activation of BH3-only proteins R-HSA-450341 Activation of the AP-1 family of transcription factors R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade R-HSA-448424 Interleukin-17 signaling R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-975871 MyD88 cascade initiated on plasma membrane R-HSA-2262752 Cellular responses to stress R-HSA-168249 Innate Immune System R-HSA-73887 Death Receptor Signalling R-HSA-1266738 Developmental Biology R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-109606 Intrinsic Pathway for Apoptosis R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinases R-HSA-73894 DNA Repair R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade R-HSA-168898 Toll-Like Receptors Cascades R-HSA-166166 MyD88-independent TLR4 cascade R-HSA-975155 MyD88 dependent cascade initiated on endosome R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade R-HSA-8953897 Cellular responses to external stimuli R-HSA-168256 Immune System R-HSA-162582 Signal Transduction R-HSA-109581 Apoptosis R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-5357801 Programmed Cell Death
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
