| Description | All JNK proteins contain a protein kinase domain that belong to a very extensive family of eukaryotic serine/threonine proteins kinase. A number of conserved regions have been identified in the catalytic domain of JNKs. In the N-terminal extremity of the catalytic domain there is a glycine-rich motif in the vicinity of a lysine residue, which has been shown to be involved in ATP binding. A conserved aspartic acid reside that is critical for the catalytic activity of kinase has also been identified in the central part of the catalytic domain. |
| Expression | JNK1 is ubiquitously expressed. |
| Localisation | Cytoplasmic and nuclear |
| Function | The members of JNK family act as an integration point for multiple intracellular biochemical signals governing a wide variety of cellular processes such as proliferation, differentiation, apoptosis, migration, transcriptional regulation, and development JNK targets specific transcription factors and thus mediates immediate-early gene expression in response to various stress signals including ultraviolet (UV) radiation, oxidative stress, protein malfolding in endoplasmic reticulum, osmotical shock, and inflammatory mediators. These transcription factors include AP-1, ATF-2, Elk-1, p53, etc... Several upstream dual specific protein kinases, such as MKK4/SEK1 and MKK7, can activate JNK through phosphorylation of the conversed Thr-Pro-Tyr motif on JNK proteins. In mammalian cells, activated JNK can phosphorylate the N-terminus of c-Jun, which contains both JNK docking site and JNK phosphorylation site (ser63 and ser73), orJunD, which lacks a JNK docking site but contains a JNK phosphorylation site. JNK is unable to phosphorylate JunB due to the lack of a JNK phosphorylation site inJunB, despite there is a functional JNK docking site. Comparison of the binding activity of JNK isoforms demonstrates that JNK2 bind c-Jun approximately 25 times more efficiently than did JNK1. Therefore, individual members of the JNK family may selectively target specific transcription factors in vivo. One of the most important functions of JNK is the regulation of apoptosis. Emerging evidence indicates that JNK activation is obligatory for apoptosis induced by both receptor-mediated ÒextrinsicÓ pathway or mitochondria-mediated ÒintrinsicÓ pathway. JNK activation may contribute to the initiation of Fas-induced apoptosis, possibly through the amplification of autocrine or paracrine Fas signaling by JNK-dependent Fas ligand (FasL) gene expression. In addition, JNK has been indicated in the apoptosis induced by Daxx, a Fas death domain (FADD) interaction protein. Through its serine/threonine kinase activity, JNK may contribute to mitochondria-mediated apoptosis by phosphorylating pro- or anti-apoptoticBcl-2 family proteins. Finally, JNK has also been indicated as an important kinase phosphorylating p53 and subsequently facilitating p53-dependent apoptotic responses. Sustained JNK activation may be responsible for the enhanced apoptosis observed in RelA-/- or Ikkb-/- mouse embryonic fibroblasts treated with TNFa. It was suggested that deficiency of RelA or IKKb caused a decreased expression of XIAP or GADD45b, which may antagonize the activation of JNK activation. However, such speculation contradicts the previous observations indicating that both GADD45b and XIAP are activators, rather than inhibitors for JNK activation. Moreover, gene profiling in our recent studies indicated no substantial difference of basal or inducible GADD45b and XIAP mRNA in wild type cells and Ikkb-/- cells. |
| Nomenclature | | HGNC | MAPK8 6881 |
| Entrez_Gene | MAPK8 5599 mitogen-activated protein kinase 8 |
| Cards |
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| Atlas | JNK1ID196 |
| GeneCards | MAPK8 |
| Ensembl | MAPK8 [Search_View] ENSG00000107643 [Gene_View] |
| Genatlas | MAPK8 |
| GeneLynx | MAPK8 |
| eGenome | MAPK8 |
| euGene | 5599 |
| Genomic and cartography |
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| GoldenPath | MAPK8 - 10q11.21 chr10:49279693-49313189 + 10q11 [Description] (hg18-Mar_2006) |
| Ensembl | MAPK8 - 10q11 [CytoView] |
| NCBI | Mapview |
| OMIM | Disease map [OMIM] |
| HomoloGene | MAPK8 |
| Gene and transcription | | Genbank | AK292523 [ ENTREZ ] |
| Genbank | AL137667 [ ENTREZ ] |
| Genbank | BC130570 [ ENTREZ ] |
| Genbank | BC130572 [ ENTREZ ] |
| Genbank | CR614448 [ ENTREZ ] |
| RefSeq | NM_002750 [ SRS ] NM_002750 [ ENTREZ ] |
| RefSeq | NM_139046 [ SRS ] NM_139046 [ ENTREZ ] |
| RefSeq | NM_139047 [ SRS ] NM_139047 [ ENTREZ ] |
| RefSeq | NM_139049 [ SRS ] NM_139049 [ ENTREZ ] |
| RefSeq | AC_000053 [ SRS ] AC_000053 [ ENTREZ ] |
| RefSeq | AC_000142 [ SRS ] AC_000142 [ ENTREZ ] |
| RefSeq | NC_000010 [ SRS ] NC_000010 [ ENTREZ ] |
| RefSeq | NT_017696 [ SRS ] NT_017696 [ ENTREZ ] |
| RefSeq | NW_001837974 [ SRS ] NW_001837974 [ ENTREZ ] |
| RefSeq | NW_924685 [ SRS ] NW_924685 [ ENTREZ ] |
| AceView | MAPK8 AceView - NCBI |
| Unigene | Hs.138211 [ SRS ] Hs.138211 [ NCBI ]
HS138211 [ spliceNest ] |
| Fast-db | 10044 (alternative variants) |
| Protein : pattern, domain, 3D structure |
|---|
| SwissProt | P45983 [ SRS] P45983 [ EXPASY ] P45983 [ INTERPRO ] P45983 [ UNIPROT ] |
| Prosite | PS01351 MAPK [ SRS ] PS01351 MAPK [ Expasy ] |
| Prosite | PS00107 PROTEIN_KINASE_ATP [ SRS ] PS00107 PROTEIN_KINASE_ATP [ Expasy ] |
| Prosite | PS50011 PROTEIN_KINASE_DOM [ SRS ] PS50011 PROTEIN_KINASE_DOM [ Expasy ] |
| Prosite | PS00108 PROTEIN_KINASE_ST [ SRS ] PS00108 PROTEIN_KINASE_ST [ Expasy ] |
| Interpro | IPR008351 JNK_MAPK [ SRS ] IPR008351 JNK_MAPK [ EBI ] |
| Interpro | IPR003527 MAP_kin_CS [ SRS ] IPR003527 MAP_kin_CS [ EBI ] |
| Interpro | IPR000719 Prot_kinase_core [ SRS ] IPR000719 Prot_kinase_core [ EBI ] |
| Interpro | IPR017441 Protein_kinase_ATP_bd_CS [ SRS ] IPR017441 Protein_kinase_ATP_bd_CS [ EBI ] |
| Interpro | IPR017442 Se/Thr_pkinase-rel [ SRS ] IPR017442 Se/Thr_pkinase-rel [ EBI ] |
| Interpro | IPR008271 Ser_thr_pkin_AS [ SRS ] IPR008271 Ser_thr_pkin_AS [ EBI ] |
| Interpro | IPR002290 Ser_thr_pkinase [ SRS ] IPR002290 Ser_thr_pkinase [ EBI ] |
| CluSTr | P45983 |
| Pfam | PF00069 Pkinase [ SRS ] PF00069 Pkinase [ Sanger ] pfam00069 [ NCBI-CDD ] |
| Smart | SM00220 S_TKc [EMBL] |
| Prodom | PD000001 Prot_kinase[INRA-Toulouse] |
| Prodom | P45983 MK08_HUMAN [ Domain structure ] P45983 MK08_HUMAN [ sequences sharing at least 1 domain ] |
| Blocks | P45983 |
| PDB | 1UKH [ SRS ] 1UKH [ PdbSum ], 1UKH [ IMB ] 1UKH [ RSDB ] |
| PDB | 1UKI [ SRS ] 1UKI [ PdbSum ], 1UKI [ IMB ] 1UKI [ RSDB ] |
| PDB | 2G01 [ SRS ] 2G01 [ PdbSum ], 2G01 [ IMB ] 2G01 [ RSDB ] |
| PDB | 2GMX [ SRS ] 2GMX [ PdbSum ], 2GMX [ IMB ] 2GMX [ RSDB ] |
| PDB | 2H96 [ SRS ] 2H96 [ PdbSum ], 2H96 [ IMB ] 2H96 [ RSDB ] |
| PDB | 2NO3 [ SRS ] 2NO3 [ PdbSum ], 2NO3 [ IMB ] 2NO3 [ RSDB ] |
| HPRD | 03100 |
| Protein Interaction databases |
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| DIP | P45983 |
| IntAct | P45983 |
| Polymorphism : SNP, mutations, diseases |
|---|
| OMIM | 601158 [ map ] |
| GENECLINICS | 601158 |
| SNP | MAPK8 [dbSNP-NCBI] |
| SNP | NM_002750 [SNP-NCI] |
| SNP | NM_139046 [SNP-NCI] |
| SNP | NM_139047 [SNP-NCI] |
| SNP | NM_139049 [SNP-NCI] |
| SNP | MAPK8 [GeneSNPs - Utah] MAPK8] [HGBASE - SRS] |
| HAPMAP | MAPK8 [HAPMAP] |
| COSMIC | MAPK8 [Somatic mutation (COSMIC-CGP-Sanger)] |
| HGMD | MAPK8 |
| General knowledge |
|---|
| Family Browser | MAPK8 [UCSC Family Browser] |
| SOURCE | NM_002750 |
| SOURCE | NM_139046 |
| SOURCE | NM_139047 |
| SOURCE | NM_139049 |
| SMD | Hs.138211 |
| SAGE | Hs.138211 |
| Enzyme | 2.7.11.24 [ Enzyme-Expasy ] 2.7.11.24 [ Enzyme-SRS ] 2.7.11.24 [ IntEnz-EBI ] 2.7.11.24 [ BRENDA ] 2.7.11.24 [ KEGG ] 2.7.11.24 [ WIT ] |
| GO | nucleotide binding [Amigo] nucleotide binding |
| GO | protein serine/threonine kinase activity [Amigo] protein serine/threonine kinase activity |
| GO | protein serine/threonine kinase activity [Amigo] protein serine/threonine kinase activity |
| GO | JUN kinase activity [Amigo] JUN kinase activity |
| GO | MAP kinase activity [Amigo] MAP kinase activity |
| GO | protein binding [Amigo] protein binding |
| GO | ATP binding [Amigo] ATP binding |
| GO | cytosol [Amigo] cytosol |
| GO | protein amino acid phosphorylation [Amigo] protein amino acid phosphorylation |
| GO | cell motility [Amigo] cell motility |
| GO | response to stress [Amigo] response to stress |
| GO | signal transduction [Amigo] signal transduction |
| GO | JUN phosphorylation [Amigo] JUN phosphorylation |
| GO | activation of pro-apoptotic gene products [Amigo] activation of pro-apoptotic gene products |
| GO | response to UV [Amigo] response to UV |
| GO | transferase activity [Amigo] transferase activity |
| GO | negative regulation of apoptosis [Amigo] negative regulation of apoptosis |
| BIOCARTA | The 4-1BB-dependent immune response [Genes] |
| BIOCARTA | Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling [Genes] |
| BIOCARTA | Pertussis toxin-insensitive CCR5 Signaling in Macrophage [Genes] |
| BIOCARTA | HIV-I Nef: negative effector of Fas and TNF [Genes] |
| BIOCARTA | IL12 and Stat4 Dependent Signaling Pathway in Th1 Development [Genes] |
| BIOCARTA | Agrin in Postsynaptic Differentiation [Genes] |
| BIOCARTA | Oxidative Stress Induced Gene Expression Via Nrf2 [Genes] |
| BIOCARTA | ATM Signaling Pathway [Genes] |
| BIOCARTA | BCR Signaling Pathway [Genes] |
| BIOCARTA | Bioactive Peptide Induced Signaling Pathway [Genes] |
| BIOCARTA | Ceramide Signaling Pathway [Genes] |
| BIOCARTA | Regulation of MAP Kinase Pathways Through Dual Specificity Phosphatases [Genes] |
| BIOCARTA | EGF Signaling Pathway [Genes] |
| BIOCARTA | EPO Signaling Pathway [Genes] |
| BIOCARTA | FAS signaling pathway ( CD95 ) [Genes] |
| BIOCARTA | Fc Epsilon Receptor I Signaling in Mast Cells [Genes] |
| BIOCARTA | Inhibition of Cellular Proliferation by Gleevec [Genes] |
| BIOCARTA | IGF-1 Signaling Pathway [Genes] |
| BIOCARTA | Signal transduction through IL1R [Genes] |
| BIOCARTA | IL 2 signaling pathway [Genes] |
| BIOCARTA | Insulin Signaling Pathway [Genes] |
| BIOCARTA | Integrin Signaling Pathway [Genes] |
| BIOCARTA | Keratinocyte Differentiation [Genes] |
| BIOCARTA | Role of MAL in Rho-Mediated Activation of SRF [Genes] |
| BIOCARTA | MAPKinase Signaling Pathway [Genes] |
| BIOCARTA | Signaling of Hepatocyte Growth Factor Receptor [Genes] |
| BIOCARTA | NFAT and Hypertrophy of the heart (Transcription in the broken heart) [Genes] |
| BIOCARTA | Nerve growth factor pathway (NGF) [Genes] |
| BIOCARTA | Hypoxia and p53 in the Cardiovascular system [Genes] |
| BIOCARTA | PDGF Signaling Pathway [Genes] |
| BIOCARTA | Links between Pyk2 and Map Kinases [Genes] |
| BIOCARTA | Bone Remodelling [Genes] |
| BIOCARTA | TNF/Stress Related Signaling [Genes] |
| BIOCARTA | TACI and BCMA stimulation of B cell immune responses. [Genes] |
| BIOCARTA | T Cell Receptor Signaling Pathway [Genes] |
| BIOCARTA | TNFR1 Signaling Pathway [Genes] |
| BIOCARTA | Toll-Like Receptor Pathway [Genes] |
| KEGG | MAPK signaling pathway |
| KEGG | Wnt signaling pathway |
| KEGG | Focal adhesion |
| KEGG | Toll-like receptor signaling pathway |
| KEGG | Fc epsilon RI signaling pathway |
| KEGG | Insulin signaling pathway |
| KEGG | GnRH signaling pathway |
| KEGG | Adipocytokine signaling pathway |
| KEGG | Type II diabetes mellitus |
| KEGG | Epithelial cell signaling in Helicobacter pylori infection |
| KEGG | Colorectal cancer |
| PubGene | MAPK8 |
| TreeFam | MAPK8 |
| CTD | 5599 [Comparative ToxicoGenomics Database] |
| Other databases |
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| Probes |
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| Probe | MAPK8 Related clones (RZPD - Berlin) |
| PubMed |
|---|
| PubMed | 308 Pubmed reference(s) in Entrez |
| Daxx, a novel Fas-binding protein that activates JNK and apoptosis. |
| Yang X, Khosravi-Far R, Chang HY, Baltimore D |
| Cell. 1997 ; 89 (7) : 1067-1076. |
| PMID 9215629 |
| |
| Stress-induced Fas ligand expression in T cells is mediated through a MEK kinase 1-regulated response element in the Fas ligand promoter. |
| Faris M, Latinis KM, Kempiak SJ, Koretzky GA, Nel A |
| Molecular and cellular biology. 1998 ; 18 (9) : 5414-5424. |
| PMID 9710625 |
| |
| JNK targets p53 ubiquitination and degradation in nonstressed cells. |
| Fuchs SY, Adler V, Buschmann T, Yin Z, Wu X, Jones SN, Ronai Z |
| Genes & development. 1998 ; 12 (17) : 2658-2663. |
| PMID 9732264 |
| |
| A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK. |
| Takekawa M, Saito H |
| Cell. 1998 ; 95 (4) : 521-530. |
| PMID 9827804 |
| |
| Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase. |
| Jacobs D, Glossip D, Xing H, Muslin AJ, Kornfeld K |
| Genes & development. 1999 ; 13 (2) : 163-175. |
| PMID 9925641 |
| |
| Signal transduction by the JNK group of MAP kinases. |
| Davis RJ |
| Cell. 2000 ; 103 (2) : 239-252. |
| PMID 11057897 |
| |
| Induction of gadd45beta by NF-kappaB downregulates pro-apoptotic JNK signalling. |
| De Smaele E, Zazzeroni F, Papa S, Nguyen DU, Jin R, Jones J, Cong R, Franzoso G |
| Nature. 2001 ; 414 (6861) : 308-313. |
| PMID 11713530 |
| |
| Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. |
| Suzuki Y, Nakabayashi Y, Takahashi R |
| Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (15) : 8662-8667. |
| PMID 11447297 |
| |
| Inhibition of JNK activation through NF-kappaB target genes. |
| Tang G, Minemoto Y, Dibling B, Purcell NH, Li Z, Karin M, Lin A |
| Nature. 2001 ; 414 (6861) : 313-317. |
| PMID 11713531 |
| |
