Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

MAPK8 (mitogen-activated protein kinase 8)

Identity

Other namesJNK1 (C-Jun N-terminal kinase 1)
Stress-activated protein kinase 1 (SAPK1)
HGNC (Hugo) MAPK8
LocusID (NCBI) 5599
Location 10q11.22
Location_base_pair Starts at 49514682 and ends at 49647402 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

 
Description The JNK1 gene maps on chromosome 10q11.21 spanning 130089bp. It contains 22 confirmed introns, 20 of which are alternative.
Transcription By alternative splicing, JNK1 gene encodes 13 different transcripts that translate to 13 JNK1 isoforms. The predicted molecular weight of JNK1 protein is 44.2 kD.

Protein

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 “extrinsic” pathway or mitochondria-mediated “intrinsic” 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.

Implicated in

Entity Obesity, insulin resistance, neurodegenerative diseases, inflammation, cancer.
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias t0817q24q22ID1494 t1119q23p13ID1540 t614p25q32IRF4IGHID1175 t1213p13q14ID1323 t1117q23q12AF17ID1027
t1117p15p13ID2134 t1114ID1070 dic920ID1143 dic0709p11p12ID1554 i17qID1038
t0109p34q34ID2143

External links

Nomenclature
HGNC (Hugo)MAPK8   6881
Cards
AtlasJNK1ID196
Entrez_Gene (NCBI)MAPK8  5599  mitogen-activated protein kinase 8
GeneCards (Weizmann)MAPK8
Ensembl (Hinxton)ENSG00000107643 [Gene_View]  chr10:49514682-49647402 [Contig_View]  MAPK8 [Vega]
ICGC DataPortalENSG00000107643
cBioPortalMAPK8
AceView (NCBI)MAPK8
Genatlas (Paris)MAPK8
WikiGenes5599
SOURCE (Princeton)NM_001278547 NM_001278548 NM_002750 NM_139046 NM_139049
Genomic and cartography
GoldenPath (UCSC)MAPK8  -  10q11.22   chr10:49514682-49647402 +  10q11   [Description]    (hg19-Feb_2009)
EnsemblMAPK8 - 10q11 [CytoView]
Mapping of homologs : NCBIMAPK8 [Mapview]
OMIM601158   
Gene and transcription
Genbank (Entrez)AA808177 AB451231 AB451271 AB451354 AB451398
RefSeq transcript (Entrez)NM_001278547 NM_001278548 NM_002750 NM_139046 NM_139049
RefSeq genomic (Entrez)AC_000142 NC_000010 NC_018921 NG_029053 NT_030059 NW_001837974 NW_004929376
Consensus coding sequences : CCDS (NCBI)MAPK8
Cluster EST : UnigeneHs.522924 [ NCBI ]
CGAP (NCI)Hs.522924
Alternative Splicing : Fast-db (Paris)GSHG0003350
Alternative Splicing GalleryENSG00000107643
Gene ExpressionMAPK8 [ NCBI-GEO ]     MAPK8 [ SEEK ]   MAPK8 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP45983 (Uniprot)
NextProtP45983  [Medical]
With graphics : InterProP45983
Splice isoforms : SwissVarP45983 (Swissvar)
Catalytic activity : Enzyme2.7.11.24 [ Enzyme-Expasy ]   2.7.11.242.7.11.24 [ IntEnz-EBI ]   2.7.11.24 [ BRENDA ]   2.7.11.24 [ KEGG ]   
Domaine pattern : Prosite (Expaxy)MAPK (PS01351)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (EBI)Kinase-like_dom [organisation]   MAP_kinase_CS [organisation]   MAPK_JNK [organisation]   Prot_kinase_dom [organisation]   Ser/Thr_dual-sp_kinase_dom [organisation]   Ser/Thr_kinase_AS [organisation]  
Related proteins : CluSTrP45983
Domain families : Pfam (Sanger)Pkinase (PF00069)   
Domain families : Pfam (NCBI)pfam00069   
Domain families : Smart (EMBL)S_TKc (SM00220)  
DMDM Disease mutations5599
Blocks (Seattle)P45983
PDB (SRS)1UKH    1UKI    2G01    2GMX    2H96    2NO3    2XRW    2XS0    3ELJ    3O17    3O2M    3PZE    3V3V    3VUD    3VUG    3VUH    3VUI    3VUK    3VUL    3VUM    4AWI    4E73   
PDB (PDBSum)1UKH    1UKI    2G01    2GMX    2H96    2NO3    2XRW    2XS0    3ELJ    3O17    3O2M    3PZE    3V3V    3VUD    3VUG    3VUH    3VUI    3VUK    3VUL    3VUM    4AWI    4E73   
PDB (IMB)1UKH    1UKI    2G01    2GMX    2H96    2NO3    2XRW    2XS0    3ELJ    3O17    3O2M    3PZE    3V3V    3VUD    3VUG    3VUH    3VUI    3VUK    3VUL    3VUM    4AWI    4E73   
PDB (RSDB)1UKH    1UKI    2G01    2GMX    2H96    2NO3    2XRW    2XS0    3ELJ    3O17    3O2M    3PZE    3V3V    3VUD    3VUG    3VUH    3VUI    3VUK    3VUL    3VUM    4AWI    4E73   
Human Protein AtlasENSG00000107643 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP45983
HPRD03100
IPIIPI00024672   IPI00003145   IPI00220305   IPI00220306   IPI00646929   IPI00639865   IPI00854859   
Protein Interaction databases
DIP (DOE-UCLA)P45983
IntAct (EBI)P45983
FunCoupENSG00000107643
BioGRIDMAPK8
InParanoidP45983
Interologous Interaction database P45983
IntegromeDBMAPK8
STRING (EMBL)MAPK8
Ontologies - Pathways
Ontology : AmiGOossification  toll-like receptor signaling pathway  MyD88-dependent toll-like receptor signaling pathway  MyD88-independent toll-like receptor signaling pathway  protein serine/threonine kinase activity  JUN kinase activity  protein binding  ATP binding  nucleus  nucleoplasm  mitochondrion  cytosol  apoptotic process  response to stress  JNK cascade  JNK cascade  JUN phosphorylation  response to UV  positive regulation of gene expression  peptidyl-serine phosphorylation  peptidyl-threonine phosphorylation  peptidyl-threonine phosphorylation  regulation of histone deacetylation  negative regulation of protein binding  regulation of protein localization  toll-like receptor 2 signaling pathway  toll-like receptor 3 signaling pathway  toll-like receptor 4 signaling pathway  toll-like receptor 5 signaling pathway  toll-like receptor 9 signaling pathway  toll-like receptor 10 signaling pathway  histone deacetylase regulator activity  TRIF-dependent toll-like receptor signaling pathway  Fc-epsilon receptor signaling pathway  toll-like receptor TLR1:TLR2 signaling pathway  toll-like receptor TLR6:TLR2 signaling pathway  histone deacetylase binding  positive regulation of apoptotic process  negative regulation of apoptotic process  innate immune response  response to cadmium ion  neurotrophin TRK receptor signaling pathway  regulation of sequence-specific DNA binding transcription factor activity  stress-activated MAPK cascade  cellular response to mechanical stimulus  positive regulation of deacetylase activity  apoptotic signaling pathway  intrinsic apoptotic signaling pathway  positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway  positive regulation of determination of dorsal identity  positive regulation of apoptotic signaling pathway  
Ontology : EGO-EBIossification  toll-like receptor signaling pathway  MyD88-dependent toll-like receptor signaling pathway  MyD88-independent toll-like receptor signaling pathway  protein serine/threonine kinase activity  JUN kinase activity  protein binding  ATP binding  nucleus  nucleoplasm  mitochondrion  cytosol  apoptotic process  response to stress  JNK cascade  JNK cascade  JUN phosphorylation  response to UV  positive regulation of gene expression  peptidyl-serine phosphorylation  peptidyl-threonine phosphorylation  peptidyl-threonine phosphorylation  regulation of histone deacetylation  negative regulation of protein binding  regulation of protein localization  toll-like receptor 2 signaling pathway  toll-like receptor 3 signaling pathway  toll-like receptor 4 signaling pathway  toll-like receptor 5 signaling pathway  toll-like receptor 9 signaling pathway  toll-like receptor 10 signaling pathway  histone deacetylase regulator activity  TRIF-dependent toll-like receptor signaling pathway  Fc-epsilon receptor signaling pathway  toll-like receptor TLR1:TLR2 signaling pathway  toll-like receptor TLR6:TLR2 signaling pathway  histone deacetylase binding  positive regulation of apoptotic process  negative regulation of apoptotic process  innate immune response  response to cadmium ion  neurotrophin TRK receptor signaling pathway  regulation of sequence-specific DNA binding transcription factor activity  stress-activated MAPK cascade  cellular response to mechanical stimulus  positive regulation of deacetylase activity  apoptotic signaling pathway  intrinsic apoptotic signaling pathway  positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway  positive regulation of determination of dorsal identity  positive regulation of apoptotic signaling pathway  
Pathways : BIOCARTAOxidative Stress Induced Gene Expression Via Nrf2 [Genes]    Regulation of MAP Kinase Pathways Through Dual Specificity Phosphatases [Genes]    EPO Signaling Pathway [Genes]    Signal transduction through IL1R [Genes]    Insulin Signaling Pathway [Genes]    Keratinocyte Differentiation [Genes]    Role of MAL in Rho-Mediated Activation of SRF [Genes]    MAPKinase Signaling Pathway [Genes]    Toll-Like Receptor Pathway [Genes]    IL12 and Stat4 Dependent Signaling Pathway in Th1 Development [Genes]    Nerve growth factor pathway (NGF) [Genes]    Links between Pyk2 and Map Kinases [Genes]    Bone Remodelling [Genes]    TNFR1 Signaling Pathway [Genes]    The 4-1BB-dependent immune response [Genes]    ATM Signaling Pathway [Genes]    EGF Signaling Pathway [Genes]    FAS signaling pathway ( CD95 ) [Genes]    TACI and BCMA stimulation of B cell immune responses. [Genes]    T Cell Receptor Signaling Pathway [Genes]    Hypoxia and p53 in the Cardiovascular system [Genes]    Agrin in Postsynaptic Differentiation [Genes]    Ceramide Signaling Pathway [Genes]    Fc Epsilon Receptor I Signaling in Mast Cells [Genes]    Signaling of Hepatocyte Growth Factor Receptor [Genes]    NFAT and Hypertrophy of the heart (Transcription in the broken heart) [Genes]    PDGF Signaling Pathway [Genes]    Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling [Genes]    Pertussis toxin-insensitive CCR5 Signaling in Macrophage [Genes]    BCR Signaling Pathway [Genes]    IL 2 signaling pathway [Genes]    TNF/Stress Related Signaling [Genes]    HIV-I Nef: negative effector of Fas and TNF [Genes]    Bioactive Peptide Induced Signaling Pathway [Genes]    Inhibition of Cellular Proliferation by Gleevec [Genes]    IGF-1 Signaling Pathway [Genes]    Integrin Signaling Pathway [Genes]   
Pathways : KEGGMAPK signaling pathway    ErbB signaling pathway    Ras signaling pathway    FoxO signaling pathway    Protein processing in endoplasmic reticulum    Wnt signaling pathway    Osteoclast differentiation    Focal adhesion    Toll-like receptor signaling pathway    NOD-like receptor signaling pathway    RIG-I-like receptor signaling pathway    Fc epsilon RI signaling pathway    TNF signaling pathway    Neurotrophin signaling pathway    Retrograde endocannabinoid signaling    Dopaminergic synapse    Insulin signaling pathway    GnRH signaling pathway    Progesterone-mediated oocyte maturation    Prolactin signaling pathway    Adipocytokine signaling pathway    Type II diabetes mellitus    Non-alcoholic fatty liver disease (NAFLD)    Epithelial cell signaling in Helicobacter pylori infection    Shigellosis    Salmonella infection    Pertussis    Chagas disease (American trypanosomiasis)    Toxoplasmosis    Tuberculosis    Hepatitis C    Hepatitis B    Influenza A    HTLV-I infection    Herpes simplex infection    Epstein-Barr virus infection    Pathways in cancer    Colorectal cancer    Pancreatic cancer   
Protein Interaction DatabaseMAPK8
Wikipedia pathwaysMAPK8
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)MAPK8
snp3D : Map Gene to Disease5599
SNP (GeneSNP Utah)MAPK8
SNP : HGBaseMAPK8
Genetic variants : HAPMAPMAPK8
Exome VariantMAPK8
1000_GenomesMAPK8 
ICGC programENSG00000107643 
Somatic Mutations in Cancer : COSMICMAPK8 
CONAN: Copy Number AnalysisMAPK8 
Mutations and Diseases : HGMDMAPK8
Genomic VariantsMAPK8  MAPK8 [DGVbeta]
dbVarMAPK8
ClinVarMAPK8
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM601158   
MedgenMAPK8
GENETestsMAPK8
Disease Genetic AssociationMAPK8
Huge Navigator MAPK8 [HugePedia]  MAPK8 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneMAPK8
Homology/Alignments : Family Browser (UCSC)MAPK8
Phylogenetic Trees/Animal Genes : TreeFamMAPK8
Chemical/Protein Interactions : CTD5599
Chemical/Pharm GKB GenePA283
Clinical trialMAPK8
Cancer Resource (Charite)ENSG00000107643
Other databases
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineMAPK8
iHOPMAPK8

Bibliography

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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written01-2003Fei Chen

Citation

This paper should be referenced as such :
Chen, F
MAPK8 (mitogen-activated protein kinase 8)
Atlas Genet Cytogenet Oncol Haematol. 2003;7(2):88-89.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/JNK1ID196.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Jul 11 17:12:18 CEST 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.