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MAPK9 (mitogen-activated protein kinase 9)

Written2003-01Fei Chen
Health Effects Laboratory Division, NIOSH, 1095 Willowdale Rd, Morgantown, WV 26505, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesPRKM9
Alias_symbol (synonym)JNK2
p54a
SAPK
HGNC (Hugo) MAPK9
LocusID (NCBI) 5601
Atlas_Id 426
Location 5q35.3  [Link to chromosome band 5q35]
Location_base_pair Starts at 179673028 and ends at 179719071 bp from pter ( according to hg19-Feb_2009)  [Mapping MAPK9.png]
Fusion genes
(updated 2016)
MAPK9 (5q35.3) / ITPR1 (3p26.1)MAPK9 (5q35.3) / MAPK9 (5q35.3)MAPK9 (5q35.3) / S100A6 (1q21.3)
MAPK9 (5q35.3) / UBL7 (15q24.1)PRELID2 (5q32) / MAPK9 (5q35.3)RFTN1 (3p25.1) / MAPK9 (5q35.3)

DNA/RNA

Description The JNK2 gene maps on chromosome 5q35 spanning 58494bp. It contains 17 confirmed introns, 14 of which are alternative.
Transcription By alternative splicing, JNK2 gene encodes 12 types of transcripts that translate to 12 distinct JNK2 isoforms. The molecular weight of JNK2 is about 55 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

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

Bibliography

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
 
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
 
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
 
JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation.
Kallunki T, Su B, Tsigelny I, Sluss HK, Dérijard B, Moore G, Davis R, Karin M
Genes & development. 1994 ; 8 (24) : 2996-3007.
PMID 8001819
 
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
 
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
 
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
 
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
 

Citation

This paper should be referenced as such :
Chen, F
MAPK9 (mitogen-activated protein kinase 9)
Atlas Genet Cytogenet Oncol Haematol. 2003;7(2):90-91.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/JNK2ID426.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  dic(9;17)(p13;q11) PAX5/TAOK1


External links

Nomenclature
HGNC (Hugo)MAPK9   6886
Cards
AtlasJNK2ID426
Entrez_Gene (NCBI)MAPK9  5601  mitogen-activated protein kinase 9
AliasesJNK-55; JNK2; JNK2A; JNK2ALPHA; 
JNK2B; JNK2BETA; PRKM9; SAPK; SAPK1a; p54a; p54aSAPK
GeneCards (Weizmann)MAPK9
Ensembl hg19 (Hinxton)ENSG00000050748 [Gene_View]  chr5:179673028-179719071 [Contig_View]  MAPK9 [Vega]
Ensembl hg38 (Hinxton)ENSG00000050748 [Gene_View]  chr5:179673028-179719071 [Contig_View]  MAPK9 [Vega]
ICGC DataPortalENSG00000050748
TCGA cBioPortalMAPK9
AceView (NCBI)MAPK9
Genatlas (Paris)MAPK9
WikiGenes5601
SOURCE (Princeton)MAPK9
Genetics Home Reference (NIH)MAPK9
Genomic and cartography
GoldenPath hg19 (UCSC)MAPK9  -     chr5:179673028-179719071 -  5q35   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)MAPK9  -     5q35   [Description]    (hg38-Dec_2013)
EnsemblMAPK9 - 5q35 [CytoView hg19]  MAPK9 - 5q35 [CytoView hg38]
Mapping of homologs : NCBIMAPK9 [Mapview hg19]  MAPK9 [Mapview hg38]
OMIM602896   
Gene and transcription
Genbank (Entrez)AB451302 AB451355 AB451433 AK289638 BC032539
RefSeq transcript (Entrez)NM_001135044 NM_001308244 NM_002752 NM_139068 NM_139069 NM_139070
RefSeq genomic (Entrez)NC_000005 NC_018916 NG_029059 NT_023133 NW_004929325
Consensus coding sequences : CCDS (NCBI)MAPK9
Cluster EST : UnigeneHs.484371 [ NCBI ]
CGAP (NCI)Hs.484371
Alternative Splicing GalleryENSG00000050748
Gene ExpressionMAPK9 [ NCBI-GEO ]   MAPK9 [ EBI - ARRAY_EXPRESS ]   MAPK9 [ SEEK ]   MAPK9 [ MEM ]
Gene Expression Viewer (FireBrowse)MAPK9 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5601
GTEX Portal (Tissue expression)MAPK9
Protein : pattern, domain, 3D structure
UniProt/SwissProtP45984   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP45984  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP45984
Splice isoforms : SwissVarP45984
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 ]   
PhosPhoSitePlusP45984
Domaine pattern : Prosite (Expaxy)MAPK (PS01351)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (EBI)Kinase-like_dom    MAP_kinase_CS    MAPK_JNK    Prot_kinase_dom    Ser/Thr_dual-sp_kinase    Ser/Thr_kinase_AS   
Domain families : Pfam (Sanger)Pkinase (PF00069)   
Domain families : Pfam (NCBI)pfam00069   
Domain families : Smart (EMBL)S_TKc (SM00220)  
Conserved Domain (NCBI)MAPK9
DMDM Disease mutations5601
Blocks (Seattle)MAPK9
PDB (SRS)3E7O    3NPC   
PDB (PDBSum)3E7O    3NPC   
PDB (IMB)3E7O    3NPC   
PDB (RSDB)3E7O    3NPC   
Structural Biology KnowledgeBase3E7O    3NPC   
SCOP (Structural Classification of Proteins)3E7O    3NPC   
CATH (Classification of proteins structures)3E7O    3NPC   
SuperfamilyP45984
Human Protein AtlasENSG00000050748
Peptide AtlasP45984
HPRD04206
IPIIPI00024673   IPI00220382   IPI00220383   IPI00303550   IPI00969365   IPI00913982   IPI00973093   IPI00973153   IPI00980971   
Protein Interaction databases
DIP (DOE-UCLA)P45984
IntAct (EBI)P45984
FunCoupENSG00000050748
BioGRIDMAPK9
STRING (EMBL)MAPK9
ZODIACMAPK9
Ontologies - Pathways
QuickGOP45984
Ontology : AmiGOrelease of cytochrome c from mitochondria  positive regulation of protein phosphorylation  JUN kinase activity  protein binding  ATP binding  nucleoplasm  mitochondrion  cytosol  protein phosphorylation  protein targeting to mitochondrion  activation of cysteine-type endopeptidase activity involved in apoptotic process  response to stress  JNK cascade  JNK cascade  JUN phosphorylation  central nervous system development  transcription factor binding  cysteine-type endopeptidase activator activity involved in apoptotic process  response to mechanical stimulus  response to toxic substance  positive regulation of gene expression  positive regulation of macrophage derived foam cell differentiation  positive regulation of cell morphogenesis involved in differentiation  response to amine  neuron projection development  positive regulation of prostaglandin biosynthetic process  regulation of protein ubiquitination  mitogen-activated protein kinase kinase kinase binding  positive regulation of prostaglandin secretion  positive regulation of chemokine production  cellular response to UV  Fc-epsilon receptor signaling pathway  response to drug  regulation of circadian rhythm  positive regulation of nitric oxide biosynthetic process  positive regulation of transcription, DNA-templated  regulation of JNK cascade  response to cadmium ion  rhythmic process  regulation of sequence-specific DNA binding transcription factor activity  positive regulation of nitric-oxide synthase biosynthetic process  cellular response to lipopolysaccharide  cellular response to interleukin-1  cellular response to tumor necrosis factor  cellular response to growth factor stimulus  positive regulation of podosome assembly  positive regulation of apoptotic signaling pathway  
Ontology : EGO-EBIrelease of cytochrome c from mitochondria  positive regulation of protein phosphorylation  JUN kinase activity  protein binding  ATP binding  nucleoplasm  mitochondrion  cytosol  protein phosphorylation  protein targeting to mitochondrion  activation of cysteine-type endopeptidase activity involved in apoptotic process  response to stress  JNK cascade  JNK cascade  JUN phosphorylation  central nervous system development  transcription factor binding  cysteine-type endopeptidase activator activity involved in apoptotic process  response to mechanical stimulus  response to toxic substance  positive regulation of gene expression  positive regulation of macrophage derived foam cell differentiation  positive regulation of cell morphogenesis involved in differentiation  response to amine  neuron projection development  positive regulation of prostaglandin biosynthetic process  regulation of protein ubiquitination  mitogen-activated protein kinase kinase kinase binding  positive regulation of prostaglandin secretion  positive regulation of chemokine production  cellular response to UV  Fc-epsilon receptor signaling pathway  response to drug  regulation of circadian rhythm  positive regulation of nitric oxide biosynthetic process  positive regulation of transcription, DNA-templated  regulation of JNK cascade  response to cadmium ion  rhythmic process  regulation of sequence-specific DNA binding transcription factor activity  positive regulation of nitric-oxide synthase biosynthetic process  cellular response to lipopolysaccharide  cellular response to interleukin-1  cellular response to tumor necrosis factor  cellular response to growth factor stimulus  positive regulation of podosome assembly  positive regulation of apoptotic signaling pathway  
Pathways : BIOCARTAMAPKinase 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    T cell 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    Herpes simplex infection    Epstein-Barr virus infection    Pathways in cancer    Colorectal cancer    Pancreatic cancer   
REACTOMEP45984 [protein]
REACTOME PathwaysR-HSA-450341 Activation of the AP-1 family of transcription factors [pathway]
REACTOME PathwaysR-HSA-2559580 Oxidative Stress Induced Senescence [pathway]
REACTOME PathwaysR-HSA-2871796 FCERI mediated MAPK activation [pathway]
REACTOME PathwaysR-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 [pathway]
NDEx NetworkMAPK9
Atlas of Cancer Signalling NetworkMAPK9
Wikipedia pathwaysMAPK9
Orthology - Evolution
OrthoDB5601
GeneTree (enSembl)ENSG00000050748
Phylogenetic Trees/Animal Genes : TreeFamMAPK9
HOVERGENP45984
HOGENOMP45984
Homologs : HomoloGeneMAPK9
Homology/Alignments : Family Browser (UCSC)MAPK9
Gene fusions - Rearrangements
Fusion : MitelmanMAPK9/UBL7 [5q35.3/15q24.1]  
Fusion : MitelmanPRELID2/MAPK9 [5q32/5q35.3]  [t(5;5)(q32;q35)]  
Fusion: TCGAMAPK9 5q35.3 UBL7 15q24.1 OV
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMAPK9 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MAPK9
dbVarMAPK9
ClinVarMAPK9
1000_GenomesMAPK9 
Exome Variant ServerMAPK9
ExAC (Exome Aggregation Consortium)MAPK9 (select the gene name)
Genetic variants : HAPMAP5601
Genomic Variants (DGV)MAPK9 [DGVbeta]
DECIPHER (Syndromes)5:179673028-179719071  ENSG00000050748
CONAN: Copy Number AnalysisMAPK9 
Mutations
ICGC Data PortalMAPK9 
TCGA Data PortalMAPK9 
Broad Tumor PortalMAPK9
OASIS PortalMAPK9 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMAPK9  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDMAPK9
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MAPK9
DgiDB (Drug Gene Interaction Database)MAPK9
DoCM (Curated mutations)MAPK9 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MAPK9 (select a term)
intoGenMAPK9
NCG5 (London)MAPK9
Cancer3DMAPK9(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602896   
Orphanet
MedgenMAPK9
Genetic Testing Registry MAPK9
NextProtP45984 [Medical]
TSGene5601
GENETestsMAPK9
Huge Navigator MAPK9 [HugePedia]
snp3D : Map Gene to Disease5601
BioCentury BCIQMAPK9
ClinGenMAPK9
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5601
Chemical/Pharm GKB GenePA30630
Clinical trialMAPK9
Miscellaneous
canSAR (ICR)MAPK9 (select the gene name)
Probes
Litterature
PubMed216 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMAPK9
EVEXMAPK9
GoPubMedMAPK9
iHOPMAPK9
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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