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MAPK10 (mitogen-activated protein kinase 10)

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

(Note : for Links provided by Atlas : click)

Identity

Alias_namesPRKM10
Alias_symbol (synonym)JNK3
p493F12
p54bSAPK
Other aliasJNK3 (C-Jun N-terminal kinase 3)
Stress-activated protein kinase 3 (SAPK3)
HGNC (Hugo) MAPK10
LocusID (NCBI) 5602
Atlas_Id 427
Location 4q21.3  [Link to chromosome band 4q21]
Location_base_pair Starts at 86012296 and ends at 86354644 bp from pter ( according to hg19-Feb_2009)  [Mapping MAPK10.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
MAPK10 (4q21.3) / CCSER1 (4q22.1)MAPK10 (4q21.3) / COL1A2 (7q21.3)MAPK10 (4q21.3) / FAM13A (4q22.1)
MAPK10 (4q21.3) / INPP4B (4q31.21)MAPK10 (4q21.3) / NUP188 (9q34.11)MAPK10 (4q21.3) / UGT8 (4q26)

DNA/RNA

Description The JNK3 gene maps on chromosome 4q22.1-q23 spanning 143716bp. It contains 19 confirmed introns, 16 of which are alternative.
Transcription Through alternative splicing, 7 types of transcripts are generated which produce 7 distinct JNK3 proteins. Due to the alternative splicing, the molecular weight of JNK3 varied from 45 to 57 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 JNK3 is mainly expressed in nervous system, heart and testis.
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.
Oncogenesis Loss of expression of JNK3 has been found in some brain tumors.
  

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
 
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
 
The c-Jun NH2-terminal kinase3 (JNK3) gene: genomic structure, chromosomal assignment, and loss of expression in brain tumors.
Yoshida S, Fukino K, Harada H, Nagai H, Imoto I, Inazawa J, Takahashi H, Teramoto A, Emi M
Journal of human genetics. 2001 ; 46 (4) : 182-187.
PMID 11322657
 

Citation

This paper should be referenced as such :
Chen, F
MAPK10 (mitogen-activated protein kinase 10)
Atlas Genet Cytogenet Oncol Haematol. 2003;7(2):92-93.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/JNK3ID427.html


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


External links

Nomenclature
HGNC (Hugo)MAPK10   6872
Cards
AtlasJNK3ID427
Entrez_Gene (NCBI)MAPK10  5602  mitogen-activated protein kinase 10
AliasesJNK3; JNK3A; PRKM10; SAPK1b; 
p493F12; p54bSAPK
GeneCards (Weizmann)MAPK10
Ensembl hg19 (Hinxton)ENSG00000109339 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000109339 [Gene_View]  chr4:86012296-86354644 [Contig_View]  MAPK10 [Vega]
ICGC DataPortalENSG00000109339
TCGA cBioPortalMAPK10
AceView (NCBI)MAPK10
Genatlas (Paris)MAPK10
WikiGenes5602
SOURCE (Princeton)MAPK10
Genetics Home Reference (NIH)MAPK10
Genomic and cartography
GoldenPath hg38 (UCSC)MAPK10  -     chr4:86012296-86354644 -  4q21.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MAPK10  -     4q21.3   [Description]    (hg19-Feb_2009)
EnsemblMAPK10 - 4q21.3 [CytoView hg19]  MAPK10 - 4q21.3 [CytoView hg38]
Mapping of homologs : NCBIMAPK10 [Mapview hg19]  MAPK10 [Mapview hg38]
OMIM602897   
Gene and transcription
Genbank (Entrez)AF052141 AK022161 AK057723 AK091104 AK124791
RefSeq transcript (Entrez)NM_001318067 NM_001318068 NM_001318069 NM_002753 NM_138980 NM_138981 NM_138982
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)MAPK10
Cluster EST : UnigeneHs.125503 [ NCBI ]
CGAP (NCI)Hs.125503
Alternative Splicing GalleryENSG00000109339
Gene ExpressionMAPK10 [ NCBI-GEO ]   MAPK10 [ EBI - ARRAY_EXPRESS ]   MAPK10 [ SEEK ]   MAPK10 [ MEM ]
Gene Expression Viewer (FireBrowse)MAPK10 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5602
GTEX Portal (Tissue expression)MAPK10
Human Protein AtlasENSG00000109339-MAPK10 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP53779   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP53779  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP53779
Splice isoforms : SwissVarP53779
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 ]   
PhosPhoSitePlusP53779
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_kinase_AS   
Domain families : Pfam (Sanger)Pkinase (PF00069)   
Domain families : Pfam (NCBI)pfam00069   
Domain families : Smart (EMBL)S_TKc (SM00220)  
Conserved Domain (NCBI)MAPK10
DMDM Disease mutations5602
Blocks (Seattle)MAPK10
PDB (SRS)1JNK    1PMN    1PMU    1PMV    2B1P    2EXC    2O0U    2O2U    2OK1    2P33    2R9S    2WAJ    2ZDT    2ZDU    3CGF    3CGO    3DA6    3FI2    3FI3    3FV8    3G90    3G9L    3G9N    3KVX    3OXI    3OY1    3PTG    3RTP    3TTI    3TTJ    3V6R    3V6S    4H36    4H39    4H3B    4KKE    4KKG    4KKH    4U79    4W4V    4W4W    4W4X    4W4Y    4WHZ    4X21    4Y46    4Y5H    4Z9L   
PDB (PDBSum)1JNK    1PMN    1PMU    1PMV    2B1P    2EXC    2O0U    2O2U    2OK1    2P33    2R9S    2WAJ    2ZDT    2ZDU    3CGF    3CGO    3DA6    3FI2    3FI3    3FV8    3G90    3G9L    3G9N    3KVX    3OXI    3OY1    3PTG    3RTP    3TTI    3TTJ    3V6R    3V6S    4H36    4H39    4H3B    4KKE    4KKG    4KKH    4U79    4W4V    4W4W    4W4X    4W4Y    4WHZ    4X21    4Y46    4Y5H    4Z9L   
PDB (IMB)1JNK    1PMN    1PMU    1PMV    2B1P    2EXC    2O0U    2O2U    2OK1    2P33    2R9S    2WAJ    2ZDT    2ZDU    3CGF    3CGO    3DA6    3FI2    3FI3    3FV8    3G90    3G9L    3G9N    3KVX    3OXI    3OY1    3PTG    3RTP    3TTI    3TTJ    3V6R    3V6S    4H36    4H39    4H3B    4KKE    4KKG    4KKH    4U79    4W4V    4W4W    4W4X    4W4Y    4WHZ    4X21    4Y46    4Y5H    4Z9L   
PDB (RSDB)1JNK    1PMN    1PMU    1PMV    2B1P    2EXC    2O0U    2O2U    2OK1    2P33    2R9S    2WAJ    2ZDT    2ZDU    3CGF    3CGO    3DA6    3FI2    3FI3    3FV8    3G90    3G9L    3G9N    3KVX    3OXI    3OY1    3PTG    3RTP    3TTI    3TTJ    3V6R    3V6S    4H36    4H39    4H3B    4KKE    4KKG    4KKH    4U79    4W4V    4W4W    4W4X    4W4Y    4WHZ    4X21    4Y46    4Y5H    4Z9L   
Structural Biology KnowledgeBase1JNK    1PMN    1PMU    1PMV    2B1P    2EXC    2O0U    2O2U    2OK1    2P33    2R9S    2WAJ    2ZDT    2ZDU    3CGF    3CGO    3DA6    3FI2    3FI3    3FV8    3G90    3G9L    3G9N    3KVX    3OXI    3OY1    3PTG    3RTP    3TTI    3TTJ    3V6R    3V6S    4H36    4H39    4H3B    4KKE    4KKG    4KKH    4U79    4W4V    4W4W    4W4X    4W4Y    4WHZ    4X21    4Y46    4Y5H    4Z9L   
SCOP (Structural Classification of Proteins)1JNK    1PMN    1PMU    1PMV    2B1P    2EXC    2O0U    2O2U    2OK1    2P33    2R9S    2WAJ    2ZDT    2ZDU    3CGF    3CGO    3DA6    3FI2    3FI3    3FV8    3G90    3G9L    3G9N    3KVX    3OXI    3OY1    3PTG    3RTP    3TTI    3TTJ    3V6R    3V6S    4H36    4H39    4H3B    4KKE    4KKG    4KKH    4U79    4W4V    4W4W    4W4X    4W4Y    4WHZ    4X21    4Y46    4Y5H    4Z9L   
CATH (Classification of proteins structures)1JNK    1PMN    1PMU    1PMV    2B1P    2EXC    2O0U    2O2U    2OK1    2P33    2R9S    2WAJ    2ZDT    2ZDU    3CGF    3CGO    3DA6    3FI2    3FI3    3FV8    3G90    3G9L    3G9N    3KVX    3OXI    3OY1    3PTG    3RTP    3TTI    3TTJ    3V6R    3V6S    4H36    4H39    4H3B    4KKE    4KKG    4KKH    4U79    4W4V    4W4W    4W4X    4W4Y    4WHZ    4X21    4Y46    4Y5H    4Z9L   
SuperfamilyP53779
Human Protein Atlas [tissue]ENSG00000109339-MAPK10 [tissue]
Peptide AtlasP53779
HPRD04207
IPIIPI00023547   IPI00003148   IPI00873275   IPI00985141   IPI00376687   IPI00795397   IPI00148567   IPI01014824   IPI00967705   IPI00963857   IPI00967472   IPI00968205   IPI00965895   IPI00967368   IPI00964167   IPI00967780   IPI00964615   IPI00964932   
Protein Interaction databases
DIP (DOE-UCLA)P53779
IntAct (EBI)P53779
FunCoupENSG00000109339
BioGRIDMAPK10
STRING (EMBL)MAPK10
ZODIACMAPK10
Ontologies - Pathways
QuickGOP53779
Ontology : AmiGOactivation of MAPK activity  JUN kinase activity  JUN kinase activity  MAP kinase kinase activity  protein binding  ATP binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  cytoplasm  mitochondrion  cytosol  plasma membrane  protein phosphorylation  protein phosphorylation  signal transduction  JNK cascade  JNK cascade  JNK cascade  JUN phosphorylation  response to light stimulus  regulation of gene expression  Fc-epsilon receptor signaling pathway  regulation of circadian rhythm  neuron projection  rhythmic process  neuron development  regulation of sequence-specific DNA binding transcription factor activity  
Ontology : EGO-EBIactivation of MAPK activity  JUN kinase activity  JUN kinase activity  MAP kinase kinase activity  protein binding  ATP binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  cytoplasm  mitochondrion  cytosol  plasma membrane  protein phosphorylation  protein phosphorylation  signal transduction  JNK cascade  JNK cascade  JNK cascade  JUN phosphorylation  response to light stimulus  regulation of gene expression  Fc-epsilon receptor signaling pathway  regulation of circadian rhythm  neuron projection  rhythmic process  neuron development  regulation of sequence-specific DNA binding transcription factor activity  
Pathways : BIOCARTAMAPKinase Signaling Pathway [Genes]   
Pathways : KEGG   
REACTOMEP53779 [protein]
REACTOME PathwaysR-HSA-450341 [pathway]   
NDEx NetworkMAPK10
Atlas of Cancer Signalling NetworkMAPK10
Wikipedia pathwaysMAPK10
Orthology - Evolution
OrthoDB5602
GeneTree (enSembl)ENSG00000109339
Phylogenetic Trees/Animal Genes : TreeFamMAPK10
HOVERGENP53779
HOGENOMP53779
Homologs : HomoloGeneMAPK10
Homology/Alignments : Family Browser (UCSC)MAPK10
Gene fusions - Rearrangements
Fusion : MitelmanMAPK10/CCSER1 [4q21.3/4q22.1]  
Fusion : MitelmanMAPK10/FAM13A [4q21.3/4q22.1]  [t(4;4)(q21;q22)]  
Fusion : MitelmanMAPK10/UGT8 [4q21.3/4q26]  [t(4;4)(q21;q26)]  
Fusion: TCGAMAPK10 4q21.3 FAM13A 4q22.1 PRAD
Fusion: TCGAMAPK10 4q21.3 FAM190A HNSC
Fusion: TCGAMAPK10 4q21.3 UGT8 4q26 LUSC
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMAPK10 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MAPK10
dbVarMAPK10
ClinVarMAPK10
1000_GenomesMAPK10 
Exome Variant ServerMAPK10
ExAC (Exome Aggregation Consortium)ENSG00000109339
GNOMAD BrowserENSG00000109339
Genetic variants : HAPMAP5602
Genomic Variants (DGV)MAPK10 [DGVbeta]
DECIPHERMAPK10 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMAPK10 
Mutations
ICGC Data PortalMAPK10 
TCGA Data PortalMAPK10 
Broad Tumor PortalMAPK10
OASIS PortalMAPK10 [ Somatic mutations - Copy number]
Mutations and Diseases : HGMDMAPK10
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Mendelian genes
BioMutasearch MAPK10
DgiDB (Drug Gene Interaction Database)MAPK10
DoCM (Curated mutations)MAPK10 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MAPK10 (select a term)
intoGenMAPK10
NCG5 (London)MAPK10
Cancer3DMAPK10(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602897   
Orphanet885   
MedgenMAPK10
Genetic Testing Registry MAPK10
NextProtP53779 [Medical]
TSGene5602
GENETestsMAPK10
Target ValidationMAPK10
Huge Navigator MAPK10 [HugePedia]
snp3D : Map Gene to Disease5602
BioCentury BCIQMAPK10
ClinGenMAPK10
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5602
Chemical/Pharm GKB GenePA30617
Clinical trialMAPK10
Miscellaneous
canSAR (ICR)MAPK10 (select the gene name)
Probes
Litterature
PubMed99 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMAPK10
EVEXMAPK10
GoPubMedMAPK10
iHOPMAPK10
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 12 16:25:17 CEST 2017

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