MAPK10 (mitogen-activated protein kinase 10)

2003-01-01   Fei Chen 

Health Effects Laboratory Division, NIOSH, 1095 Willowdale Rd, Morgantown, WV 26505, USA

Identity

HGNC
LOCATION
4q21.3
LOCUSID
ALIAS
JNK3,JNK3A,PRKM10,SAPK1b,p493F12,p54bSAPK
FUSION GENES

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.

Proteins

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

Entity name
Obesity, insulin resistance, neurodegenerative diseases, inflammation, cancer.
Oncogenesis
Loss of expression of JNK3 has been found in some brain tumors.

Bibliography

Pubmed IDLast YearTitleAuthors
110578972000Signal transduction by the JNK group of MAP kinases.Davis RJ et al
117135302001Induction of gadd45beta by NF-kappaB downregulates pro-apoptotic JNK signalling.De Smaele E et al
97106251998Stress-induced Fas ligand expression in T cells is mediated through a MEK kinase 1-regulated response element in the Fas ligand promoter.Faris M et al
97322641998JNK targets p53 ubiquitination and degradation in nonstressed cells.Fuchs SY et al
99256411999Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase.Jacobs D et al
114472972001Ubiquitin-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 et al
98278041998A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK.Takekawa M et al
117135312001Inhibition of JNK activation through NF-kappaB target genes.Tang G et al
92156291997Daxx, a novel Fas-binding protein that activates JNK and apoptosis.Yang X et al
113226572001The c-Jun NH2-terminal kinase3 (JNK3) gene: genomic structure, chromosomal assignment, and loss of expression in brain tumors.Yoshida S et al

Other Information

Locus ID:

NCBI: 5602
MIM: 602897
HGNC: 6872
Ensembl: ENSG00000109339

Variants:

dbSNP: 5602
ClinVar: 5602
TCGA: ENSG00000109339
COSMIC: MAPK10

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000109339ENST00000310816A8MPV1
ENSG00000109339ENST00000359221D6RJF9
ENSG00000109339ENST00000361569A0A286YEX7
ENSG00000109339ENST00000395157P53779
ENSG00000109339ENST00000395160A0A1P0B7D2
ENSG00000109339ENST00000395166P53779
ENSG00000109339ENST00000395169A0A1P0B7D2
ENSG00000109339ENST00000449047Q499Y8
ENSG00000109339ENST00000472236A0A1W2PPZ3
ENSG00000109339ENST00000479377A0A1W2PRF2
ENSG00000109339ENST00000502302D6RC26
ENSG00000109339ENST00000503911D6RFX8
ENSG00000109339ENST00000509464D6RBH2
ENSG00000109339ENST00000511167D6RCB1
ENSG00000109339ENST00000511328D6RAJ0
ENSG00000109339ENST00000512017D6RAU3
ENSG00000109339ENST00000512046A0A1W2PRZ2
ENSG00000109339ENST00000512564D6R9C1
ENSG00000109339ENST00000512689D6RJF9
ENSG00000109339ENST00000513186D6RDG1
ENSG00000109339ENST00000513839A0A1W2PQX4
ENSG00000109339ENST00000515400P53779
ENSG00000109339ENST00000515650P53779
ENSG00000109339ENST00000564854A0A1W2PQX4
ENSG00000109339ENST00000638225P53779
ENSG00000109339ENST00000638313P53779
ENSG00000109339ENST00000638499A0A1W2PPW1
ENSG00000109339ENST00000638867A0A1W2PNF5
ENSG00000109339ENST00000638946A0A1W2PRG9
ENSG00000109339ENST00000639175P53779
ENSG00000109339ENST00000639234P53779
ENSG00000109339ENST00000639242P53779
ENSG00000109339ENST00000639972D6RJF9
ENSG00000109339ENST00000639989A0A1W2PQ03
ENSG00000109339ENST00000640064A0A1W2PPM4
ENSG00000109339ENST00000640445A0A1W2PPM4
ENSG00000109339ENST00000640490D6RJF9
ENSG00000109339ENST00000640527D6RFZ7
ENSG00000109339ENST00000640858P53779
ENSG00000109339ENST00000640970P53779
ENSG00000109339ENST00000641010A0A286YF62
ENSG00000109339ENST00000641016A0A286YF04
ENSG00000109339ENST00000641020A0A286YFB6
ENSG00000109339ENST00000641032A0A286YFA3
ENSG00000109339ENST00000641041A0A1W2PQX4
ENSG00000109339ENST00000641047A0A286YF02
ENSG00000109339ENST00000641050P53779
ENSG00000109339ENST00000641051P53779
ENSG00000109339ENST00000641052A0A286YFM6
ENSG00000109339ENST00000641061A0A286YFA7
ENSG00000109339ENST00000641066P53779
ENSG00000109339ENST00000641072A0A286YFC0
ENSG00000109339ENST00000641102A0A286YEW9
ENSG00000109339ENST00000641110P53779
ENSG00000109339ENST00000641116A0A286YEV5
ENSG00000109339ENST00000641120A0A286YEQ0
ENSG00000109339ENST00000641148A0A286YEW4
ENSG00000109339ENST00000641157P53779
ENSG00000109339ENST00000641166A0A286YFD7
ENSG00000109339ENST00000641170P53779
ENSG00000109339ENST00000641203A0A1W2PQX4
ENSG00000109339ENST00000641207P53779
ENSG00000109339ENST00000641208A0A286YEQ0
ENSG00000109339ENST00000641217A0A286YES0
ENSG00000109339ENST00000641221A0A1W2PPM4
ENSG00000109339ENST00000641227A0A286YEY2
ENSG00000109339ENST00000641237D6RJF9
ENSG00000109339ENST00000641253A0A1W2PPM4
ENSG00000109339ENST00000641265A0A286YF83
ENSG00000109339ENST00000641274P53779
ENSG00000109339ENST00000641283P53779
ENSG00000109339ENST00000641287P53779
ENSG00000109339ENST00000641297P53779
ENSG00000109339ENST00000641306A0A1W2PPM4
ENSG00000109339ENST00000641313D6RJF9
ENSG00000109339ENST00000641317A0A1W2PPW1
ENSG00000109339ENST00000641324A0A286YEN5
ENSG00000109339ENST00000641341P53779
ENSG00000109339ENST00000641358A0A286YFC3
ENSG00000109339ENST00000641379A8MPV1
ENSG00000109339ENST00000641384A0A286YEQ7
ENSG00000109339ENST00000641385A0A1W2PPM4
ENSG00000109339ENST00000641391P53779
ENSG00000109339ENST00000641405A0A286YEX7
ENSG00000109339ENST00000641408A0A286YF80
ENSG00000109339ENST00000641410P53779
ENSG00000109339ENST00000641430D6RJF9
ENSG00000109339ENST00000641435A0A1W2PQX4
ENSG00000109339ENST00000641452A0A286YFB7
ENSG00000109339ENST00000641459A0A286YFA6
ENSG00000109339ENST00000641462P53779
ENSG00000109339ENST00000641467A0A286YFB7
ENSG00000109339ENST00000641485A0A286YFJ6
ENSG00000109339ENST00000641493A0A286YEX7
ENSG00000109339ENST00000641531A0A286YFB7
ENSG00000109339ENST00000641537D6RJF9
ENSG00000109339ENST00000641553A0A286YF97
ENSG00000109339ENST00000641555D6RJF9
ENSG00000109339ENST00000641595A0A1W2PPM4
ENSG00000109339ENST00000641607A0A286YES0
ENSG00000109339ENST00000641609A0A1W2PQX4
ENSG00000109339ENST00000641629A0A286YF95
ENSG00000109339ENST00000641634A0A1W2PQX4
ENSG00000109339ENST00000641647P53779
ENSG00000109339ENST00000641653A0A1W2PQX4
ENSG00000109339ENST00000641656A0A286YFD9
ENSG00000109339ENST00000641657P53779
ENSG00000109339ENST00000641675A0A286YFJ0
ENSG00000109339ENST00000641677A0A286YFJ4
ENSG00000109339ENST00000641718A0A286YF97
ENSG00000109339ENST00000641724P53779
ENSG00000109339ENST00000641737P53779
ENSG00000109339ENST00000641762A0A286YEX7
ENSG00000109339ENST00000641767D6RJF9
ENSG00000109339ENST00000641777A0A286YF53
ENSG00000109339ENST00000641782A0A286YEZ1
ENSG00000109339ENST00000641798A0A1W2PQX4
ENSG00000109339ENST00000641803P53779
ENSG00000109339ENST00000641823P53779
ENSG00000109339ENST00000641826A0A286YFK3
ENSG00000109339ENST00000641831A0A286YF97
ENSG00000109339ENST00000641854A0A1W2PPW1
ENSG00000109339ENST00000641855A0A286YFH4
ENSG00000109339ENST00000641858A0A286YES8
ENSG00000109339ENST00000641862P53779
ENSG00000109339ENST00000641864A0A286YFI3
ENSG00000109339ENST00000641873A0A286YEV3
ENSG00000109339ENST00000641881A0A286YEV8
ENSG00000109339ENST00000641902P53779
ENSG00000109339ENST00000641903A0A286YES9
ENSG00000109339ENST00000641911P53779
ENSG00000109339ENST00000641917A0A286YF35
ENSG00000109339ENST00000641943P53779
ENSG00000109339ENST00000641952P53779
ENSG00000109339ENST00000641954A0A286YF85
ENSG00000109339ENST00000641983P53779
ENSG00000109339ENST00000641989D6RJF9
ENSG00000109339ENST00000641997A0A286YEY0
ENSG00000109339ENST00000642006A0A286YF02
ENSG00000109339ENST00000642009P53779
ENSG00000109339ENST00000642013A0A286YF19
ENSG00000109339ENST00000642015P53779
ENSG00000109339ENST00000642019A0A286YFE2
ENSG00000109339ENST00000642023A0A286YFN2
ENSG00000109339ENST00000642032D6RJF9
ENSG00000109339ENST00000642035A8MPV1
ENSG00000109339ENST00000642038P53779
ENSG00000109339ENST00000642048A0A286YF43
ENSG00000109339ENST00000642060A0A1W2PQX4
ENSG00000109339ENST00000642081A0A286YFE9
ENSG00000109339ENST00000642103P53779

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45

Pathways

PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
ErbB signaling pathwayKEGGko04012
Autophagy - animalKEGGko04140
ApoptosisKEGGko04210
Wnt signaling pathwayKEGGko04310
Focal adhesionKEGGko04510
Tight junctionKEGGko04530
Toll-like receptor signaling pathwayKEGGko04620
Fc epsilon RI signaling pathwayKEGGko04664
Insulin signaling pathwayKEGGko04910
GnRH signaling pathwayKEGGko04912
Progesterone-mediated oocyte maturationKEGGko04914
Adipocytokine signaling pathwayKEGGko04920
Type II diabetes mellitusKEGGko04930
Epithelial cell signaling in Helicobacter pylori infectionKEGGko05120
Colorectal cancerKEGGko05210
Pancreatic cancerKEGGko05212
MAPK signaling pathwayKEGGhsa04010
ErbB signaling pathwayKEGGhsa04012
Autophagy - animalKEGGhsa04140
ApoptosisKEGGhsa04210
Wnt signaling pathwayKEGGhsa04310
Focal adhesionKEGGhsa04510
Tight junctionKEGGhsa04530
Toll-like receptor signaling pathwayKEGGhsa04620
Fc epsilon RI signaling pathwayKEGGhsa04664
Insulin signaling pathwayKEGGhsa04910
GnRH signaling pathwayKEGGhsa04912
Adipocytokine signaling pathwayKEGGhsa04920
Type II diabetes mellitusKEGGhsa04930
Epithelial cell signaling in Helicobacter pylori infectionKEGGhsa05120
ShigellosisKEGGhsa05131
Pathways in cancerKEGGhsa05200
Colorectal cancerKEGGhsa05210
Pancreatic cancerKEGGhsa05212
Neurotrophin signaling pathwayKEGGko04722
Neurotrophin signaling pathwayKEGGhsa04722
RIG-I-like receptor signaling pathwayKEGGko04622
RIG-I-like receptor signaling pathwayKEGGhsa04622
Progesterone-mediated oocyte maturationKEGGhsa04914
NOD-like receptor signaling pathwayKEGGko04621
NOD-like receptor signaling pathwayKEGGhsa04621
Chagas disease (American trypanosomiasis)KEGGko05142
Chagas disease (American trypanosomiasis)KEGGhsa05142
Protein processing in endoplasmic reticulumKEGGko04141
Protein processing in endoplasmic reticulumKEGGhsa04141
ToxoplasmosisKEGGko05145
ToxoplasmosisKEGGhsa05145
Hepatitis CKEGGko05160
Hepatitis CKEGGhsa05160
Osteoclast differentiationKEGGko04380
Osteoclast differentiationKEGGhsa04380
TuberculosisKEGGko05152
TuberculosisKEGGhsa05152
Influenza AKEGGko05164
Influenza AKEGGhsa05164
PertussisKEGGko05133
PertussisKEGGhsa05133
Salmonella infectionKEGGko05132
Salmonella infectionKEGGhsa05132
Herpes simplex infectionKEGGko05168
Herpes simplex infectionKEGGhsa05168
Dopaminergic synapseKEGGko04728
Dopaminergic synapseKEGGhsa04728
Retrograde endocannabinoid signalingKEGGhsa04723
Retrograde endocannabinoid signalingKEGGko04723
Epstein-Barr virus infectionKEGGhsa05169
Epstein-Barr virus infectionKEGGko05169
Hepatitis BKEGGhsa05161
TNF signaling pathwayKEGGhsa04668
TNF signaling pathwayKEGGko04668
Prolactin signaling pathwayKEGGhsa04917
Prolactin signaling pathwayKEGGko04917
Non-alcoholic fatty liver disease (NAFLD)KEGGhsa04932
Non-alcoholic fatty liver disease (NAFLD)KEGGko04932
Ras signaling pathwayKEGGhsa04014
FoxO signaling pathwayKEGGhsa04068
Inflammatory mediator regulation of TRP channelsKEGGhsa04750
Inflammatory mediator regulation of TRP channelsKEGGko04750
cAMP signaling pathwayKEGGhsa04024
cAMP signaling pathwayKEGGko04024
Choline metabolism in cancerKEGGhsa05231
Choline metabolism in cancerKEGGko05231
MAPK (JNK) signalingKEGGhsa_M00688
MAPK (JNK) signalingKEGGM00688
Sphingolipid signaling pathwayKEGGhsa04071
Sphingolipid signaling pathwayKEGGko04071
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Toll-Like Receptors CascadesREACTOMER-HSA-168898
Toll Like Receptor 10 (TLR10) CascadeREACTOMER-HSA-168142
MyD88 cascade initiated on plasma membraneREACTOMER-HSA-975871
MAP kinase activation in TLR cascadeREACTOMER-HSA-450294
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1REACTOMER-HSA-450321
MAPK targets/ Nuclear events mediated by MAP kinasesREACTOMER-HSA-450282
Activation of the AP-1 family of transcription factorsREACTOMER-HSA-450341
Toll Like Receptor 3 (TLR3) CascadeREACTOMER-HSA-168164
MyD88-independent TLR3/TLR4 cascadeREACTOMER-HSA-166166
TRIF-mediated TLR3/TLR4 signalingREACTOMER-HSA-937061
Toll Like Receptor 5 (TLR5) CascadeREACTOMER-HSA-168176
Toll Like Receptor 7/8 (TLR7/8) CascadeREACTOMER-HSA-168181
MyD88 dependent cascade initiated on endosomeREACTOMER-HSA-975155
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activationREACTOMER-HSA-975138
Toll Like Receptor 9 (TLR9) CascadeREACTOMER-HSA-168138
Toll Like Receptor 4 (TLR4) CascadeREACTOMER-HSA-166016
Activated TLR4 signallingREACTOMER-HSA-166054
MyD88:Mal cascade initiated on plasma membraneREACTOMER-HSA-166058
Toll Like Receptor 2 (TLR2) CascadeREACTOMER-HSA-181438
Toll Like Receptor TLR1:TLR2 CascadeREACTOMER-HSA-168179
Toll Like Receptor TLR6:TLR2 CascadeREACTOMER-HSA-168188
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated MAPK activationREACTOMER-HSA-2871796
Cellular responses to stressREACTOMER-HSA-2262752
Cellular SenescenceREACTOMER-HSA-2559583
Oxidative Stress Induced SenescenceREACTOMER-HSA-2559580
Insulin resistanceKEGGhsa04931
AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
Apoptosis - multiple speciesKEGGko04215
Apoptosis - multiple speciesKEGGhsa04215
Endocrine resistanceKEGGko01522
Endocrine resistanceKEGGhsa01522
Th1 and Th2 cell differentiationKEGGko04658
Th1 and Th2 cell differentiationKEGGhsa04658
Th17 cell differentiationKEGGko04659
Th17 cell differentiationKEGGhsa04659
IL-17 signaling pathwayKEGGko04657
Fluid shear stress and atherosclerosisKEGGko05418
IL-17 signaling pathwayKEGGhsa04657
Fluid shear stress and atherosclerosisKEGGhsa05418
Mitophagy - animalKEGGko04137
Mitophagy - animalKEGGhsa04137

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA284MAP2K7GenePathwayassociated20124951
PA30584MAP2K1GenePathwayassociated20124951
PA30587MAP2K2GenePathwayassociated20124951
PA30588MAP2K3GenePathwayassociated20124951
PA30589MAP2K4GenePathwayassociated20124951
PA30590MAP2K5GenePathwayassociated20124951
PA30591MAP2K6GenePathwayassociated20124951
PA7000sorafenibChemicalPathwayassociated20124951

References

Pubmed IDYearTitleCitations
167379652006Visual and both non-visual arrestins in their "inactive" conformation bind JNK3 and Mdm2 and relocalize them from the nucleus to the cytoplasm.69
190013752009How does arrestin assemble MAPKs into a signaling complex?68
225230772012Silent scaffolds: inhibition OF c-Jun N-terminal kinase 3 activity in cell by dominant-negative arrestin-3 mutant.48
176809912007Cone arrestin binding to JNK3 and Mdm2: conformational preference and localization of interaction sites.36
220474472011Nonvisual arrestins function as simple scaffolds assembling the MKK4-JNK3α2 signaling complex.29
244127492014Arrestin-3 binds the MAP kinase JNK3α2 via multiple sites on both domains.20
268681422016Peptide mini-scaffold facilitates JNK3 activation in cells.19
233290672013Characterisation of de novo MAPK10/JNK3 truncation mutations associated with cognitive disorders in two unrelated patients.18
254553492015Increased levels of cerebrospinal fluid JNK3 associated with amyloid pathology: links to cognitive decline.18
231423462012Structural mechanisms of allostery and autoinhibition in JNK family kinases.17

Citation

Fei Chen

MAPK10 (mitogen-activated protein kinase 10)

Atlas Genet Cytogenet Oncol Haematol. 2003-01-01

Online version: http://atlasgeneticsoncology.org/gene/427/mapk10