UniProtKB - Q91Y86 (MK08_MOUSE)
Mitogen-activated protein kinase 8
Mapk8
Functioni
Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (By similarity).
Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692).
Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (By similarity).
Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (PubMed:29153991).
Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (By similarity).
In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity).
Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly (By similarity).
By similarity7 PublicationsCatalytic activityi
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 55 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 151 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 32 – 40 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- enzyme binding Source: MGI
- histone deacetylase binding Source: MGI
- histone deacetylase regulator activity Source: MGI
- JUN kinase activity Source: UniProtKB
- kinase activity Source: MGI
- kinesin binding Source: MGI
- MAP kinase activity Source: GO_Central
- protein kinase activity Source: MGI
- protein serine/threonine/tyrosine kinase activity Source: UniProtKB
- protein serine/threonine kinase activity Source: MGI
- protein serine kinase activity Source: RHEA
GO - Biological processi
- cellular response to amino acid starvation Source: MGI
- cellular response to cadmium ion Source: MGI
- cellular response to hydrogen peroxide Source: MGI
- cellular response to lipopolysaccharide Source: MGI
- cellular response to nitric oxide Source: MGI
- cellular response to reactive oxygen species Source: MGI
- dendrite morphogenesis Source: CACAO
- determination of dorsal identity Source: MGI
- inflammatory response Source: MGI
- intracellular signal transduction Source: GO_Central
- JNK cascade Source: UniProtKB
- JUN phosphorylation Source: MGI
- negative regulation of apoptotic process Source: MGI
- negative regulation of protein binding Source: MGI
- neuronal stem cell population maintenance Source: MGI
- neuron migration Source: CACAO
- neuron projection development Source: MGI
- ossification Source: MGI
- peptidyl-serine phosphorylation Source: MGI
- peptidyl-threonine phosphorylation Source: MGI
- positive regulation of apoptotic process Source: GO_Central
- positive regulation of apoptotic signaling pathway Source: MGI
- positive regulation of cardiac muscle cell apoptotic process Source: MGI
- positive regulation of cell migration Source: MGI
- positive regulation of cyclase activity Source: MGI
- positive regulation of deacetylase activity Source: MGI
- positive regulation of determination of dorsal identity Source: MGI
- positive regulation of DNA replication Source: MGI
- positive regulation of gene expression Source: MGI
- positive regulation of glial cell apoptotic process Source: MGI
- positive regulation of microtubule polymerization Source: MGI
- positive regulation of neuroblast proliferation Source: MGI
- positive regulation of neuron apoptotic process Source: MGI
- positive regulation of neuron migration Source: MGI
- positive regulation of podosome assembly Source: MGI
- positive regulation of protein metabolic process Source: MGI
- positive regulation of protein ubiquitination Source: UniProtKB
- positive regulation of transcription factor catabolic process Source: UniProtKB
- programmed necrotic cell death Source: MGI
- protein localization to tricellular tight junction Source: MGI
- protein phosphorylation Source: MGI
- regulation of centrosome cycle Source: MGI
- regulation of circadian rhythm Source: UniProtKB
- regulation of dense core granule transport Source: MGI
- regulation of DNA replication origin binding Source: MGI
- regulation of gene expression Source: MGI
- regulation of neuron differentiation Source: MGI
- regulation of protein localization Source: MGI
- regulation of transcription, DNA-templated Source: MGI
- response to cadmium ion Source: MGI
- response to heat Source: MGI
- response to hydrogen peroxide Source: MGI
- response to mechanical stimulus Source: GO_Central
- response to osmotic stress Source: MGI
- response to oxidative stress Source: MGI
- response to UV Source: MGI
- rhythmic process Source: UniProtKB-KW
- signal transduction Source: MGI
- stress-activated MAPK cascade Source: MGI
- type B pancreatic cell apoptotic process Source: MGI
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Biological rhythms |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.24, 3474 |
Reactomei | R-MMU-111446, Activation of BIM and translocation to mitochondria R-MMU-139910, Activation of BMF and translocation to mitochondria R-MMU-193648, NRAGE signals death through JNK R-MMU-2559580, Oxidative Stress Induced Senescence R-MMU-2871796, FCERI mediated MAPK activation R-MMU-376172, DSCAM interactions R-MMU-450321, JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 R-MMU-450341, Activation of the AP-1 family of transcription factors R-MMU-5693565, Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-MMU-9007892, Interleukin-38 signaling |
Names & Taxonomyi
Protein namesi | Recommended name: Mitogen-activated protein kinase 8 (EC:2.7.11.247 Publications)Short name: MAP kinase 8 Short name: MAPK 8 Alternative name(s): Stress-activated protein kinase JNK1 c-Jun N-terminal kinase 1 |
Gene namesi | Name:Mapk8 Synonyms:Jnk1, Prkm8 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1346861, Mapk8 |
VEuPathDBi | HostDB:ENSMUSG00000021936 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Other locations
- synapse By similarity
Note: In the cortical neurons, predominantly cytoplasmic and associated with the Golgi apparatus and endosomal fraction. Increased neuronal activity increases phosphorylated form at synapses (By similarity). Colocalizes with POU5F1 in the nucleus (By similarity) (PubMed:29153991).By similarity1 Publication
Cytoskeleton
- podosome Source: MGI
Cytosol
- cytosol Source: MGI
Mitochondrion
- mitochondrion Source: MGI
Nucleus
- nucleus Source: MGI
Other locations
- axon Source: ARUK-UCL
- basal dendrite Source: ARUK-UCL
- cytoplasm Source: MGI
- dendrite cytoplasm Source: MGI
- perikaryon Source: MGI
- synapse Source: UniProtKB
- vesicle Source: MGI
Keywords - Cellular componenti
Cell junction, Cytoplasm, Nucleus, SynapsePathology & Biotechi
Disruption phenotypei
Chemistry databases
ChEMBLi | CHEMBL1795174 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000186263 | 1 – 384 | Mitogen-activated protein kinase 8Add BLAST | 384 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 116 | S-nitrosocysteineBy similarity | 1 | |
Modified residuei | 183 | Phosphothreonine; by MAP2K71 Publication | 1 | |
Modified residuei | 185 | Phosphotyrosine; by MAP2K41 Publication | 1 | |
Modified residuei | 377 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, S-nitrosylationProteomic databases
MaxQBi | Q91Y86 |
PaxDbi | Q91Y86 |
PRIDEi | Q91Y86 |
ProteomicsDBi | 295946 |
PTM databases
iPTMneti | Q91Y86 |
PhosphoSitePlusi | Q91Y86 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000021936, Expressed in embryo and 313 other tissues |
ExpressionAtlasi | Q91Y86, baseline and differential |
Genevisiblei | Q91Y86, MM |
Interactioni
Subunit structurei
Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4 (PubMed:10523642, PubMed:12391307, PubMed:11562351). These proteins also bind other components of the JNK signaling pathway.
Forms a complex with MAPK8IP1 and ARHGEF28 (PubMed:14499478).
Interacts with TP53 and WWOX (By similarity).
Interacts with JAMP (PubMed:16166642).
Interacts with NFATC4 (By similarity).
Interacts with MECOM; regulates JNK signaling (By similarity).
Interacts with PIN1; this interaction mediates MAPK8 conformational changes leading to the binding of MAPK8 to its substrates (By similarity).
Interacts with HSF1 (via D domain and preferentially with hyperphosphorylated form); this interaction occurs under both normal growth conditions and immediately upon heat shock (By similarity).
Interacts (phosphorylated form) with NFE2; the interaction phosphorylates NFE2 in undifferentiated cells (PubMed:19966288).
Interacts with GRIPAP1 (By similarity).
Interacts with POU5F1; phosphorylates POU5F1 at 'Ser-347' (PubMed:29153991).
Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8IP1/JIP1 (PubMed:23963642).
Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK9/JNK2 (PubMed:27084103).
By similarity9 PublicationsBinary interactionsi
Q91Y86
With | #Exp. | IntAct |
---|---|---|
Jun [P05627] | 2 | EBI-298784,EBI-764369 |
GO - Molecular functioni
- enzyme binding Source: MGI
- histone deacetylase binding Source: MGI
- kinesin binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 204971, 24 interactors |
DIPi | DIP-31075N |
ELMi | Q91Y86 |
IntActi | Q91Y86, 8 interactors |
MINTi | Q91Y86 |
STRINGi | 10090.ENSMUSP00000107576 |
Miscellaneous databases
RNActi | Q91Y86, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 26 – 321 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 296 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 183 – 185 | TXY | 3 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0665, Eukaryota |
GeneTreei | ENSGT00940000153692 |
InParanoidi | Q91Y86 |
PhylomeDBi | Q91Y86 |
TreeFami | TF105100 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR003527, MAP_kinase_CS IPR008351, MAPK_JNK IPR000719, Prot_kinase_dom IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PRINTSi | PR01772, JNKMAPKINASE |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS01351, MAPK, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MSRSKRDNNF YSVEIGDSTF TVLKRYQNLK PIGSGAQGIV CAAYDAILER
60 70 80 90 100
NVAIKKLSRP FQNQTHAKRA YRELVLMKCV NHKNIIGLLN VFTPQKSLEE
110 120 130 140 150
FQDVYIVMEL MDANLCQVIQ MELDHERMSY LLYQMLCGIK HLHSAGIIHR
160 170 180 190 200
DLKPSNIVVK SDCTLKILDF GLARTAGTSF MMTPYVVTRY YRAPEVILGM
210 220 230 240 250
GYKENVDLWS VGCIMGEMVC HKILFPGRDY IDQWNKVIEQ LGTPCPEFMK
260 270 280 290 300
KLQPTVRTYV ENRPKYAGYS FEKLFPDVLF PADSEHNKLK ASQARDLLSK
310 320 330 340 350
MLVIDASKRI SVDEALQHPY INVWYDPSEA EAPPPKIPDK QLDEREHTIE
360 370 380
EWKELIYKEV MDLEERTKNG VIRGQPSPLA QVQQ
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketG3X8U9 | G3X8U9_MOUSE | Stress-activated protein kinase JNK | Mapk8 | 427 | Annotation score: | ||
Q7TSJ7 | Q7TSJ7_MOUSE | Stress-activated protein kinase JNK | Mapk8 | 427 | Annotation score: | ||
A6P3E4 | A6P3E4_MOUSE | Stress-activated protein kinase JNK | Mapk8 | 384 | Annotation score: | ||
D3Z1Z4 | D3Z1Z4_MOUSE | Stress-activated protein kinase JNK | Mapk8 | 308 | Annotation score: | ||
A0A2I3BPL3 | A0A2I3BPL3_MOUSE | Mitogen-activated protein kinase 8 | Mapk8 | 40 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB005663 mRNA Translation: BAA85875.1 |
CCDSi | CCDS36869.1 |
RefSeqi | NP_057909.1, NM_016700.4 |
Genome annotation databases
Ensembli | ENSMUST00000111945; ENSMUSP00000107576; ENSMUSG00000021936 |
GeneIDi | 26419 |
KEGGi | mmu:26419 |
UCSCi | uc007szt.3, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB005663 mRNA Translation: BAA85875.1 |
CCDSi | CCDS36869.1 |
RefSeqi | NP_057909.1, NM_016700.4 |
3D structure databases
SMRi | Q91Y86 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 204971, 24 interactors |
DIPi | DIP-31075N |
ELMi | Q91Y86 |
IntActi | Q91Y86, 8 interactors |
MINTi | Q91Y86 |
STRINGi | 10090.ENSMUSP00000107576 |
Chemistry databases
ChEMBLi | CHEMBL1795174 |
PTM databases
iPTMneti | Q91Y86 |
PhosphoSitePlusi | Q91Y86 |
Proteomic databases
MaxQBi | Q91Y86 |
PaxDbi | Q91Y86 |
PRIDEi | Q91Y86 |
ProteomicsDBi | 295946 |
Protocols and materials databases
Antibodypediai | 3846, 1682 antibodies from 47 providers |
DNASUi | 26419 |
Genome annotation databases
Ensembli | ENSMUST00000111945; ENSMUSP00000107576; ENSMUSG00000021936 |
GeneIDi | 26419 |
KEGGi | mmu:26419 |
UCSCi | uc007szt.3, mouse |
Organism-specific databases
CTDi | 5599 |
MGIi | MGI:1346861, Mapk8 |
VEuPathDBi | HostDB:ENSMUSG00000021936 |
Phylogenomic databases
eggNOGi | KOG0665, Eukaryota |
GeneTreei | ENSGT00940000153692 |
InParanoidi | Q91Y86 |
PhylomeDBi | Q91Y86 |
TreeFami | TF105100 |
Enzyme and pathway databases
BRENDAi | 2.7.11.24, 3474 |
Reactomei | R-MMU-111446, Activation of BIM and translocation to mitochondria R-MMU-139910, Activation of BMF and translocation to mitochondria R-MMU-193648, NRAGE signals death through JNK R-MMU-2559580, Oxidative Stress Induced Senescence R-MMU-2871796, FCERI mediated MAPK activation R-MMU-376172, DSCAM interactions R-MMU-450321, JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 R-MMU-450341, Activation of the AP-1 family of transcription factors R-MMU-5693565, Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-MMU-9007892, Interleukin-38 signaling |
Miscellaneous databases
BioGRID-ORCSi | 26419, 0 hits in 63 CRISPR screens |
ChiTaRSi | Mapk8, mouse |
PROi | PR:Q91Y86 |
RNActi | Q91Y86, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000021936, Expressed in embryo and 313 other tissues |
ExpressionAtlasi | Q91Y86, baseline and differential |
Genevisiblei | Q91Y86, MM |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR003527, MAP_kinase_CS IPR008351, MAPK_JNK IPR000719, Prot_kinase_dom IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PRINTSi | PR01772, JNKMAPKINASE |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS01351, MAPK, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | MK08_MOUSE | |
Accessioni | Q91Y86Primary (citable) accession number: Q91Y86 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 30, 2002 |
Last sequence update: | December 1, 2001 | |
Last modified: | February 23, 2022 | |
This is version 199 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families