MAPK8 - Mitogen-activated protein kinase 8 - human protein (Function)
 
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MAPK8 »  Mitogen-activated protein kinase 8   [ EC 2.7.11.24 ]  (MAPK 8)
 
Protein also known as:  Stress-activated protein kinase JNK1.
Gene name:  MAPK8
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH.  
8
  • CuratedUniProtKB
JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.  
8
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Histone deacetylase bindingdefinition[GO:0042826]  
1
  • IPIBHF-UCL
Histone deacetylase regulator activitydefinition[GO:0035033]  
1
  • IMPBHF-UCL
JUN kinase activitydefinition[GO:0004705]  
2
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
14
  • IPIIntAct
  • IPIUniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
4
  • IDAUniProtKB
  • IDABHF-UCL
  • IDAMGI
GO biological process 
Cellular response to lipopolysaccharidedefinition[GO:0071222]  
1
  • IDAMGI
Cellular response to mechanical stimulusdefinition[GO:0071260]  
1
  • IEPUniProtKB
JNK cascadedefinition[GO:0007254]  
1
  • IDAUniProtKB
JUN phosphorylationdefinition[GO:0007258]  
2
  • IDAUniProtKB
  • IDAMGI
Negative regulation of apoptotic processdefinition[GO:0043066]  
2
  • IDAUniProtKB
  • IDAMGI
Negative regulation of protein bindingdefinition[GO:0032091]  
1
  • IDAUniProtKB
Ossificationdefinition[GO:0001503] silver  
  • IEAOrtholog Compara
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
3
  • IDAUniProtKB
  • IDABHF-UCL
Peptidyl-threonine phosphorylationdefinition[GO:0018107]  
2
  • IDAUniProtKB
  • IMPBHF-UCL
Positive regulation of apoptotic signaling pathwaydefinition[GO:2001235] silver  
  • IEAOrtholog Compara
Positive regulation of deacetylase activitydefinition[GO:0090045]  
1
  • IMPBHF-UCL
Positive regulation of determination of dorsal identitydefinition[GO:2000017] silver  
  • IEAOrtholog Compara
Positive regulation of gene expressiondefinition[GO:0010628]  
1
  • IMPBHF-UCL
Regulation of histone deacetylationdefinition[GO:0031063]  
1
  • IMPGOC
Regulation of protein localizationdefinition[GO:0032880]  
1
  • IDABHF-UCL
Response to cadmium iondefinition[GO:0046686] silver  
  • IEAOrtholog Compara
Response to stressdefinition[GO:0006950]  
1
  • TASPINC
Response to UVdefinition[GO:0009411]  
1
  • IDAMGI
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.24: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It requires the following cofactor
Magnesium.  
1
  • CuratedUniProtKB
It is regulated in the following manner
Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by SERPINB3.  
1
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Adipocytokine signaling pathway  hsa04920+5599  
Chagas disease (American trypanosomiasis)  hsa05142+5599  
Colorectal cancer  hsa05210+5599  
Dopaminergic synapse  hsa04728+5599  
Epithelial cell signaling in Helicobacter pylori infection  hsa05120+5599  
ErbB signaling pathway  hsa04012+5599  
Fc epsilon RI signaling pathway  hsa04664+5599  
Focal adhesion  hsa04510+5599  
GnRH signaling pathway  hsa04912+5599  
Hepatitis C  hsa05160+5599  
Herpes simplex infection  hsa05168+5599  
HTLV-I infection  hsa05166+5599  
Influenza A  hsa05164+5599  
Insulin signaling pathway  hsa04910+5599  
MAPK signaling pathway  hsa04010+5599  
Neurotrophin signaling pathway  hsa04722+5599  
NOD-like receptor signaling pathway  hsa04621+5599  
Osteoclast differentiation  hsa04380+5599  
Pancreatic cancer  hsa05212+5599  
Pathways in cancer  hsa05200+5599  
Pertussis  hsa05133+5599  
Progesterone-mediated oocyte maturation  hsa04914+5599  
Protein processing in endoplasmic reticulum  hsa04141+5599  
RIG-I-like receptor signaling pathway  hsa04622+5599  
Salmonella infection  hsa05132+5599  
Shigellosis  hsa05131+5599  
Toll-like receptor signaling pathway  hsa04620+5599  
Toxoplasmosis  hsa05145+5599  
Tuberculosis  hsa05152+5599  
Type II diabetes mellitus  hsa04930+5599  
Wnt signaling pathway  hsa04310+5599  
According to Reactome, this protein belongs to the following pathways:
Activation of BMF and translocation to mitochondria  REACT_2100  
Activation of the AP-1 family of transcription factors  REACT_21326  
DSCAM interactions  REACT_25299  
FCERI mediated MAPK activation  REACT_163701  
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1  REACT_21368  
NRAGE signals death through JNK  REACT_13638  
NRIF signals cell death from the nucleus  REACT_13643  
Oxidative Stress Induced Senescence  REACT_169436  
 

Keywords

Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: MAPK8
GenomeRNAi: 5599
PRO: PR:P45983
Chemistry
GuidetoPHARMACOLOGY: 1496