MGP Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins
MGP002438

UniProt Annotations

Entry Information
Gene Namemitogen-activated protein kinase 8
Protein EntryMK08_HUMAN
UniProt IDP45983
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=5; Name=2; Synonyms=JNK1-alpha-2; IsoId=P45983-1; Sequence=Displayed; Name=1; Synonyms=JNK1-alpha-1; IsoId=P45983-2; Sequence=VSP_004833; Note=Contains a phosphoserine at position 377.; Name=3; Synonyms=JNK1-beta-1; IsoId=P45983-3; Sequence=VSP_004831, VSP_004832, VSP_004833; Note=Contains a phosphoserine at position 377.; Name=4; Synonyms=JNK1-beta-2; IsoId=P45983-4; Sequence=VSP_004831, VSP_004832; Name=5; IsoId=P45983-5; Sequence=VSP_054554, VSP_004833;
Catalytic ActivityATP + a protein = ADP + a phosphoprotein.
CofactorName=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:11062067};
DomainThe TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Enzyme RegulationActivated 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. {ECO:0000269|PubMed:19166818}.
FunctionJNK1 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.
FunctionSerine/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. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). {ECO:0000269|PubMed:22441692}.
InteractionQ92934:BAD; NbExp=2; IntAct=EBI-286483, EBI-700771; P22681:CBL; NbExp=2; IntAct=EBI-286483, EBI-518228; P46108:CRK; NbExp=2; IntAct=EBI-286483, EBI-886; P05412:JUN; NbExp=4; IntAct=EBI-286483, EBI-852823; O14733-2:MAP2K7; NbExp=3; IntAct=EBI-286483, EBI-492627; Q9UQF2:MAPK8IP1; NbExp=7; IntAct=EBI-286483, EBI-78404; Q9WVI9-1:Mapk8ip1 (xeno); NbExp=2; IntAct=EBI-286483, EBI-288461; P27986:PIK3R1; NbExp=2; IntAct=EBI-286483, EBI-79464;
PtmDually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme. Phosphorylated by TAOK2. {ECO:0000269|PubMed:11062067, ECO:0000269|PubMed:17158878}.
SimilarityBelongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. {ECO:0000305}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:21148294}. Nucleus {ECO:0000269|PubMed:21148294}.
SubunitBinds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway. Interacts with TP53 and WWOX. Interacts with JAMP. Forms a complex with MAPK8IP1 and ARHGEF28 (By similarity). Interacts (phosphorylated form) with NFE2; the interaction phosphorylates NFE2 in undifferentiated cells (By similarity). Interacts with NFATC4. Interacts with MECOM; regulates JNK signaling. Interacts with PIN1; this interaction mediates MAPK8 conformational changes leading to the binding of MAPK8 to its substrates. {ECO:0000250, ECO:0000269|PubMed:10856240, ECO:0000269|PubMed:12514174, ECO:0000269|PubMed:15693750, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:17875713, ECO:0000269|PubMed:19166818, ECO:0000269|PubMed:21660049}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/JNK1ID196.html";
Web ResourceName=Wikipedia; Note=C-Jun N-terminal kinases entry; URL="http://en.wikipedia.org/wiki/C-Jun_N-terminal_kinases";
  logo