Mitogen-activated protein kinase 8 (MAP kinase 8) (MAPK 8) (EC 2.7.11.24) (JNK-46) (Stress-activated protein kinase 1c) (SAPK1c) (Stress-activated protein kinase JNK1) (c-Jun N-terminal kinase 1)
1_MSRSK 6_ RDNNF 11_ YSVEI 16_ GDSTF 21_ TVLKR 26_ YQNLK 31_ PIGSG 36_ AQGIV 41_ CAAYD 46_ AILER 51_ NVAIK 56_ KLSRP 61_ FQNQT 66_ HAKRA 71_ YRELV 76_ LMKCV 81_ NHKNI 86_ IGLLN 91_ VFTPQ 96_ KSLEE 101_ FQDVY 106_ IVMEL 111_ MDANL 116_ CQVIQ 121_ MELDH 126_ ERMSY 131_ LLYQM 136_ LCGIK 141_ HLHSA 146_ GIIHR 151_ DLKPS 156_ NIVVK 161_ SDCTL 166_ KILDF 171_ GLART 176_ AGTSF 181_ MMTPY 186_ VVTRY 191_ YRAPE 196_ VILGM 201_ GYKEN 206_ VDLWS 211_ VGCIM 216_ GEMVC 221_ HKILF 226_ PGRDY 231_ IDQWN 236_ KVIEQ 241_ LGTPC 246_ PEFMK 251_ KLQPT 256_ VRTYV 261_ ENRPK 266_ YAGYS 271_ FEKLF 276_ PDVLF 281_ PADSE 286_ HNKLK 291_ ASQAR 296_ DLLSK 301_ MLVID 306_ ASKRI 311_ SVDEA 316_ LQHPY 321_ INVWY 326_ DPSEA 331_ EAPPP 336_ KIPDK 341_ QLDER 346_ EHTIE 351_ EWKEL 356_ IYKEV 361_ MDLEE 366_ RTKNG 371_ VIRGQ 376_ PSPLG 381_ AAVIN 386_ GSQHP 391_ SSSSS 396_ VNDVS 401_ SMSTD 406_ PTLAS 411_ DTDSS 416_ LEAAA 421_GPLGC
1: Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway (PubMed:28943315). 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 (PubMed:18307971). Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins (PubMed:21856198). Loss of this interaction abrogates the acetylation required for replication initiation (PubMed:21856198). Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1 (PubMed:21364637). 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 (PubMed:21095239). Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy (PubMed:18570871). Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons (By similarity). 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 (PubMed:16581800, PubMed:17296730, PubMed:20027304). Phosphorylates the CLOCK-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 (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). 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 (PubMed:22966201). Phosphorylates SIRT6 in response to oxidative stress, stimulating its mono-ADP-ribosyltransferase activity (PubMed:27568560). Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome (PubMed:28943315). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (PubMed:34048572)
2: 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