DegronMD - P45983(MAPK8)

FUNCTION: 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. 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:20027304, PubMed:16581800, PubMed:17296730). 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 (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal 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). {ECO:0000250|UniProtKB:P49185, ECO:0000250|UniProtKB:Q91Y86, ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:18307971, ECO:0000269|PubMed:18570871, ECO:0000269|PubMed:20027304, ECO:0000269|PubMed:21095239, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:22966201, ECO:0000269|PubMed:27568560}.; FUNCTION: 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. View more >>

GO - Biological processes (BP): View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.M402V	TCGA-3H-AB3X	MESO	TCGA	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation rewiring degron network	0.1111
p.S387C	TCGA-55-1594	LUAD	TCGA	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation rewiring degron network	0.25
p.S387C	DO24722	LUAD	ICGC	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation rewiring degron network	0.25
p.S387C	DO35236	PACA	ICGC	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation rewiring degron network	0.25
p.S394L	TCGA-AP-A056	UCEC	TCGA	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation altering degron motif	0.7667
p.S394L	TCGA-E6-A1LX	UCEC	TCGA	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation altering degron motif	0.7667
p.S394L	DO41020	UCEC	ICGC	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation altering degron motif	0.7667
p.S394L	DO43971	UCEC	ICGC	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation altering degron motif	0.7667
p.S393L	TCGA-AX-A2HJ	UCEC	TCGA	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation altering degron motif	0.7667
p.S393L	DO42105	UCEC	ICGC	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation altering degron motif	0.7667
p.Q388K	DO48425	BLCA	ICGC	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation rewiring degron network	0.2778
p.A381S	DO229028	LICA	ICGC	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation rewiring degron network	0.0833
p.S393P	DO232009	ORCA	ICGC	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation altering degron motif	0.6752
p.N385S	SIDM00735	Small Cell Lung Carcinoma	GDSC	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation rewiring degron network	0.1944
p.N385S	ACH-000298	Lung Cancer	CCLE	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation rewiring degron network	0.1944
p.N385S	NCI-H2029	lung	COSMIC	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation rewiring degron network	0.1944
p.V383M	SIDM01519	Head and Neck Carcinoma	GDSC	PSSSS	DEG_SPOP_SBC_1	390:394	Mutation rewiring degron network	0.1389

DegronMD: protein-targeted degradation, mutation and drug response to degrons

MAPK8

UniProt ID: P45983

Entrez ID: 5599

Protein name: 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)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for MAPK8 in