DegronMD - P45984(MAPK9)

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 MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (By similarity). {ECO:0000250|UniProtKB:Q9WTU6, ECO:0000269|PubMed:22441692}.; FUNCTION: MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.V303L	TCGA-91-6836	LUAD	TCGA	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation rewiring degron network	0.3056
p.V303L	DO23854	LUAD	ICGC	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation rewiring degron network	0.3056
p.R309Q	TCGA-BP-4161	KIRC	TCGA	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation rewiring degron network	0.1389
p.R309Q	DO17769	KIRC	ICGC	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation rewiring degron network	0.1389
p.Q293E	TCGA-Q1-A73O	CESC	TCGA	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation rewiring degron network	0.3056
p.Q293E	DO51612	CESC	ICGC	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation rewiring degron network	0.3056
p.S311F	DO225136	BRCA	ICGC	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation blocking phosphorylation signal	0.5278
p.K300E	DO229211	THCA	ICGC	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation altering degron motif	0.591
p.P306S	SIDM00250	Esophageal Squamous Cell Carcinoma	GDSC	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation rewiring degron network	0.2222
p.P306S	TE-4	oesophagus	COSMIC	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation rewiring degron network	0.2222
p.R286Q	SIDM00783	Colorectal Carcinoma	GDSC	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation rewiring degron network	0.1111
p.R286Q	ACH-000971	Colon/Colorectal Cancer	CCLE	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation rewiring degron network	0.1111
p.R286Q	HCT-116	large intestine	COSMIC	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation rewiring degron network	0.1111
p.S307L	ACH-002309	Sarcoma	CCLE	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation rewiring degron network	0.1944
p.S307L	SW684	soft tissue	COSMIC	ARDLLSKML	DEG_APCC_DBOX_1	294:302	Mutation rewiring degron network	0.1944

Kaplan plot for MAPK9 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

MAPK9

UniProt ID: P45984

Entrez ID: 5601

Protein name: Mitogen-activated protein kinase 9 (MAP kinase 9) (MAPK 9) (EC 2.7.11.24) (JNK-55) (Stress-activated protein kinase 1a) (SAPK1a) (Stress-activated protein kinase JNK2) (c-Jun N-terminal kinase 2)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for MAPK9 in