DegronMD - P49137(MAPKAPK2)

FUNCTION: Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831, ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544, ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084, ECO:0000269|PubMed:8774846}. View more >>

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

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.H322Y	TCGA-AP-A1DK	UCEC	TCGA	VPQTPLHT	DEG_SCF_FBW7_1	331:338	Mutation rewiring degron network	0.0833
p.H322Y	DO42033	UCEC	ICGC	VPQTPLHT	DEG_SCF_FBW7_1	331:338	Mutation rewiring degron network	0.0833
p.H322Y	SIDM00548	Squamous Cell Lung Carcinoma	GDSC	VPQTPLHT	DEG_SCF_FBW7_1	331:338	Mutation rewiring degron network	0.0833
p.H322Y	ACH-000769	Lung Cancer	CCLE	VPQTPLHT	DEG_SCF_FBW7_1	331:338	Mutation rewiring degron network	0.0833
p.H322Y	LK-2	lung	COSMIC	VPQTPLHT	DEG_SCF_FBW7_1	331:338	Mutation rewiring degron network	0.0833
p.P332H	TCGA-DA-A1IB	SKCM	TCGA	VPQTPLHT	DEG_SCF_FBW7_1	331:338	Mutation altering degron motif	0.6583
p.P332H	DO38033	SKCM	ICGC	VPQTPLHT	DEG_SCF_FBW7_1	331:338	Mutation altering degron motif	0.6583
p.S339N	TCGA-DF-A2KU	UCEC	TCGA	VPQTPLHT	DEG_SCF_FBW7_1	331:338	Mutation blocking phosphorylation signal	0.75
p.S339N	DO223286	UCEC	ICGC	VPQTPLHT	DEG_SCF_FBW7_1	331:338	Mutation blocking phosphorylation signal	0.75

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

MAPKAPK2

UniProt ID: P49137

Entrez ID: 9261

Protein name: MAP kinase-activated protein kinase 2 (MAPK-activated protein kinase 2) (MAPKAP kinase 2) (MAPKAP-K2) (MAPKAPK-2) (MK-2) (MK2) (EC 2.7.11.1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for MAPKAPK2 in