UniProt Accession

 MAPK2_MOUSE; P49138; Q6P561 

Genbank Protein ID

 X76850; BC063064 

Genbank Nucleotide ID

 CAA54183.1; AAH63064.1 

Protein Name

 MAP kinase-activated protein kinase 2 

Protein Synonyms/Alias

 MAPK-activated protein kinase 2; MAPKAP kinase 2; MAPKAP-K2; MAPKAPK-2; MK-2; MK2 

Gene Name

 Mapkapk2 

Gene Synonyms/Alias

 Rps6kc1 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
50	NAITDDYKVTSQVLG	acetylation	[1]
75	FDKRTQQKFALKMLQ	acetylation	[1, 2]
339	KERWEDVKEEMTSAL	sumoylation	[3]

Reference

 [1] Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns.
 Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV.
 Cell Rep. 2012 Aug 30;2(2):419-31. [PMID: 22902405]
 [2] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [3] MK2 SUMOylation regulates actin filament remodeling and subsequent migration in endothelial cells by inhibiting MK2 kinase and HSP27 phosphorylation.
 Chang E, Heo KS, Woo CH, Lee H, Le NT, Thomas TN, Fujiwara K, Abe J.
 Blood. 2011 Feb 24;117(8):2527-37. [PMID: 21131586] 

Functional Description

 Stress-activated serine/threonine-protein kinase involved in cytokines 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, ELAVL1, HNRNPA0, HSF1, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat- shock protein (sHsps) oligomers and impair 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 regulate 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 transcript. 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 stabilize GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. 

Sequence Annotation

 DOMAIN 50 311 Protein kinase.
 NP_BIND 56 64 ATP (By similarity).
 REGION 125 127 Staurosporine binding (By similarity).
 REGION 314 350 Autoinhibitory helix.
 REGION 331 354 Nuclear export signal (NES).
 REGION 352 376 p38 MAPK-binding site (By similarity).
 MOTIF 342 351 Nuclear export signal (NES) (By
 MOTIF 357 360 Bipartite nuclear localization signal 1.
 MOTIF 371 375 Bipartite nuclear localization signal 2.
 ACT_SITE 172 172 Proton acceptor (By similarity).
 BINDING 79 79 ATP (By similarity).
 MOD_RES 208 208 Phosphothreonine; by MAPK14.
 MOD_RES 258 258 Phosphoserine; by MAPK14 (By similarity).
 MOD_RES 314 314 Phosphoserine; by autocatalysis (By
 MOD_RES 320 320 Phosphothreonine; by MAPK14.
 MOD_RES 324 324 Phosphothreonine.
 CROSSLNK 339 339 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 ATP-binding; Complete proteome; Cytoplasm; DNA damage; Isopeptide bond; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 386 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IDA:UniProtKB.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0070935; P:3'-UTR-mediated mRNA stabilization; ISS:UniProtKB.
 GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IEA:Compara.
 GO:0031572; P:G2 DNA damage checkpoint; ISS:UniProtKB.
 GO:0006954; P:inflammatory response; IMP:UniProtKB.
 GO:0048839; P:inner ear development; IDA:MGI.
 GO:0044351; P:macropinocytosis; IMP:UniProtKB.
 GO:0018105; P:peptidyl-serine phosphorylation; IEA:Compara.
 GO:0032675; P:regulation of interleukin-6 production; IMP:UniProtKB.
 GO:0032680; P:regulation of tumor necrosis factor production; IMP:UniProtKB.
 GO:0032496; P:response to lipopolysaccharide; IMP:UniProtKB.
 GO:0002224; P:toll-like receptor signaling pathway; IMP:UniProtKB.
 GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IEA:Compara. 

Interpro

 IPR011009; Kinase-like_dom.
 IPR027442; MAPKAPK_C.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF00069; Pkinase 

SMART

 SM00220; S_TKc 

PROSITE

 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS