CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008115
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
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
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
64NAIIDDYKVTSQVLGacetylation[1]
84KVLQIFNKRTQEKFAubiquitination[2]
100KMLQDCPKARREVELubiquitination[2]
307MLIRNLLKTEPTQRMubiquitination[2]
353KERWEDVKEEMTSALubiquitination[2]
371RVDYEQIKIKKIEDAubiquitination[2]
Reference
 [1] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
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 64 325 Protein kinase.
 NP_BIND 70 78 ATP (By similarity).
 REGION 139 141 Staurosporine binding.
 REGION 328 364 Autoinhibitory helix (By similarity).
 REGION 366 390 p38 MAPK-binding site.
 MOTIF 356 365 Nuclear export signal (NES).
 MOTIF 371 374 Bipartite nuclear localization signal 1.
 MOTIF 385 389 Bipartite nuclear localization signal 2.
 ACT_SITE 186 186 Proton acceptor.
 BINDING 93 93 ATP (By similarity).
 MOD_RES 9 9 Phosphoserine.
 MOD_RES 25 25 Phosphothreonine.
 MOD_RES 222 222 Phosphothreonine; by MAPK14.
 MOD_RES 272 272 Phosphoserine; by MAPK14.
 MOD_RES 328 328 Phosphoserine; by autocatalysis (By
 MOD_RES 334 334 Phosphothreonine; by MAPK14.
 MOD_RES 338 338 Phosphothreonine (By similarity).
 CROSSLNK 353 353 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; DNA damage; Isopeptide bond; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 400 AA 
Protein Sequence
MLSNSQGQSP PVPFPAPAPP PQPPTPALPH PPAQPPPPPP QQFPQFHVKS GLQIKKNAII 60
DDYKVTSQVL GLGINGKVLQ IFNKRTQEKF ALKMLQDCPK ARREVELHWR ASQCPHIVRI 120
VDVYENLYAG RKCLLIVMEC LDGGELFSRI QDRGDQAFTE REASEIMKSI GEAIQYLHSI 180
NIAHRDVKPE NLLYTSKRPN AILKLTDFGF AKETTSHNSL TTPCYTPYYV APEVLGPEKY 240
DKSCDMWSLG VIMYILLCGY PPFYSNHGLA ISPGMKTRIR MGQYEFPNPE WSEVSEEVKM 300
LIRNLLKTEP TQRMTITEFM NHPWIMQSTK VPQTPLHTSR VLKEDKERWE DVKEEMTSAL 360
ATMRVDYEQI KIKKIEDASN PLLLKRRKKA RALEAAALAH 400 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0004871; F:signal transducer activity; TAS:ProtInc.
 GO:0070935; P:3'-UTR-mediated mRNA stabilization; IDA:UniProtKB.
 GO:0000187; P:activation of MAPK activity; TAS:Reactome.
 GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome.
 GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IMP:BHF-UCL.
 GO:0031572; P:G2 DNA damage checkpoint; IMP:UniProtKB.
 GO:0010467; P:gene expression; TAS:Reactome.
 GO:0006954; P:inflammatory response; ISS:UniProtKB.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0048839; P:inner ear development; IEA:Compara.
 GO:0006691; P:leukotriene metabolic process; TAS:Reactome.
 GO:0044351; P:macropinocytosis; ISS:UniProtKB.
 GO:0016071; P:mRNA metabolic process; TAS:Reactome.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
 GO:0007265; P:Ras protein signal transduction; TAS:Reactome.
 GO:0032675; P:regulation of interleukin-6 production; ISS:UniProtKB.
 GO:0032680; P:regulation of tumor necrosis factor production; IDA:UniProtKB.
 GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
 GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:BHF-UCL. 
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