Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  MAP kinase-activated protein kinase 2  

UniProtKB / Swiss-Prot ID :  MAPK2_HUMAN

Gene Name (Synonyms) : 
MAPKAPK2  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cytoplasm. Nucleus. Note=Phosphorylation and subsequent activation releases the autoinhibitory helix, resulting in the export from the nucleus into the cytoplasm. 

Protein Function :  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. 

Protein Sequence MLSNSQGQSPPVPFPAPAPPPQPPTPALPHPPAQPPPPPPQQFPQFHVKSGLQIKKNAIIDDYKVTSQVL...
Predicted Secondary Structure CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCEEEEEEEC...
Protein Variant
LocationDescription
173A -> G (in dbSNP:rs35671930). VAR_040753
361A -> S (in dbSNP:rs55894011). VAR_040754
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
9Phosphoserine (MAPK1)SQGQSPPVP
CCCCCCCCC
37.69PhosphoELM
Link-
9Phosphoserine.SQGQSPPVP
CCCCCCCCC
37.69UniProtKB
Link-
25Phosphothreonine (MAPK14)PQPPTPALP
CCCCCCCCC
28.07HPRD
Link-
25Phosphothreonine (MAPK_group;MAPK14)PQPPTPALP
CCCCCCCCC
28.07PhosphoELM
Link-
25Phosphothreonine.PQPPTPALP
CCCCCCCCC
28.07UniProtKB
Link-
63PhosphotyrosineIIDDYKVTS
CCCCEEEEE
12.01HPRD
Link
63PhosphotyrosineIIDDYKVTS
CCCCEEEEE
12.01PhosphoELM
Link
63PhosphotyrosineIIDDYKVTS
CCCCEEEEE
12.01Phosphositeplus
Link
63PhosphotyrosineIIDDYKVTS
CCCCEEEEE
12.01SysPTM
Link
63Phosphotyrosine.IIDDYKVTS
CCCCEEEEE
12.01UniProtKB
Link
206Phosphothreonine (MAPK14)ILKLTDFGF
CEEEEECEE
27.91HPRD
Link
222PhosphothreonineNSLTTPCYT
CEEEEEECC
19.36Phosphositeplus
Link-
222Phosphothreonine (MAPK14)NSLTTPCYT
CEEEEEECC
19.36HPRD
Link-
222Phosphothreonine (MAPK_group;MAPK14)NSLTTPCYT
CEEEEEECC
19.36PhosphoELM
Link-
222Phosphothreonine; by MAPK14.NSLTTPCYT
CEEEEEECC
19.36UniProtKB
Link-
225PhosphotyrosineTTPCYTPYY
EEEECCHHH
16.38Phosphositeplus
Link-
226PhosphothreonineTPCYTPYYV
EEECCHHHC
16.13Phosphositeplus
Link-
272Phosphoserine (MAPK14)GLAISPGMK
HHHHHHHHH
15.14HPRD
Link
272Phosphoserine (MAPK_group;MAPK14)GLAISPGMK
HHHHHHHHH
15.14PhosphoELM
Link
272Phosphoserine; by MAPK14.GLAISPGMK
HHHHHHHHH
15.14UniProtKB
Link
317PhosphothreonineRMTITEFMN
CCCHHHHHC
17.63Phosphositeplus
Link
317Phosphothreonine (MAPK14)RMTITEFMN
CCCHHHHHC
17.63HPRD
Link
329PhosphothreonineIMQSTKVPQ
CCCCCCCCC
21.12Phosphositeplus
Link
334PhosphothreonineKVPQTPLHT
CCCCCCCCC
23.03Phosphositeplus
Link
334Phosphothreonine (MAPK14)KVPQTPLHT
CCCCCCCCC
23.03HPRD
Link
334Phosphothreonine (MAPK_group;MAPK14)KVPQTPLHT
CCCCCCCCC
23.03PhosphoELM
Link
334Phosphothreonine; by MAPK14.KVPQTPLHT
CCCCCCCCC
23.03UniProtKB
Link
338PhosphothreonineTPLHTSRVL
CCCCCHHCC
26.38HPRD
Link
338PhosphothreonineTPLHTSRVL
CCCCCHHCC
26.38Phosphositeplus
Link
338Phosphothreonine (MAPKAPK2)TPLHTSRVL
CCCCCHHCC
26.38PhosphoELM
Link
353Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)WEDVKEEMT
HHHHHHHHH
61.35Phosphositeplus
Link
353Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO).WEDVKEEMT
HHHHHHHHH
61.35UniProtKB
Link
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
LIMK1_HUMANphosphorylation reactionMINT-2833388MINT16456544
MPIP1_HUMANphosphorylationEBI-1213056
intact17292828
CREB1_HUMANin vitroHPRD:11882HPRD8887554
TFE2_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:11882HPRD10781029
LOX5_HUMANin vitroHPRD:11882HPRD10779545
11844797
LSP1_HUMANin vitroHPRD:11882HPRD8995217
TTP_HUMANin vitro
in vivo
HPRD:11882HPRD14688255
TSC2_HUMANin vitro
in vivo
HPRD:11882HPRD12582162
TY3H_HUMANin vitro
in vivo
HPRD:11882HPRD6150037
11359875
7901013
1433Z_HUMANin vitro
in vivo
HPRD:11882HPRD12861023
ETV1_HUMANin vitro
in vivo
HPRD:11882HPRD11551945
SRF_HUMANin vitro
in vivo
HPRD:11882HPRD10753652
8413226
10318869
12171911
BAG2_HUMANin vitro
in vivo
HPRD:11882HPRD15271996
EF2K_HUMANin vitroHPRD:11882HPRD12171600
PHC2_HUMANin vivo
yeast 2-hybrid
HPRD:11882HPRD15094067
HSPB1_HUMANin vitro
in vivo
HPRD:11882HPRD7799959
1332886
11042204
ROA0_HUMANin vitroHPRD:11882HPRD12456657
MAPK2_HUMANin vivoHPRD:11882HPRD8846784
ARPC5_HUMANin vitroHPRD:11882HPRD12829704
AKT1_HUMANin vitro
in vivo
HPRD:11882HPRD11042204
SHC1_HUMANin vivo
yeast 2-hybrid
HPRD:11882HPRD15094067
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Disease Reference
Kegg disease
There are no disease associations of PTM sites.
Drug Reference
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"Global proteomic profiling of phosphopeptides using electron transferdissociation tandem mass spectrometry.";
Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.;
Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-63, AND MASSSPECTROMETRY.
"Identification of novel phosphorylation sites required for activationof MAPKAP kinase-2.";
Ben-Levy R., Leighton I.A., Doza Y.N., Attwood P., Morrice N.,Marshall C.J., Cohen P.;
EMBO J. 14:5920-5930(1995).
Cited for: PHOSPHORYLATION AT SER-9; THR-25; THR-222; SER-272 AND THR-334, ANDMUTAGENESIS OF ASP-207; THR-222; SER-272 AND THR-334.
Sumoylation
ReferencePubMed
"MK2 SUMOylation regulates actin filament remodeling and subsequentmigration in endothelial cells by inhibiting MK2 kinase and HSP27phosphorylation.";
Chang E., Heo K.S., Woo C.H., Lee H., Le N.T., Thomas T.N.,Fujiwara K., Abe J.;
Blood 117:2527-2537(2011).
Cited for: SUMOYLATION AT LYS-353, AND MUTAGENESIS OF LYS-353.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures