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P49137 (MAPK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
MAP kinase-activated protein kinase 2

Short name=MAPK-activated protein kinase 2
Short name=MAPKAP kinase 2
Short name=MAPKAP-K2
Short name=MAPKAPK-2
Short name=MK-2
Short name=MK2
EC=2.7.11.1
Gene names
Name:MAPKAPK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length400 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.5 Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.8 Ref.27

Enzyme regulation

Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited following sumoylation. Specifically inhibited by pyrrolopyridine inhibitors.

Subunit structure

Heterodimer with p38-alpha/MAPK14. The heterodimer with p38-alpha/MAPK14 forms a stable complex: molecules are positioned 'face to face' so that the ATP-binding sites of both kinases are at the heterodimer interface. Interacts with PHC2. Ref.16 Ref.30 Ref.34

Subcellular location

Cytoplasm. Nucleus. Note: Phosphorylation and subsequent activation releases the autoinhibitory helix, resulting in the export from the nucleus into the cytoplasm. Ref.23

Tissue specificity

Expressed in all tissues examined.

Post-translational modification

Sumoylation inhibits the protein kinase activity. Ref.25

Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-222, Ser-272 and Thr-334. Ref.7

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processDNA damage
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_process3'-UTR-mediated mRNA stabilization

Inferred from direct assay Ref.14Ref.15Ref.23. Source: UniProtKB

G2 DNA damage checkpoint

Inferred from mutant phenotype Ref.23. Source: UniProtKB

MAPK cascade

Traceable author statement Ref.1. Source: ProtInc

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

RNA metabolic process

Traceable author statement. Source: Reactome

Ras protein signal transduction

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

activation of MAPK activity

Traceable author statement. Source: Reactome

arachidonic acid metabolic process

Traceable author statement. Source: Reactome

cellular response to DNA damage stimulus

Inferred from mutant phenotype Ref.23. Source: UniProtKB

cellular response to vascular endothelial growth factor stimulus

Inferred from mutant phenotype PubMed 18440775. Source: BHF-UCL

gene expression

Traceable author statement. Source: Reactome

inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

inner ear development

Inferred from electronic annotation. Source: Ensembl

leukotriene metabolic process

Traceable author statement. Source: Reactome

mRNA metabolic process

Traceable author statement. Source: Reactome

macropinocytosis

Inferred from sequence or structural similarity. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 15850461. Source: BHF-UCL

protein phosphorylation

Traceable author statement Ref.1. Source: ProtInc

regulation of interleukin-6 production

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of tumor necrosis factor production

Inferred from direct assay Ref.15. Source: UniProtKB

response to cytokine

Inferred from direct assay Ref.8. Source: UniProtKB

response to lipopolysaccharide

Inferred from sequence or structural similarity. Source: UniProtKB

response to stress

Inferred from direct assay Ref.15. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

vascular endothelial growth factor receptor signaling pathway

Inferred from mutant phenotype PubMed 18440775. Source: BHF-UCL

   Cellular_componentcentrosome

Inferred from direct assay. Source: HPA

cytoplasm

Inferred from direct assay Ref.23. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.23. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.14Ref.15Ref.23Ref.8. Source: UniProtKB

protein kinase activity

Traceable author statement Ref.1. Source: ProtInc

protein serine/threonine kinase activity

Inferred from direct assay Ref.14Ref.15Ref.23Ref.8Ref.7. Source: UniProtKB

signal transducer activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

HSF1Q006135EBI-993299,EBI-719620
HSPB1P047922EBI-993299,EBI-352682
MAPK14Q165394EBI-993299,EBI-73946
Phc2Q9QWH12EBI-993299,EBI-642357From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P49137-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Has a nuclear localization signal.
Isoform 2 (identifier: P49137-2)

The sequence of this isoform differs from the canonical sequence as follows:
     354-400: EEMTSALATMRVDYEQIKIKKIEDASNPLLLKRRKKARALEAAALAH → GCLHDKNSDQATWLTRL

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 400400MAP kinase-activated protein kinase 2
PRO_0000086288

Regions

Domain64 – 325262Protein kinase
Nucleotide binding70 – 789ATP By similarity
Region139 – 1413Staurosporine binding
Region328 – 36437Autoinhibitory helix By similarity
Region366 – 39025p38 MAPK-binding site
Motif356 – 36510Nuclear export signal (NES)
Motif371 – 3744Bipartite nuclear localization signal 1
Motif385 – 3895Bipartite nuclear localization signal 2
Compositional bias10 – 4031Pro-rich
Compositional bias35 – 406Poly-Pro

Sites

Active site1861Proton acceptor
Binding site931ATP By similarity

Amino acid modifications

Modified residue91Phosphoserine Ref.7
Modified residue251Phosphothreonine Ref.7
Modified residue2221Phosphothreonine; by MAPK14 Ref.7
Modified residue2721Phosphoserine; by MAPK14 Ref.7
Modified residue3281Phosphoserine; by autocatalysis By similarity
Modified residue3341Phosphothreonine; by MAPK14 Ref.7
Cross-link353Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.25

Natural variations

Alternative sequence354 – 40047EEMTS…AALAH → GCLHDKNSDQATWLTRL in isoform 2.
VSP_004910
Natural variant1731A → G. Ref.35
Corresponds to variant rs35671930 [ dbSNP | Ensembl ].
VAR_040753
Natural variant3611A → S. Ref.35
Corresponds to variant rs55894011 [ dbSNP | Ensembl ].
VAR_040754

Experimental info

Mutagenesis931K → R: Kinase defective mutant, abolishes activity. Ref.14
Mutagenesis2071D → A: Kinase defective mutant, abolishes activity. Ref.7
Mutagenesis2221T → A: Strong decrease in kinase activity. Ref.7 Ref.14 Ref.15
Mutagenesis2221T → D: Mimicks phosphorylation state, leading to slight increase of basal kinase activity. Ref.7 Ref.14 Ref.15
Mutagenesis2221T → E: Mimicks phosphorylation state and constitutive protein kinase activity; when associated with E-334. Ref.7 Ref.14 Ref.15
Mutagenesis2721S → A: Strong decrease in kinase activity. Ref.7
Mutagenesis2721S → D: Mimicks phosphorylation state, leading to slight increase of basal kinase activity. Ref.7
Mutagenesis3341T → A: Slight decrease in kinase activity. Ref.7 Ref.14 Ref.15
Mutagenesis3341T → D or E: Mimicks phosphorylation state, leading to elevated basal kinase activity. Ref.7 Ref.14 Ref.15
Mutagenesis3341T → E: Mimicks phosphorylation state and constitutive protein kinase activity; when associated with E-222. Ref.7 Ref.14 Ref.15
Mutagenesis3531K → R: Induces decreased sumoylation and increase in protein kinase activity. Ref.25
Sequence conflict1161H → D in CAA53094. Ref.5
Sequence conflict247 – 2482WS → LV in CAA53094. Ref.5

Secondary structure

.................................................................... 400
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: E4EFFF11CCF288DC

FASTA40045,568
        10         20         30         40         50         60 
MLSNSQGQSP PVPFPAPAPP PQPPTPALPH PPAQPPPPPP QQFPQFHVKS GLQIKKNAII 

        70         80         90        100        110        120 
DDYKVTSQVL GLGINGKVLQ IFNKRTQEKF ALKMLQDCPK ARREVELHWR ASQCPHIVRI 

       130        140        150        160        170        180 
VDVYENLYAG RKCLLIVMEC LDGGELFSRI QDRGDQAFTE REASEIMKSI GEAIQYLHSI 

       190        200        210        220        230        240 
NIAHRDVKPE NLLYTSKRPN AILKLTDFGF AKETTSHNSL TTPCYTPYYV APEVLGPEKY 

       250        260        270        280        290        300 
DKSCDMWSLG VIMYILLCGY PPFYSNHGLA ISPGMKTRIR MGQYEFPNPE WSEVSEEVKM 

       310        320        330        340        350        360 
LIRNLLKTEP TQRMTITEFM NHPWIMQSTK VPQTPLHTSR VLKEDKERWE DVKEEMTSAL 

       370        380        390        400 
ATMRVDYEQI KIKKIEDASN PLLLKRRKKA RALEAAALAH 

« Hide

Isoform 2 [UniParc].

Checksum: FF09AD93D4F73BDB
Show »

FASTA37042,203

References

« Hide 'large scale' references
[1]"The primary structure of a human MAP kinase activated protein kinase 2."
Zu Y.-L., Wu F., Gilchrist A., Ai Y., Labadia M.E., Huang C.K.
Biochem. Biophys. Res. Commun. 200:1118-1124(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Skin and Testis.
[5]"The substrate specificity and structure of mitogen-activated protein (MAP) kinase-activated protein kinase-2."
Stokoe D., Caudwell B., Cohen P.T.W., Cohen P.
Biochem. J. 296:843-849(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-400 (ISOFORM 1), FUNCTION.
[6]"Small heat shock proteins are molecular chaperones."
Jakob U., Gaestel M., Engel K., Buchner J.
J. Biol. Chem. 268:1517-1520(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HSPB1.
[7]"Identification of novel phosphorylation sites required for activation of 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) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-9; THR-25; THR-222; SER-272 AND THR-334, MUTAGENESIS OF ASP-207; THR-222; SER-272 AND THR-334.
[8]"A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP kinase-3 and their activation by cytokines and cellular stress."
Clifton A.D., Young P.R., Cohen P.
FEBS Lett. 392:209-214(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION IN PHOSPHORYLATION OF HSPB1.
[9]"Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor alpha by phosphorylation."
Rogalla T., Ehrnsperger M., Preville X., Kotlyarov A., Lutsch G., Ducasse C., Paul C., Wieske M., Arrigo A.P., Buchner J., Gaestel M.
J. Biol. Chem. 274:18947-18956(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HSPB1.
[10]"Inhibition of SAPK2a/p38 prevents hnRNP A0 phosphorylation by MAPKAP-K2 and its interaction with cytokine mRNAs."
Rousseau S., Morrice N., Peggie M., Campbell D.G., Gaestel M., Cohen P.
EMBO J. 21:6505-6514(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HNRNPA0.
[11]"Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2)."
Werz O., Szellas D., Steinhilber D., Radmark O.
J. Biol. Chem. 277:14793-14800(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF LOX5.
[12]"Affinity purification of ARE-binding proteins identifies polyA-binding protein 1 as a potential substrate in MK2-induced mRNA stabilization."
Bollig F., Winzen R., Gaestel M., Kostka S., Resch K., Holtmann H.
Biochem. Biophys. Res. Commun. 301:665-670(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PABPC1.
[13]"MAPK-activated protein kinase-2 participates in p38 MAPK-dependent and ERK-dependent functions in human neutrophils."
Coxon P.Y., Rane M.J., Uriarte S., Powell D.W., Singh S., Butt W., Chen Q., McLeish K.R.
Cell. Signal. 15:993-1001(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"Stabilization of urokinase and urokinase receptor mRNAs by HuR is linked to its cytoplasmic accumulation induced by activated mitogen-activated protein kinase-activated protein kinase 2."
Tran H., Maurer F., Nagamine Y.
Mol. Cell. Biol. 23:7177-7188(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF ELAVL1, MUTAGENESIS OF LYS-93; THR-222 AND THR-334.
[15]"MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule association and ARE-mRNA decay."
Stoecklin G., Stubbs T., Kedersha N., Wax S., Rigby W.F., Blackwell T.K., Anderson P.
EMBO J. 23:1313-1324(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF ZFP36, MUTAGENESIS OF THR-222 AND THR-334.
[16]"P66(ShcA) interacts with MAPKAP kinase 2 and regulates its activity."
Yannoni Y.M., Gaestel M., Lin L.L.
FEBS Lett. 564:205-211(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PHC2.
[17]"MAPKAP kinase-2 is a cell cycle checkpoint kinase that regulates the G2/M transition and S phase progression in response to UV irradiation."
Manke I.A., Nguyen A., Lim D., Stewart M.Q., Elia A.E., Yaffe M.B.
Mol. Cell 17:37-48(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CDC25B AND CDC25C.
[18]"MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin remodeling and cell migration."
Kobayashi M., Nishita M., Mishima T., Ohashi K., Mizuno K.
EMBO J. 25:713-726(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF LIMK1.
[19]"Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding."
Wang X., Khaleque M.A., Zhao M.J., Zhong R., Gaestel M., Calderwood S.K.
J. Biol. Chem. 281:782-791(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HSF1.
[20]"MAPKAPK2-mediated LSP1 phosphorylation and FMLP-induced neutrophil polarization."
Wu Y., Zhan L., Ai Y., Hannigan M., Gaestel M., Huang C.-K., Madri J.A.
Biochem. Biophys. Res. Commun. 358:170-175(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF LSP1.
[21]"Roles for TAB1 in regulating the IL-1-dependent phosphorylation of the TAB3 regulatory subunit and activity of the TAK1 complex."
Mendoza H., Campbell D.G., Burness K., Hastie J., Ronkina N., Shim J.H., Arthur J.S., Davis R.J., Gaestel M., Johnson G.L., Ghosh S., Cohen P.
Biochem. J. 409:711-722(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TAB3.
[22]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[23]"DNA damage activates a spatially distinct late cytoplasmic cell-cycle checkpoint network controlled by MK2-mediated RNA stabilization."
Reinhardt H.C., Hasskamp P., Schmedding I., Morandell S., van Vugt M.A., Wang X., Linding R., Ong S.E., Weaver D., Carr S.A., Yaffe M.B.
Mol. Cell 40:34-49(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HNRNPA0 AND PARN, SUBCELLULAR LOCATION.
[24]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]"MK2 SUMOylation regulates actin filament remodeling and subsequent migration in endothelial cells by inhibiting MK2 kinase and HSP27 phosphorylation."
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) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-353, MUTAGENESIS OF LYS-353.
[26]"MK2 and MK3--a pair of isoenzymes?"
Ronkina N., Kotlyarov A., Gaestel M.
Front. Biosci. 13:5511-5521(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[27]"Structure of mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 suggests a bifunctional switch that couples kinase activation with nuclear export."
Meng W., Swenson L.L., Fitzgibbon M.J., Hayakawa K., Ter Haar E., Behrens A.E., Fulghum J.R., Lippke J.A.
J. Biol. Chem. 277:37401-37405(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH ADP AND STAUROSPORINE, CATALYTIC ACTIVITY.
[28]"Catalytically active MAP KAP kinase 2 structures in complex with staurosporine and ADP reveal differences with the autoinhibited enzyme."
Underwood K.W., Parris K.D., Federico E., Mosyak L., Czerwinski R.M., Shane T., Taylor M., Svenson K., Liu Y., Hsiao C.L., Wolfrom S., Maguire M., Malakian K., Telliez J.B., Lin L.L., Kriz R.W., Seehra J., Somers W.S., Stahl M.L.
Structure 11:627-636(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
[29]"The discovery of carboline analogs as potent MAPKAP-K2 inhibitors."
Wu J.P., Wang J., Abeywardane A., Andersen D., Emmanuel M., Gautschi E., Goldberg D.R., Kashem M.A., Lukas S., Mao W., Martin L., Morwick T., Moss N., Pargellis C., Patel U.R., Patnaude L., Peet G.W., Skow D. expand/collapse author list , Snow R.J., Ward Y., Werneburg B., White A.
Bioorg. Med. Chem. Lett. 17:4664-4669(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 41-364 IN COMPLEX WITH CARBOLINE-BASED INHIBITORS.
[30]"Crystal structure of the p38 alpha-MAPKAP kinase 2 heterodimer."
ter Haar E., Prabhakar P., Liu X., Lepre C.
J. Biol. Chem. 282:9733-9739(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) IN COMPLEX WITH MAPK14, INTERACTION WITH MAPK14.
[31]Erratum
ter Haar E., Prabhakar P., Liu X., Lepre C.
J. Biol. Chem. 282:14684-14684(2007)
[32]"Pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2)."
Anderson D.R., Meyers M.J., Vernier W.F., Mahoney M.W., Kurumbail R.G., Caspers N., Poda G.I., Schindler J.F., Reitz D.B., Mourey R.J.
J. Med. Chem. 50:2647-2654(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) OF 45-371 IN COMPLEX WITH PYRROLOPYRIDINE INHIBITORS.
[33]"Structural basis for a high affinity inhibitor bound to protein kinase MK2."
Hillig R.C., Eberspaecher U., Monteclaro F., Huber M., Nguyen D., Mengel A., Muller-Tiemann B., Egner U.
J. Mol. Biol. 369:735-745(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 41-364 IN COMPLEX WITH PYRROLOPYRIDINE INHIBITOR.
[34]"Molecular basis of MAPK-activated protein kinase 2:p38 assembly."
White A., Pargellis C.A., Studts J.M., Werneburg B.G., Farmer B.T. II
Proc. Natl. Acad. Sci. U.S.A. 104:6353-6358(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 47-400 IN COMPLEX WITH MAPK14, INTERACTION WITH MAPK14.
[35]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLY-173 AND SER-361.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U12779 mRNA. Translation: AAA20851.1.
AL591846 Genomic DNA. Translation: CAI13543.1.
AL591846 Genomic DNA. Translation: CAI13544.1.
CH471100 Genomic DNA. Translation: EAW93526.1.
CH471100 Genomic DNA. Translation: EAW93529.1.
BC036060 mRNA. Translation: AAH36060.2.
BC052584 mRNA. Translation: AAH52584.1.
X75346 mRNA. Translation: CAA53094.1.
CCDSCCDS1466.1. [P49137-2]
CCDS31001.1. [P49137-1]
PIRJC2204.
S39793.
RefSeqNP_004750.1. NM_004759.4. [P49137-2]
NP_116584.2. NM_032960.3. [P49137-1]
UniGeneHs.643566.
Hs.713747.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1KWPX-ray2.80A/B1-400[»]
1NXKX-ray2.70A/B/C/D1-400[»]
1NY3X-ray3.00A1-400[»]
2JBOX-ray3.10A41-364[»]
2JBPX-ray3.31A/B/C/D/E/F/G/H/I/J/K/L41-364[»]
2OKRX-ray2.00C/F370-393[»]
2ONLX-ray4.00C/D1-400[»]
2OZAX-ray2.70A47-400[»]
2P3GX-ray3.80X45-371[»]
2PZYX-ray2.90A/B/C/D41-364[»]
3A2CX-ray2.90A/B/C/D/E/F/G/H/I/J/K/L41-364[»]
3FPMX-ray3.30A41-364[»]
3FYJX-ray3.80X45-371[»]
3FYKX-ray3.50X45-371[»]
3GOKX-ray3.20A/B/C/D/E/F/G/H/I/J/K/L41-364[»]
3KA0X-ray2.90A47-366[»]
3KC3X-ray2.90A/B/C/D/E/F/G/H/I/J/K/L41-364[»]
3KGAX-ray2.55A47-364[»]
3M2WX-ray2.41A47-364[»]
3M42X-ray2.68A47-364[»]
3R2BX-ray2.90A/B/C/D/E/F/G/H/I/J/K/L47-364[»]
3R2YX-ray3.00A46-364[»]
3R30X-ray3.20A46-364[»]
3WI6X-ray2.99A/B/C/D/E/F41-364[»]
ProteinModelPortalP49137.
SMRP49137. Positions 51-390.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114683. 33 interactions.
IntActP49137. 9 interactions.
MINTMINT-1539725.
STRING9606.ENSP00000356070.

Chemistry

BindingDBP49137.
ChEMBLCHEMBL2208.
GuidetoPHARMACOLOGY2094.

PTM databases

PhosphoSiteP49137.

Polymorphism databases

DMDM1346538.

Proteomic databases

MaxQBP49137.
PaxDbP49137.
PRIDEP49137.

Protocols and materials databases

DNASU9261.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000294981; ENSP00000294981; ENSG00000162889. [P49137-2]
ENST00000367103; ENSP00000356070; ENSG00000162889. [P49137-1]
ENST00000579291; ENSP00000461936; ENSG00000266641. [P49137-2]
ENST00000579635; ENSP00000462387; ENSG00000266641. [P49137-1]
GeneID9261.
KEGGhsa:9261.
UCSCuc001hel.2. human. [P49137-2]
uc001hem.2. human. [P49137-1]

Organism-specific databases

CTD9261.
GeneCardsGC01P206858.
HGNCHGNC:6887. MAPKAPK2.
HPACAB010297.
HPA045556.
MIM602006. gene.
neXtProtNX_P49137.
PharmGKBPA30631.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233031.
HOVERGENHBG106948.
InParanoidP49137.
KOK04443.
OMALQMLQDC.
OrthoDBEOG786H3M.
PhylomeDBP49137.
TreeFamTF312891.

Enzyme and pathway databases

BioCycMetaCyc:HS08751-MONOMER.
BRENDA2.7.11.1. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_120956. Cellular responses to stress.
REACT_21257. Metabolism of RNA.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
REACT_71. Gene Expression.
SignaLinkP49137.

Gene expression databases

BgeeP49137.
CleanExHS_MAPKAPK2.
GenevestigatorP49137.

Family and domain databases

Gene3D4.10.1170.10. 1 hit.
InterProIPR011009. Kinase-like_dom.
IPR027442. MAPKAPK_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMAPKAPK2. human.
EvolutionaryTraceP49137.
GeneWikiMAPKAPK2.
GenomeRNAi9261.
NextBio34715.
PROP49137.
SOURCESearch...

Entry information

Entry nameMAPK2_HUMAN
AccessionPrimary (citable) accession number: P49137
Secondary accession number(s): Q5SY30, Q5SY41, Q8IYD6
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: July 9, 2014
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM