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P49137

- MAPK2_HUMAN

UniProt

P49137 - MAPK2_HUMAN

Protein

MAP kinase-activated protein kinase 2

Gene

MAPKAPK2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 153 (01 Oct 2014)
      Sequence version 1 (01 Feb 1996)
      Previous versions | rss
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    Functioni

    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 RPS6KA3.16 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.2 Publications

    Enzyme regulationi

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei93 – 931ATPPROSITE-ProRule annotation
    Active sitei186 – 1861Proton acceptor

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi70 – 789ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. protein kinase activity Source: ProtInc
    4. protein serine/threonine kinase activity Source: UniProtKB
    5. signal transducer activity Source: ProtInc

    GO - Biological processi

    1. 3'-UTR-mediated mRNA stabilization Source: UniProtKB
    2. activation of MAPK activity Source: Reactome
    3. arachidonic acid metabolic process Source: Reactome
    4. cellular response to DNA damage stimulus Source: UniProtKB
    5. cellular response to vascular endothelial growth factor stimulus Source: BHF-UCL
    6. G2 DNA damage checkpoint Source: UniProtKB
    7. gene expression Source: Reactome
    8. inflammatory response Source: UniProtKB
    9. innate immune response Source: Reactome
    10. inner ear development Source: Ensembl
    11. leukotriene metabolic process Source: Reactome
    12. macropinocytosis Source: UniProtKB
    13. MAPK cascade Source: ProtInc
    14. mRNA metabolic process Source: Reactome
    15. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
    16. MyD88-independent toll-like receptor signaling pathway Source: Reactome
    17. neurotrophin TRK receptor signaling pathway Source: Reactome
    18. peptidyl-serine phosphorylation Source: BHF-UCL
    19. protein phosphorylation Source: ProtInc
    20. Ras protein signal transduction Source: Reactome
    21. regulation of interleukin-6 production Source: UniProtKB
    22. regulation of tumor necrosis factor production Source: UniProtKB
    23. response to cytokine Source: UniProtKB
    24. response to lipopolysaccharide Source: UniProtKB
    25. response to stress Source: UniProtKB
    26. RNA metabolic process Source: Reactome
    27. small molecule metabolic process Source: Reactome
    28. stress-activated MAPK cascade Source: Reactome
    29. toll-like receptor 10 signaling pathway Source: Reactome
    30. toll-like receptor 2 signaling pathway Source: Reactome
    31. toll-like receptor 3 signaling pathway Source: Reactome
    32. toll-like receptor 4 signaling pathway Source: Reactome
    33. toll-like receptor 5 signaling pathway Source: Reactome
    34. toll-like receptor 9 signaling pathway Source: Reactome
    35. toll-like receptor signaling pathway Source: UniProtKB
    36. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
    37. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
    38. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
    39. vascular endothelial growth factor receptor signaling pathway Source: BHF-UCL

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    DNA damage

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS08751-MONOMER.
    BRENDAi2.7.11.1. 2681.
    ReactomeiREACT_12065. p38MAPK events.
    REACT_12524. CREB phosphorylation.
    REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_200780. Regulation of HSF1-mediated heat shock response.
    REACT_21399. activated TAK1 mediates p38 MAPK activation.
    REACT_24915. Butyrate Response Factor 1 (BRF1) destabilizes mRNA.
    REACT_25064. Tristetraprolin (TTP) destabilizes mRNA.
    SignaLinkiP49137.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    MAP kinase-activated protein kinase 2 (EC:2.7.11.1)
    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
    Gene namesi
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:6887. MAPKAPK2.

    Subcellular locationi

    Cytoplasm 1 Publication. Nucleus 1 Publication
    Note: Phosphorylation and subsequent activation releases the autoinhibitory helix, resulting in the export from the nucleus into the cytoplasm.

    GO - Cellular componenti

    1. centrosome Source: HPA
    2. cytoplasm Source: UniProtKB
    3. cytosol Source: Reactome
    4. nucleoplasm Source: Reactome
    5. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi93 – 931K → R: Kinase defective mutant, abolishes activity. 1 Publication
    Mutagenesisi207 – 2071D → A: Kinase defective mutant, abolishes activity. 1 Publication
    Mutagenesisi222 – 2221T → A: Strong decrease in kinase activity. 3 Publications
    Mutagenesisi222 – 2221T → D: Mimicks phosphorylation state, leading to slight increase of basal kinase activity. 3 Publications
    Mutagenesisi222 – 2221T → E: Mimicks phosphorylation state and constitutive protein kinase activity; when associated with E-334. 3 Publications
    Mutagenesisi272 – 2721S → A: Strong decrease in kinase activity. 1 Publication
    Mutagenesisi272 – 2721S → D: Mimicks phosphorylation state, leading to slight increase of basal kinase activity. 1 Publication
    Mutagenesisi334 – 3341T → A: Slight decrease in kinase activity. 3 Publications
    Mutagenesisi334 – 3341T → D or E: Mimicks phosphorylation state, leading to elevated basal kinase activity. 3 Publications
    Mutagenesisi334 – 3341T → E: Mimicks phosphorylation state and constitutive protein kinase activity; when associated with E-222. 3 Publications
    Mutagenesisi353 – 3531K → R: Induces decreased sumoylation and increase in protein kinase activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA30631.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 400400MAP kinase-activated protein kinase 2PRO_0000086288Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei9 – 91Phosphoserine1 Publication
    Modified residuei25 – 251Phosphothreonine1 Publication
    Modified residuei222 – 2221Phosphothreonine; by MAPK141 Publication
    Modified residuei272 – 2721Phosphoserine; by MAPK141 Publication
    Modified residuei328 – 3281Phosphoserine; by autocatalysisBy similarity
    Modified residuei334 – 3341Phosphothreonine; by MAPK141 Publication
    Cross-linki353 – 353Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

    Post-translational modificationi

    Sumoylation inhibits the protein kinase activity.1 Publication
    Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-222, Ser-272 and Thr-334.1 Publication

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP49137.
    PaxDbiP49137.
    PRIDEiP49137.

    PTM databases

    PhosphoSiteiP49137.

    Expressioni

    Tissue specificityi

    Expressed in all tissues examined.

    Gene expression databases

    BgeeiP49137.
    CleanExiHS_MAPKAPK2.
    GenevestigatoriP49137.

    Organism-specific databases

    HPAiCAB010297.
    HPA045556.

    Interactioni

    Subunit structurei

    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 PHC2.7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    HSF1Q006135EBI-993299,EBI-719620
    HSPB1P047923EBI-993299,EBI-352682
    MAPK14Q165395EBI-993299,EBI-73946
    Phc2Q9QWH12EBI-993299,EBI-642357From a different organism.

    Protein-protein interaction databases

    BioGridi114683. 34 interactions.
    DIPiDIP-35671N.
    IntActiP49137. 12 interactions.
    MINTiMINT-1539725.
    STRINGi9606.ENSP00000356070.

    Structurei

    Secondary structure

    1
    400
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi45 – 473
    Beta strandi48 – 503
    Helixi59 – 613
    Beta strandi63 – 7311
    Beta strandi76 – 838
    Turni84 – 863
    Beta strandi89 – 968
    Helixi99 – 11113
    Beta strandi114 – 1174
    Beta strandi120 – 1289
    Beta strandi131 – 1388
    Beta strandi143 – 1453
    Helixi146 – 1527
    Helixi160 – 17920
    Helixi189 – 1913
    Beta strandi192 – 1987
    Beta strandi203 – 2053
    Beta strandi212 – 2143
    Beta strandi228 – 2303
    Helixi232 – 2343
    Helixi239 – 2424
    Helixi243 – 25816
    Beta strandi267 – 2693
    Helixi275 – 2817
    Beta strandi283 – 2853
    Helixi288 – 2914
    Helixi296 – 30510
    Turni310 – 3123
    Helixi316 – 3205
    Helixi323 – 3264
    Helixi328 – 3303
    Beta strandi335 – 3373
    Helixi338 – 3447
    Helixi346 – 3483
    Helixi349 – 36315
    Turni375 – 3773
    Helixi381 – 3899

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliP49137.
    SMRiP49137. Positions 51-390.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP49137.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini64 – 325262Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni139 – 1413Staurosporine binding
    Regioni328 – 36437Autoinhibitory helixBy similarityAdd
    BLAST
    Regioni366 – 39025p38 MAPK-binding siteAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi356 – 36510Nuclear export signal (NES)
    Motifi371 – 3744Bipartite nuclear localization signal 1
    Motifi385 – 3895Bipartite nuclear localization signal 2

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi10 – 4031Pro-richAdd
    BLAST
    Compositional biasi35 – 406Poly-Pro

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233031.
    HOVERGENiHBG106948.
    InParanoidiP49137.
    KOiK04443.
    OMAiLQMLQDC.
    OrthoDBiEOG786H3M.
    PhylomeDBiP49137.
    TreeFamiTF312891.

    Family and domain databases

    Gene3Di4.10.1170.10. 1 hit.
    InterProiIPR011009. 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]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P49137-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MLSNSQGQSP PVPFPAPAPP PQPPTPALPH PPAQPPPPPP QQFPQFHVKS    50
    GLQIKKNAII DDYKVTSQVL GLGINGKVLQ IFNKRTQEKF ALKMLQDCPK 100
    ARREVELHWR ASQCPHIVRI VDVYENLYAG RKCLLIVMEC LDGGELFSRI 150
    QDRGDQAFTE REASEIMKSI GEAIQYLHSI NIAHRDVKPE NLLYTSKRPN 200
    AILKLTDFGF AKETTSHNSL TTPCYTPYYV APEVLGPEKY DKSCDMWSLG 250
    VIMYILLCGY PPFYSNHGLA ISPGMKTRIR MGQYEFPNPE WSEVSEEVKM 300
    LIRNLLKTEP TQRMTITEFM NHPWIMQSTK VPQTPLHTSR VLKEDKERWE 350
    DVKEEMTSAL ATMRVDYEQI KIKKIEDASN PLLLKRRKKA RALEAAALAH 400

    Note: Has a nuclear localization signal.

    Length:400
    Mass (Da):45,568
    Last modified:February 1, 1996 - v1
    Checksum:iE4EFFF11CCF288DC
    GO
    Isoform 2 (identifier: P49137-2) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:370
    Mass (Da):42,203
    Checksum:iFF09AD93D4F73BDB
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti116 – 1161H → D in CAA53094. (PubMed:8280084)Curated
    Sequence conflicti247 – 2482WS → LV in CAA53094. (PubMed:8280084)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti173 – 1731A → G.1 Publication
    Corresponds to variant rs35671930 [ dbSNP | Ensembl ].
    VAR_040753
    Natural varianti361 – 3611A → S.1 Publication
    Corresponds to variant rs55894011 [ dbSNP | Ensembl ].
    VAR_040754

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei354 – 40047EEMTS…AALAH → GCLHDKNSDQATWLTRL in isoform 2. 1 PublicationVSP_004910Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS1466.1. [P49137-2]
    CCDS31001.1. [P49137-1]
    PIRiJC2204.
    S39793.
    RefSeqiNP_004750.1. NM_004759.4. [P49137-2]
    NP_116584.2. NM_032960.3. [P49137-1]
    UniGeneiHs.643566.
    Hs.713747.

    Genome annotation databases

    EnsembliENST00000294981; ENSP00000294981; ENSG00000162889. [P49137-2]
    ENST00000367103; ENSP00000356070; ENSG00000162889. [P49137-1]
    GeneIDi9261.
    KEGGihsa:9261.
    UCSCiuc001hel.2. human. [P49137-2]
    uc001hem.2. human. [P49137-1]

    Polymorphism databases

    DMDMi1346538.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS1466.1. [P49137-2 ]
    CCDS31001.1. [P49137-1 ]
    PIRi JC2204.
    S39793.
    RefSeqi NP_004750.1. NM_004759.4. [P49137-2 ]
    NP_116584.2. NM_032960.3. [P49137-1 ]
    UniGenei Hs.643566.
    Hs.713747.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1KWP X-ray 2.80 A/B 1-400 [» ]
    1NXK X-ray 2.70 A/B/C/D 1-400 [» ]
    1NY3 X-ray 3.00 A 1-400 [» ]
    2JBO X-ray 3.10 A 41-364 [» ]
    2JBP X-ray 3.31 A/B/C/D/E/F/G/H/I/J/K/L 41-364 [» ]
    2OKR X-ray 2.00 C/F 370-393 [» ]
    2ONL X-ray 4.00 C/D 1-400 [» ]
    2OZA X-ray 2.70 A 47-400 [» ]
    2P3G X-ray 3.80 X 45-371 [» ]
    2PZY X-ray 2.90 A/B/C/D 41-364 [» ]
    3A2C X-ray 2.90 A/B/C/D/E/F/G/H/I/J/K/L 41-364 [» ]
    3FPM X-ray 3.30 A 41-364 [» ]
    3FYJ X-ray 3.80 X 45-371 [» ]
    3FYK X-ray 3.50 X 45-371 [» ]
    3GOK X-ray 3.20 A/B/C/D/E/F/G/H/I/J/K/L 41-364 [» ]
    3KA0 X-ray 2.90 A 47-366 [» ]
    3KC3 X-ray 2.90 A/B/C/D/E/F/G/H/I/J/K/L 41-364 [» ]
    3KGA X-ray 2.55 A 47-364 [» ]
    3M2W X-ray 2.41 A 47-364 [» ]
    3M42 X-ray 2.68 A 47-364 [» ]
    3R2B X-ray 2.90 A/B/C/D/E/F/G/H/I/J/K/L 47-364 [» ]
    3R2Y X-ray 3.00 A 46-364 [» ]
    3R30 X-ray 3.20 A 46-364 [» ]
    3WI6 X-ray 2.99 A/B/C/D/E/F 41-364 [» ]
    ProteinModelPortali P49137.
    SMRi P49137. Positions 51-390.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114683. 34 interactions.
    DIPi DIP-35671N.
    IntActi P49137. 12 interactions.
    MINTi MINT-1539725.
    STRINGi 9606.ENSP00000356070.

    Chemistry

    BindingDBi P49137.
    ChEMBLi CHEMBL2208.
    GuidetoPHARMACOLOGYi 2094.

    PTM databases

    PhosphoSitei P49137.

    Polymorphism databases

    DMDMi 1346538.

    Proteomic databases

    MaxQBi P49137.
    PaxDbi P49137.
    PRIDEi P49137.

    Protocols and materials databases

    DNASUi 9261.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000294981 ; ENSP00000294981 ; ENSG00000162889 . [P49137-2 ]
    ENST00000367103 ; ENSP00000356070 ; ENSG00000162889 . [P49137-1 ]
    GeneIDi 9261.
    KEGGi hsa:9261.
    UCSCi uc001hel.2. human. [P49137-2 ]
    uc001hem.2. human. [P49137-1 ]

    Organism-specific databases

    CTDi 9261.
    GeneCardsi GC01P206858.
    HGNCi HGNC:6887. MAPKAPK2.
    HPAi CAB010297.
    HPA045556.
    MIMi 602006. gene.
    neXtProti NX_P49137.
    PharmGKBi PA30631.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233031.
    HOVERGENi HBG106948.
    InParanoidi P49137.
    KOi K04443.
    OMAi LQMLQDC.
    OrthoDBi EOG786H3M.
    PhylomeDBi P49137.
    TreeFami TF312891.

    Enzyme and pathway databases

    BioCyci MetaCyc:HS08751-MONOMER.
    BRENDAi 2.7.11.1. 2681.
    Reactomei REACT_12065. p38MAPK events.
    REACT_12524. CREB phosphorylation.
    REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_200780. Regulation of HSF1-mediated heat shock response.
    REACT_21399. activated TAK1 mediates p38 MAPK activation.
    REACT_24915. Butyrate Response Factor 1 (BRF1) destabilizes mRNA.
    REACT_25064. Tristetraprolin (TTP) destabilizes mRNA.
    SignaLinki P49137.

    Miscellaneous databases

    ChiTaRSi MAPKAPK2. human.
    EvolutionaryTracei P49137.
    GeneWikii MAPKAPK2.
    GenomeRNAii 9261.
    NextBioi 34715.
    PROi P49137.
    SOURCEi Search...

    Gene expression databases

    Bgeei P49137.
    CleanExi HS_MAPKAPK2.
    Genevestigatori P49137.

    Family and domain databases

    Gene3Di 4.10.1170.10. 1 hit.
    InterProi IPR011009. 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 ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. 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. 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. 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. 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. 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.
      , 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.

    Entry informationi

    Entry nameiMAPK2_HUMAN
    AccessioniPrimary (citable) accession number: P49137
    Secondary accession number(s): Q5SY30, Q5SY41, Q8IYD6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: February 1, 1996
    Last modified: October 1, 2014
    This is version 153 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3