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P49137

- MAPK2_HUMAN

UniProt

P49137 - MAPK2_HUMAN

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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

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 kinase activity Source: ProtInc
  3. protein serine/threonine kinase activity Source: UniProtKB
  4. 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
Complete GO annotation...

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_228166. VEGFA-VEGFR2 Pathway.
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
Complete GO annotation...

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 – 473Combined sources
Beta strandi48 – 503Combined sources
Helixi59 – 613Combined sources
Beta strandi63 – 7311Combined sources
Beta strandi76 – 838Combined sources
Turni84 – 863Combined sources
Beta strandi89 – 968Combined sources
Helixi99 – 11113Combined sources
Beta strandi114 – 1174Combined sources
Beta strandi120 – 1289Combined sources
Beta strandi131 – 1388Combined sources
Beta strandi143 – 1453Combined sources
Helixi146 – 1527Combined sources
Helixi160 – 17920Combined sources
Helixi189 – 1913Combined sources
Beta strandi192 – 1987Combined sources
Beta strandi203 – 2053Combined sources
Beta strandi212 – 2143Combined sources
Beta strandi228 – 2303Combined sources
Helixi232 – 2343Combined sources
Helixi239 – 2424Combined sources
Helixi243 – 25816Combined sources
Beta strandi267 – 2693Combined sources
Helixi275 – 2817Combined sources
Beta strandi283 – 2853Combined sources
Helixi288 – 2914Combined sources
Helixi296 – 30510Combined sources
Turni310 – 3123Combined sources
Helixi316 – 3205Combined sources
Helixi323 – 3264Combined sources
Helixi328 – 3303Combined sources
Beta strandi335 – 3373Combined sources
Helixi338 – 3447Combined sources
Helixi346 – 3483Combined sources
Helixi349 – 36315Combined sources
Turni375 – 3773Combined sources
Helixi381 – 3899Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00770000120509.
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.
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

        10         20         30         40         50
MLSNSQGQSP PVPFPAPAPP PQPPTPALPH PPAQPPPPPP QQFPQFHVKS
60 70 80 90 100
GLQIKKNAII DDYKVTSQVL GLGINGKVLQ IFNKRTQEKF ALKMLQDCPK
110 120 130 140 150
ARREVELHWR ASQCPHIVRI VDVYENLYAG RKCLLIVMEC LDGGELFSRI
160 170 180 190 200
QDRGDQAFTE REASEIMKSI GEAIQYLHSI NIAHRDVKPE NLLYTSKRPN
210 220 230 240 250
AILKLTDFGF AKETTSHNSL TTPCYTPYYV APEVLGPEKY DKSCDMWSLG
260 270 280 290 300
VIMYILLCGY PPFYSNHGLA ISPGMKTRIR MGQYEFPNPE WSEVSEEVKM
310 320 330 340 350
LIRNLLKTEP TQRMTITEFM NHPWIMQSTK VPQTPLHTSR VLKEDKERWE
360 370 380 390 400
DVKEEMTSAL ATMRVDYEQI KIKKIEDASN PLLLKRRKKA RALEAAALAH

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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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.
GeneTreei ENSGT00770000120509.
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_228166. VEGFA-VEGFR2 Pathway.
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.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 155 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