P49137 · MAPK2_HUMAN
- ProteinMAP kinase-activated protein kinase 2
- GeneMAPKAPK2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids400 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of 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 the regulation of 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 transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734).
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 stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Activity regulation
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMAP kinase-activated protein kinase 2
- EC number
- Short namesMAPK-activated protein kinase 2; MAPKAP kinase 2; MAPKAP-K2; MAPKAPK-2; MK-2; MK2
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP49137
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 93 | Kinase defective mutant, abolishes activity. | ||||
Sequence: K → R | ||||||
Natural variant | VAR_040753 | 173 | in dbSNP:rs35671930 | |||
Sequence: A → G | ||||||
Mutagenesis | 207 | Kinase defective mutant, abolishes activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 222 | Strong decrease in kinase activity. | ||||
Sequence: T → A | ||||||
Mutagenesis | 222 | Mimicks phosphorylation state, leading to slight increase of basal kinase activity. | ||||
Sequence: T → D | ||||||
Mutagenesis | 222 | Mimicks phosphorylation state and constitutive protein kinase activity; when associated with E-334. | ||||
Sequence: T → E | ||||||
Mutagenesis | 272 | Strong decrease in kinase activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 272 | Mimicks phosphorylation state, leading to slight increase of basal kinase activity. | ||||
Sequence: S → D | ||||||
Mutagenesis | 334 | Slight decrease in kinase activity. | ||||
Sequence: T → A | ||||||
Mutagenesis | 334 | Mimicks phosphorylation state, leading to elevated basal kinase activity. | ||||
Sequence: T → D or E | ||||||
Mutagenesis | 334 | Mimicks phosphorylation state and constitutive protein kinase activity; when associated with E-222. | ||||
Sequence: T → E | ||||||
Mutagenesis | 353 | Induces decreased sumoylation and increase in protein kinase activity. | ||||
Sequence: K → R | ||||||
Natural variant | VAR_040754 | 361 | in dbSNP:rs55894011 | |||
Sequence: A → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 324 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data), cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000086288 | 1-400 | UniProt | MAP kinase-activated protein kinase 2 | |||
Sequence: MLSNSQGQSPPVPFPAPAPPPQPPTPALPHPPAQPPPPPPQQFPQFHVKSGLQIKKNAIIDDYKVTSQVLGLGINGKVLQIFNKRTQEKFALKMLQDCPKARREVELHWRASQCPHIVRIVDVYENLYAGRKCLLIVMECLDGGELFSRIQDRGDQAFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSKRPNAILKLTDFGFAKETTSHNSLTTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSNHGLAISPGMKTRIRMGQYEFPNPEWSEVSEEVKMLIRNLLKTEPTQRMTITEFMNHPWIMQSTKVPQTPLHTSRVLKEDKERWEDVKEEMTSALATMRVDYEQIKIKKIEDASNPLLLKRRKKARALEAAALAH | |||||||
Modified residue | 9 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 25 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 222 | UniProt | Phosphothreonine; by MAPK14 | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 222 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 272 | UniProt | Phosphoserine; by MAPK14 | ||||
Sequence: S | |||||||
Modified residue | 328 | UniProt | Phosphoserine; by autocatalysis | ||||
Sequence: S | |||||||
Modified residue | 334 | UniProt | Phosphothreonine; by MAPK14 | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 334 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Cross-link | 353 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Interacts with PHC2 (PubMed:15094067).
Interacts with HSF1 (PubMed:16278218).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P49137 | HSF1 Q00613 | 5 | EBI-993299, EBI-719620 | |
BINARY | P49137 | HSPB1 P04792 | 3 | EBI-993299, EBI-352682 | |
BINARY | P49137 | MAPK14 Q16539 | 15 | EBI-993299, EBI-73946 | |
XENO | P49137 | Phc2 Q9QWH1 | 2 | EBI-993299, EBI-642357 | |
XENO | P49137-1 | Mapk14 P47811 | 2 | EBI-15629963, EBI-298727 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-43 | Disordered | ||||
Sequence: MLSNSQGQSPPVPFPAPAPPPQPPTPALPHPPAQPPPPPPQQF | ||||||
Compositional bias | 10-43 | Pro residues | ||||
Sequence: PPVPFPAPAPPPQPPTPALPHPPAQPPPPPPQQF | ||||||
Domain | 64-325 | Protein kinase | ||||
Sequence: KVTSQVLGLGINGKVLQIFNKRTQEKFALKMLQDCPKARREVELHWRASQCPHIVRIVDVYENLYAGRKCLLIVMECLDGGELFSRIQDRGDQAFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSKRPNAILKLTDFGFAKETTSHNSLTTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSNHGLAISPGMKTRIRMGQYEFPNPEWSEVSEEVKMLIRNLLKTEPTQRMTITEFMNHPWI | ||||||
Region | 328-364 | Autoinhibitory helix | ||||
Sequence: STKVPQTPLHTSRVLKEDKERWEDVKEEMTSALATMR | ||||||
Motif | 356-365 | Nuclear export signal (NES) | ||||
Sequence: MTSALATMRV | ||||||
Region | 366-390 | p38 MAPK-binding site | ||||
Sequence: DYEQIKIKKIEDASNPLLLKRRKKA | ||||||
Motif | 371-374 | Bipartite nuclear localization signal 1 | ||||
Sequence: KIKK | ||||||
Motif | 385-389 | Bipartite nuclear localization signal 2 | ||||
Sequence: KRRKK |
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
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.
- Name1
- NoteHas a nuclear localization signal.
- Length400
- Mass (Da)45,568
- Last updated1996-02-01 v1
- ChecksumE4EFFF11CCF288DC
P49137-2
- Name2
- Differences from canonical
- 354-400: EEMTSALATMRVDYEQIKIKKIEDASNPLLLKRRKKARALEAAALAH → GCLHDKNSDQATWLTRL
Features
Showing features for compositional bias, sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 10-43 | Pro residues | ||||
Sequence: PPVPFPAPAPPPQPPTPALPHPPAQPPPPPPQQF | ||||||
Sequence conflict | 116 | in Ref. 5; CAA53094 | ||||
Sequence: H → D | ||||||
Sequence conflict | 247-248 | in Ref. 5; CAA53094 | ||||
Sequence: WS → LV | ||||||
Alternative sequence | VSP_004910 | 354-400 | in isoform 2 | |||
Sequence: EEMTSALATMRVDYEQIKIKKIEDASNPLLLKRRKKARALEAAALAH → GCLHDKNSDQATWLTRL |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U12779 EMBL· GenBank· DDBJ | AAA20851.1 EMBL· GenBank· DDBJ | mRNA | ||
AL591846 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471100 EMBL· GenBank· DDBJ | EAW93526.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471100 EMBL· GenBank· DDBJ | EAW93529.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC036060 EMBL· GenBank· DDBJ | AAH36060.2 EMBL· GenBank· DDBJ | mRNA | ||
BC052584 EMBL· GenBank· DDBJ | AAH52584.1 EMBL· GenBank· DDBJ | mRNA | ||
X75346 EMBL· GenBank· DDBJ | CAA53094.1 EMBL· GenBank· DDBJ | mRNA |