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Q66H84 (MAPK3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
MAP kinase-activated protein kinase 3

Short name=MAPK-activated protein kinase 3
Short name=MAPKAP kinase 3
Short name=MAPKAP-K3
Short name=MAPKAPK-3
Short name=MK-3
EC=2.7.11.1
Gene names
Name:Mapkapk3
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length384 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling 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. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, 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, such as 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. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited by ligand 5B (2'-[2-(1,3-benzodioxol-5-yl)pyrimidin-4-yl]-5',6'-dihydrospiro[piperidine-4,7'-pyrrolo[3,2-c]pyridin]- 4'(1'h)-one) and ligand P4O (2-[2-(2-fluorophenyl)pyridin-4-yl]-1,5,6,7-tetrahydro- 4h-pyrrolo[3,2-c]pyridin-4-one), 2 ATP-competitive inhibitors By similarity.

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 TCF3 and with polycomb proteins, such as PCH2 and BMI1/PCGF4 By similarity.

Subcellular location

Nucleus By similarity. Cytoplasm By similarity. Note: Predominantly located in the nucleus, when activated it translocates to the cytoplasm By similarity.

Post-translational modification

Phosphorylated and activated by MAPK1/ERK2 and MAPK3/ERK1 By similarity. Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-203, Ser-253 and Thr-315 By similarity.

Sequence similarities

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

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 384384MAP kinase-activated protein kinase 3
PRO_0000086295

Regions

Domain46 – 306261Protein kinase
Nucleotide binding52 – 609ATP By similarity
Region309 – 34537Autoinhibitory helix By similarity
Region347 – 37125p38 MAPK-binding site By similarity
Motif337 – 34610Nuclear export signal (NES) By similarity
Motif352 – 3554Bipartite nuclear localization signal 1 By similarity
Motif366 – 3705Bipartite nuclear localization signal 2 By similarity

Sites

Active site1681Proton acceptor By similarity
Binding site751ATP By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue2031Phosphothreonine; by MAPK14 By similarity
Modified residue2531Phosphoserine; by MAPK14 By similarity
Modified residue3091Phosphoserine; by autocatalysis By similarity
Modified residue3151Phosphothreonine; by MAPK14 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q66H84 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: E094358C901F7E70

FASTA38443,222
        10         20         30         40         50         60 
MDGETAGEKG SLVPQPGALG APALGGAPAP GVRREPKKYA VTDDYQLSKQ VLGLGVNGKV 

        70         80         90        100        110        120 
LECYHRRSGQ KCALKLLYDS PKARQEVDHH WQASGGPHIV RILDVYENMH HGKRCLLIVM 

       130        140        150        160        170        180 
ECMEGGELFS RIQERGDQAF TEREAAEIMR DIGTAIQFLH SQNIAHRDVK PENLLYTSKE 

       190        200        210        220        230        240 
KDAVLKLTDF GFAKETTQNA LQTPCYTPYY VAPEVLGPEK YDKSCDMWSL GVIMYILLCG 

       250        260        270        280        290        300 
FPPFYSNTGQ AISPGMKRRI RLGQYGFPKP EWADVSEDAK QLIRLLLKTD PTERLTIMQF 

       310        320        330        340        350        360 
MNHPWINQSM EVPQTPLHTA RVLEEDKDHW DDVKEEMTSA LATMRVDYDQ VKIKDLKTSN 

       370        380 
NRLLNKRRKK QGGSSSASPG CNNQ 

« Hide

References

[1]"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].
Tissue: Kidney.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC081974 mRNA. Translation: AAH81974.1.
RefSeqNP_001012127.1. NM_001012127.1.
XP_006243838.1. XM_006243776.1.
UniGeneRn.8789.

3D structure databases

ProteinModelPortalQ66H84.
SMRQ66H84. Positions 37-370.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000020065.

PTM databases

PhosphoSiteQ66H84.

Proteomic databases

PaxDbQ66H84.
PRIDEQ66H84.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000020065; ENSRNOP00000020065; ENSRNOG00000014832.
GeneID315994.
KEGGrno:315994.
UCSCRGD:1304980. rat.

Organism-specific databases

CTD7867.
RGD1304980. Mapkapk3.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110339.
HOGENOMHOG000233031.
HOVERGENHBG106948.
InParanoidQ66H84.
KOK04444.
OMAIRMGQYG.
OrthoDBEOG786H3M.
PhylomeDBQ66H84.
TreeFamTF312891.

Gene expression databases

GenevestigatorQ66H84.

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

NextBio670215.
PROQ66H84.

Entry information

Entry nameMAPK3_RAT
AccessionPrimary (citable) accession number: Q66H84
Entry history
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: October 11, 2004
Last modified: April 16, 2014
This is version 88 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families