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Protein

MAP kinase-activated protein kinase 3

Gene

Mapkapk3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei75 – 751ATPPROSITE-ProRule annotation
Active sitei168 – 1681Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi52 – 609ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. calcium-dependent protein serine/threonine kinase activity Source: GO_Central
  3. calmodulin binding Source: GO_Central
  4. calmodulin-dependent protein kinase activity Source: GO_Central
  5. mitogen-activated protein kinase binding Source: GO_Central
  6. protein serine/threonine kinase activity Source: UniProtKB
  7. signal transducer activity Source: GO_Central

GO - Biological processi

  1. cell surface receptor signaling pathway Source: GO_Central
  2. macropinocytosis Source: UniProtKB
  3. MAPK cascade Source: GO_Central
  4. peptidyl-serine phosphorylation Source: GO_Central
  5. protein autophosphorylation Source: GO_Central
  6. response to cytokine Source: UniProtKB
  7. response to lipopolysaccharide Source: UniProtKB
  8. toll-like receptor signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_301330. VEGFA-VEGFR2 Pathway.
REACT_302239. Oxidative Stress Induced Senescence.
REACT_312904. p38MAPK events.
REACT_347906. activated TAK1 mediates p38 MAPK activation.

Names & Taxonomyi

Protein namesi
Recommended name:
MAP kinase-activated protein kinase 3 (EC:2.7.11.1)
Short name:
MAPK-activated protein kinase 3
Short name:
MAPKAP kinase 3
Short name:
MAPKAP-K3
Short name:
MAPKAPK-3
Short name:
MK-3
Gene namesi
Name:Mapkapk3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi1304980. Mapkapk3.

Subcellular locationi

  1. Nucleus By similarity
  2. Cytoplasm By similarity

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

GO - Cellular componenti

  1. cytoplasm Source: GO_Central
  2. nuclear membrane Source: Ensembl
  3. nucleus Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 384384MAP kinase-activated protein kinase 3PRO_0000086295Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei203 – 2031Phosphothreonine; by MAPK14By similarity
Modified residuei253 – 2531Phosphoserine; by MAPK14By similarity
Modified residuei309 – 3091Phosphoserine; by autocatalysisBy similarity
Modified residuei315 – 3151Phosphothreonine; by MAPK14By similarity

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ66H84.
PRIDEiQ66H84.

PTM databases

PhosphoSiteiQ66H84.

Expressioni

Gene expression databases

GenevestigatoriQ66H84.

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000020065.

Structurei

3D structure databases

ProteinModelPortaliQ66H84.
SMRiQ66H84. Positions 37-370.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini46 – 306261Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni309 – 34537Autoinhibitory helixBy similarityAdd
BLAST
Regioni347 – 37125p38 MAPK-binding siteBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi337 – 34610Nuclear export signal (NES)By similarity
Motifi352 – 3554Bipartite nuclear localization signal 1By similarity
Motifi366 – 3705Bipartite nuclear localization signal 2By similarity

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00780000121860.
HOGENOMiHOG000233031.
HOVERGENiHBG106948.
InParanoidiQ66H84.
KOiK04444.
OMAiIRMGQYG.
OrthoDBiEOG786H3M.
PhylomeDBiQ66H84.
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]

Sequencei

Sequence statusi: Complete.

Q66H84-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDGETAGEKG SLVPQPGALG APALGGAPAP GVRREPKKYA VTDDYQLSKQ
60 70 80 90 100
VLGLGVNGKV LECYHRRSGQ KCALKLLYDS PKARQEVDHH WQASGGPHIV
110 120 130 140 150
RILDVYENMH HGKRCLLIVM ECMEGGELFS RIQERGDQAF TEREAAEIMR
160 170 180 190 200
DIGTAIQFLH SQNIAHRDVK PENLLYTSKE KDAVLKLTDF GFAKETTQNA
210 220 230 240 250
LQTPCYTPYY VAPEVLGPEK YDKSCDMWSL GVIMYILLCG FPPFYSNTGQ
260 270 280 290 300
AISPGMKRRI RLGQYGFPKP EWADVSEDAK QLIRLLLKTD PTERLTIMQF
310 320 330 340 350
MNHPWINQSM EVPQTPLHTA RVLEEDKDHW DDVKEEMTSA LATMRVDYDQ
360 370 380
VKIKDLKTSN NRLLNKRRKK QGGSSSASPG CNNQ
Length:384
Mass (Da):43,222
Last modified:October 11, 2004 - v1
Checksum:iE094358C901F7E70
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC081974 mRNA. Translation: AAH81974.1.
RefSeqiNP_001012127.1. NM_001012127.1.
XP_006243838.1. XM_006243776.2.
XP_008764753.1. XM_008766531.1.
UniGeneiRn.8789.

Genome annotation databases

EnsembliENSRNOT00000020065; ENSRNOP00000020065; ENSRNOG00000014832.
GeneIDi315994.
KEGGirno:315994.
UCSCiRGD:1304980. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC081974 mRNA. Translation: AAH81974.1.
RefSeqiNP_001012127.1. NM_001012127.1.
XP_006243838.1. XM_006243776.2.
XP_008764753.1. XM_008766531.1.
UniGeneiRn.8789.

3D structure databases

ProteinModelPortaliQ66H84.
SMRiQ66H84. Positions 37-370.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000020065.

PTM databases

PhosphoSiteiQ66H84.

Proteomic databases

PaxDbiQ66H84.
PRIDEiQ66H84.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000020065; ENSRNOP00000020065; ENSRNOG00000014832.
GeneIDi315994.
KEGGirno:315994.
UCSCiRGD:1304980. rat.

Organism-specific databases

CTDi7867.
RGDi1304980. Mapkapk3.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00780000121860.
HOGENOMiHOG000233031.
HOVERGENiHBG106948.
InParanoidiQ66H84.
KOiK04444.
OMAiIRMGQYG.
OrthoDBiEOG786H3M.
PhylomeDBiQ66H84.
TreeFamiTF312891.

Enzyme and pathway databases

ReactomeiREACT_301330. VEGFA-VEGFR2 Pathway.
REACT_302239. Oxidative Stress Induced Senescence.
REACT_312904. p38MAPK events.
REACT_347906. activated TAK1 mediates p38 MAPK activation.

Miscellaneous databases

NextBioi670215.
PROiQ66H84.

Gene expression databases

GenevestigatoriQ66H84.

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]
ProtoNetiSearch...

Publicationsi

  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.

Entry informationi

Entry nameiMAPK3_RAT
AccessioniPrimary (citable) accession number: Q66H84
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: October 11, 2004
Last modified: April 29, 2015
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.