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UniProtKB - Q3UMW7 (MAPK3_MOUSE)

UniProt

Q3UMW7 - MAPK3_MOUSE

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Protein

MAP kinase-activated protein kinase 3

Gene

Mapkapk3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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.2 Publications

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

GO - Biological processi

  • cell surface receptor signaling pathway Source: GO_Central
  • macropinocytosis Source: UniProtKB
  • MAPK cascade Source: GO_Central
  • peptidyl-serine phosphorylation Source: MGI
  • protein autophosphorylation Source: GO_Central
  • response to cytokine Source: UniProtKB
  • response to lipopolysaccharide Source: UniProtKB
  • 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

ReactomeiR-MMU-171007. p38MAPK events.
R-MMU-2559580. Oxidative Stress Induced Senescence.
R-MMU-4420097. VEGFA-VEGFR2 Pathway.
R-MMU-450302. 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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:2143163. Mapkapk3.

Subcellular locationi

Isoform 1 :
  • Nucleus
  • Cytoplasm

    • Note: Predominantly located in the nucleus, when activated it translocates to the cytoplasm.
Isoform 3 :
  • Nucleus
  • Cytoplasm

    • Note: Localizes throughout the cell. Degraded in response to osmotic stress.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Mice are fertile and do not exhibit behavioral phenotype. Mice do not show decreased production of inflammatory cytokines such as TNF and IL6 upon LPS-stimulation. Mice lacking both Mapkapk2 and Mapkapk3 show further reduction of TNF production, compared to mice lacking only Mapkapk2. These data suggest that Mapkapk3 may function additively in stress-induced cytokine production.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi203 – 2031T → A: Prevents degradation of isoform 3. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 384384MAP kinase-activated protein kinase 3PRO_0000086294Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei203 – 2031Phosphothreonine; by MAPK142 Publications
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 (By similarity). Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-201, Ser-251 and Thr-313. Isoform 3 is degraded following phosphorylation at Thr-203.By similarity2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ3UMW7.
MaxQBiQ3UMW7.
PaxDbiQ3UMW7.
PeptideAtlasiQ3UMW7.
PRIDEiQ3UMW7.

PTM databases

iPTMnetiQ3UMW7.
PhosphoSiteiQ3UMW7.

Expressioni

Tissue specificityi

Ubiquitously expressed (at protein level). Isoform 3 is expressed in skeletal muscles and heart.1 Publication

Gene expression databases

BgeeiENSMUSG00000032577.
ExpressionAtlasiQ3UMW7. baseline and differential.
GenevisibleiQ3UMW7. MM.

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi221912. 1 interaction.
STRINGi10090.ENSMUSP00000035194.

Structurei

3D structure databases

ProteinModelPortaliQ3UMW7.
SMRiQ3UMW7. Positions 35-350.
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

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0604. Eukaryota.
ENOG410XP8F. LUCA.
GeneTreeiENSGT00830000128274.
HOGENOMiHOG000233031.
HOVERGENiHBG106948.
InParanoidiQ3UMW7.
KOiK04444.
OMAiSGCRHIV.
OrthoDBiEOG091G14PL.
PhylomeDBiQ3UMW7.
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.
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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q3UMW7-1) [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
MDGETAGEKG SLVPPPGALG GSALGGAPAP 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 SRNIAHRDVK PENLLYTSKE KDAVLKLTDF GFAKETTQNA 
       210        220        230        240        250
LQTPCYTPYY VAPEVLGPEK YDKSCDMWSL GVIMYILLCG FPPFYSNTGQ 
       260        270        280        290        300
AISPGMKRRI RLGQYSFPNP EWLDVSEDAK QLIRLLLKTD PTERLTIMQF 
       310        320        330        340        350
MNHPWINQSM VVPQTPLYTA RVLQEDKDHW DDVKEEMTSA LATMRVDYDQ 
       360        370        380 
VKIKDLKTSN NRLLNKRRKK QAGSSSASQG CNNQ
Length:384
Mass (Da):43,293
Last modified:December 6, 2005 - v2
Checksum:i7DDE2C8E01BBD244
GO
Isoform 2 (identifier: Q3UMW7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     212-249: APEVLGPEKYDKSCDMWSLGVIMYILLCGFPPFYSNTG → GESFACGLHPHCCRML
     250-384: Missing.

Note: No experimental confirmation available.
Show »
Length:227
Mass (Da):25,156
Checksum:i5D0DAB4EE4E4EEEF
GO
Isoform 3 (identifier: Q3UMW7-3) [UniParc]FASTAAdd to basket
Also known as: MK3.2

The sequence of this isoform differs from the canonical sequence as follows:
     238-266: LCGFPPFYSNTGQAISPGMKRRIRLGQYS → NPWWSHRPHSTQPECSRKTKITGMTSRKR
     267-384: Missing.

Show »
Length:266
Mass (Da):29,829
Checksum:iD4424AD21F082FD5
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti216 – 2161L → P in BAE25981 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei212 – 24938APEVL…YSNTG → GESFACGLHPHCCRML in isoform 2. 1 PublicationVSP_016386Add
BLAST
Alternative sequencei238 – 26629LCGFP…LGQYS → NPWWSHRPHSTQPECSRKTK ITGMTSRKR in isoform 3. CuratedVSP_042175Add
BLAST
Alternative sequencei250 – 384135Missing in isoform 2. 1 PublicationVSP_016387Add
BLAST
Alternative sequencei267 – 384118Missing in isoform 3. CuratedVSP_042176Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK087496 mRNA. Translation: BAC39897.1.
AK144637 mRNA. Translation: BAE25981.1.
AK151881 mRNA. Translation: BAE30767.1.
AK172344 mRNA. Translation: BAE42958.1.
AK172578 mRNA. Translation: BAE43076.1.
AL672070 Genomic DNA. Translation: CAQ12134.1.
CH466560 Genomic DNA. Translation: EDL21175.1.
BC031467 mRNA. Translation: AAH31467.1.
CCDSiCCDS23487.1. [Q3UMW7-1]
RefSeqiNP_001303620.1. NM_001316691.1. [Q3UMW7-3]
NP_849238.1. NM_178907.3. [Q3UMW7-1]
XP_006511679.1. XM_006511616.2. [Q3UMW7-1]
UniGeneiMm.222612.
Mm.445242.

Genome annotation databases

EnsembliENSMUST00000035194; ENSMUSP00000035194; ENSMUSG00000032577. [Q3UMW7-1]
ENSMUST00000192054; ENSMUSP00000141342; ENSMUSG00000032577. [Q3UMW7-3]
GeneIDi102626.
KEGGimmu:102626.
UCSCiuc009rkx.1. mouse. [Q3UMW7-1]
uc009rla.1. mouse. [Q3UMW7-2]
uc012hab.1. mouse. [Q3UMW7-3]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK087496 mRNA. Translation: BAC39897.1.
AK144637 mRNA. Translation: BAE25981.1.
AK151881 mRNA. Translation: BAE30767.1.
AK172344 mRNA. Translation: BAE42958.1.
AK172578 mRNA. Translation: BAE43076.1.
AL672070 Genomic DNA. Translation: CAQ12134.1.
CH466560 Genomic DNA. Translation: EDL21175.1.
BC031467 mRNA. Translation: AAH31467.1.
CCDSiCCDS23487.1. [Q3UMW7-1]
RefSeqiNP_001303620.1. NM_001316691.1. [Q3UMW7-3]
NP_849238.1. NM_178907.3. [Q3UMW7-1]
XP_006511679.1. XM_006511616.2. [Q3UMW7-1]
UniGeneiMm.222612.
Mm.445242.

3D structure databases

ProteinModelPortaliQ3UMW7.
SMRiQ3UMW7. Positions 35-350.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi221912. 1 interaction.
STRINGi10090.ENSMUSP00000035194.

PTM databases

iPTMnetiQ3UMW7.
PhosphoSiteiQ3UMW7.

Proteomic databases

EPDiQ3UMW7.
MaxQBiQ3UMW7.
PaxDbiQ3UMW7.
PeptideAtlasiQ3UMW7.
PRIDEiQ3UMW7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000035194; ENSMUSP00000035194; ENSMUSG00000032577. [Q3UMW7-1]
ENSMUST00000192054; ENSMUSP00000141342; ENSMUSG00000032577. [Q3UMW7-3]
GeneIDi102626.
KEGGimmu:102626.
UCSCiuc009rkx.1. mouse. [Q3UMW7-1]
uc009rla.1. mouse. [Q3UMW7-2]
uc012hab.1. mouse. [Q3UMW7-3]

Organism-specific databases

CTDi7867.
MGIiMGI:2143163. Mapkapk3.

Phylogenomic databases

eggNOGiKOG0604. Eukaryota.
ENOG410XP8F. LUCA.
GeneTreeiENSGT00830000128274.
HOGENOMiHOG000233031.
HOVERGENiHBG106948.
InParanoidiQ3UMW7.
KOiK04444.
OMAiSGCRHIV.
OrthoDBiEOG091G14PL.
PhylomeDBiQ3UMW7.
TreeFamiTF312891.

Enzyme and pathway databases

ReactomeiR-MMU-171007. p38MAPK events.
R-MMU-2559580. Oxidative Stress Induced Senescence.
R-MMU-4420097. VEGFA-VEGFR2 Pathway.
R-MMU-450302. activated TAK1 mediates p38 MAPK activation.

Miscellaneous databases

PROiQ3UMW7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032577.
ExpressionAtlasiQ3UMW7. baseline and differential.
GenevisibleiQ3UMW7. MM.

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.
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...

Entry informationi

Entry nameiMAPK3_MOUSE
AccessioniPrimary (citable) accession number: Q3UMW7
Secondary accession number(s): B0QZU7
, E9QNE1, Q3T9E6, Q8K0G3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 6, 2005
Last modified: September 7, 2016
This is version 107 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.