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Protein

Mitogen-activated protein kinase 3

Gene

Mapk3

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

Functioni

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-203 and Tyr-205 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei72ATPPROSITE-ProRule annotation1
Active sitei167Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi49 – 57ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • MAP kinase activity Source: MGI
  • phosphatase binding Source: MGI
  • phosphotyrosine binding Source: MGI
  • protein kinase activity Source: MGI
  • protein serine/threonine kinase activity Source: Reactome

GO - Biological processi

  • animal organ morphogenesis Source: MGI
  • apoptotic process Source: UniProtKB-KW
  • arachidonic acid metabolic process Source: Ensembl
  • Bergmann glial cell differentiation Source: MGI
  • BMP signaling pathway Source: MGI
  • cardiac neural crest cell development involved in heart development Source: MGI
  • cartilage development Source: MGI
  • caveolin-mediated endocytosis Source: UniProtKB
  • cell cycle Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: MGI
  • cellular response to mechanical stimulus Source: Ensembl
  • DNA damage induced protein phosphorylation Source: MGI
  • ERK1 and ERK2 cascade Source: MGI
  • face development Source: MGI
  • interleukin-1-mediated signaling pathway Source: MGI
  • lipopolysaccharide-mediated signaling pathway Source: MGI
  • lung morphogenesis Source: MGI
  • MAPK import into nucleus Source: Ensembl
  • negative regulation of apolipoprotein binding Source: BHF-UCL
  • neural crest cell development Source: MGI
  • outer ear morphogenesis Source: MGI
  • peptidyl-serine phosphorylation Source: Ensembl
  • peptidyl-tyrosine autophosphorylation Source: MGI
  • phosphorylation Source: MGI
  • positive regulation of cyclase activity Source: MGI
  • positive regulation of ERK1 and ERK2 cascade Source: MGI
  • positive regulation of histone acetylation Source: MGI
  • positive regulation of histone phosphorylation Source: MGI
  • positive regulation of protein phosphorylation Source: MGI
  • positive regulation of telomerase activity Source: MGI
  • positive regulation of telomere capping Source: MGI
  • positive regulation of telomere maintenance via telomerase Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of translation Source: Ensembl
  • positive regulation of xenophagy Source: MGI
  • protein complex assembly Source: Ensembl
  • protein phosphorylation Source: MGI
  • regulation of cytoskeleton organization Source: UniProtKB
  • regulation of early endosome to late endosome transport Source: UniProtKB
  • regulation of Golgi inheritance Source: UniProtKB
  • regulation of ossification Source: MGI
  • regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • regulation of stress-activated MAPK cascade Source: UniProtKB
  • response to epidermal growth factor Source: UniProtKB
  • response to exogenous dsRNA Source: MGI
  • response to lipopolysaccharide Source: MGI
  • response to toxic substance Source: Ensembl
  • sensory perception of pain Source: UniProtKB
  • signal transduction Source: MGI
  • thymus development Source: MGI
  • thyroid gland development Source: MGI
  • trachea formation Source: MGI
  • transcription, DNA-templated Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-110056. MAPK3 (ERK1) activation.
R-MMU-112409. RAF-independent MAPK1/3 activation.
R-MMU-1169408. ISG15 antiviral mechanism.
R-MMU-1295596. Spry regulation of FGF signaling.
R-MMU-162658. Golgi Cisternae Pericentriolar Stack Reorganization.
R-MMU-198753. ERK/MAPK targets.
R-MMU-202670. ERKs are inactivated.
R-MMU-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-MMU-2559580. Oxidative Stress Induced Senescence.
R-MMU-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-MMU-2559585. Oncogene Induced Senescence.
R-MMU-2871796. FCERI mediated MAPK activation.
R-MMU-3371453. Regulation of HSF1-mediated heat shock response.
R-MMU-375165. NCAM signaling for neurite out-growth.
R-MMU-445144. Signal transduction by L1.
R-MMU-450341. Activation of the AP-1 family of transcription factors.
R-MMU-456926. Thrombin signalling through proteinase activated receptors (PARs).
R-MMU-5654726. Negative regulation of FGFR1 signaling.
R-MMU-5654727. Negative regulation of FGFR2 signaling.
R-MMU-5654732. Negative regulation of FGFR3 signaling.
R-MMU-5654733. Negative regulation of FGFR4 signaling.
R-MMU-5663213. RHO GTPases Activate WASPs and WAVEs.
R-MMU-5673001. RAF/MAP kinase cascade.
R-MMU-5674135. MAP2K and MAPK activation.
R-MMU-5674499. Negative feedback regulation of MAPK pathway.
R-MMU-5675221. Negative regulation of MAPK pathway.
R-MMU-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-MMU-74749. Signal attenuation.
R-MMU-881907. Gastrin-CREB signalling pathway via PKC and MAPK.
R-MMU-982772. Growth hormone receptor signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 3 (EC:2.7.11.24)
Short name:
MAP kinase 3
Short name:
MAPK 3
Alternative name(s):
ERT2
Extracellular signal-regulated kinase 1
Short name:
ERK-1
Insulin-stimulated MAP2 kinase
MAP kinase isoform p44
Short name:
p44-MAPK
MNK1
Microtubule-associated protein 2 kinase
p44-ERK1
Gene namesi
Name:Mapk3
Synonyms:Erk1, Prkm3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1346859. Mapk3.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Autophosphorylation at Thr-207 promotes nuclear localization (By similarity). PEA15-binding redirects the biological outcome of MAPK3 kinase-signaling by sequestering MAPK3 into the cytoplasm.By similarity

GO - Cellular componenti

  • caveola Source: UniProtKB
  • cytoplasm Source: MGI
  • cytoskeleton Source: UniProtKB
  • cytosol Source: UniProtKB
  • early endosome Source: UniProtKB
  • extracellular exosome Source: MGI
  • focal adhesion Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • late endosome Source: UniProtKB
  • microtubule cytoskeleton Source: MGI
  • mitochondrion Source: UniProtKB
  • nuclear envelope Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
  • protein complex Source: Ensembl
  • pseudopodium Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL5510.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001862522 – 380Mitogen-activated protein kinase 3Add BLAST379

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei199PhosphothreonineBy similarity1
Modified residuei203Phosphothreonine; by MAP2K1 and MAP2K2Combined sources1
Modified residuei205Phosphotyrosine; by MAP2K1 and MAP2K2Combined sources1
Modified residuei208Phosphothreonine; by autocatalysisBy similarity1
Modified residuei264PhosphoserineBy similarity1
Modified residuei266PhosphoserineBy similarity1
Modified residuei302PhosphoserineBy similarity1

Post-translational modificationi

Dually phosphorylated on Thr-203 and Tyr-205, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation (By similarity). Dephosphorylated by PTPRJ at Tyr-205 (By similarity). Autophosphorylated on threonine and tyrosine residues in vitro. Phosphorylated upon FLT3 and KIT signaling (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ63844.
MaxQBiQ63844.
PaxDbiQ63844.
PeptideAtlasiQ63844.
PRIDEiQ63844.

PTM databases

iPTMnetiQ63844.
PhosphoSitePlusiQ63844.
SwissPalmiQ63844.

Expressioni

Gene expression databases

BgeeiENSMUSG00000063065.
CleanExiMM_MAPK3.
ExpressionAtlasiQ63844. baseline and differential.
GenevisibleiQ63844. MM.

Interactioni

Subunit structurei

Binds both upstream activators and downstream substrates in multimolecular complexes. Found in a complex with at least BRAF, HRAS, MAP2K1/MEK1, MAPK3 and RGS14. Interacts with TPR (By similarity). Interacts with ADAM15, ARRB2, CANX, DAPK1 (via death domain), HSF4, IER3, MAP2K1/MEK1, NISCH, and SGK1 (By similarity). Interacts with MORG1, PEA15 and MKNK2. MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation. Interacts with CDKN2AIP.By similarity3 Publications

GO - Molecular functioni

  • phosphatase binding Source: MGI
  • phosphotyrosine binding Source: MGI

Protein-protein interaction databases

BioGridi204970. 14 interactors.
DIPiDIP-31078N.
IntActiQ63844. 7 interactors.
MINTiMINT-1524109.
STRINGi10090.ENSMUSP00000051619.

Chemistry databases

BindingDBiQ63844.

Structurei

3D structure databases

ProteinModelPortaliQ63844.
SMRiQ63844.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini43 – 331Protein kinasePROSITE-ProRule annotationAdd BLAST289

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi203 – 205TXY3

Domaini

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ63844.
KOiK04371.
OrthoDBiEOG091G08QL.
PhylomeDBiQ63844.
TreeFamiTF105097.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008349. MAPK_ERK1/2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01770. ERK1ERK2MAPK.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q63844-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAAAAAPGG GGGEPRGTAG VVPVVPGEVE VVKGQPFDVG PRYTQLQYIG
60 70 80 90 100
EGAYGMVSSA YDHVRKTRVA IKKISPFEHQ TYCQRTLREI QILLRFRHEN
110 120 130 140 150
VIGIRDILRA PTLEAMRDVY IVQDLMETDL YKLLKSQQLS NDHICYFLYQ
160 170 180 190 200
ILRGLKYIHS ANVLHRDLKP SNLLINTTCD LKICDFGLAR IADPEHDHTG
210 220 230 240 250
FLTEYVATRW YRAPEIMLNS KGYTKSIDIW SVGCILAEML SNRPIFPGKH
260 270 280 290 300
YLDQLNHILG ILGSPSQEDL NCIINMKARN YLQSLPSKTK VAWAKLFPKS
310 320 330 340 350
DSKALDLLDR MLTFNPNKRI TVEEALAHPY LEQYYDPTDE PVAEEPFTFD
360 370 380
MELDDLPKER LKELIFQETA RFQPGAPEGP
Length:380
Mass (Da):43,066
Last modified:January 23, 2007 - v5
Checksum:i49C14A95B627237F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti178T → P in CAA45889 (PubMed:8444355).Curated1
Sequence conflicti178T → P no nucleotide entry (PubMed:1459009).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC013754 mRNA. Translation: AAH13754.1.
BC029712 mRNA. Translation: AAH29712.1.
S58470 mRNA. Translation: AAB19973.1.
X64605 mRNA. Translation: CAA45889.1.
CCDSiCCDS21841.1.
PIRiS28184.
RefSeqiNP_036082.1. NM_011952.2.
UniGeneiMm.8385.

Genome annotation databases

EnsembliENSMUST00000057669; ENSMUSP00000051619; ENSMUSG00000063065.
GeneIDi26417.
KEGGimmu:26417.
UCSCiuc009jsm.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC013754 mRNA. Translation: AAH13754.1.
BC029712 mRNA. Translation: AAH29712.1.
S58470 mRNA. Translation: AAB19973.1.
X64605 mRNA. Translation: CAA45889.1.
CCDSiCCDS21841.1.
PIRiS28184.
RefSeqiNP_036082.1. NM_011952.2.
UniGeneiMm.8385.

3D structure databases

ProteinModelPortaliQ63844.
SMRiQ63844.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204970. 14 interactors.
DIPiDIP-31078N.
IntActiQ63844. 7 interactors.
MINTiMINT-1524109.
STRINGi10090.ENSMUSP00000051619.

Chemistry databases

BindingDBiQ63844.
ChEMBLiCHEMBL5510.

PTM databases

iPTMnetiQ63844.
PhosphoSitePlusiQ63844.
SwissPalmiQ63844.

Proteomic databases

EPDiQ63844.
MaxQBiQ63844.
PaxDbiQ63844.
PeptideAtlasiQ63844.
PRIDEiQ63844.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000057669; ENSMUSP00000051619; ENSMUSG00000063065.
GeneIDi26417.
KEGGimmu:26417.
UCSCiuc009jsm.1. mouse.

Organism-specific databases

CTDi5595.
MGIiMGI:1346859. Mapk3.

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ63844.
KOiK04371.
OrthoDBiEOG091G08QL.
PhylomeDBiQ63844.
TreeFamiTF105097.

Enzyme and pathway databases

ReactomeiR-MMU-110056. MAPK3 (ERK1) activation.
R-MMU-112409. RAF-independent MAPK1/3 activation.
R-MMU-1169408. ISG15 antiviral mechanism.
R-MMU-1295596. Spry regulation of FGF signaling.
R-MMU-162658. Golgi Cisternae Pericentriolar Stack Reorganization.
R-MMU-198753. ERK/MAPK targets.
R-MMU-202670. ERKs are inactivated.
R-MMU-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-MMU-2559580. Oxidative Stress Induced Senescence.
R-MMU-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-MMU-2559585. Oncogene Induced Senescence.
R-MMU-2871796. FCERI mediated MAPK activation.
R-MMU-3371453. Regulation of HSF1-mediated heat shock response.
R-MMU-375165. NCAM signaling for neurite out-growth.
R-MMU-445144. Signal transduction by L1.
R-MMU-450341. Activation of the AP-1 family of transcription factors.
R-MMU-456926. Thrombin signalling through proteinase activated receptors (PARs).
R-MMU-5654726. Negative regulation of FGFR1 signaling.
R-MMU-5654727. Negative regulation of FGFR2 signaling.
R-MMU-5654732. Negative regulation of FGFR3 signaling.
R-MMU-5654733. Negative regulation of FGFR4 signaling.
R-MMU-5663213. RHO GTPases Activate WASPs and WAVEs.
R-MMU-5673001. RAF/MAP kinase cascade.
R-MMU-5674135. MAP2K and MAPK activation.
R-MMU-5674499. Negative feedback regulation of MAPK pathway.
R-MMU-5675221. Negative regulation of MAPK pathway.
R-MMU-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-MMU-74749. Signal attenuation.
R-MMU-881907. Gastrin-CREB signalling pathway via PKC and MAPK.
R-MMU-982772. Growth hormone receptor signaling.

Miscellaneous databases

ChiTaRSiMapk3. mouse.
PROiQ63844.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000063065.
CleanExiMM_MAPK3.
ExpressionAtlasiQ63844. baseline and differential.
GenevisibleiQ63844. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008349. MAPK_ERK1/2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01770. ERK1ERK2MAPK.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMK03_MOUSE
AccessioniPrimary (citable) accession number: Q63844
Secondary accession number(s): Q61531, Q8K0X5, Q91YW5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 180 of the entry and version 5 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, 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.