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Protein

Mitogen-activated protein kinase 1

Gene

Mapk1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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, DCC, 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. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity).3 PublicationsBy similarity3 Publications
Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Activity regulationi

Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-183 and Tyr-185 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. Phosphorylation on Ser-27 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Dephosphorylated and inactivated by DUSP1, DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei52ATPPROSITE-ProRule annotation1
Binding sitei52InhibitorBy similarity1
Binding sitei106Inhibitor; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei112InhibitorBy similarity1
Active sitei147Proton acceptorPROSITE-ProRule annotation1
Binding sitei152InhibitorBy similarity1
Binding sitei164InhibitorBy similarity1
Binding sitei165InhibitorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi29 – 37ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Cell cycle
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24 3474
ReactomeiR-MMU-111995 phospho-PLA2 pathway
R-MMU-112409 RAF-independent MAPK1/3 activation
R-MMU-112411 MAPK1 (ERK2) activation
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-437239 Recycling pathway of L1
R-MMU-442742 CREB phosphorylation through the activation of Ras
R-MMU-444257 RSK activation
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-6798695 Neutrophil degranulation
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-8939211 ESR-mediated signaling
R-MMU-982772 Growth hormone receptor signaling

Protein family/group databases

MoonDBiP63085 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 1 (EC:2.7.11.24)
Short name:
MAP kinase 1
Short name:
MAPK 1
Alternative name(s):
ERT1
Extracellular signal-regulated kinase 2
Short name:
ERK-2
MAP kinase isoform p42
Short name:
p42-MAPK
Mitogen-activated protein kinase 2
Short name:
MAP kinase 2
Short name:
MAPK 2
Gene namesi
Name:Mapk1
Synonyms:Erk2, Mapk, Prkm1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1346858 Mapk1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2207

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001862482 – 358Mitogen-activated protein kinase 1Add BLAST357

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei27Phosphoserine; by SGK1By similarity1
Modified residuei183Phosphothreonine; by MAP2K1 and MAP2K2Combined sources1 Publication1
Modified residuei185Phosphotyrosine; by MAP2K1 and MAP2K2Combined sources1 Publication1
Modified residuei188Phosphothreonine; by autocatalysisBy similarity1
Modified residuei244PhosphoserineBy similarity1
Modified residuei246PhosphoserineBy similarity1
Modified residuei282PhosphoserineBy similarity1

Post-translational modificationi

Dually phosphorylated on Thr-183 and Tyr-185, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation (By similarity). Dephosphorylated by PTPRJ at Tyr-185 (By similarity). Phosphorylated upon FLT3 and KIT signaling (By similarity). Dephosphorylated by DUSP1 at Thr-183 and Tyr-185 (PubMed:8221888).By similarity1 Publication
ISGylated.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP63085
MaxQBiP63085
PaxDbiP63085
PeptideAtlasiP63085
PRIDEiP63085

PTM databases

iPTMnetiP63085
PhosphoSitePlusiP63085
SwissPalmiP63085

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

BgeeiENSMUSG00000063358 Expressed in 329 organ(s), highest expression level in olfactory tubercle
CleanExiMM_MAPK1
GenevisibleiP63085 MM

Interactioni

Subunit structurei

Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with ADAM15, ARHGEF2, ARRB2, DAPK1 (via death domain), HSF4, IER3, IPO7, DUSP6, NISCH, SGK1, and isoform 1 of NEK2. Interacts (via phosphorylated form) with TPR (via C-terminal region and phosphorylated form); the interaction requires dimerization of MAPK1/ERK2 and increases following EGF stimulation (By similarity). Interacts (phosphorylated form) with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation. Interacts with DCC (By similarity). Interacts with MORG1 (PubMed:15118098). Interacts with PEA15 (PubMed:16162500). Interacts with MKNK2. MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation (PubMed:11702783). The phosphorylated form interacts with PML. Interacts with STYX. Interacts with CDK2AP2. Interacts with CAVIN4 (By similarity). Interacts with DUSP7; the interaction enhances DUSP7 phosphatase activity (PubMed:27783954).By similarity4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204966, 47 interactors
CORUMiP63085
DIPiDIP-661N
ELMiP63085
IntActiP63085, 42 interactors
MINTiP63085
STRINGi10090.ENSMUSP00000023462

Chemistry databases

BindingDBiP63085

Structurei

3D structure databases

ProteinModelPortaliP63085
SMRiP63085
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini23 – 311Protein kinasePROSITE-ProRule annotationAdd BLAST289

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni103 – 106Inhibitor-bindingBy similarity4
Regioni151 – 152Inhibitor-bindingBy similarity2

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi183 – 185TXY3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi2 – 7Poly-Ala6

Domaini

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00910000144035
HOGENOMiHOG000233024
HOVERGENiHBG014652
InParanoidiP63085
KOiK04371
OMAiMEKCLTF
OrthoDBiEOG091G08QL
PhylomeDBiP63085
TreeFamiTF105097

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008349 MAPK_ERK1/2
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01770 ERK1ERK2MAPK
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS01351 MAPK, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

P63085-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAAAAAAGPE MVRGQVFDVG PRYTNLSYIG EGAYGMVCSA YDNLNKVRVA
60 70 80 90 100
IKKISPFEHQ TYCQRTLREI KILLRFRHEN IIGINDIIRA PTIEQMKDVY
110 120 130 140 150
IVQDLMETDL YKLLKTQHLS NDHICYFLYQ ILRGLKYIHS ANVLHRDLKP
160 170 180 190 200
SNLLLNTTCD LKICDFGLAR VADPDHDHTG FLTEYVATRW YRAPEIMLNS
210 220 230 240 250
KGYTKSIDIW SVGCILAEML SNRPIFPGKH YLDQLNHILG ILGSPSQEDL
260 270 280 290 300
NCIINLKARN YLLSLPHKNK VPWNRLFPNA DSKALDLLDK MLTFNPHKRI
310 320 330 340 350
EVEQALAHPY LEQYYDPSDE PIAEAPFKFD MELDDLPKEK LKELIFEETA

RFQPGYRS
Length:358
Mass (Da):41,276
Last modified:January 23, 2007 - v3
Checksum:i3BBCF22471EDBA0B
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A338P781A0A338P781_MOUSE
Mitogen-activated protein kinase 1
Mapk1
108Annotation score:
A0A338P736A0A338P736_MOUSE
Mitogen-activated protein kinase 1
Mapk1
134Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X58712 mRNA Translation: CAA41548.1
AK035386 mRNA Translation: BAC29053.1
AK048127 mRNA Translation: BAC33251.1
AK087925 mRNA Translation: BAC40044.1
AK132241 mRNA Translation: BAE21053.1
BC058258 mRNA Translation: AAH58258.1
D10939 mRNA Translation: BAA01733.1
CCDSiCCDS27992.1
PIRiS16444
RefSeqiNP_001033752.1, NM_001038663.1
NP_036079.1, NM_011949.3
XP_006522210.1, XM_006522147.3
UniGeneiMm.196581

Genome annotation databases

EnsembliENSMUST00000069107; ENSMUSP00000065983; ENSMUSG00000063358
ENSMUST00000115731; ENSMUSP00000111396; ENSMUSG00000063358
ENSMUST00000232611; ENSMUSP00000156154; ENSMUSG00000063358
GeneIDi26413
KEGGimmu:26413
UCSCiuc007yjq.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X58712 mRNA Translation: CAA41548.1
AK035386 mRNA Translation: BAC29053.1
AK048127 mRNA Translation: BAC33251.1
AK087925 mRNA Translation: BAC40044.1
AK132241 mRNA Translation: BAE21053.1
BC058258 mRNA Translation: AAH58258.1
D10939 mRNA Translation: BAA01733.1
CCDSiCCDS27992.1
PIRiS16444
RefSeqiNP_001033752.1, NM_001038663.1
NP_036079.1, NM_011949.3
XP_006522210.1, XM_006522147.3
UniGeneiMm.196581

3D structure databases

ProteinModelPortaliP63085
SMRiP63085
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204966, 47 interactors
CORUMiP63085
DIPiDIP-661N
ELMiP63085
IntActiP63085, 42 interactors
MINTiP63085
STRINGi10090.ENSMUSP00000023462

Chemistry databases

BindingDBiP63085
ChEMBLiCHEMBL2207

Protein family/group databases

MoonDBiP63085 Predicted

PTM databases

iPTMnetiP63085
PhosphoSitePlusiP63085
SwissPalmiP63085

Proteomic databases

EPDiP63085
MaxQBiP63085
PaxDbiP63085
PeptideAtlasiP63085
PRIDEiP63085

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000069107; ENSMUSP00000065983; ENSMUSG00000063358
ENSMUST00000115731; ENSMUSP00000111396; ENSMUSG00000063358
ENSMUST00000232611; ENSMUSP00000156154; ENSMUSG00000063358
GeneIDi26413
KEGGimmu:26413
UCSCiuc007yjq.1 mouse

Organism-specific databases

CTDi5594
MGIiMGI:1346858 Mapk1

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00910000144035
HOGENOMiHOG000233024
HOVERGENiHBG014652
InParanoidiP63085
KOiK04371
OMAiMEKCLTF
OrthoDBiEOG091G08QL
PhylomeDBiP63085
TreeFamiTF105097

Enzyme and pathway databases

BRENDAi2.7.11.24 3474
ReactomeiR-MMU-111995 phospho-PLA2 pathway
R-MMU-112409 RAF-independent MAPK1/3 activation
R-MMU-112411 MAPK1 (ERK2) activation
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-437239 Recycling pathway of L1
R-MMU-442742 CREB phosphorylation through the activation of Ras
R-MMU-444257 RSK activation
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-6798695 Neutrophil degranulation
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-8939211 ESR-mediated signaling
R-MMU-982772 Growth hormone receptor signaling

Miscellaneous databases

ChiTaRSiMapk1 mouse
PROiPR:P63085
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000063358 Expressed in 329 organ(s), highest expression level in olfactory tubercle
CleanExiMM_MAPK1
GenevisibleiP63085 MM

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008349 MAPK_ERK1/2
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01770 ERK1ERK2MAPK
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS01351 MAPK, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMK01_MOUSE
AccessioniPrimary (citable) accession number: P63085
Secondary accession number(s): P27703, Q3V1U6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 13, 2004
Last sequence update: January 23, 2007
Last modified: October 10, 2018
This is version 172 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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