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Names & Taxonomy

Uniprot ID:: P27361
Entry Name:: MK03_HUMAN
Status:: reviewed
Protein Names:: Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (Microtubule-associated protein 2 kinase) (p44-ERK1)
Gene Names:: MAPK3 ERK1 PRKM3
Gene Names Primary:: MAPK3
Organism:: Homo sapiens (Human)

Structure

Length:: 379
Sequence:: MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAYDHVRKTRVAIKKISPFEHQTYCQRTLREIQILLRFRHENVIGIRDILRASTLEAMRDVYIVQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDLKICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINMKARNYLQSLPSKTKVAWAKLFPKSDSKALDLLDRMLTFNPNKRITVEEALAHPYLEQYYDPTDEPVAEEPFTFAMELDDLPKERLKELIFQETARFQPGVLEAP
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Cytoplasm. Nucleus. Note=Autophosphorylation at Thr-207 promotes nuclear localization.

Function

Function:: 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.
Catalytic Activity:: ATP + a protein = ADP + a phosphoprotein.
Cofactor:: COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme Regulation:: ENZYME REGULATION: Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-202 and Tyr-204 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.
Active Site:: ACT_SITE 166 166 Proton acceptor.
Cross Reference Drug Bank:: DB01169 DB00605
Gene Ontology Go:: caveola
cytoskeleton
cytosol
early endosome
extracellular exosome
focal adhesion
Golgi apparatus
late endosome
microtubule cytoskeleton
mitochondrion
nuclear envelope
nucleoplasm
nucleus
protein complex
pseudopodium
ATP binding
MAP kinase activity
phosphatase binding
activation of MAPK activity
activation of MAPKK activity
apoptotic process
arachidonic acid metabolic process
axon guidance
Bergmann glial cell differentiation
blood coagulation
BMP signaling pathway
cardiac neural crest cell development involved in heart development
cartilage development
caveolin-mediated endocytosis
cell cycle
cellular response to heat
cellular response to mechanical stimulus
cytokine-mediated signaling pathway
DNA damage induced protein phosphorylation
epidermal growth factor receptor signaling pathway
ERK1 and ERK2 cascade
face development
Fc-epsilon receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
fibroblast growth factor receptor signaling pathway
gene expression
innate immune response
insulin receptor signaling pathway
interleukin-1-mediated signaling pathway
JAK-STAT cascade involved in growth hormone signaling pathway
lipopolysaccharide-mediated signaling pathway
lung morphogenesis
MAPK cascade
MAPK import into nucleus
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of apolipoprotein binding
neurotrophin TRK receptor signaling pathway
outer ear morphogenesis
peptidyl-serine phosphorylation
peptidyl-tyrosine autophosphorylation
phosphorylation
platelet activation
positive regulation of cyclase activity
positive regulation of ERK1 and ERK2 cascade
positive regulation of histone acetylation
positive regulation of histone phosphorylation
positive regulation of protein phosphorylation
positive regulation of telomerase activity
positive regulation of telomere capping
positive regulation of telomere maintenance via telomerase
positive regulation of transcription from RNA polymerase II promoter
positive regulation of translation
positive regulation of xenophagy
protein complex assembly
protein phosphorylation
Ras protein signal transduction
regulation of cellular response to heat
regulation of cytoskeleton organization
regulation of early endosome to late endosome transport
regulation of Golgi inheritance
regulation of sequence-specific DNA binding transcription factor activity
regulation of stress-activated MAPK cascade
response to epidermal growth factor
response to exogenous dsRNA
response to toxic substance
sensory perception of pain
small GTPase mediated signal transduction
stress-activated MAPK cascade
thymus development
thyroid gland development
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
trachea formation
transcription from RNA polymerase I promoter
transcription initiation from RNA polymerase I promoter
TRIF-dependent toll-like receptor signaling pathway
vascular endothelial growth factor receptor signaling pathway
viral process
Gene Ontology Biological Process:: activation of MAPK activity
activation of MAPKK activity
apoptotic process
arachidonic acid metabolic process
axon guidance
Bergmann glial cell differentiation
blood coagulation
BMP signaling pathway
cardiac neural crest cell development involved in heart development
cartilage development
caveolin-mediated endocytosis
cell cycle
cellular response to heat
cellular response to mechanical stimulus
cytokine-mediated signaling pathway
DNA damage induced protein phosphorylation
epidermal growth factor receptor signaling pathway
ERK1 and ERK2 cascade
face development
Fc-epsilon receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
fibroblast growth factor receptor signaling pathway
gene expression
innate immune response
insulin receptor signaling pathway
interleukin-1-mediated signaling pathway
JAK-STAT cascade involved in growth hormone signaling pathway
lipopolysaccharide-mediated signaling pathway
lung morphogenesis
MAPK cascade
MAPK import into nucleus
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of apolipoprotein binding
neurotrophin TRK receptor signaling pathway
outer ear morphogenesis
peptidyl-serine phosphorylation
peptidyl-tyrosine autophosphorylation
phosphorylation
platelet activation
positive regulation of cyclase activity
positive regulation of ERK1 and ERK2 cascade
positive regulation of histone acetylation
positive regulation of histone phosphorylation
positive regulation of protein phosphorylation
positive regulation of telomerase activity
positive regulation of telomere capping
positive regulation of telomere maintenance via telomerase
positive regulation of transcription from RNA polymerase II promoter
positive regulation of translation
positive regulation of xenophagy
protein complex assembly
protein phosphorylation
Ras protein signal transduction
regulation of cellular response to heat
regulation of cytoskeleton organization
regulation of early endosome to late endosome transport
regulation of Golgi inheritance
regulation of sequence-specific DNA binding transcription factor activity
regulation of stress-activated MAPK cascade
response to epidermal growth factor
response to exogenous dsRNA
response to toxic substance
sensory perception of pain
small GTPase mediated signal transduction
stress-activated MAPK cascade
thymus development
thyroid gland development
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
trachea formation
transcription from RNA polymerase I promoter
transcription initiation from RNA polymerase I promoter
TRIF-dependent toll-like receptor signaling pathway
vascular endothelial growth factor receptor signaling pathway
viral process
Gene Ontology Molecular Function:: ATP binding
MAP kinase activity
phosphatase binding
Gene Ontology Cellular Component:: caveola
cytoskeleton
cytosol
early endosome
extracellular exosome
focal adhesion
Golgi apparatus
late endosome
microtubule cytoskeleton
mitochondrion
nuclear envelope
nucleoplasm
nucleus
protein complex
pseudopodium
Keywords:: 3D-structure
ATP-binding
Acetylation
Alternative splicing
Apoptosis
Cell cycle
Complete proteome
Cytoplasm
Direct protein sequencing
Host-virus interaction
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase
Interacts With:: P53355; P49366; P28562; P19419; Q02750; P28482; Q16539; Q9EPI6; P14618-1; Q8N490; P23467; Q12913; Q62132; Q15349; Q14160

Names & Taxonomy

Structure

Subcellular location

Function

Publication