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Names & Taxonomy

Uniprot ID:: P28482
Entry Name:: MK01_HUMAN
Status:: reviewed
Protein Names:: Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
Gene Names:: MAPK1 ERK2 PRKM1 PRKM2
Gene Names Primary:: MAPK1
Organism:: Homo sapiens (Human)

Structure

Length:: 360
Sequence:: MAAAAAAGAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNVNKVRVAIKKISPFEHQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQHLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLARVADPDHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDKMLTFNPHKRIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETARFQPGYRS
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Cytoplasm, cytoskeleton, spindle

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, 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.; Acts as a transcriptional repressor. Binds to a AAA 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.
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-185 and Tyr-187 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-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors.
Active Site:: ACT_SITE 149 149 Proton acceptor.
Cross Reference Drug Bank:: DB01169 DB01064
Gene Ontology Go:: axon
caveola
cytoplasm
cytoskeleton
cytosol
dendrite cytoplasm
early endosome
extracellular exosome
focal adhesion
Golgi apparatus
late endosome
microtubule cytoskeleton
microtubule organizing center
mitochondrion
mitotic spindle
nucleoplasm
nucleus
perikaryon
protein complex
pseudopodium
ATP binding
DNA binding
identical protein binding
MAP kinase activity
phosphatase binding
protein serine/threonine kinase activity
RNA polymerase II carboxy-terminal domain kinase activity
activation of MAPK activity
activation of MAPKK activity
apoptotic process
axon guidance
B cell receptor signaling pathway
Bergmann glial cell differentiation
blood coagulation
cardiac neural crest cell development involved in heart development
caveolin-mediated endocytosis
cell cycle
cellular response to DNA damage stimulus
cellular response to granulocyte macrophage colony-stimulating factor stimulus
cellular response to heat
chemotaxis
cytosine metabolic process
epidermal growth factor receptor signaling pathway
ERBB 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
innate immune response
insulin receptor signaling pathway
JAK-STAT cascade involved in growth hormone signaling pathway
labyrinthine layer blood vessel development
lipopolysaccharide-mediated signaling pathway
long-term synaptic potentiation
lung morphogenesis
mammary gland epithelial cell proliferation
MAPK cascade
MAPK import into nucleus
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of cell differentiation
neurotrophin TRK receptor signaling pathway
outer ear morphogenesis
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
platelet activation
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of peptidyl-threonine phosphorylation
positive regulation of telomerase activity
positive regulation of telomere capping
positive regulation of telomere maintenance via telomerase
positive regulation of transcription, DNA-templated
positive regulation of translation
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 protein stability
regulation of sequence-specific DNA binding transcription factor activity
regulation of stress-activated MAPK cascade
response to epidermal growth factor
response to estrogen
response to exogenous dsRNA
response to stress
response to toxic substance
sensory perception of pain
signal transduction
small GTPase mediated signal transduction
stress-activated MAPK cascade
synaptic transmission
T cell receptor signaling pathway
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, DNA-templated
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
axon guidance
B cell receptor signaling pathway
Bergmann glial cell differentiation
blood coagulation
cardiac neural crest cell development involved in heart development
caveolin-mediated endocytosis
cell cycle
cellular response to DNA damage stimulus
cellular response to granulocyte macrophage colony-stimulating factor stimulus
cellular response to heat
chemotaxis
cytosine metabolic process
epidermal growth factor receptor signaling pathway
ERBB 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
innate immune response
insulin receptor signaling pathway
JAK-STAT cascade involved in growth hormone signaling pathway
labyrinthine layer blood vessel development
lipopolysaccharide-mediated signaling pathway
long-term synaptic potentiation
lung morphogenesis
mammary gland epithelial cell proliferation
MAPK cascade
MAPK import into nucleus
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of cell differentiation
neurotrophin TRK receptor signaling pathway
outer ear morphogenesis
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
platelet activation
positive regulation of cell migration
positive regulation of cell proliferation
positive regulation of peptidyl-threonine phosphorylation
positive regulation of telomerase activity
positive regulation of telomere capping
positive regulation of telomere maintenance via telomerase
positive regulation of transcription, DNA-templated
positive regulation of translation
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 protein stability
regulation of sequence-specific DNA binding transcription factor activity
regulation of stress-activated MAPK cascade
response to epidermal growth factor
response to estrogen
response to exogenous dsRNA
response to stress
response to toxic substance
sensory perception of pain
signal transduction
small GTPase mediated signal transduction
stress-activated MAPK cascade
synaptic transmission
T cell receptor signaling pathway
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, DNA-templated
TRIF-dependent toll-like receptor signaling pathway
vascular endothelial growth factor receptor signaling pathway
viral process
Gene Ontology Molecular Function:: ATP binding
DNA binding
identical protein binding
MAP kinase activity
phosphatase binding
protein serine/threonine kinase activity
RNA polymerase II carboxy-terminal domain kinase activity
Gene Ontology Cellular Component:: axon
caveola
cytoplasm
cytoskeleton
cytosol
dendrite cytoplasm
early endosome
extracellular exosome
focal adhesion
Golgi apparatus
late endosome
microtubule cytoskeleton
microtubule organizing center
mitochondrion
mitotic spindle
nucleoplasm
nucleus
perikaryon
protein complex
pseudopodium
Keywords:: 3D-structure
ATP-binding
Acetylation
Alternative splicing
Apoptosis
Cell cycle
Complete proteome
Cytoplasm
Cytoskeleton
DNA-binding
Direct protein sequencing
Host-virus interaction
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Reference proteome
Repressor
Serine/threonine-protein kinase
Transcription
Transcription regulation
Transferase
Ubl conjugation
Interacts With:: Itself; P32121; Q9U1H0; Q7L5N1; P28562; Q05922; Q16690; P14921; Q02750; Q16539-3; P27361; P02687; P35813; P35236; Q12913; Q15256; P51812; Q69559

Names & Taxonomy

Structure

Subcellular location

Function

Publication