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, G (updated: April 1, 2015)

Protein identification was indicated in the following studies:

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

Publication	Identification ¹	Uniprot mapping ²	Not mapped / Obsolete	TrEMBL	Swiss-Prot
Goodman (2013)	2289 (gene list)	2278	53	20599	2269
Lange (2014)	1234	1234	7	28	1224
Hegedus (2015)	2638	2622	0	235	2387
Wilson (2016)	1658	1528	170	291	1068
d'Alessandro (2017)	1826	1817	2	0	1815
Bryk (2017)	2090	2060	10	108	1942
Chu (2018)	1853	1804	55	362	1387

¹ as available in the article and/or in supplementary material
² uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Protein sequence (FASTA)

Protein coevolution profile (FreeContact)

Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology.

Total structural coverage: 100%

Model score: 100

(right-click above to access to more options from the contextual menu)

Biological Process

Activation of MAPK activity

Activation of MAPKK activity

Aging

Animal organ morphogenesis

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

Cell surface receptor signaling pathway

Cellular response to amino acid starvation

Cellular response to cadmium ion

Cellular response to DNA damage stimulus

Cellular response to dopamine

Cellular response to granulocyte macrophage colony-stimulating factor stimulus

Cellular response to heat

Cellular response to organic substance

Cellular response to reactive oxygen species

Cellular response to tumor necrosis factor

Chemical synaptic transmission

Chemotaxis

Cytosine metabolic process

Decidualization

Diadenosine tetraphosphate biosynthetic 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

Growth hormone receptor signaling pathway via JAK-STAT

Innate immune response

Insulin receptor signaling pathway

Intracellular signal transduction

Labyrinthine layer blood vessel development

Learning or memory

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 by symbiont of host apoptotic process

Negative regulation of cell differentiation

Neurotrophin TRK receptor signaling pathway

Neutrophil degranulation

Outer ear morphogenesis

Peptidyl-serine phosphorylation

Peptidyl-threonine phosphorylation

Platelet activation

Positive regulation of cardiac muscle cell proliferation

Positive regulation of cell migration

Positive regulation of cell population proliferation

Positive regulation of gene expression

Positive regulation of macrophage chemotaxis

Positive regulation of macrophage proliferation

Positive regulation of peptidyl-threonine phosphorylation

Positive regulation of protein import into nucleus

Positive regulation of protein import into nucleus, translocation

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 pH

Regulation of cellular response to heat

Regulation of cytoskeleton organization

Regulation of DNA-binding transcription factor activity

Regulation of early endosome to late endosome transport

Regulation of gene expression

Regulation of Golgi inheritance

Regulation of ossification

Regulation of phosphatidylinositol 3-kinase signaling

Regulation of protein stability

Regulation of stress-activated MAPK cascade

Response to epidermal growth factor

Response to estrogen

Response to exogenous dsRNA

Response to nicotine

Response to stress

Response to toxic substance

Sensory perception of pain

Signal transduction

Small GTPase mediated signal transduction

Stress-activated MAPK cascade

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

Cellular Component

Axon

Azurophil granule lumen

Caveola

Cytoplasm

Cytoskeleton

Cytosol

Dendrite cytoplasm

Early endosome

Endoplasmic reticulum lumen

Extracellular exosome

Extracellular region

Ficolin-1-rich granule lumen

Focal adhesion

Golgi apparatus

Late endosome

Microtubule cytoskeleton

Microtubule organizing center

Mitochondrion

Mitotic spindle

Nucleoplasm

Nucleus

Obsolete cell

Perikaryon

Plasma membrane

Postsynaptic density

Protein complex

Protein-containing complex

Pseudopodium

Molecular Function

ATP binding

DNA binding

Double-stranded DNA binding

Identical protein binding

Kinase activity

MAP kinase activity

MAP kinase kinase activity

Mitogen-activated protein kinase kinase kinase binding

Phosphatase binding

Phosphotyrosine residue binding

Protein serine kinase activity

Protein serine/threonine kinase activity

Protein threonine kinase activity

RNA polymerase II CTD heptapeptide repeat kinase activity

Transcription factor binding

The reference OMIM entry for this protein is 176948

Mitogen-activated protein kinase 1; mapk1
Protein kinase, mitogen-activated, 1; prkm1
Protein kinase, mitogen-activated, 2; prkm2
Extracellular signal-regulated kinase 2; erk2
Protein tyrosine kinase erk2
P42mapk

CLONING

Boulton et al. (1991) cloned 2 rat enzymes that are S6 kinases and a third related kinase and named them extracellular signal-regulated kinase (Erk)-1, -2, and -3. Owaki et al. (1992) isolated cDNAs for human ERK1 (MAPK3; 601795) and ERK2. The deduced 360-amino acid human ERK2 protein shares 98% identity with rat Erk2.

MAPPING

By a combination of fluorescence in situ hybridization and Southern blot analysis of genomic DNA from a panel of human/hamster cell hybrids, Li et al. (1994) mapped the MAPK1 gene to 22q11.2. Saba-El-Leil et al. (1997) mapped the mouse Mapk1 gene to chromosome 16, in a region showing homology of synteny with human 22q11.2.

GENE FUNCTION

ERKs are also known as maturation- or mitogen-activated protein (MAP) kinases. Cobb et al. (1991) provided a review. Thomas (1992) gave a review of MAP kinases and Seger and Krebs (1995) reviewed the MAP kinase signaling cascade. The MAP kinase ERK2 is widely involved in eukaryotic signal transduction. Upon activation, it translocates to the nucleus of the stimulated cell, where it phosphorylates nuclear targets. Khokhlatchev et al. (1998) found that nuclear accumulation of microinjected ERK2 depends on its phosphorylation state rather than on its activity or on upstream components of its signaling pathway. Phosphorylated ERK2 forms dimers with phosphorylated and unphosphorylated ERK2 partners. Disruption of dimerization by mutagenesis of ERK2 reduces its ability to accumulate in the nucleus, suggesting that dimerization is essential for its normal ligand-dependent relocalization. Other MAP kinase family members also form dimers. Khokhlatchev et al. (1998) concluded that dimerization is part of the mechanism of action of the MAP kinase family. Influenza A viruses are significant causes of morbidity and mortality worldwide. Annually updated vaccines may prevent disease, and antivirals are effective treatment early in disease when symptoms are often nonspecific. Viral replication is supported by intracellular signaling events. Using U0126, a nontoxic inhibitor of MEK1 (176872) and MEK2 (601263), and thus an inhibitor of the RAF1 (164760)/MEK/ERK pathway (see Favata et al. (1998)), Pleschka et al. (2001) examined the cellular response to infection with influenza A. U0126 suppressed both the early and late ERK activation phases after virus infection. Inhibition of the signaling pathway occurred without impairing the synthesis of viral RNA or protein, or the import of viral ribonucleoprotein complexes (RNP) into the nucleus. Instead, U0126 inhibited RAF/MEK/ERK signaling and the export of viral RNP without affecting the cellular mRNA export pathway. Pleschka et al. (2001) proposed that ERK regulates a cellular factor involved in the viral nuclear export protein function. They suggested that local application of MEK inhibitors may have only minor toxic effects on the host while inhibiting viral replication without giving rise to drug-resistant virus variants. Stefanovsky et al. (2001) showed that epidermal growth factor (131530) induces immediate, ERK1/ERK2-dependent activation of endogenous ribosomal transcription, while inactivation of ERK1/ERK2 causes an equally immediate reversion to the basal transcription level. ERK1/ERK2 was found to phosphorylate the architectural transcription factor UBF (600673) at amino acids 117 and 201 within HMG boxes 1 and 2, preventing their interaction with DNA. Mutation of these sites inhibited transcription acti ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 176948 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed

Mitogen-activated protein kinase 1 (MAPK1)