ERK2 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. 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. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: CMGC group; EC; ERK1 subfamily; Kinase, protein; MAPK family; MAPK/ERK subfamily; Protein kinase, CMGC; Protein kinase, Ser/Thr (non-receptor)
Chromosomal Location of human Ortholog: 22q11.22
Cellular Component:  azurophil granule lumen; caveola; cytoplasm; cytoskeleton; cytosol; early endosome; endoplasmic reticulum lumen; extracellular region; ficolin-1-rich granule lumen; focal adhesion; Golgi apparatus; late endosome; microtubule organizing center; mitochondrion; mitotic spindle; nucleoplasm; nucleus; plasma membrane; pseudopodium; synapse
Molecular Function:  ATP binding; DNA binding; identical protein binding; MAP kinase activity; MAP kinase kinase activity; phosphatase binding; phosphotyrosine residue binding; protein binding; protein serine kinase activity; protein serine/threonine kinase activity; RNA polymerase II CTD heptapeptide repeat kinase activity
Biological Process:  androgen receptor signaling pathway; apoptotic process; B cell receptor signaling pathway; Bergmann glial cell differentiation; 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 reactive oxygen species; cellular response to tumor necrosis factor; chemical synaptic transmission; chemotaxis; cytosine metabolic process; DNA damage response; ERBB signaling pathway; ERK1 and ERK2 cascade; face development; insulin receptor signaling pathway; insulin-like growth factor 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; negative regulation of cell differentiation; outer ear morphogenesis; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; positive regulation of macrophage chemotaxis; positive regulation of macrophage proliferation; positive regulation of peptidyl-threonine phosphorylation; positive regulation of telomerase activity; positive regulation of telomere capping; positive regulation of telomere maintenance via telomerase; progesterone receptor signaling pathway; protein phosphorylation; regulation of cellular pH; regulation of cytoskeleton organization; regulation of early endosome to late endosome transport; regulation of Golgi inheritance; regulation of ossification; regulation of protein stability; regulation of stress-activated MAPK cascade; regulation of transcription by RNA polymerase II; response to epidermal growth factor; response to exogenous dsRNA; response to nicotine; signal transduction; steroid hormone mediated signaling pathway; stress-activated MAPK cascade; T cell receptor signaling pathway; thymus development; thyroid gland development; trachea formation
Disease: Noonan Syndrome 13
Reference #:  P28482 (UniProtKB)
Alt. Names/Synonyms: ERK; ERK-2; ERK2; ERT1; Extracellular signal-regulated kinase 2; extracellular signal-regulated kinase-2; MAP kinase 1; MAP kinase 2; MAP kinase isoform p42; MAPK 1; MAPK 2; MAPK1; MAPK2; Mitogen-activated protein kinase 1; Mitogen-activated protein kinase 2; MK01; p38; p40; p41; p41mapk; p42-MAPK; P42MAPK; PRKM1; PRKM2; protein tyrosine kinase ERK2
Gene Symbols: MAPK1
Molecular weight: 41,390 Da
Basal Isoelectric point: 6.5  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis  |  Apoptosis Regulation  |  B Cell Receptor Signaling  |  ErbB/HER Signaling  |  ESC Pluripotency and Differentiation  |  GPCR Signaling to MAPKs  |  Growth And Differentiation Control by MAPKs  |  IL6 Signaling  |  Inhibition of Apoptosis  |  Insulin Receptor Signaling  |  Microtubule Dynamics  |  Mitochondrial Control of Apoptosis  |  mTOR Signaling  |  T Cell Receptor Signaling  |  TGF-ß Signaling  |  Translation: eIF4E and p70S6K  |  Warburg Effect
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
Select Structure to View Below


Protein Structure Not Found.

Substrate Sequence Logo
Open Substrate Page

Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  InnateDB  |  Ensembl Protein