Mitogen-activated protein kinase 1

Details

Name
Mitogen-activated protein kinase 1
Synonyms
  • 2.7.11.24
  • ERK-2
  • ERK2
  • ERT1
  • Extracellular signal-regulated kinase 2
  • MAP kinase 1
  • MAP kinase 2
  • MAP kinase isoform p42
  • MAPK 2
  • Mitogen-activated protein kinase 2
  • p42-MAPK
  • PRKM1
  • PRKM2
Gene Name
MAPK1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001838|Mitogen-activated protein kinase 1
MAAAAAAGAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNVNKVRVAIKKISPFE
HQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQH
LSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLARVADPDHDH
TGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHI
LGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDKMLTFNPHK
RIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETARFQPGYRS
Number of residues
360
Molecular Weight
41389.265
Theoretical pI
6.99
GO Classification
Functions
ATP binding / DNA binding / MAP kinase activity / phosphatase binding / protein serine/threonine kinase activity / RNA polymerase II carboxy-terminal domain kinase activity
Processes
activation of MAPK activity / activation of MAPKK activity / apoptotic process / axon guidance / B cell receptor signaling pathway / blood coagulation / 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 / 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 / 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 / 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 / toll-like receptor TLR6 / trachea formation / transcription, DNA-templated / TRIF-dependent toll-like receptor signaling pathway / vascular endothelial growth factor receptor signaling pathway / viral process
Components
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
General Function
Rna polymerase ii carboxy-terminal domain kinase activity
Specific 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 [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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0010648|Mitogen-activated protein kinase 1 (MAPK1)
ATGGCGGCGGCGGCGGCGGCGGGCGCGGGCCCGGAGATGGTCCGCGGGCAGGTGTTCGAC
GTGGGGCCGCGCTACACCAACCTCTCGTACATCGGCGAGGGCGCCTACGGCATGGTGTGC
TCTGCTTATGATAATGTCAACAAAGTTCGAGTAGCTATCAAGAAAATCAGCCCCTTTGAG
CACCAGACCTACTGCCAGAGAACCCTGAGGGAGATAAAAATCTTACTGCGCTTCAGACAT
GAGAACATCATTGGAATCAATGACATTATTCGAGCACCAACCATCGAGCAAATGAAAGAT
GTATATATAGTACAGGACCTCATGGAAACAGATCTTTACAAGCTCTTGAAGACACAACAC
CTCAGCAATGACCATATCTGCTATTTTCTCTACCAGATCCTCAGAGGGTTAAAATATATC
CATTCAGCTAACGTTCTGCACCGTGACCTCAAGCCTTCCAACCTGCTGCTCAACACCACC
TGTGATCTCAAGATCTGTGACTTTGGCCTGGCCCGTGTTGCAGATCCAGACCATGATCAC
ACAGGGTTCCTGACAGAATATGTGGCCACACGTTGGTACAGGGCTCCAGAAATTATGTTG
AATTCCAAGGGCTACACCAAGTCCATTGATATTTGGTCTGTAGGCTGCATTCTGGCAGAA
ATGCTTTCTAACAGGCCCATCTTTCCAGGGAAGCATTATCTTGACCAGCTGAACCACATT
TTGGGTATTCTTGGATCCCCATCACAAGAAGACCTGAATTGTATAATAAATTTAAAAGCT
AGGAACTATTTGCTTTCTCTTCCACACAAAAATAAGGTGCCATGGAACAGGCTGTTCCCA
AATGCTGACTCCAAAGCTCTGGACTTATTGGACAAAATGTTGACATTCAACCCACACAAG
AGGATTGAAGTAGAACAGGCTCTGGCCCACCCATATCTGGAGCAGTATTACGACCCGAGT
GACGAGCCCATCGCCGAAGCACCATTCAAGTTCGACATGGAATTGGATGACTTGCCTAAG
GAAAAGCTCAAAGAACTAATTTTTGAAGAGACTGCTAGATTCCAGCCAGGATACAGATCT
TAA
Chromosome Location
22
Locus
22q11.2|22q11.21
External Identifiers
ResourceLink
UniProtKB IDP28482
UniProtKB Entry NameMK01_HUMAN
GenBank Protein ID182191
GenBank Gene IDM84489
GenAtlas IDMAPK1
HGNC IDHGNC:6871
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01169Arsenic trioxideapproved, investigationalyesinducerDetails
DB02482PhosphonothreonineexperimentalunknownDetails
DB02733PurvalanolexperimentalunknowninhibitorDetails
DB06195SeliciclibinvestigationalunknownDetails
DB06641PerifosineinvestigationalunknownDetails
DB01064Isoprenalineapproved, investigationalunknowninducerDetails
DB06877N,N-DIMETHYL-4-(4-PHENYL-1H-PYRAZOL-3-YL)-1H-PYRROLE-2-CARBOXAMIDEexperimentalunknownDetails
DB07010N-BENZYL-4-[4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL]-1H-PYRROLE-2-CARBOXAMIDEexperimentalunknownDetails
DB07264(S)-N-(1-(3-CHLORO-4-FLUOROPHENYL)-2-HYDROXYETHYL)-4-(4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL)-1H-PYRROLE-2-CARBOXAMIDEexperimentalunknownDetails
DB07788(3R,5Z,8S,9S,11E)-8,9,16-TRIHYDROXY-14-METHOXY-3-METHYL-3,4,9,10-TETRAHYDRO-1H-2-BENZOXACYCLOTETRADECINE-1,7(8H)-DIONEexperimentalunknownDetails
DB077945-(2-PHENYLPYRAZOLO[1,5-A]PYRIDIN-3-YL)-1H-PYRAZOLO[3,4-C]PYRIDAZIN-3-AMINEexperimentalunknownDetails
DB07905(1aR,8S,13S,14S,15aR)-5,13,14-trihydroxy-3-methoxy-8-methyl-8,9,13,14,15,15a-hexahydro-6H-oxireno[k][2]benzoxacyclotetradecine-6,12(1aH)-dioneexperimentalunknownDetails
DB02116OlomoucineexperimentalunknownDetails
DB08513[4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACIDexperimentalunknownDetails
DB085214-[5-(4-FLUORO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-3H-IMIDAZOL-4-YL]-PYRIDINEexperimentalunknownDetails
DB04338SB220025experimentalunknownDetails
DB11120Turpentineapproved, experimentalunknownDetails
DB13930UlixertinibinvestigationalunknowninhibitorDetails
DB00945Acetylsalicylic acidapproved, vet_approvedunknownDetails