Mitogen-activated protein kinase 1

Details

Name
Mitogen-activated protein kinase 1
Kind
protein
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 1
  • MAPK 2
  • Mitogen-activated protein kinase 2
  • p42-MAPK
  • PRKM1
  • PRKM2
Gene Name
MAPK1
UniProtKB Entry
P28482Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
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
Processes
apoptotic process / B cell receptor signaling pathway / caveolin-mediated endocytosis / chemotaxis / cytosine metabolic process / ERBB signaling pathway / ERK1 and ERK2 cascade / insulin receptor signaling pathway / labyrinthine layer blood vessel development / lipopolysaccharide-mediated signaling pathway / long-term synaptic potentiation / lung morphogenesis / mammary gland epithelial cell proliferation / negative regulation of cell differentiation / peptidyl-serine phosphorylation / peptidyl-threonine phosphorylation / positive regulation of peptidyl-threonine phosphorylation / positive regulation of telomerase activity / positive regulation of telomere capping / positive regulation of telomere maintenance via telomerase / protein phosphorylation / regulation of cytoskeleton organization / regulation of early endosome to late endosome transport / regulation of Golgi inheritance / regulation of protein stability / regulation of stress-activated MAPK cascade / response to epidermal growth factor / response to exogenous dsRNA / signal transduction / stress-activated MAPK cascade / T cell receptor signaling pathway / trachea formation
Components
caveola / cytoplasm / cytoskeleton / cytosol / early endosome / focal adhesion / Golgi apparatus / late endosome / mitochondrion / mitotic spindle / nucleoplasm / nucleus / pseudopodium
General 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 also plays 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 FXR1) 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 response 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 (By similarity)
Specific Function
ATP binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm, cytoskeleton, spindle
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
22q11.22
External Identifiers
ResourceLink
UniProtKB IDP28482
UniProtKB Entry NameMK01_HUMAN
GenBank Protein ID182191
GenBank Gene IDM84489
GeneCard IDMAPK1
GenAtlas IDMAPK1
HGNC IDHGNC:6871
PDB ID(s)1PME, 1TVO, 1WZY, 2OJG, 2OJI, 2OJJ, 2Y9Q, 3D42, 3D44, 3I5Z, 3I60, 3SA0, 3TEI, 3W55, 4FMQ, 4FUX, 4FUY, 4FV0, 4FV1, 4FV2, 4FV3, 4FV4, 4FV5, 4FV6, 4FV7, 4FV8, 4FV9, 4G6N, 4G6O, 4H3P, 4H3Q, 4IZ5, 4IZ7, 4IZA, 4N0S, 4NIF, 4O6E, 4QP1, 4QP2, 4QP3, 4QP4, 4QP6, 4QP7, 4QP8, 4QP9, 4QPA, 4QTA, 4QTE, 4XJ0, 4ZXT, 4ZZM, 4ZZN, 4ZZO, 5AX3, 5BUE, 5BUI, 5BUJ, 5BVD, 5BVE, 5BVF, 5K4I, 5LCJ, 5LCK, 5NGU, 5NHF, 5NHH, 5NHJ, 5NHL, 5NHO, 5NHP, 5NHV, 5V60, 5V61, 5V62, 5WP1, 6D5Y, 6DMG, 6G54, 6G8X, 6G91, 6G92, 6G93, 6G97, 6G9A, 6G9D, 6G9H, 6G9J, 6G9K, 6G9M, 6G9N, 6GDM, 6GDQ, 6GE0, 6GJB, 6GJD, 6NBS, 6OPG, 6OPH, 6OPI, 6Q7K, 6Q7S, 6Q7T, 6QA1, 6QA3, 6QA4, 6QAG, 6QAH, 6QAL, 6QAQ, 6QAW, 6RQ4, 6SLG, 7AUV, 7E73, 7E75, 7NQQ, 7NQW, 7NR3, 7NR5, 7NR8, 7NR9, 7OPM, 7W5O, 7X4U, 7XC1, 8AO2, 8AO3, 8AO4, 8AO5, 8AO6, 8AO7, 8AO8, 8AO9, 8AOA, 8AOB, 8AOC, 8AOD, 8AOE, 8AOF, 8AOG, 8AOH, 8AOI, 8AOJ, 8U8J, 8U8K, 8ZJV
KEGG IDhsa:5594
IUPHAR/Guide To Pharmacology ID1495
NCBI Gene ID5594
General References
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Arsenic trioxideapproved, investigationalyestargetinducerDetails
PhosphonothreonineexperimentalyestargetinhibitorDetails
PurvalanolexperimentalunknowntargetinhibitorDetails
SeliciclibinvestigationalunknowntargetDetails
PerifosineinvestigationalunknowntargetDetails
N,N-DIMETHYL-4-(4-PHENYL-1H-PYRAZOL-3-YL)-1H-PYRROLE-2-CARBOXAMIDEexperimentalunknowntargetDetails
N-BENZYL-4-[4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL]-1H-PYRROLE-2-CARBOXAMIDEexperimentalunknowntargetDetails
(S)-N-(1-(3-CHLORO-4-FLUOROPHENYL)-2-HYDROXYETHYL)-4-(4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL)-1H-PYRROLE-2-CARBOXAMIDEexperimentalunknowntargetDetails
(3R,5Z,8S,9S,11E)-8,9,16-TRIHYDROXY-14-METHOXY-3-METHYL-3,4,9,10-TETRAHYDRO-1H-2-BENZOXACYCLOTETRADECINE-1,7(8H)-DIONEexperimentalunknowntargetDetails
5-(2-PHENYLPYRAZOLO[1,5-A]PYRIDIN-3-YL)-1H-PYRAZOLO[3,4-C]PYRIDAZIN-3-AMINEexperimentalyestargetinhibitorDetails
HypothemycinexperimentalunknowntargetDetails
OlomoucineexperimentalunknowntargetDetails
[4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACIDexperimentalunknowntargetDetails
4-[4-(4-Fluorophenyl)-2-[4-[(R)-methylsulfinyl]phenyl]-1H-imidazol-5-yl]pyridineexperimentalunknowntargetDetails
SB220025experimentalyestargetinhibitorDetails
Turpentineapproved, experimentalunknowntargetDetails
UlixertinibinvestigationalunknowntargetinhibitorDetails
CI-1040investigationalyestargetinhibitorDetails
Bisindolylmaleimide IexperimentalyestargetinhibitorDetails
DebromohymenialdisineexperimentalyestargetinhibitorDetails
Tetrabromo-2-BenzotriazoleexperimentalyestargetinhibitorDetails
RavoxertinibinvestigationalyestargetmodulatorDetails
TemuterkibinvestigationalyestargetinhibitorDetails