Mapk1
entrez
116590
canonical
uniprot
P63086
canonical
ensembl
ENSRNOG00000001849
resolver
ensembl
ENSRNOG00055003901
resolver
ensembl
ENSRNOG00060002574
resolver
ensembl
ENSRNOG00065008439
resolver
ensp
ENSRNOP00000002533
resolver
ensp
ENSRNOP00055004732
resolver
ensp
ENSRNOP00060002931
resolver
ensp
ENSRNOP00065009913
resolver
enst
ENSRNOT00000002533
resolver
enst
ENSRNOT00055006213
resolver
enst
ENSRNOT00060004151
resolver
enst
ENSRNOT00065013385
resolver
genesymbol
Mapk1
resolver
genesymbol_syn
Erk2
resolver
genesymbol_syn
Mapk
resolver
genesymbol_syn
Prkm1
resolver
uniprot
P27703
resolver
uniprot_entry
MK01_RAT
resolver
uniprot_sec
P27703
resolver
activity_regulation
ACTIVITY REGULATION: Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-183 and Tyr-185 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-27 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Dephosphorylated and inactivated by DUSP1, DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors.
uniprot
proteins
amino_acid_sequence
MAAAAAAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNLNKVRVAIKKISPFEHQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQHLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLARVADPDHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDKMLTFNPHKRIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETARFQPGYRS
uniprot
proteins
ec_number
2.7.11.24
uniprot
proteins
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 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, GLI1 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 (By similarity). Phosphorylates CDK2AP2 (PubMed:12944431). Phosphorylates phosphoglycerate kinase PGK1 under hypoxic conditions to promote its targeting to the mitochondrion and suppress the formation of acetyl-coenzyme A from pyruvate (By similarity). Phosphorylates GJA1 at 'Ser-279' and 'Ser-282' resulting in an increase in GJA1 ubiquitination and ultimately lysosomal degradation (PubMed:29959233). Acts as a positive regulator of smoothened signaling by mediating phosphorylation of GLI1 in response to smoothened activation, promoting its dissociation from SUFU inhibitor and translocation to the nucleus (By similarity). {ECO:0000250|UniProtKB:P28482, ECO:0000269|PubMed:12944431, ECO:0000269|PubMed:21070949, ECO:0000269|PubMed:29959233, ECO:0000303|PubMed:16393692, ECO:0000303|PubMed:19565474, ECO:0000303|PubMed:21779493}.; FUNCTION: 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. {ECO:0000250|UniProtKB:P28482}.
uniprot
proteins
mass_dalton
41276
uniprot
proteins
mutagenesis
MUTAGEN 117; /note="Q->A: Reduced affinity for DCC. Strongly reduced affinity for DCC; when associated with A-123."; /evidence="ECO:0000269|PubMed:21070949"; MUTAGEN 123; /note="H->A: Reduced affinity for DCC. Strongly reduced affinity for DCC; when associated with A-117."; /evidence="ECO:0000269|PubMed:21070949"; MUTAGEN 155; /note="L->A: Reduced affinity for DCC."; /evidence="ECO:0000269|PubMed:21070949
uniprot
proteins
post_translational_modification
PTM: Dually phosphorylated on Thr-183 and Tyr-185, which activates the enzyme. Phosphorylated upon FLT3 and KIT signaling. Ligand-activated ALK induces tyrosine phosphorylation (By similarity). Dephosphorylated by PTPRJ at Tyr-185 (By similarity). Autophosphorylated on threonine and tyrosine residues in vitro, which correlates with a slow and low level of activation. Phosphorylation on Ser-27 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2 (By similarity). Dephosphorylated by DUSP1 and DUSP2 at Thr-183 and Tyr-185 (By similarity). {ECO:0000250|UniProtKB:P28482, ECO:0000250|UniProtKB:P63085}.; PTM: ISGylated. {ECO:0000250}.; PTM: Ubiquitinated by TRIM15 via 'Lys-63'-linked ubiquitination; leading to activation. Deubiquitinated by CYLD. {ECO:0000250|UniProtKB:P27361}.
uniprot
proteins
protein_family
CMGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
MAP kinase subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
11226259
uniprot
proteins
pubmed
12944431
uniprot
proteins
pubmed
15923189
uniprot
proteins
pubmed
16393692
uniprot
proteins
pubmed
16567630
uniprot
proteins
pubmed
16641100
uniprot
proteins
pubmed
16765894
uniprot
proteins
pubmed
1712480
uniprot
proteins
pubmed
18571434
uniprot
proteins
pubmed
18767165
uniprot
proteins
pubmed
19427337
uniprot
proteins
pubmed
19565474
uniprot
proteins
pubmed
19778377
uniprot
proteins
pubmed
2032290
uniprot
proteins
pubmed
21070949
uniprot
proteins
pubmed
21779493
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
24567387
uniprot
proteins
pubmed
27783954
uniprot
proteins
pubmed
29959233
uniprot
proteins
pubmed
7939721
uniprot
proteins
pubmed
8107865
uniprot
proteins
pubmed
8639522
uniprot
proteins
pubmed
9298898
uniprot
proteins
pubmed
9753691
uniprot
proteins
sequence_length
358
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}. Cytoplasm {ECO:0000269|PubMed:24567387}. Membrane, caveola {ECO:0000269|PubMed:24567387}. Cell junction, focal adhesion {ECO:0000250|UniProtKB:P63085}. Note=Associated with the spindle during prometaphase and metaphase. PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention. Phosphorylation at Ser- 244 and Ser-246 as well as autophosphorylation at Thr-188 promote nuclear localization. {ECO:0000250}.
uniprot
proteins