MAPK1
entrez
5594
canonical
uniprot
P28482
canonical
ensembl
ENSG00000100030
resolver
ensp
ENSP00000215832
resolver
ensp
ENSP00000381803
resolver
genesymbol
MAPK1
resolver
genesymbol_syn
ERK2
resolver
genesymbol_syn
PRKM1
resolver
genesymbol_syn
PRKM2
resolver
hgnc
HGNC:6871
resolver
uniprot
A8CZ64
resolver
uniprot
Q499G7
resolver
uniprot_entry
MK01_HUMAN
resolver
uniprot_entry
Q499G7_HUMAN
resolver
uniprot_sec
A8CZ64
resolver
activity_regulation
ACTIVITY REGULATION: Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-185 and Tyr-187 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-29 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. {ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:19060905}.
uniprot
proteins
amino_acid_sequence
MAAAAAAGAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNVNKVRVAIKKISPFEHQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQHLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLARVADPDHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDKMLTFNPHKRIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETARFQPGYRS
uniprot
proteins
disease_involvement
DISEASE: Noonan syndrome 13 (NS13) [MIM:619087]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. NS13 inheritance is autosomal dominant. There is considerable variability in severity. {ECO:0000269|PubMed:32721402}. Note=The disease is caused by variants affecting the gene represented in this entry.
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) (PubMed:35831023). 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). Phosphorylates phosphoglycerate kinase PGK1 under hypoxic conditions to promote its targeting to the mitochondrion and suppress the formation of acetyl-coenzyme A from pyruvate (PubMed:26942675). Phosphorylates GJA1 at 'Ser-279' and 'Ser-282' resulting in an increase in GJA1 ubiquitination and ultimately lysosomal degradation (By similarity). 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 (PubMed:35831023). {ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:10637505, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:12794087, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15184391, ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19879846, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:32721402, ECO:0000269|PubMed:35831023, ECO:0000269|PubMed:7588608, ECO:0000269|PubMed:8622688, ECO:0000269|PubMed:9480836, ECO:0000269|PubMed:9596579, ECO:0000269|PubMed:9649500, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:15526160, 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:0000269|PubMed:19879846}.
uniprot
proteins
mass_dalton
41390
uniprot
proteins
mutagenesis
MUTAGEN 54; /note="K->R: Does not inhibit interaction with MAP2K1."; /evidence="ECO:0000269|PubMed:18794356"; MUTAGEN 176..179; /note="Missing: Inhibits homodimerization and interaction with TPR."; /evidence="ECO:0000269|PubMed:18794356"; MUTAGEN 185; /note="T->A: Inhibits interaction with TPR; when associated with A-187."; /evidence="ECO:0000269|PubMed:18794356"; MUTAGEN 187; /note="Y->A: Inhibits interaction with TPR; when associated with A-185."; /evidence="ECO:0000269|PubMed:18794356"; MUTAGEN 234; /note="L->A: Inhibits interaction with TPR."; /evidence="ECO:0000269|PubMed:18794356"; MUTAGEN 318; /note="D->A: Loss of dephosphorylation by PTPRJ."; /evidence="ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19494114"; MUTAGEN 318; /note="D->N: Inhibits interaction with MAP2K1 but not with TPR; when associated with N-321."; /evidence="ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19494114"; MUTAGEN 321; /note="D->N: Inhibits interaction with MAP2K1 but not with TPR; when associated with N-318."; /evidence="ECO:0000269|PubMed:18794356
uniprot
proteins
post_translational_modification
PTM: Phosphorylated upon KIT and FLT3 signaling (By similarity). Dually phosphorylated on Thr-185 and Tyr-187, which activates the enzyme. Undergoes regulatory phosphorylation on additional residues such as Ser-246 and Ser-248 in the kinase insert domain (KID) These phosphorylations, which are probably mediated by more than one kinase, are important for binding of MAPK1/ERK2 to importin-7 (IPO7) and its nuclear translocation. In addition, autophosphorylation of Thr-190 was shown to affect the subcellular localization of MAPK1/ERK2 as well. Ligand-activated ALK induces tyrosine phosphorylation. Dephosphorylated by PTPRJ at Tyr-187. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. DUSP3 and DUSP6 dephosphorylate specifically MAPK1/ERK2 and MAPK3/ERK1 whereas DUSP9 dephosphorylates a broader range of MAPKs. Dephosphorylated by DUSP1 and DUSP2 at Thr-185 and Tyr-187 (By similarity) (PubMed:16288922). {ECO:0000250, ECO:0000250|UniProtKB:P63085, ECO:0000269|PubMed:16288922, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:18760948, ECO:0000269|PubMed:19053285, ECO:0000269|PubMed:19060905, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19447520, ECO:0000269|PubMed:19494114}.; PTM: ISGylated. {ECO:0000250}.; PTM: Ubiquitinated by TRIM15 via 'Lys-63'-linked ubiquitination; leading to activation. Deubiquitinated by CYLD. {ECO:0000269|PubMed:34497368}.
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
10224087
uniprot
proteins
pubmed
10591208
uniprot
proteins
pubmed
10617468
uniprot
proteins
pubmed
10637505
uniprot
proteins
pubmed
11154262
uniprot
proteins
pubmed
11912194
uniprot
proteins
pubmed
12110590
uniprot
proteins
pubmed
12356731
uniprot
proteins
pubmed
12665801
uniprot
proteins
pubmed
12792650
uniprot
proteins
pubmed
12794087
uniprot
proteins
pubmed
12974390
uniprot
proteins
pubmed
1319925
uniprot
proteins
pubmed
15184391
uniprot
proteins
pubmed
15241487
uniprot
proteins
pubmed
15358203
uniprot
proteins
pubmed
1540184
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15526160
uniprot
proteins
pubmed
15616583
uniprot
proteins
pubmed
15664191
uniprot
proteins
pubmed
15788397
uniprot
proteins
pubmed
15952796
uniprot
proteins
pubmed
16139248
uniprot
proteins
pubmed
16242327
uniprot
proteins
pubmed
16288922
uniprot
proteins
pubmed
16393692
uniprot
proteins
pubmed
16581800
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17194451
uniprot
proteins
pubmed
17274988
uniprot
proteins
pubmed
17300186
uniprot
proteins
pubmed
18211802
uniprot
proteins
pubmed
18296648
uniprot
proteins
pubmed
18435604
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18760948
uniprot
proteins
pubmed
18794356
uniprot
proteins
pubmed
19053285
uniprot
proteins
pubmed
19060905
uniprot
proteins
pubmed
19265199
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19447520
uniprot
proteins
pubmed
19494114
uniprot
proteins
pubmed
19565474
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19827834
uniprot
proteins
pubmed
19879846
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21779493
uniprot
proteins
pubmed
22033920
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23847209
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
26942675
uniprot
proteins
pubmed
32051553
uniprot
proteins
pubmed
32721402
uniprot
proteins
pubmed
34497368
uniprot
proteins
pubmed
35831023
uniprot
proteins
pubmed
7588608
uniprot
proteins
pubmed
8622688
uniprot
proteins
pubmed
8794306
uniprot
proteins
pubmed
9480836
uniprot
proteins
pubmed
9596579
uniprot
proteins
pubmed
9649500
uniprot
proteins
pubmed
9687510
uniprot
proteins
pubmed
9788880
uniprot
proteins
pubmed
9827991
uniprot
proteins
sequence_length
360
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle {ECO:0000250}. Nucleus {ECO:0000269|PubMed:32721402}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm {ECO:0000269|PubMed:32721402}. Membrane, caveola {ECO:0000250|UniProtKB:P63086}. Cell junction, focal adhesion {ECO:0000250|UniProtKB:P63085}. Note=Associated with the spindle during prometaphase and metaphase (By similarity). PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention. Phosphorylation at Ser- 246 and Ser-248 as well as autophosphorylation at Thr-190 promote nuclear localization. {ECO:0000250}.
uniprot
proteins