Mapk1
entrez
26413
canonical
uniprot
P63085
canonical
ensembl
ENSMUSG00000063358
resolver
ensp
ENSMUSP00000065983
resolver
ensp
ENSMUSP00000111396
resolver
ensp
ENSMUSP00000156154
resolver
enst
ENSMUST00000069107
resolver
enst
ENSMUST00000115731
resolver
enst
ENSMUST00000232611
resolver
genesymbol
Mapk1
resolver
genesymbol_syn
Erk2
resolver
genesymbol_syn
Mapk
resolver
genesymbol_syn
Prkm1
resolver
uniprot
P27703
resolver
uniprot
Q3V1U6
resolver
uniprot_entry
MK01_MOUSE
resolver
uniprot_sec
P27703
resolver
uniprot_sec
Q3V1U6
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. {ECO:0000269|PubMed:8221888}.
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. 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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P28482, ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:10753946, ECO:0000269|PubMed:11702783, ECO:0000269|PubMed:12134156, ECO:0000269|PubMed:26240334, 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
post_translational_modification
PTM: Dually phosphorylated on Thr-183 and Tyr-185, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation (By similarity). Dephosphorylated by PTPRJ at Tyr-185 (By similarity). Phosphorylated upon FLT3 and KIT signaling (By similarity). Dephosphorylated by DUSP1 and DUSP2 at Thr-183 and Tyr-185 (By similarity) (PubMed:8221888). {ECO:0000250, ECO:0000250|UniProtKB:P28482, ECO:0000269|PubMed:8221888}.; PTM: ISGylated. {ECO:0000269|PubMed:22022510}.; 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
10080542
uniprot
proteins
pubmed
10753946
uniprot
proteins
pubmed
11090077
uniprot
proteins
pubmed
11702783
uniprot
proteins
pubmed
12134156
uniprot
proteins
pubmed
15118098
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15899793
uniprot
proteins
pubmed
15923189
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16162500
uniprot
proteins
pubmed
16393692
uniprot
proteins
pubmed
1649458
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
17947660
uniprot
proteins
pubmed
18034455
uniprot
proteins
pubmed
1849075
uniprot
proteins
pubmed
19131326
uniprot
proteins
pubmed
19565474
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21262971
uniprot
proteins
pubmed
21779493
uniprot
proteins
pubmed
22022510
uniprot
proteins
pubmed
26240334
uniprot
proteins
pubmed
27783954
uniprot
proteins
pubmed
8221888
uniprot
proteins
pubmed
8444355
uniprot
proteins
sequence_length
358
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle {ECO:0000250}. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}. Cytoplasm. Membrane, caveola {ECO:0000250|UniProtKB:P63086}. Cell junction, focal adhesion {ECO:0000269|PubMed:15923189}. Note=Associated with the spindle during prometaphase and metaphase (By similarity). 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 (By similarity). Localization to focal adhesions is stimulated by EGF (PubMed:15923189). {ECO:0000250, ECO:0000269|PubMed:15923189}.
uniprot
proteins