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Details on Person UniProt:P63086 Mapk1
| Class:Id | ReferenceGeneProduct:95260 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 6 2015;chain:2-358 added on Fri February 6 2015;initiator methionine:1 for 95260 removed on Fri Nov 03 2023;initiator methionine: for 95260 added on Fri Nov 03 2023;initiator methionine: for 95260 removed on Fri Aug 15 2025;initiator methionine:1 for 95260 added on Fri Aug 15 2025 |
| _displayName | UniProt:P63086 Mapk1 |
| _timestamp | 2026-02-20 22:45:51 |
| chain | initiator methionine:1 chain:2-358 |
| checksum | 3BBCF22471EDBA0B |
| comment | 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 (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).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.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)COFACTOR 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.SUBUNIT Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with ADAM15, ARHGEF2, DAPK1 (via death domain), HSF4, IER3, IPO7, MKNK2, MORG1, NISCH, PEA15, SGK1, and isoform 1 of NEK2 (By similarity). Interacts (via phosphorylated form) with TPR (via C-terminal region and phosphorylated form); the interaction requires dimerization of MAPK1/ERK2 and increases following EGF stimulation (By similarity). Interacts with MAP2K1 (By similarity). Interacts with DUSP6 (PubMed:16567630). Interacts with ARRB2 (PubMed:11226259). Interacts (phosphorylated form) with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation (PubMed:19427337, PubMed:19778377). MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation (By similarity). Interacts with DCC (PubMed:21070949). The phosphorylated form interacts with PML (By similarity). Interacts with STYX (By similarity). Interacts with CDK2AP2 (PubMed:12944431). Interacts with CAVIN4 (PubMed:24567387). Interacts with DUSP7; the interaction enhances DUSP7 phosphatase activity (PubMed:27783954). Interacts with GIT1; this interaction is necessary for MAPK1 localization to focal adhesions (PubMed:15923189). Interacts with ZNF263 (By similarity). Interacts with phosphoglycerate kinase PGK1; the interaction is direct, occurs under hypoxic conditions, and promotes interaction between PGK1 and PIN1 (By similarity).INTERACTION 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.TISSUE SPECIFICITY Highest levels within the nervous system, expressed in different tissues, mostly in muscle, thymus and heart.DEVELOPMENTAL STAGE Increased expression during development.DOMAIN The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.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).PTM ISGylated.PTM Ubiquitinated by TRIM15 via 'Lys-63'-linked ubiquitination; leading to activation. Deubiquitinated by CYLD.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. |
| created | [InstanceEdit:84067] Schmidt, EE, 2003-12-18 04:29:09 |
| description | recommendedName: fullName evidence="21"Mitogen-activated protein kinase 1 shortName: MAP kinase 1 shortName: MAPK 1 ecNumber evidence="3"2.7.11.24 alternativeName: ERT1 alternativeName: Extracellular signal-regulated kinase 2 shortName: ERK-2 alternativeName: MAP kinase isoform p42 shortName: p42-MAPK alternativeName: Mitogen-activated protein kinase 2 shortName: MAP kinase 2 shortName: MAPK 2 |
| geneName | Mapk1 Erk2 Mapk Prkm1 |
| identifier | P63086 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Apoptosis ATP-binding Cell cycle Cell junction Cytoplasm Cytoskeleton Direct protein sequencing Kinase Membrane Nucleotide-binding Nucleus Phosphoprotein Reference proteome Serine/threonine-protein kinase Transferase Ubl conjugation |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:2587579] Weiser, JD [InstanceEdit:3445779] Weiser, JD [InstanceEdit:5083144] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:9015733] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9616384] Weiser, JD [InstanceEdit:9627708] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9750299] Weiser, JD [InstanceEdit:9767224] Weiser, Joel [InstanceEdit:9796772] Weiser, Joel [InstanceEdit:9834092] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | Mapk1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | MK01_RAT P27703 |
| sequenceLength | 358 |
| species | [Species:48895] Rattus norvegicus |
| (referenceEntity) | [EntityWithAccessionedSequence:112351] phospho-ERK2 [cytosol] [Rattus norvegicus] [EntityWithAccessionedSequence:112357] phospho-ERK2 [nucleoplasm] [Rattus norvegicus] [EntityWithAccessionedSequence:205803] p-T183,Y185-Mapk1 [nucleoplasm] [Rattus norvegicus] [EntityWithAccessionedSequence:206115] Erk2 [nucleoplasm] [Rattus norvegicus] [EntityWithAccessionedSequence:206197] Phospho (2 sites) Erk2 [cytosol] [Rattus norvegicus] [EntityWithAccessionedSequence:206232] Erk2 [cytosol] [Rattus norvegicus] |
| (referenceSequence) | [ModifiedResidue:112349] O-phospho-L-threonine at unknown position [ModifiedResidue:112350] O4'-phospho-L-tyrosine at unknown position [ModifiedResidue:112355] O-phospho-L-threonine at unknown position [ModifiedResidue:112356] O4'-phospho-L-tyrosine at unknown position [ModifiedResidue:205815] O-phospho-L-threonine at 183 [ModifiedResidue:206182] O4'-phospho-L-tyrosine at 185 |
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No pathways have been reviewed or authored by UniProt:P63086 Mapk1 (95260)
