| Aspect | Key points | Evidence citation IDs | Key source (first author year, journal) | Publication date | URL |
|---|---|---|---|---|---|
| Identity | UniProt P63086 is explicitly annotated in a native rat IMCD dataset as Mapk1, Mitogen-activated protein kinase 1, i.e. ERK2. It is distinguished from Mapk3/ERK1 by a separate related TEY phosphopeptide entry. | (pqac-00000005, pqac-00000003) | Chou 2025, AJP Renal Physiology | Jan 2025 | https://doi.org/10.1152/ajprenal.00182.2024 |
| Enzymatic activity/activation sites | Rat Mapk1/ERK2 was detected with dual phosphorylation in the TEY activation segment region: T179 and Y185 in the UniProt-mapped rat table; MS peptide VADPDHDHTGFLpTEpYVATR was mapped to residues 183 and 185 in the dataset view. EGF response for the Mapk1 phosphopeptide was log2(EGF/Control)=0.354 with P=0.083. | (pqac-00000005, pqac-00000003) | Chou 2025, AJP Renal Physiology | Jan 2025 | https://doi.org/10.1152/ajprenal.00182.2024 |
| Upstream activation | The rat phosphoproteomic network places Map2k2/MEK upstream of Mapk1 and annotates Mapk1 T179 and Y185 phosphorylation as increased after EGF. The study concludes that EGF activates the canonical MAPK pathway through the RAS-MEK-RAF cascade in native rat IMCD cells. | (pqac-00000000, pqac-00000002, pqac-00000004) | Chou 2025, AJP Renal Physiology | Jan 2025 | https://doi.org/10.1152/ajprenal.00182.2024 |
| Localization control | ERK nuclear translocation is functionally important. PEA-15 binds ERK1/2, contains a nuclear export sequence, sequesters ERK in the cytoplasm, prevents nuclear accumulation, and protects ERK2 from dephosphorylation; disabling PEA-15 increases proliferation, while blocking nuclear translocation reduces melanoma survival. In rat IMCD, PEA15 phosphorylation decreased after EGF, consistent with localization control. | (pqac-00000001, pqac-00000002, pqac-00000006, pqac-00000011, pqac-00000007) | Chou 2025, AJP Renal Physiology; Deschenes-Simard 2023, Cancers | Jan 2025; Dec 2023 | https://doi.org/10.1152/ajprenal.00182.2024; https://doi.org/10.3390/cancers16010095 |
| Example substrates/outputs | In rat IMCD, ERK2 is linked to phosphorylation of NHE1/Slc9a1 at Ser727 and Ser730, and NHE1 can scaffold ERK2. ERK2 is also linked to translation-control nodes including Eif4ebp1 and Eef2k. Broader ERK outputs in recent review evidence include BIM Ser69 phosphorylation, FoxO3 regulation, ELK-1 multisite phosphorylation, and RSK regulation. | (pqac-00000002, pqac-00000000, pqac-00000001, pqac-00000006) | Chou 2025, AJP Renal Physiology; Deschenes-Simard 2023, Cancers | Jan 2025; Dec 2023 | https://doi.org/10.1152/ajprenal.00182.2024; https://doi.org/10.3390/cancers16010095 |
| Recent quantitative data/statistics | Native rat IMCD phosphoproteomics quantified 29881 phosphosites across 5457 proteins; 135 phosphosites increased and 119 decreased after EGF. Enriched terms included MAPK signaling pathway with 9 proteins, nucleocytoplasmic transport with 16, and cellular response to growth factor stimulus with 19. Site-selection thresholds were P<0.1 and absolute log2(EGF/Control)>0.3428; EGFR pY1091 immunoblot increase was significant with n=3 and P<0.05. In the 2023 ERK review, phospho-ERK was reported as less than 10 percent in colorectal cancer cells and 2 to 3 percent by MS in drug-addicted tumor cells; more than 85 percent pathway suppression was suggested for antiproliferative effects. | (pqac-00000003, pqac-00000002, pqac-00000006) | Chou 2025, AJP Renal Physiology; Deschenes-Simard 2023, Cancers | Jan 2025; Dec 2023 | https://doi.org/10.1152/ajprenal.00182.2024; https://doi.org/10.3390/cancers16010095 |
| Recent mechanistic/therapeutic developments | A 2024 study targeting ERK-MYD88 interaction via the ERK DRS/CD pocket reported preserved ERK phosphorylation and RSK phosphorylation but phospho-ERK cytoplasmic accumulation after 6 h, ISR activation, and cancer-selective apoptosis. Quantitative values included LLC in vitro IC50 of 4 uM, bioavailability of 52.9 percent, and AUC of 1129 ng/ml/h, about 3 umol/L/h. Another 2024 study showed ERK activation-state-dependent, kinase-activity-independent interaction with DHPS; NAD lowered the DHPS-ERK2 Kd 5-fold and spermidine plus NAD reduced Kd to about 1 uM. | (pqac-00000014, pqac-00000015, pqac-00000017, pqac-00000016) | Virard 2024, Nature Communications; Becker 2024, Cell Reports | Aug 2024; Oct 2024 | https://doi.org/10.1038/s41467-024-51275-z; https://doi.org/10.1016/j.celrep.2024.114831 |


*Table: This table summarizes verified identity, activation, localization, representative outputs, quantitative findings, and recent mechanistic developments for rat Mapk1/ERK2 (UniProt P63086). It provides a compact evidence map for functional annotation with direct citation IDs, dates, and URLs.*