MAP2K1

Summary: MAPK cascade (IBA). MEK1 is the MAP2K tier of the RAF-MEK-ERK cascade; the PAINT node PTN000684494 covers MAP2Ks whose defining role is MAPK cascade signalling.

Reason: The IBA reflects inheritance of MAPK-cascade participation across the MAP2K clade; MEK1 is a canonical cascade kinase. The more specific GO:0070371 ERK1 and ERK2 cascade is used in core_functions, but the IBA is correct at its level.

Summary: MAPK cascade transferred from mouse Map2k1 (IEA, Ensembl Compara).

Reason: Correct; MEK1 is a core MAPK cascade component. Consistent with the IBA row.

Summary: Regulation of vascular smooth muscle contraction, transferred from rat Map2k1.

Reason: Rat source annotations of this type derive from pharmacological MEK inhibitor readouts in vascular tissue. Any effect is a downstream, tissue-specific consequence of ERK activation, not a MEK1 function; the deep research explicitly frames such outcomes as consequences of ERK activation.

Summary: Protein kinase activity from InterPro Ser/Thr kinase active-site signature (IEA).

Reason: Correct but uninformative; MEK1 is a dual-specificity MAP kinase kinase that phosphorylates the ERK TEY motif. Replace with GO:0004708.

Proposed replacements: MAP kinase kinase activity

Summary: Protein kinase activity (TAS) citing a paper on SDF-1/CXCR4 signalling in T cells in which MEK was probed only with the inhibitor PD098059.

Reason: The cited paper does not characterise MEK1 catalysis, but MEK1 kinase activity is not in doubt. Use the informative GO:0004708 MAP kinase kinase activity.

Proposed replacements: MAP kinase kinase activity

Summary: Protein serine/threonine kinase activity from mouse ortholog (IEA).

Reason: MEK1 phosphorylates both Thr and Tyr of ERK; Ser/Thr kinase activity alone under-describes it. GO:0004708 is the precise term (consistent with the MAP2K2 review).

Proposed replacements: MAP kinase kinase activity

Summary: Protein serine/threonine kinase activity (TAS) from Reactome 'MAP2K1 phosphorylates MAPK3'.

Reason: The Reactome reaction itself states that MEK1 phosphorylates both Thr202 and Tyr204 of ERK1, i.e. MAP kinase kinase activity rather than Ser/Thr-only kinase activity.

Proposed replacements: MAP kinase kinase activity

Summary: MAP kinase kinase activity (IBA) from PAINT node PTN000684494.

Reason: Core catalytic function; MEK1 has experimental evidence for this activity (PMID:8388392, PMID:28166211), so its presence among the IBA sources is expected grounding, not circularity.

Summary: MAP kinase kinase activity (IDA, FlyBase) from reconstituted assays with purified ERK2, MEK1 variants and ATP.

Reason: Direct biochemical evidence that human MEK1 phosphorylates ERK2.

Summary: MAP kinase kinase activity (IDA) from the original cloning of human MEK1/MEK2.

Reason: Recombinant MEK1 activated recombinant human ERK1 in vitro; core function.

Summary: MAP kinase kinase activity from combined IEA methods (EC 2.7.12.2, ARBA, orthologs).

Reason: Correct and core.

Summary: Protein serine/threonine/tyrosine kinase activity (TAS) from a review on ERK cascade compartmentalization.

Reason: Accurate parent of GO:0004708 describing MEK1's dual Thr/Tyr specificity; retained as consistent with MAP2K2.

Summary: Protein tyrosine kinase activity from Rhea mapping (RHEA:10596, tyrosyl-protein phosphorylation).

Reason: MEK1 tyrosine phosphorylation is restricted to the ERK TEY motif as part of dual-specificity activity; GO:0004708 captures this correctly, while 'protein tyrosine kinase activity' implies a general tyrosine kinase.

Proposed replacements: MAP kinase kinase activity

Summary: MAP kinase scaffold activity (ARBA IEA).

Reason: There is direct experimental support in MEK1 for a non-catalytic, scaffold-like role in bringing KSR and BRAF together (PMID:29433126); consistent with the IMP row.

Summary: MAP kinase scaffold activity (IMP, UniProt) from MEK-driven BRAF-KSR dimerization.

Reason: MEK1 binds KSR1/2 and BRAF face-to-face and promotes KSR-BRAF side-to-side dimerization independently of its catalytic activity; the MEK1 F311S interface mutant abolishes this. This fits the definition (binding multiple kinases of the cascade so they function in a coordinated way) and is a second, non-catalytic core activity alongside MAP kinase kinase activity.

Summary: Protein binding (IDA, MGI) citing PMID:22572157, a platelet-alloantibody biosensor paper with no MEK1 content. The digit-transposed PMID:22752157 (VRK2 anchors KSR1-MEK1 to ER) matches the claim.

Reason: Cited identifier appears to be a transposition of PMID:22752157, which shows MEK1 in a KSR1-VRK2A complex at the ER. The informative function is binding the scaffold KSR1: GO:0097110.

Proposed replacements: scaffold protein binding

Summary: Protein binding (IPI) with TRIB3 from a study of human tribbles and MAPK kinases.

Reason: Tribbles pseudokinases interact with MAPKKs and regulate their levels, but no informative MEK1 molecular function follows. Removal reflects that generic 'protein binding' is uninformative; it does not imply the reported interaction is false.

Summary: Protein binding (IPI) with TRIB1 from the same tribbles study.

Reason: As for TRIB3: uninformative generic binding. Removal reflects that generic 'protein binding' is uninformative; it does not imply the reported interaction is false.

Summary: Protein binding (IPI) with c-FLIP(L) (CFLAR).

Reason: c-FLIP(L) binds activated MEK1 and dampens MEK1-ERK signalling; this is a regulatory interaction acting on MEK1, not a MEK1 function that a specific MF term can capture. Removal reflects that generic 'protein binding' is uninformative; it does not imply the reported interaction is false.

Summary: Protein binding (IPI) with ERK2 (MAPK1) from the Mxi2 study.

Reason: MEK1 binds ERK1/2 as substrate and cytoplasmic anchor; GO:0051019 mitogen-activated protein kinase binding (consistent with MAP2K2 review).

Proposed replacements: mitogen-activated protein kinase binding

Summary: Protein binding (IPI) with RAF1 from the RKTG study.

Reason: RAF1 is the MAP3K that phosphorylates MEK1; GO:0031435 MAPKKK binding.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with RAF1 from SF-TAP purification of Raf complexes.

Reason: MEK1 recovered as a RAF binding partner; GO:0031435 MAPKKK binding.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with BRAF from SF-TAP purification of Raf complexes.

Reason: BRAF is a MEK1-activating MAP3K; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with BIRC6/BRUCE from a cytokinesis study.

Reason: BRUCE serves as a midbody platform for mitotic regulators; the abstract does not define a MEK1 molecular function. Removal reflects that generic 'protein binding' is uninformative; it does not imply the reported interaction is false.

Summary: Protein binding (IPI) with RAF1 from the PEBP4 scaffold study.

Reason: RAF1-MEK interaction scaffolded by PEBP4; informative term is GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with ERK1 (MAPK3) from the PEBP4 study.

Reason: ERK1 is the MEK1 substrate; GO:0051019.

Proposed replacements: mitogen-activated protein kinase binding

Summary: Protein binding (IPI) with PIN1.

Reason: Pin1 binds MEK1 and enhances EGF-induced MEK phosphorylation; this regulates MEK1 but gives no informative MEK1 MF. Removal reflects that generic 'protein binding' is uninformative; it does not imply the reported interaction is false.

Summary: Protein binding (IPI) with mouse ERK2 (Mapk1, P63085) in a pseudorabies Us2 study that mapped the MEK-binding region of ERK.

Reason: MEK1-ERK binding is canonical; GO:0051019 mitogen-activated protein kinase binding.

Proposed replacements: mitogen-activated protein kinase binding

Summary: Protein binding (IPI) with VRK2.

Reason: VRK2A binds MEK1 and KSR1 and inhibits signal transmission from MEK to ERK; VRK2 is a regulator of MEK1 and the MEK1-side MF is not informatively captured by a binding term beyond the KSR scaffold binding already annotated. Removal reflects that generic 'protein binding' is uninformative; it does not imply the reported interaction is false.

Summary: Protein binding (IPI) with mouse Ksr1 (Q61097) in a study of KSR1 kinase activity.

Reason: KSR1 is the ERK-cascade scaffold; GO:0097110 scaffold protein binding.

Proposed replacements: scaffold protein binding

Summary: Protein binding (IPI) with VRK2 isoform A from the VRK2-KSR1-MEK1 ER complex paper.

Reason: VRK2A anchors KSR1-MEK1 complexes to the ER; the informative MEK1 function here is KSR binding (annotated separately), not VRK2 binding per se. Removal reflects that generic 'protein binding' is uninformative; it does not imply the reported interaction is false.

Summary: Protein binding (IPI) with ERK2 from the Golgi fragmentation/Myt1 study.

Reason: MEK1-ERK2 binding; GO:0051019 mitogen-activated protein kinase binding.

Proposed replacements: mitogen-activated protein kinase binding

Summary: Protein binding (IPI) with RAF1 from a structural/pharmacology study of MEK inhibitors.

Reason: RAF-MEK complex; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with BRAF from the same MEK inhibitor study.

Reason: BRAF-MEK complex; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with YAP1 in liver cancer cells.

Reason: A reported MEK1-YAP interaction in hepatocarcinoma; no informative MEK1 MF can be assigned. Removal reflects that generic 'protein binding' is uninformative; it does not imply the reported interaction is false.

Summary: Protein binding (IPI) with BTRC from the MEK1-YAP liver cancer study.

Reason: Abstract reports MEK1 inhibition reduces BTRC levels; the binding does not define an informative MEK1 MF. Removal reflects that generic 'protein binding' is uninformative; it does not imply the reported interaction is false.

Summary: Protein binding (IPI) with RAF1 (CRAF) in KRAS-mutant tumour cells.

Reason: CRAF-MEK binding; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with BRAF in KRAS-mutant tumour cells.

Reason: BRAF-MEK binding; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with RAF1 in the BRAF-MEK1 structure paper.

Reason: RAF-MEK1 complex; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with BRAF; crystal structure of the BRAF kinase domain in complex with MEK1.

Reason: Structurally defined BRAF-MEK1 face-to-face complex; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with BANP from the HI-II-14 binary interactome screen.

Reason: High-throughput Y2H hit with no functional follow-up; uninformative. Removal reflects that generic 'protein binding' is uninformative; it does not imply the reported interaction is false.

Summary: Protein binding (IPI) with BRAF from the BRAF monomer crystal structure paper.

Reason: BRAF-MEK1 interaction; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with BRAF from a study of acquired resistance to BRAF/MEK co-targeting in melanoma.

Reason: BRAF-MEK1 binding; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with RAF1 from the HeLa quantitative interactome (AP-MS).

Reason: RAF1-MEK1 interaction is well established; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with BRAF from the HeLa quantitative interactome (AP-MS).

Reason: BRAF-MEK1; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with BRAF from the MEK-KSR allosteric activation paper.

Reason: MEK1 binds BRAF face-to-face; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with human KSR1 (Q8IVT5) from the MEK-KSR allosteric activation paper.

Reason: KSR1 is the ERK-cascade scaffold whose allosteric control by MEK1 drives BRAF activation; GO:0097110 scaffold protein binding.

Proposed replacements: scaffold protein binding

Summary: Protein binding (IPI) with RAF1 from EGFR-network AP-MS in colorectal cancer cells.

Reason: RAF1-MEK1; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with BRAF from EGFR-network AP-MS in colorectal cancer cells.

Reason: BRAF-MEK1; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with BANP isoform 2 from the HuRI binary interactome.

Reason: High-throughput Y2H hit; uninformative. Removal reflects that generic 'protein binding' is uninformative; it does not imply the reported interaction is false.

Summary: Protein binding (IPI) with TCP11 isoform from the HuRI binary interactome.

Reason: High-throughput Y2H hit; uninformative. Removal reflects that generic 'protein binding' is uninformative; it does not imply the reported interaction is false.

Summary: Protein binding (IPI) with PLEKHF2 from the HuRI binary interactome.

Reason: High-throughput Y2H hit; uninformative. Removal reflects that generic 'protein binding' is uninformative; it does not imply the reported interaction is false.

Summary: Protein binding (IPI) with RAF1 from the kinase interaction network (AP-MS) study.

Reason: RAF1-MEK1; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with BRAF from the kinase interaction network (AP-MS) study.

Reason: BRAF-MEK1; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with ERK2 (MAPK1) from the MAPK1 RASopathy study.

Reason: MEK1-ERK2 binding, altered by disease variants; GO:0051019.

Proposed replacements: mitogen-activated protein kinase binding

Summary: Protein binding (IPI) with BRAF from dual proteome-scale AP-MS networks (HEK293T/HCT116).

Reason: BRAF-MEK1; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with MOS from a study of MOS variants in female infertility.

Reason: MOS is a MAP3K that phosphorylates MEK1 in oocytes; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with RAF1 from OpenCell endogenous tagging/IP-MS.

Reason: RAF1-MEK1; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: Protein binding (IPI) with BRAF from the mutation-directed neo-PPI screen.

Reason: BRAF-MEK1; GO:0031435.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: ATP binding (IEA) from kinase domain signatures and orthologs.

Reason: MEK1 is an ATP-dependent kinase with a canonical ATP-binding site.

Summary: Nucleus (EXP) from PPARgamma nuclear export study.

Reason: MEK1 shuttles into the nucleus upon stimulation and exports PPARgamma (and ERK) via its NES, but it is predominantly cytoplasmic at steady state.

Summary: Nucleus (IEA, UniProt SubCell mapping).

Reason: Transient nuclear pool; non-core.

Summary: Nucleus (TAS) from a review on ERK cascade compartments.

Reason: Consistent with stimulation-induced nuclear shuttling; non-core.

Summary: Cytoplasm (EXP) from the KSR study.

Reason: MEK1 is predominantly cytoplasmic.

Summary: Cytoplasm (EXP) from the PPARgamma study.

Reason: MEK1 is predominantly cytoplasmic.

Summary: Cytoplasm (IEA, SubCell mapping).

Reason: Correct.

Summary: Mitochondrion from the ARBA rule ARBA00026962 (IEA); a minor, stimulus-dependent MEK1 pool at the mitochondria is reported in primary rodent studies.

Reason: ORGANELLES check (2026-11-03), previously UNDECIDED. The ARBA rule ARBA00026962 is a multi-condition-set association rule, pooling condition sets from unrelated families (MEK matches the IPR000719 plus IPR050915 MAP kinase kinase set in Euarchontoglires), that carries no evidence of its own and is presumably learned from existing mitochondrion annotations such as the parallel TAS row, so it is not used as support here. The organelle claim is supported at the level of MEK1/2 by two primary studies from the Poderoso group. In mouse LP07 lung tumour cells, mitochondrial subfractionation (fraction identity checked with complex I, VDAC1, SOD2 and COX VIc antibodies) placed MEK1/2 with ERK1/2 in the outer-membrane and intermembrane-space fractions (PMID:18545666), and phospho-MEK1/2 was detected in rat brain mitochondria whose ERK1/2 sat in the outer membrane/intermembrane space fraction (PMID:15030409, abstract-only). Caveats that keep this non-core and at the root: both studies used MEK1/2 antibodies that do not separate MAP2K1 from its paralog, neither reports an ER marker for the mitochondrial fraction (only the IMS subfraction argues against ER/MAM carry-over), and the pool is a transient signalling association with the ERK module (TRAF3/BRAF precedent for recruited kinases). MEK1 has no transit peptide or membrane anchor, and the sub-mitochondrial data split between outer membrane and IMS, so no sub-compartment row is added. The main MEK1 locations (cytoplasm, membrane via KSR1, nucleus) are captured elsewhere in this review.

Summary: Mitochondrion (TAS) from the Yao and Seger review of ERK-cascade compartments (abstract-only here); a minor, stimulus-dependent MEK1 pool at the mitochondria is reported in primary rodent studies.

Reason: ORGANELLES check (2026-11-03), previously UNDECIDED. The TAS source PMID:19565474 is a review whose cached text is abstract-only and does not name the mitochondrion, so the row is judged on the primary papers it summarises. The organelle claim is supported at the level of MEK1/2 by two primary studies from the Poderoso group. In mouse LP07 lung tumour cells, mitochondrial subfractionation (fraction identity checked with complex I, VDAC1, SOD2 and COX VIc antibodies) placed MEK1/2 with ERK1/2 in the outer-membrane and intermembrane-space fractions (PMID:18545666), and phospho-MEK1/2 was detected in rat brain mitochondria whose ERK1/2 sat in the outer membrane/intermembrane space fraction (PMID:15030409, abstract-only). Caveats that keep this non-core and at the root: both studies used MEK1/2 antibodies that do not separate MAP2K1 from its paralog, neither reports an ER marker for the mitochondrial fraction (only the IMS subfraction argues against ER/MAM carry-over), and the pool is a transient signalling association with the ERK module (TRAF3/BRAF precedent for recruited kinases). MEK1 has no transit peptide or membrane anchor, and the sub-mitochondrial data split between outer membrane and IMS, so no sub-compartment row is added. The main MEK1 locations (cytoplasm, membrane via KSR1, nucleus) are captured elsewhere in this review.

Summary: Early endosome (ARBA IEA).

Reason: MEK1 is recruited to signalling endosomes (e.g. BRAF-dependent NGF signalling); plausible non-core location.

Summary: Early endosome (TAS) from ERK-compartment review.

Reason: Supported by Reactome endosomal recruitment of MAP2Ks; non-core.

Summary: Late endosome (ARBA IEA).

Reason: LAMTOR3/MP1 (MEK partner 1) with LAMTOR2 scaffolds MEK1 on late endosomes; non-core location.

Summary: Late endosome (TAS) from the ERK-compartment review.

Reason: Consistent with the LAMTOR2/3 endosomal MEK1 scaffold; non-core.

Summary: Endoplasmic reticulum (IDA, MGI) citing PMID:22572157, which is an unrelated biosensor paper; the evidence evidently derives from PMID:22752157 (VRK2 anchors KSR1-MEK1 to ER).

Reason: A fraction of KSR1-MEK1 complexes is retained on the ER surface by VRK2A. Keep as non-core; the reference identifier should be corrected to PMID:22752157.

Summary: Golgi apparatus (TAS) from the ERK-compartment review.

Reason: MEK1 acts at Golgi membranes with the IL17RD/Sef scaffold and has a MEK1-specific role in G2 Golgi fragmentation.

Summary: Centrosome (IEA, SubCell mapping from PMID:14737111).

Reason: MEK1 is found at centrosomes in prometaphase and at the midzone/midbody later in mitosis; cell-cycle-specific, non-core.

Summary: Cytosol (IDA, HPA immunofluorescence).

Reason: MEK1 is a soluble cytosolic kinase where it meets and phosphorylates ERK.

Summary: Cytosol (TAS) from the ERK-compartment review.

Reason: Correct; principal site of MEK1 action.

Summary: Cytosol (TAS) from Reactome reaction 'MAP2K1 binds MAPK3'.

Reason: Reactome places the MEK1-containing step 'MAP2K1 binds MAPK3' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'MAP2K1 phosphorylates MAPK3'.

Reason: Reactome places the MEK1-containing step 'MAP2K1 phosphorylates MAPK3' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Dissociation of p-T,Y-MAPK3:MAP2K1'.

Reason: Reactome places the MEK1-containing step 'Dissociation of p-T,Y-MAPK3:MAP2K1' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Inactivation of MAP2K1 by CDK1'.

Reason: Reactome places the MEK1-containing step 'Inactivation of MAP2K1 by CDK1' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Anthrax lef cleaves target cell MAP2K1 (MEK1)'.

Reason: Reactome places the MEK1-containing step 'Anthrax lef cleaves target cell MAP2K1 (MEK1)' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'MAP2Ks and MAPKs bind to the activated RAF complex'.

Reason: Reactome places the MEK1-containing step 'MAP2Ks and MAPKs bind to the activated RAF complex' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'MAP2Ks phosphorylate MAPKs'.

Reason: Reactome places the MEK1-containing step 'MAP2Ks phosphorylate MAPKs' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'RAF phosphorylates MAP2K dimer'.

Reason: Reactome places the MEK1-containing step 'RAF phosphorylates MAP2K dimer' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Dissociation of RAS:RAF complex'.

Reason: Reactome places the MEK1-containing step 'Dissociation of RAS:RAF complex' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'MAP2Ks and MAPKs are phosphorylated at the endosome membrane'.

Reason: Reactome places the MEK1-containing step 'MAP2Ks and MAPKs are phosphorylated at the endosome membrane' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'WDR83:LAMTOR2:LAMTOR3 binds MAPK components'.

Reason: Reactome places the MEK1-containing step 'WDR83:LAMTOR2:LAMTOR3 binds MAPK components' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'IL17RD binds p-2S MAP2Ks and MAPKs'.

Reason: Reactome places the MEK1-containing step 'IL17RD binds p-2S MAP2Ks and MAPKs' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'MAP2Ks phosphorylate MAPK at the Golgi membrane'.

Reason: Reactome places the MEK1-containing step 'MAP2Ks phosphorylate MAPK at the Golgi membrane' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Activated MAPKs phosphorylate MAP2K1'.

Reason: Reactome places the MEK1-containing step 'Activated MAPKs phosphorylate MAP2K1' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Activated MAP2Ks phosphorylate MAPKs downstream of high kinase activity'.

Reason: Reactome places the MEK1-containing step 'Activated MAP2Ks phosphorylate MAPKs downstream of high kinase activity' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'High kinase activity BRAF complexes phosphorylate MAP2Ks'.

Reason: Reactome places the MEK1-containing step 'High kinase activity BRAF complexes phosphorylate MAP2Ks' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'High kinase activity BRAF mutants bind MAP2Ks and MAPKs'.

Reason: Reactome places the MEK1-containing step 'High kinase activity BRAF mutants bind MAP2Ks and MAPKs' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs'.

Reason: Reactome places the MEK1-containing step 'RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants'.

Reason: Reactome places the MEK1-containing step 'Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks'.

Reason: Reactome places the MEK1-containing step 'RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity'.

Reason: Reactome places the MEK1-containing step 'Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS'.

Reason: Reactome places the MEK1-containing step 'Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs'.

Reason: Reactome places the MEK1-containing step 'Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Mutant RAS:p-RAF complexes phosphorylate MAP2Ks'.

Reason: Reactome places the MEK1-containing step 'Mutant RAS:p-RAF complexes phosphorylate MAP2Ks' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Dissociation of BRAF/RAF fusion complex'.

Reason: Reactome places the MEK1-containing step 'Dissociation of BRAF/RAF fusion complex' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'p-BRAF and RAF fusion dimers phosphorylate MAP2Ks'.

Reason: Reactome places the MEK1-containing step 'p-BRAF and RAF fusion dimers phosphorylate MAP2Ks' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'p-BRAF and RAF fusion dimers bind MAP2Ks and MAPKs'.

Reason: Reactome places the MEK1-containing step 'p-BRAF and RAF fusion dimers bind MAP2Ks and MAPKs' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'MAPKs are phosphorylated downstream of BRAF and RAF fusion dimers'.

Reason: Reactome places the MEK1-containing step 'MAPKs are phosphorylated downstream of BRAF and RAF fusion dimers' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs'.

Reason: Reactome places the MEK1-containing step 'RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks'.

Reason: Reactome places the MEK1-containing step 'RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Dissociation of high activity BRAF complexes'.

Reason: Reactome places the MEK1-containing step 'Dissociation of high activity BRAF complexes' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Dissociation of moderate activity BRAF complexes'.

Reason: Reactome places the MEK1-containing step 'Dissociation of moderate activity BRAF complexes' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Dissociation of oncogenic RAS:RAF complex'.

Reason: Reactome places the MEK1-containing step 'Dissociation of oncogenic RAS:RAF complex' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Dissociation of paradoxically activated RAS:BRAF complexes'.

Reason: Reactome places the MEK1-containing step 'Dissociation of paradoxically activated RAS:BRAF complexes' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Activated BRAF recruits MAP2Ks and MAPKs to the endosome'.

Reason: Reactome places the MEK1-containing step 'Activated BRAF recruits MAP2Ks and MAPKs to the endosome' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Activated BRAF phosphorylates MAP2K dimers downstream of RAP1 and NGF'.

Reason: Reactome places the MEK1-containing step 'Activated BRAF phosphorylates MAP2K dimers downstream of RAP1 and NGF' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Dissociation of phosphorylated MAP2Ks and MAPKs'.

Reason: Reactome places the MEK1-containing step 'Dissociation of phosphorylated MAP2Ks and MAPKs' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'MAP2Ks phosphorylate MAPKs downstream of BRAF and NGF'.

Reason: Reactome places the MEK1-containing step 'MAP2Ks phosphorylate MAPKs downstream of BRAF and NGF' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'MAP2K mutants constitutively phosphorylate MAPKs'.

Reason: Reactome places the MEK1-containing step 'MAP2K mutants constitutively phosphorylate MAPKs' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Dissociation of RAS:RAF1 mutant complex'.

Reason: Reactome places the MEK1-containing step 'Dissociation of RAS:RAF1 mutant complex' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'MAP2Ks and MAPKs bind to the activated mutant RAF1 complex'.

Reason: Reactome places the MEK1-containing step 'MAP2Ks and MAPKs bind to the activated mutant RAF1 complex' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'MAP2Ks phosphorylate MAPKs downstream of RAF1 mutants'.

Reason: Reactome places the MEK1-containing step 'MAP2Ks phosphorylate MAPKs downstream of RAF1 mutants' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'RAF1 mutant complexes phosphorylate MAP2K dimer'.

Reason: Reactome places the MEK1-containing step 'RAF1 mutant complexes phosphorylate MAP2K dimer' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Dual mechanism MAP2K inhibitors bind MAP2Ks'.

Reason: Reactome places the MEK1-containing step 'Dual mechanism MAP2K inhibitors bind MAP2Ks' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Dual mechanism MAPK inhibitors bind MAPKs'.

Reason: Reactome places the MEK1-containing step 'Dual mechanism MAPK inhibitors bind MAPKs' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Single mechanism MAP2K inhibitors bind phosphorylated MAP2Ks'.

Reason: Reactome places the MEK1-containing step 'Single mechanism MAP2K inhibitors bind phosphorylated MAP2Ks' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Cytosol (TAS) from Reactome reaction 'Single mechanism MAPK inhibitors bind phosphorylated MAPK'.

Reason: Reactome places the MEK1-containing step 'Single mechanism MAPK inhibitors bind phosphorylated MAPK' in the cytosol, consistent with MEK1 being a soluble cytosolic kinase that is recruited to RAF complexes and phosphorylates ERK.

Summary: Microtubule (IEA from rat Map2k1).

Reason: MEK1 is a soluble cytosolic kinase; co-sedimentation/association with microtubules in the rat source is not a defining location and is not supported for human MEK1 by cached evidence. Mitotic centrosome/spindle association is captured by the centrosome term.

Summary: Plasma membrane (IDA, HPA immunofluorescence).

Reason: MEK1 is transiently recruited to membrane-proximal RAS-RAF/KSR complexes; it is a peripheral, not integral, membrane protein.

Summary: Focal adhesion (ARBA IEA).

Reason: Adhesion-dependent MEK1 phosphorylation (Thr292/Ser298) is documented, but direct focal adhesion localization of human MEK1 could not be verified from cached sources.

Summary: Focal adhesion (TAS) from the ERK-compartment review.

Reason: Review is abstract-only here; cannot verify.

Summary: Cell cortex (IEA from rat).

Reason: Consistent with a cytosolic kinase recruited near the plasma membrane; non-core.

Summary: Chemotaxis (TAS) citing an SDF-1/CXCR4 T-cell study in which the MEK inhibitor PD098059 partially attenuated chemotaxis.

Reason: Inhibitor evidence (not MEK1-specific) for a partial effect on a downstream cell behaviour; MEK1 participates via ERK signalling rather than the chemotaxis machinery.

Summary: Response to oxidative stress (IEA from rat).

Reason: Stress-induced ERK activation is a context-specific consequence of the cascade, not a MEK1-specific function.

Summary: Signal transduction (TAS) from the SDF-1 T-cell study.

Reason: Correct but very general; MEK1 acts specifically in the ERK1/2 cascade.

Proposed replacements: ERK1 and ERK2 cascade

Summary: Neuromuscular junction development (IEA from mouse Map2k1).

Reason: Developmental role of ERK signalling observed in Mek1/2 mouse genetics; pleiotropic, non-core.

Summary: Negative regulation of cell population proliferation (IDA) from constitutively active MEK1 inducing premature senescence in primary cells.

Reason: Oncogene-induced growth arrest caused by constitutive MEK/MAPK signalling (paper title: premature senescence involving p53 and p16 in response to constitutive MEK/MAPK signalling) is real biology but a gain-of-function context; non-core. Cached PMID:9765203 has no abstract text to quote.

Summary: Positive regulation of autophagy (IEA from rat).

Reason: Context-specific downstream effect of ERK pathway activity, typically inferred from inhibitor studies.

Summary: Positive regulation of gene expression (IEA from rat).

Reason: Indirect; changes in gene expression lie many steps downstream of MEK1 via ERK and transcription factors.

Summary: Positive regulation of gene expression (IMP) from PV1 upregulation by PMA, which required the Erk1/2 pathway.

Reason: Pathway-level inhibitor evidence for an indirect transcriptional outcome in endothelial cells; not a MEK1 function.

Summary: Positive regulation of gene expression (IMP) from AZD6244 (MEK1/2 inhibitor) effects on miR-92a in lymphoma cells.

Reason: Evidence is a MEK1/2 inhibitor acting through ERK1/2-AP1; the gene-expression outcome is indirect.

Summary: Negative regulation of gene expression (IEA from rat).

Reason: Indirect downstream transcriptional effect of ERK signalling.

Summary: Schwann cell development (IEA from mouse Map2k1).

Reason: Mouse Mek1/2 genetics implicate ERK signalling in Schwann cell development; developmental, non-core role.

Summary: Postsynaptic density (is_active_in, IEA from rat).

Reason: MEK1 is a soluble cytosolic kinase; an 'active in' PSD claim is a tissue-specific over-extension.

Summary: Membrane (EXP) from KSR-dependent MEK membrane association.

Reason: KSR binding shifts MEK1 into membrane-associated fractions; MEK1 is a peripheral membrane protein.

Summary: Membrane (IEA, SubCell mapping).

Reason: Consistent with peripheral membrane association via KSR.

Summary: Protein kinase binding (IEA from rat).

Reason: MEK1's kinase partners are its MAP3K activators (RAF1, BRAF, MOS) and its ERK substrates; the specific terms are more informative.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding mitogen-activated protein kinase binding

Summary: Neuron differentiation (IBA).

Reason: PAINT propagated neuron differentiation across the MAP2K clade; ERK signalling contributes to neuronal differentiation (e.g. NGF/PC12), but this is a context-dependent downstream role, not a core MEK1 function.

Summary: Neuron differentiation (IEA from rat).

Reason: As for the IBA row; non-core developmental role via ERK.

Summary: Protein kinase activator activity (IDA, GO_Central) from coupled Raf-1 -> MEK-1 -> ERK-2 kinase assays in an HCV core protein study.

Reason: In this assay MEK-1 activates ERK-2 by phosphorylating it; that is catalytic MAP kinase kinase activity, not non-catalytic activator activity.

Proposed replacements: MAP kinase kinase activity

Summary: Positive regulation of cell migration (IEA from rat).

Reason: ERK signalling promotes migration in many contexts; downstream, non-core.

Summary: Axon (IEA from rat).

Reason: MEK1 is cytosolic and distributes into neuronal processes; non-core.

Summary: Dendrite (IEA from rat).

Reason: Cytosolic distribution in neurons; non-core.

Summary: Small GTPase binding (IEA from rat).

Reason: MEK1 is brought to RAS-GTP via RAF and KSR; direct small-GTPase binding is not an established MEK1 function in cached evidence.

Summary: MAPKKK binding (IEA from rat).

Reason: MEK1 binds RAF-family MAP3Ks (BRAF, RAF1) and MOS; well supported.

Summary: Melanosome transport (IEA from rat).

Reason: No MEK1-specific role in melanosome transport in cached evidence; likely inhibitor-based downstream effect.

Summary: Dendrite cytoplasm (IEA from rat).

Reason: Consistent with cytosolic localization in neurons; non-core.

Summary: Regulation of stress-activated MAPK cascade (ARBA IEA).

Reason: The same term is marked as an over-annotation on the author-statement row of this review, and the claim is the same here. MEK1 acts in the ERK1/2 cascade and does not phosphorylate JNK or p38, so regulation of the stress-activated cascade over-states its role; rows that share a term are judged alike, and the machine-generated row is marked in the same way rather than removed.

Summary: Regulation of stress-activated MAPK cascade (TAS) from the ERK-compartment review.

Reason: The review (abstract only) concerns the ERK cascade; MEK1 is ERK-specific, so any effect on SAPK cascades would be indirect cross-talk.

Summary: Positive regulation of transcription elongation by RNA polymerase II (IEA from rat).

Reason: Indirect downstream effect of ERK signalling on transcription.

Summary: Negative regulation of homotypic cell-cell adhesion (IEA from rat).

Reason: Cell-type-specific downstream outcome; not a MEK1 function.

Summary: Ciliary basal body (IDA, HPA immunofluorescence).

Reason: HPA staining at the basal body is consistent with MEK1's centrosomal association; functional significance unclear.

Summary: ERBB signaling pathway (IEA from mouse Map2k1).

Reason: MEK1 is a component of the MAPK arm downstream of ERBB receptors (e.g. NRG1-ERBB in Schwann cells); non-core as it is a generic downstream relay.

Summary: ERBB2-ERBB3 signaling pathway (IEA from mouse Map2k1).

Reason: As above; MEK1 relays ERBB2/3 signals to ERK; non-core.

Summary: Myelination (IEA from mouse Map2k1).

Reason: Developmental role of MEK1/2-ERK signalling in Schwann cells; non-core.

Summary: Perikaryon (IEA from rat).

Reason: Cytosolic distribution in neurons; non-core.

Summary: Positive regulation of MAPK cascade (IEA from rat).

Reason: MEK1 is a core component of the ERK cascade rather than a regulator of it; GO:0070371 is the appropriate process.

Proposed replacements: ERK1 and ERK2 cascade

Summary: Protein serine/threonine kinase activator activity (IDA) from the MEK1/MEK2 cloning paper, based on activation of ERK1.

Reason: In PMID:8388392 MEK activates ERK1 by phosphorylating it (catalysis); the correct MF for that evidence is GO:0004708. (A non-catalytic activator role of MEK1 toward BRAF exists, see ARBA row and PMID:29433126, but is not the basis of this annotation.)

Proposed replacements: MAP kinase kinase activity

Summary: Protein serine/threonine kinase activator activity (ARBA IEA).

Reason: As for the IDA row, 'activator' annotations for MEK1 rest on its activation of ERK, which is catalytic; GO:0004708 is the correct MF. MEK1's genuinely non-catalytic promotion of KSR-BRAF dimerization is captured by the (non-core) MAP kinase scaffold activity rows.

Proposed replacements: MAP kinase kinase activity

Summary: Protein-containing complex binding (IEA from rat).

Reason: Uninformative; MEK1's complex partners (RAF, KSR, ERK) are captured by specific binding terms.

Summary: Positive regulation of DNA-templated transcription (IMP) from AZD6244 (MEK1/2 inhibitor) effects on miR-92a transcription via ERK1/2-AP1.

Reason: Indirect effect through ERK and AP-1, shown with a pan-MEK1/2 inhibitor.

Summary: Positive regulation of muscle contraction (IEA from rat).

Reason: Tissue-specific pharmacological readout; not a MEK1 function.

Summary: Vesicle transport along microtubule (IEA from rat).

Reason: MEK1 has no known motor/transport function; any effect is indirect via ERK.

Summary: Insulin-like growth factor receptor signaling pathway (IEA from mouse).

Reason: MEK1 relays IGF1R signals to ERK as a generic downstream component; non-core.

Summary: Golgi inheritance (IEA from rat).

Reason: MEK1 (specifically, not MEK2) is required for G2 Golgi fragmentation that precedes Golgi partitioning in mitosis.

Summary: Perinuclear region of cytoplasm (IEA from rat).

Reason: Cytoplasmic distribution; non-core.

Summary: Response to axon injury (IEA from rat).

Reason: Injury-induced ERK activation is a context response of the cascade, not a MEK1-specific function.

Summary: Neuron projection morphogenesis (IEA from rat).

Reason: Downstream developmental outcome of ERK signalling.

Summary: Response to glucocorticoid (IEA from rat).

Reason: Expression/response readouts in rat tissue; not informative for MEK1 function.

Summary: Triglyceride homeostasis (IEA from rat/mouse genetics).

Reason: Systemic metabolic phenotype far downstream of MEK1 catalysis.

Summary: ERK1 and ERK2 cascade (TAS) from Reactome 'MAPK3 (ERK1) activation'.

Reason: Core process: MEK1 phosphorylates and activates ERK1/2.

Summary: Regulation of ERK1 and ERK2 cascade (IEA from rat).

Reason: MEK1 is a core component of the ERK1/2 cascade rather than an external regulator; GO:0070371.

Proposed replacements: ERK1 and ERK2 cascade

Summary: Positive regulation of ERK1 and ERK2 cascade (IMP) from AZD6244 (MEK1/2 inhibitor) study.

Reason: The evidence (MEK1/2 inhibitor reduces ERK1/2-AP1 signalling) shows MEK1/2 is part of the ERK cascade; MEK1 is a core cascade kinase, not a regulator. GO:0070371 is more accurate.

Proposed replacements: ERK1 and ERK2 cascade

Summary: Positive regulation of protein serine/threonine kinase activity (IDA) from MEK1 activation of ERK1 in vitro.

Reason: MEK1 does increase ERK kinase activity, but this is the direct consequence of its own MAP kinase kinase activity, already captured by GO:0004708 and GO:0070371.

Summary: Regulation of Golgi inheritance (ARBA IEA).

Reason: Supported by MEK1-dependent Golgi fragmentation in G2 via Myt1 inactivation.

Summary: Regulation of Golgi inheritance (TAS) from the ERK-compartment review.

Reason: Supported by MEK1-dependent Golgi fragmentation in G2.

Summary: Cellular senescence (IMP) from constitutively active MEK1 inducing premature senescence.

Reason: Oncogene-induced senescence from constitutive MEK/MAPK signalling (per the paper title); genuine but a gain-of-function context, so non-core. Cached PMID:9765203 has no abstract text to quote.

Summary: Scaffold protein binding (ARBA IEA).

Reason: MEK1 binds the ERK-cascade scaffolds KSR1/KSR2.

Summary: Scaffold protein binding (IPI) with mouse KSR1.

Reason: KSR binds MEK and acts as a Ras-MAPK scaffold.

Summary: Regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (IEA from rat).

Reason: Synapse-specific downstream effect of ERK signalling, likely inhibitor-based.

Summary: Glutamatergic synapse (is_active_in, IEA from rat).

Reason: MEK1 is a ubiquitous cytosolic kinase; 'active in glutamatergic synapse' is a tissue-specific over-extension.

Summary: Protein serine kinase activity from Rhea mapping (RHEA:17989).

Reason: The catalytic activity is the dual Thr/Tyr MAP kinase kinase activity toward ERK; GO:0004708 (consistent with MAP2K2).

Proposed replacements: MAP kinase kinase activity

Summary: Negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway (IEA from rat).

Reason: Context-specific survival effect of ERK signalling; not a MEK1 function.

Summary: Regulation of early endosome to late endosome transport (ARBA IEA).

Reason: UniProt describes MAPK/ERK cascade involvement in endosomal dynamics; non-core.

Summary: Regulation of early endosome to late endosome transport (TAS) from the ERK-compartment review.

Reason: As for the ARBA row; non-core.

Summary: Positive regulation of ATP biosynthetic process (IEA from rat).

Reason: Metabolic outcome downstream of ERK; not a MEK1 function.