MAP2K2

Summary: IBA from PAINT node PTN000684494 (MAP2K clade) for MAPK cascade; MAP2K2 participates as the MAP2K tier of the ERK1/ERK2 cascade.

Reason: The PAINT placement is sound: MAP2K2 sits in the MEK2 subfamily (PTHR47448:SF3 in UniProt; PTHR48013:SF8 in the PANTHER 19.0 per-organism file, both named MAP2K2) under a MAP2K node whose members all act in MAPK cascades. For MAP2K2 itself the evidence identifies which cascade: it phosphorylates ERK1 and ERK2. The general term is correct but less specific than supported, so it is refined to ERK1 and ERK2 cascade (GO:0070371), which this gene already carries from Reactome and IMP rows.

Proposed replacements: ERK1 and ERK2 cascade

Summary: InterPro kinase-signature IEA for generic protein kinase activity.

Reason: Correct but too general. MAP2K2 is a dual-specificity MAP2K that phosphorylates the Thr and Tyr of the ERK TEY motif; MAP kinase kinase activity (GO:0004708), already carried by IDA and IBA rows, is the specific supported term.

Proposed replacements: MAP kinase kinase activity

Summary: Reactome TAS for protein serine/threonine kinase activity (MAP2K2 phosphorylates MAPK1).

Reason: MEK2 phosphorylates both threonine and tyrosine of the ERK activation loop; a Ser/Thr-only kinase term misdescribes the dual specificity. MAP kinase kinase activity (GO:0004708) captures the Reactome reaction exactly.

Proposed replacements: MAP kinase kinase activity

Summary: IBA from PAINT node PTN000684494 for MAP kinase kinase activity.

Reason: Core molecular function. Direct biochemical evidence for the human protein (dual Thr/Tyr phosphorylation and activation of ERK1) agrees with the PAINT inference for the MAP2K clade and with the conserved catalytic machinery (active-site Asp194, ATP-binding Lys101 region).

Summary: IDA: recombinant human MEK2 phosphorylated ERK1 on Thr and Tyr and activated it >100-fold (PMID:8388392).

Reason: Core molecular function. Direct biochemical evidence for the human protein (dual Thr/Tyr phosphorylation and activation of ERK1) agrees with the PAINT inference for the MAP2K clade and with the conserved catalytic machinery (active-site Asp194, ATP-binding Lys101 region).

Summary: Combined IEA for MAP kinase kinase activity.

Reason: Core molecular function. Direct biochemical evidence for the human protein (dual Thr/Tyr phosphorylation and activation of ERK1) agrees with the PAINT inference for the MAP2K clade and with the conserved catalytic machinery (active-site Asp194, ATP-binding Lys101 region).

Summary: TAS from a review for protein serine/threonine/tyrosine kinase activity.

Reason: True but general: MAP kinase kinase activity (GO:0004708) is an is_a child of this term and is the specific activity supported for MAP2K2.

Proposed replacements: MAP kinase kinase activity

Summary: Protein tyrosine kinase activity, from the UniProt Rhea catalytic-activity mapping of PMID:10409742 (EXP) and the Rhea IEA.

Reason: MEK2 phosphorylates a tyrosine only as part of concomitant Thr/Tyr phosphorylation of the MAPK TEY motif; it is not a general tyrosine kinase. The Rhea-split reactions are better represented by MAP kinase kinase activity (GO:0004708).

Proposed replacements: MAP kinase kinase activity

Summary: Protein tyrosine kinase activity, from the UniProt Rhea catalytic-activity mapping of PMID:10409742 (EXP) and the Rhea IEA.

Reason: MEK2 phosphorylates a tyrosine only as part of concomitant Thr/Tyr phosphorylation of the MAPK TEY motif; it is not a general tyrosine kinase. The Rhea-split reactions are better represented by MAP kinase kinase activity (GO:0004708).

Proposed replacements: MAP kinase kinase activity

Summary: MAP kinase scaffold activity (IMP, PMID:29433126; IEA ARBA). In Lavoie et al. 2018, MEK1/MEK2 binding to KSR1 drives KSR1-BRAF heterodimerization and BRAF activation; shMEK2 reduces BRAF-KSR1 association.

Reason: PMID:29433126 (full text read) shows a genuine non-catalytic MEK function: an 'activator' MEK bound to KSR1 promotes assembly of the KSR1-BRAF dimer, i.e. MEK supports assembly of a multi-kinase MAPK module, which is the closest existing GO notion. The authors frame this as KSR acting as a MEK-dependent allosteric activator of BRAF rather than as classical scaffolding, so the term is an approximation; it is kept, as curated, but non-core relative to the catalytic MAP2K activity. A better-fitting term is raised as a suggested question.

Summary: MAP kinase scaffold activity (IMP, PMID:29433126; IEA ARBA). In Lavoie et al. 2018, MEK1/MEK2 binding to KSR1 drives KSR1-BRAF heterodimerization and BRAF activation; shMEK2 reduces BRAF-KSR1 association.

Reason: PMID:29433126 (full text read) shows a genuine non-catalytic MEK function: an 'activator' MEK bound to KSR1 promotes assembly of the KSR1-BRAF dimer, i.e. MEK supports assembly of a multi-kinase MAPK module, which is the closest existing GO notion. The authors frame this as KSR acting as a MEK-dependent allosteric activator of BRAF rather than as classical scaffolding, so the term is an approximation; it is kept, as curated, but non-core relative to the catalytic MAP2K activity. A better-fitting term is raised as a suggested question.

Summary: IPI for MAP2K2 binding RAF1 (CRAF), an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:11909642).

Reason: Bare protein binding is uninformative. The partner RAF1 (CRAF) is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding ARAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:11909642).

Reason: Bare protein binding is uninformative. The partner ARAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding KSR1, the RAF-MEK-ERK scaffold protein (PMID:11909642). MEK binding to KSR releases KSR autoinhibition and promotes KSR-BRAF dimerization (PMID:29433126).

Reason: Bare protein binding is uninformative. The partner KSR1 is a MAPK-pathway scaffold, so scaffold protein binding (GO:0097110) is the informative replacement, consistent with the accepted GO:0097110 annotations on this gene.

Proposed replacements: scaffold protein binding

Summary: IPI for MAP2K2 binding BRAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:17979178).

Reason: Bare protein binding is uninformative. The partner BRAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding hDlg/SAP97 (DLG1): identified by yeast two-hybrid, confirmed by co-IP of endogenous proteins, and mapped to DLG1 PDZ domain 2 and the MEK2 C-terminal RTAV motif; DLG1 binds MEK2 but not MEK1.

Reason: Bare protein binding is uninformative. The paper shows the interaction is between the MAP2K2 C-terminal PDZ-binding motif and a PDZ domain of the scaffold protein DLG1, so PDZ domain binding (GO:0030165) and scaffold protein binding (GO:0097110) are the informative replacements.

Proposed replacements: PDZ domain binding scaffold protein binding

Summary: IPI for MAP2K2 binding RAF1 (CRAF), an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:21988832).

Reason: Bare protein binding is uninformative. The partner RAF1 (CRAF) is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding ARAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:21988832).

Reason: Bare protein binding is uninformative. The partner ARAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding RAF1 (CRAF), an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:24746704).

Reason: Bare protein binding is uninformative. The partner RAF1 (CRAF) is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding ARAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:24746704).

Reason: Bare protein binding is uninformative. The partner ARAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding BRAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:24746704).

Reason: Bare protein binding is uninformative. The partner BRAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: High-throughput interactome IPI for MAP2K2 binding CCNDBP1 (PMID:25416956); no functional characterization of the interaction is reported.

Reason: Bare protein binding carries no functional information, and the screen provides no basis for a more informative MF term for this partner. Removal reflects only the lack of functional information in the bare GO:0005515 term; it does not mean the reported interaction is false.

Summary: IPI for MAP2K2 binding BRAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:25600339).

Reason: Bare protein binding is uninformative. The partner BRAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding ARAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:25852190).

Reason: Bare protein binding is uninformative. The partner ARAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding KSR1, the RAF-MEK-ERK scaffold protein (PMID:27086506). MEK binding to KSR releases KSR autoinhibition and promotes KSR-BRAF dimerization (PMID:29433126).

Reason: Bare protein binding is uninformative. The partner KSR1 is a MAPK-pathway scaffold, so scaffold protein binding (GO:0097110) is the informative replacement, consistent with the accepted GO:0097110 annotations on this gene.

Proposed replacements: scaffold protein binding

Summary: IPI for MAP2K2 binding BRAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:28514442).

Reason: Bare protein binding is uninformative. The partner BRAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding BRAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:29433126).

Reason: Bare protein binding is uninformative. The partner BRAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding KSR1, the RAF-MEK-ERK scaffold protein (PMID:29433126). MEK binding to KSR releases KSR autoinhibition and promotes KSR-BRAF dimerization (PMID:29433126).

Reason: Bare protein binding is uninformative. The partner KSR1 is a MAPK-pathway scaffold, so scaffold protein binding (GO:0097110) is the informative replacement, consistent with the accepted GO:0097110 annotations on this gene.

Proposed replacements: scaffold protein binding

Summary: IPI for MAP2K2 binding RAF1 (CRAF), an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:31980649).

Reason: Bare protein binding is uninformative. The partner RAF1 (CRAF) is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding ARAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:31980649).

Reason: Bare protein binding is uninformative. The partner ARAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding BRAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:31980649).

Reason: Bare protein binding is uninformative. The partner BRAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding KSR1, the RAF-MEK-ERK scaffold protein (PMID:31980649). MEK binding to KSR releases KSR autoinhibition and promotes KSR-BRAF dimerization (PMID:29433126).

Reason: Bare protein binding is uninformative. The partner KSR1 is a MAPK-pathway scaffold, so scaffold protein binding (GO:0097110) is the informative replacement, consistent with the accepted GO:0097110 annotations on this gene.

Proposed replacements: scaffold protein binding

Summary: IPI for MAP2K2 binding MOS, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:32296183).

Reason: Bare protein binding is uninformative. The partner MOS is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: High-throughput interactome IPI for MAP2K2 binding HNRNPK (isoform 2) (PMID:32296183); no functional characterization of the interaction is reported.

Reason: Bare protein binding carries no functional information, and the screen provides no basis for a more informative MF term for this partner. Removal reflects only the lack of functional information in the bare GO:0005515 term; it does not mean the reported interaction is false.

Summary: Binary Y2H IPI (HuRI, PMID:32296183) with UniProtKB:Q96II5, which UniProt's interaction table identifies as an ARAF entry.

Reason: Bare protein binding is uninformative. The partner is an ARAF product, a MAP3K that binds and phosphorylates MEK2 (A-Raf/MEK2 binding is independently shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement, consistent with the other ARAF rows.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding RAF1 (CRAF), an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:32707033).

Reason: Bare protein binding is uninformative. The partner RAF1 (CRAF) is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding ARAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:32707033).

Reason: Bare protein binding is uninformative. The partner ARAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding BRAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:32707033).

Reason: Bare protein binding is uninformative. The partner BRAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding KSR1, the RAF-MEK-ERK scaffold protein (PMID:32707033). MEK binding to KSR releases KSR autoinhibition and promotes KSR-BRAF dimerization (PMID:29433126).

Reason: Bare protein binding is uninformative. The partner KSR1 is a MAPK-pathway scaffold, so scaffold protein binding (GO:0097110) is the informative replacement, consistent with the accepted GO:0097110 annotations on this gene.

Proposed replacements: scaffold protein binding

Summary: High-throughput interactome IPI for MAP2K2 binding APP (PMID:32814053); no functional characterization of the interaction is reported.

Reason: Bare protein binding carries no functional information, and the screen provides no basis for a more informative MF term for this partner. Removal reflects only the lack of functional information in the bare GO:0005515 term; it does not mean the reported interaction is false.

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:O96018. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding BRAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:33961781).

Reason: Bare protein binding is uninformative. The partner BRAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding RAF1 (CRAF), an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:35271311).

Reason: Bare protein binding is uninformative. The partner RAF1 (CRAF) is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding ARAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:35271311).

Reason: Bare protein binding is uninformative. The partner ARAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding KSR1, the RAF-MEK-ERK scaffold protein (PMID:35271311). MEK binding to KSR releases KSR autoinhibition and promotes KSR-BRAF dimerization (PMID:29433126).

Reason: Bare protein binding is uninformative. The partner KSR1 is a MAPK-pathway scaffold, so scaffold protein binding (GO:0097110) is the informative replacement, consistent with the accepted GO:0097110 annotations on this gene.

Proposed replacements: scaffold protein binding

Summary: IPI for MAP2K2 binding BRAF, an upstream MAP kinase kinase kinase that phosphorylates and activates MEK in the RAF-MEK-ERK cascade (PMID:35512704).

Reason: Bare protein binding is uninformative. The partner BRAF is a MAPKKK that directly binds and phosphorylates MAP2K2 (A-Raf binding to MEK2 via its kinase domain is shown in PMID:11909642), so mitogen-activated protein kinase kinase kinase binding (GO:0031435) is the informative replacement.

Proposed replacements: mitogen-activated protein kinase kinase kinase binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:A4D2P6. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:O00560. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:O15018. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:O75970. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:O95049. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:O96018. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:P78352. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q07157. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q12923. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q12959. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q14005. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q14160. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q15599. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q15700. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q5T2W1. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q5TCQ9. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q68DX3. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q6ZMN7. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q70Z35. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q86UL8. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q86UT5. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q8N448. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q8NI35. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q8TDM6. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q8TEW0. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q8TEW8. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q92796. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q96QZ7. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q99767. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q9C0E4. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q9H190. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q9H5P4. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q9P202. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q9UDY2. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q9UPQ7. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q9Y3R0. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: IPI for MAP2K2 binding the PDZ-domain protein UniProtKB:Q9Y6N9. PMID:36115835 is a holdup-assay affinity map of human PDZ domains against C-terminal PDZ-binding motifs (PBMs); MAP2K2 carries a C-terminal class I PBM (RTAV) that is known to engage PDZ domains (PMID:21615688).

Reason: Bare protein binding is uninformative. The partner is a PDZ-domain protein and the interaction is mediated by the MAP2K2 C-terminal PDZ-binding motif, so PDZ domain binding (GO:0030165) is the informative replacement. This is a peptide/domain-level affinity measurement and is not a core function of MAP2K2.

Proposed replacements: PDZ domain binding

Summary: InterPro IEA for ATP binding.

Reason: MAP2K2 has the canonical kinase glycine-rich loop and Lys101 ATP-binding site; ATP binding is correct and as precise as warranted, but it is a cofactor-level property subsumed by the core kinase activity.

Summary: NAS 'extracellular region' attributed to the MEK1/MEK2 cloning paper (PMID:8388392).

Reason: The cited abstract describes intracellular cascade biochemistry only; the 'extracellular' wording comes from the name 'extracellular signal-regulated kinase' (ERK), the substrate. MEK2 has no signal peptide or transmembrane segment and is a cytosolic kinase. This NAS is a non-experimental name-derived assignment and is demonstrably not a location of the protein.

Summary: TAS nucleus from a review of ERK-cascade compartmentalization (PMID:19565474).

Reason: MEK1/2 can enter the nucleus transiently but are kept predominantly cytoplasmic by an N-terminal nuclear export signal; nuclear residence is minor relative to the cytosolic pool. Kept, non-core.

Summary: Cytoplasm (UniProt EXP from PMID:10409742 fractionation; SubCell IEA).

Reason: Correct but general. The soluble pool of MEK2 is cytosolic (HPA IDA and many Reactome TAS rows for cytosol in this review), and the remainder is membrane-associated through scaffolds (kept separately as membrane). Refine to cytosol (GO:0005829).

Proposed replacements: cytosol

Summary: Cytoplasm (UniProt EXP from PMID:10409742 fractionation; SubCell IEA).

Reason: Correct but general. The soluble pool of MEK2 is cytosolic (HPA IDA and many Reactome TAS rows for cytosol in this review), and the remainder is membrane-associated through scaffolds (kept separately as membrane). Refine to cytosol (GO:0005829).

Proposed replacements: cytosol

Summary: Mitochondrion from the ARBA rule ARBA00026962 (IEA); a minor, stimulus-dependent MEK2 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 MAP2K2 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). MEK2 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 MEK2 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 MEK2 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 MAP2K2 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). MEK2 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 MEK2 locations (cytoplasm, membrane via KSR1, nucleus) are captured elsewhere in this review.

Summary: early endosome (TAS from review PMID:19565474; ARBA IEA).

Reason: Endosomal MEK/ERK signalling is well described, but the best-characterised endosomal adaptor (LAMTOR3/MP1) was reported as MEK1-selective, so MEK1/2-level statements may not transfer to MEK2. The review's full text is not available to check what it says about MEK2 specifically, and the ARBA rows are unvetted. Left UNDECIDED pending MEK2-specific evidence.

Summary: early endosome (TAS from review PMID:19565474; ARBA IEA).

Reason: Endosomal MEK/ERK signalling is well described, but the best-characterised endosomal adaptor (LAMTOR3/MP1) was reported as MEK1-selective, so MEK1/2-level statements may not transfer to MEK2. The review's full text is not available to check what it says about MEK2 specifically, and the ARBA rows are unvetted. Left UNDECIDED pending MEK2-specific evidence.

Summary: late endosome (TAS from review PMID:19565474; ARBA IEA).

Reason: Endosomal MEK/ERK signalling is well described, but the best-characterised endosomal adaptor (LAMTOR3/MP1) was reported as MEK1-selective, so MEK1/2-level statements may not transfer to MEK2. The review's full text is not available to check what it says about MEK2 specifically, and the ARBA rows are unvetted. Left UNDECIDED pending MEK2-specific evidence.

Summary: late endosome (TAS from review PMID:19565474; ARBA IEA).

Reason: Endosomal MEK/ERK signalling is well described, but the best-characterised endosomal adaptor (LAMTOR3/MP1) was reported as MEK1-selective, so MEK1/2-level statements may not transfer to MEK2. The review's full text is not available to check what it says about MEK2 specifically, and the ARBA rows are unvetted. Left UNDECIDED pending MEK2-specific evidence.

Summary: HDA: MEK2 among proteins co-purified with Protein-A-tagged PEX14 from digitonin-solubilised membranes (PMID:21525035).

Reason: A single proteomic co-purification with a peroxisomal membrane bait is the only support; the paper's conclusions concern peroxins and tubulin, and no MEK2 function at peroxisomes is known. Likely an abundant cytosolic kinase recovered non-specifically; over-annotation rather than a demonstrated location.

Summary: IDA endoplasmic reticulum from the DLG1-MEK2 study (PMID:21615688).

Reason: The abstract attributes ER and microtubule association to hDlg in VSMCs; whether MEK2 itself was shown at these structures is in the full text, which is not available. MeSH indexing (Endoplasmic Reticulum/enzymology, Microtubules/enzymology) suggests the curator read MEK2 colocalization there, so this is not removed, but it cannot be verified.

Summary: Golgi apparatus (IDA, PMID:21615688).

Reason: Golgi-associated MEK/ERK signalling has been reported, chiefly for MEK1, and Reactome models MAP2K phosphorylation of MAPK at the Golgi membrane at the MAP2K-class level. The Golgi result is not described in the cached abstracts of either source, and their full texts are unavailable.

Summary: Golgi apparatus (TAS, PMID:19565474).

Reason: Golgi-associated MEK/ERK signalling has been reported, chiefly for MEK1, and Reactome models MAP2K phosphorylation of MAPK at the Golgi membrane at the MAP2K-class level. The Golgi result is not described in the cached abstracts of either source, and their full texts are unavailable.

Summary: Cytosol (IDA, GO_REF:0000052).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, PMID:19565474).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-109858).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-109862).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-109864).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-5211356).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-5672972).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-5672973).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-5672978).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-5672980).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-5674130).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-5674132).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-5674366).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-5674373).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-5674496).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802910).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802911).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802912).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802914).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802918).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802919).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802921).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802922).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802925).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802926).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802932).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802933).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802934).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802935).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802942).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6802943).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6803227).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6803230).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6803233).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-6803234).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-9610152).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-9610153).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-9610154).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-9610156).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-9652165).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-9656209).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-9656211).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-9656214).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-9656215).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-9657599).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-9657603).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-9657606).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: Cytosol (TAS, Reactome:R-HSA-9657608).

Reason: MEK2 is a soluble cytoplasmic kinase (UniProt; HPA immunofluorescence) whose activation by RAF and phosphorylation of ERK1/2 occur on the cytosolic face of membranes and in the cytosol, as modelled in the Reactome reactions. Core location.

Summary: IDA microtubule from the DLG1-MEK2 study (PMID:21615688).

Reason: The abstract attributes ER and microtubule association to hDlg in VSMCs; whether MEK2 itself was shown at these structures is in the full text, which is not available. MeSH indexing (Endoplasmic Reticulum/enzymology, Microtubules/enzymology) suggests the curator read MEK2 colocalization there, so this is not removed, but it cannot be verified.

Summary: IDA cell-cell junction (PMID:21615688).

Reason: DLG1 is a junctional MAGUK and the abstract reports MEK2-DLG1 colocalization at the inner plasma membrane of confluent HEK293 cells, which may underlie this annotation, but a junction-specific MEK2 localization is not stated in the abstract and the full text is unavailable.

Summary: Focal adhesion (TAS from review PMID:19565474; ARBA IEA).

Reason: ERK-module components are recruited to focal adhesions, but MEK2-specific evidence is not visible in the cached abstract and the full text is unavailable; ARBA is an unvetted prediction.

Summary: Focal adhesion (TAS from review PMID:19565474; ARBA IEA).

Reason: ERK-module components are recruited to focal adhesions, but MEK2-specific evidence is not visible in the cached abstract and the full text is unavailable; ARBA is an unvetted prediction.

Summary: IDA cytoplasmic side of plasma membrane: MEK2 colocalizes with DLG1 at the inner layer of the plasma membrane in confluent HEK293 cells (PMID:21615688).

Reason: Directly stated for MEK2 in the abstract; consistent with scaffold-mediated membrane recruitment. A context-dependent pool, non-core.

Summary: IMP positive regulation of gene expression from a lymphoma study using the MEK1/2 inhibitor AZD6244 (PMID:24375836).

Reason: The experiment shows that inhibiting MEK1/2 lowers miR-92a via ERK1/2-AP1. Changes in gene expression and transcription are downstream outputs of ERK and AP-1; MEK2 does no part of the transcriptional work. The inhibitor is also not MEK2-selective. These are indirect consequences of the ERK cascade rather than MEK2 process participation.

Summary: Membrane (UniProt EXP from PMID:10409742; SubCell IEA). KSR binding moves MEK into membrane-associated fractions.

Reason: The fractionation experiment supports membrane association but not a specific membrane, so 'membrane' is as precise as this evidence allows. MEK2 is a peripheral, scaffold-recruited membrane protein; the predominant pool is cytosolic, so this is non-core.

Summary: Membrane (UniProt EXP from PMID:10409742; SubCell IEA). KSR binding moves MEK into membrane-associated fractions.

Reason: The fractionation experiment supports membrane association but not a specific membrane, so 'membrane' is as precise as this evidence allows. MEK2 is a peripheral, scaffold-recruited membrane protein; the predominant pool is cytosolic, so this is non-core.

Summary: IDA PDZ domain binding: the MEK2 C-terminal RTAV motif binds DLG1 PDZ2 (PMID:21615688).

Reason: The class I PDZ-binding motif at the MEK2 C terminus (absent from MEK1) is experimentally mapped and is confirmed by the PDZ-domain holdup map (PMID:36115835). It is a MEK2-specific targeting property, peripheral to the catalytic core function.

Summary: Regulation of stress-activated MAPK cascade (TAS from review PMID:19565474; ARBA IEA).

Reason: MEK2 is an ERK-specific MAP2K; the stress-activated (JNK/p38) cascades use MAP2K3/4/6/7. Any effect of MEK2 on stress-activated signalling would be indirect crosstalk, and no MEK2-specific experiment is cited. Likely an over-annotation.

Summary: Regulation of stress-activated MAPK cascade (TAS from review PMID:19565474; ARBA IEA).

Reason: MEK2 is an ERK-specific MAP2K; the stress-activated (JNK/p38) cascades use MAP2K3/4/6/7. Any effect of MEK2 on stress-activated signalling would be indirect crosstalk, and no MEK2-specific experiment is cited. Likely an over-annotation.

Summary: IDA peptidyl-serine autophosphorylation for recombinant MEK2 (PMID:8388392).

Reason: The cached abstract does not describe the autophosphorylation assay, but the paper characterised purified recombinant MEK2 kinase activity and the curator read the full text; recombinant MEKs are known to autophosphorylate weakly. Deferred to the curator and kept as a non-core biochemical property; physiological activation is by RAF trans-phosphorylation of Ser222/Ser226.

Summary: Protein serine/threonine kinase activator activity (IDA, PMID:8388392; IEA ARBA).

Reason: The cited experiment shows MEK2 activating ERK1 by phosphorylating it. That is the catalytic activity MAP kinase kinase activity (GO:0004708); 'kinase activator activity' is intended for non-catalytic regulators that bind and activate a kinase, and using it for the upstream kinase of a cascade duplicates the MF. The KSR1-dependent BRAF activation described in PMID:29433126 is handled under the MAP kinase scaffold activity rows.

Proposed replacements: MAP kinase kinase activity

Summary: Protein serine/threonine kinase activator activity (IDA, PMID:8388392; IEA ARBA).

Reason: The cited experiment shows MEK2 activating ERK1 by phosphorylating it. That is the catalytic activity MAP kinase kinase activity (GO:0004708); 'kinase activator activity' is intended for non-catalytic regulators that bind and activate a kinase, and using it for the upstream kinase of a cascade duplicates the MF. The KSR1-dependent BRAF activation described in PMID:29433126 is handled under the MAP kinase scaffold activity rows.

Proposed replacements: MAP kinase kinase activity

Summary: IMP positive regulation of DNA-templated transcription from a lymphoma study using the MEK1/2 inhibitor AZD6244 (PMID:24375836).

Reason: The experiment shows that inhibiting MEK1/2 lowers miR-92a via ERK1/2-AP1. Changes in gene expression and transcription are downstream outputs of ERK and AP-1; MEK2 does no part of the transcriptional work. The inhibitor is also not MEK2-selective. These are indirect consequences of the ERK cascade rather than MEK2 process participation.

Summary: IDA perinuclear region of cytoplasm: MEK2-DLG1 colocalization in a perinuclear area of VSMCs (PMID:21615688).

Reason: Stated for the two proteins in the abstract; a cell-type-specific pool, non-core.

Summary: IMP ERK1 and ERK2 cascade (PMID:24375836): MEK1/2 inhibition suppresses ERK1/2 signalling to AP-1.

Reason: MEK2 is a direct participant (the MAP2K tier) of the ERK1/ERK2 cascade. This inhibitor-based row is weak on paralog specificity but the claim is strongly supported by direct biochemistry and Reactome.

Summary: Reactome TAS: MAPK1 (ERK2) activation pathway.

Reason: Core process: MEK2 phosphorylates and activates ERK1 and ERK2.

Summary: IDA positive regulation of protein serine/threonine kinase activity: MEK2 activated ERK1 >100-fold (PMID:8388392).

Reason: Correct but general; the regulated kinase is a MAP kinase (ERK1). Refine to positive regulation of MAP kinase activity (GO:0043406), an is_a child of this term.

Proposed replacements: positive regulation of MAP kinase activity

Summary: Regulation of Golgi inheritance (TAS from review PMID:19565474; ARBA IEA).

Reason: Mitotic Golgi fragmentation via MEK/ERK has been reported mainly for MEK1; whether MEK2 contributes is not visible in the cached abstract, the full text is unavailable, and the ARBA row is unvetted.

Summary: Regulation of Golgi inheritance (TAS from review PMID:19565474; ARBA IEA).

Reason: Mitotic Golgi fragmentation via MEK/ERK has been reported mainly for MEK1; whether MEK2 contributes is not visible in the cached abstract, the full text is unavailable, and the ARBA row is unvetted.

Summary: ARBA IEA for scaffold protein binding.

Reason: MAP2K2 binds the ERK-module scaffolds KSR1 (PMID:10409742, PMID:29433126) and DLG1/SAP97 (PMID:21615688). Scaffold binding positions MEK2 for activation by RAF and controls its localization; it is part of how the core function is executed.

Summary: IPI with KSR1: KSR forms a >700 kDa complex containing MEK1 and MEK2 (PMID:10409742).

Reason: KSR1 is the archetypal ERK-pathway scaffold and binds MEK directly; binding shifts MEK into membrane-associated fractions. Consistent with PMID:29433126.

Summary: IPI with DLG1 (hDlg/SAP97), mapped to DLG1 PDZ2 and the MEK2 C-terminal RTAV (PMID:21615688).

Reason: DLG1 is a MAGUK scaffold that binds MEK2 but not MEK1; the paper proposes it as a MEK2-specific ERK-pathway scaffold.

Summary: Protein serine kinase activity from the UniProt Rhea mapping (EXP, PMID:10409742) and Rhea IEA.

Reason: The serine-phosphorylation Rhea reaction is an artefact of splitting the EC 2.7.12.2 reaction into residue types; MEK2's substrate residues are the Thr and Tyr of the ERK TEY motif. MAP kinase kinase activity (GO:0004708) is the correct specific term.

Proposed replacements: MAP kinase kinase activity

Summary: Protein serine kinase activity from the UniProt Rhea mapping (EXP, PMID:10409742) and Rhea IEA.

Reason: The serine-phosphorylation Rhea reaction is an artefact of splitting the EC 2.7.12.2 reaction into residue types; MEK2's substrate residues are the Thr and Tyr of the ERK TEY motif. MAP kinase kinase activity (GO:0004708) is the correct specific term.

Proposed replacements: MAP kinase kinase activity

Summary: Regulation of early endosome to late endosome transport (TAS from review PMID:19565474; ARBA IEA).

Reason: Endosomal maturation effects of the ERK module are linked mainly to the LAMTOR3/MP1-MEK1 complex; MEK2-specific evidence is not visible in the cached abstract and the full text is unavailable.

Summary: Regulation of early endosome to late endosome transport (TAS from review PMID:19565474; ARBA IEA).

Reason: Endosomal maturation effects of the ERK module are linked mainly to the LAMTOR3/MP1-MEK1 complex; MEK2-specific evidence is not visible in the cached abstract and the full text is unavailable.