MAP2K2 (MEK2) is a dual-specificity protein kinase in the RAF–MEK–ERK signaling cascade. It phosphorylates the activation-loop threonine and tyrosine residues of ERK MAP kinases, linking upstream signaling to changes in cellular proliferation and differentiation.
Summary: MAP2K2 is the MEK2 kinase in the RAF–MEK–ERK cascade.
Reason: MAP2K2 is the MEK2 kinase in the RAF–MEK–ERK cascade. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/MAP2K2/MAP2K2-uniprot.txt
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
Summary: The kinase binds ATP as the phosphate donor.
Reason: The kinase binds ATP as the phosphate donor. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
Reason: MAP kinase kinase activity specifies the conserved MEK2 substrate class. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
GO:0004674 protein serine/threonine kinase activity
IEA GO_REF:0000120
MODIFY
Summary: MEK2 phosphorylates both threonine and tyrosine in ERK activation loops; MAP kinase kinase activity is the informative function.
Reason: MEK2 phosphorylates both threonine and tyrosine in ERK activation loops; MAP kinase kinase activity is the informative function. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
Summary: Recombinant human MEK2 phosphorylated ERK1 on threonine and tyrosine and activated its kinase activity over100-fold. The conserved horse MEK2 catalytic architecture supports transfer of this mechanism.
Both MEK1 and MEK2 were expressed in Escherichia coli and shown to be able to activate recombinant human ERK1 in vitro. The purified MEK2 protein stimulated threonine and tyrosine phosphorylation on ERK1 and concomitantly activated ERK1 kinase activity more than 100-fold.
Summary: ATP is the phosphate donor for the conserved MAP2K2 reaction.
Reason: ATP is the phosphate donor for the conserved MAP2K2 reaction. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/MAP2K2/MAP2K2-uniprot.txt
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
Reason: Mitochondrial localization needs compartment-specific evidence beyond conservation of kinase activity. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/MAP2K2/MAP2K2-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10409742}. Membrane CC {ECO:0000269|PubMed:10409742}; Peripheral membrane protein CC {ECO:0000269|PubMed:10409742}. Note=Membrane localization is probably CC regulated by its interaction with KSR1. {ECO:0000269|PubMed:10409742}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
Summary: An early-endosome pool is context-specific and cannot be resolved from the conserved kinase sequence alone.
Reason: An early-endosome pool is context-specific and cannot be resolved from the conserved kinase sequence alone. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/MAP2K2/MAP2K2-uniprot.txt
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
Summary: A late-endosome pool requires localization evidence; the core MEK2 reaction does not establish it.
Reason: A late-endosome pool requires localization evidence; the core MEK2 reaction does not establish it. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/MAP2K2/MAP2K2-uniprot.txt
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
Summary: Focal-adhesion localization requires a distinct cellular experiment or grounded transfer of that observation.
Reason: Focal-adhesion localization requires a distinct cellular experiment or grounded transfer of that observation. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/MAP2K2/MAP2K2-uniprot.txt
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
Reason: The kinase substrate family is known. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
Summary: MAP kinase kinase activity is the specific conserved transferase function.
Reason: MAP kinase kinase activity is the specific conserved transferase function. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
GO:0032872 regulation of stress-activated MAPK cascade
IEA GO_REF:0000117
UNDECIDED
Summary: Participation in ERK signaling does not by itself establish regulation of a stress-activated MAPK cascade; pathway cross-talk requires evidence.
Reason: Participation in ERK signaling does not by itself establish regulation of a stress-activated MAPK cascade; pathway cross-talk requires evidence. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/MAP2K2/MAP2K2-uniprot.txt
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
Summary: The specific Golgi-inheritance role requires the relevant cell-cycle experiments.
Reason: The specific Golgi-inheritance role requires the relevant cell-cycle experiments. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/MAP2K2/MAP2K2-uniprot.txt
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
GO:2000641 regulation of early endosome to late endosome transport
IEA GO_REF:0000117
UNDECIDED
Summary: Regulation of early-to-late endosome transport is not established merely by the conserved MEK2 catalytic domain.
Reason: Regulation of early-to-late endosome transport is not established merely by the conserved MEK2 catalytic domain. This assessment transfers characterized mammalian biology to the selected horse sequence with the sequence limitations stated in the comparison.
Supporting Evidence:
file:human/MAP2K2/MAP2K2-uniprot.txt
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
Core Functions
MAP2K2 (MEK2) is a dual-specificity protein kinase in the RAF–MEK–ERK signaling cascade. It phosphorylates the activation-loop threonine and tyrosine residues of ERK MAP kinases, linking upstream signaling to changes in cellular proliferation and differentiation.
CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}.
The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence.
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Assessment of 1 ProtNLM GO predictions for the selected horse MAP2K2 protein, using mammalian experimental findings and an explicit comparison of the horse sequence.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: MAP2K2 is a MAP kinase kinase that phosphorylates ERK-family substrates. The horse protein retains 97.5% of the human reference at 90.26% identity and the kinase active-site features. The experimentally characterized mammalian kinase mechanism supports the broad protein phosphorylation process. This BP term is absent from the target GOA; kinase MF overlap does not establish identical GO-aspect annotation or training membership. Training-set membership is unknown.
Supporting Evidence:
file:human/MAP2K2/MAP2K2-uniprot.txt: "CC -!- FUNCTION: Catalyzes the concomitant phosphorylation of a threonine and CC a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. CC Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF CC in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases CC the inhibitory intramolecular interaction between KSR1 or KSR2 protein CC kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF CC dimerization and BRAF activation (PubMed:29433126). CC {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}."
file:HORSE/MAP2K2/MAP2K2-bioinformatics/RESULTS.md: "The horse sequence A0A9L0SHX8 (390 residues) aligns to human P36507 (400 residues) with 90.26% identity across 390 paired residues. Paired coverage is 97.5% of the human sequence and 100.0% of the horse sequence."
PMID:8388392: "Both MEK1 and MEK2 were expressed in Escherichia coli and shown to be able to activate recombinant human ERK1 in vitro. The purified MEK2 protein stimulated threonine and tyrosine phosphorylation on ERK1 and concomitantly activated ERK1 kinase activity more than 100-fold."