Protein / target
Dual specificity mitogen-activated protein kinase kinase 2
Protein at a glance
Biological role
Protein serine/threonine kinase activator
Strongest disease association
RASopathy
Therapeutic position
Established drug target
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases.
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Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126)
Subcellular location
Domains and Gene Ontology detail (40)Hide
Domains & features
Gene Ontology
- Ccell-cell junction
- Ccytoplasmic side of plasma membrane
- Ccytosol
- Cearly endosome
- Cendoplasmic reticulum
- Cextracellular region
- Cfocal adhesion
- CGolgi apparatus
- Clate endosome
- Cmicrotubule
- Cmitochondrion
- Cnucleus
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Receptor tyrosine kinase signalling
- ·ERBB2-ERBB3 signaling pathway
Growth-factor signalling
- ·insulin-like growth factor receptor signaling pathway
Cell migration
- ·positive regulation of cell motility
Transcriptional regulation
- ·positive regulation of DNA-templated transcription
- ·positive regulation of gene expression
View underlying pathways (14)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
8 medicines meet Open Targets' target-level approved-medicine definition; the 3 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
Dual specificity mitogen-activated protein kinase kinase 2 inhibitor
Indicated for Melanoma, Neoplasms
Dual specificity mitogen-activated protein kinase kinase 2 inhibitor
Indicated for Neoplasms
Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor
Indicated for Neoplasms
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene MAP2K2
Gene-level evidence surfaced through the gene MAP2K2that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (5)Hide
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.
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Drug development
18 compounds recorded · 8 approved · 10 in clinical development
View all recorded compounds (10)Hide
Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (10)Hide
Raw Open Targets tractability assessment buckets, by modality.
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 3 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- Label change
Label change: COBIMETINIB (NDA206192)
- Trial status changed
Phase I Study of the Pan-ERBB Inhibitor Neratinib Given in Combination With Everolimus, Palbociclib, or Trametinib in Advanced Cancer Subjects With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation
- Trial status changed
Phase 1b Study of IDH Inhibition With Enasidenib and MEK Inhibition With Cobimetinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia Who Have Co-Occurring IDH2 and RAS Signaling Gene Mutations
- New publicationMolecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial.
- Regulatory approval
Approval: Spexotras (EMA)
- Label change
Label change: COBIMETINIB (NDA206192)
- Indication expanded
Indication expansion: COBIMETINIB (NDA206192)
- New publicationCombination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced <i>BRAF</i>-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134.
- Indication expanded
Indication expansion: COBIMETINIB (NDA206192)
- New publicationEncorafenib, Binimetinib, and Cetuximab in <i>BRAF</i> V600E-Mutated Colorectal Cancer.
- Safety communication
Drug Safety Update: Trametinib (Mekinist▼): risk of gastrointestinal perforation and colitis
- New publicationImproved overall survival in melanoma with combined dabrafenib and trametinib.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.
Related family literature
Papers about “Mitogen-Activated Protein Kinase Kinases” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.
via Mitogen-Activated Protein Kinase Kinases
via Mitogen-Activated Protein Kinase Kinases
via Mitogen-Activated Protein Kinase Kinases
via Mitogen-Activated Protein Kinase Kinases
via Mitogen-Activated Protein Kinase Kinases
via Mitogen-Activated Protein Kinase Kinases
via Mitogen-Activated Protein Kinase Kinases
via Mitogen-Activated Protein Kinase Kinases
via Mitogen-Activated Protein Kinase Kinases
via Mitogen-Activated Protein Kinase Kinases
Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.