Protein / target
Breakpoint cluster region protein
Protein at a glance
Biological role
Guanyl-nucleotide exchange factor
Strongest disease association
chronic myelogenous leukemia, BCR-ABL1 positive
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins.
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Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:17116687, PubMed:1903516, PubMed:7479768). The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:23940119, PubMed:7479768). The amino terminus contains an intrinsic kinase activity (PubMed:1657398). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687). Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (PubMed:23940119)
Subcellular location
Domains and Gene Ontology detail (32)Hide
Domains & features
Gene Ontology
- Caxon
- Ccytosol
- Cdendritic spine
- Cextracellular exosome
- Cglutamatergic synapse
- Cmembrane
- Cplasma membrane
- Cpostsynaptic density
- Cprotein-containing complex
- CSchaffer collateral - CA1 synapse
- FATP binding
- FGTPase activator activity
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Synaptic signalling
- ·Postsynaptic density
- ·Synapse
- ·glutamatergic synapse
- ·postsynaptic density
Kinase signalling
- ·Protein with a unique structure having two opposing regulatory activities toward small G…
- ·protein serine kinase activity
- ·protein serine/threonine kinase activity
- ·protein tyrosine kinase activity
View underlying pathways (9)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.
12 medicines meet Open Targets' target-level approved-medicine definition; the 2 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.
Bcr/Abl fusion protein inhibitor
Indicated for Gastrointestinal Stromal Tumors, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic-Myeloproliferative Diseases, Precursor Cell Lymphoblastic Leukemia-Lymphoma
Bcr/Abl fusion protein inhibitor
Indicated for Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Precursor Cell Lymphoblastic Leukemia-Lymphoma
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 BCR
Gene-level evidence surfaced through the gene BCRthat 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.
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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
15 compounds recorded · 12 approved · 3 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 (9)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 2 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: IMATINIB MESYLATE (NDA021588)
- Label change
Label change: IMATINIB MESYLATE (NDA021588)
- Label change
Label change: IMATINIB (ANDA204644)
- New publicationThe Differential Effect of Senolytics on SASP Cytokine Secretion and Regulation of EMT by CAFs.
- Supplemental approval
Supplemental approval: IMATINIB MESYLATE (NDA021588)
- New publicationKIT mutations and expression: current knowledge and new insights for overcoming IM resistance in GIST.
- New publicationGenomic profiling in GIST: Implications in clinical outcome and future challenges.
- Label change
Label change: IMATINIB (ANDA204644)
- Label change
Label change: IMATINIB (ANDA204644)
- Label change
Label change: IMATINIB (ANDA204644)
- Label change
Label change: IMATINIB (ANDA204644)
- New publicationImatinib therapy for patients with recent-onset type 1 diabetes: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.
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.