Protein / target
Breakpoint cluster region protein
Protein at a glance
Biological role
Guanyl-nucleotide exchange factor activity
Primary system
Nervous system
Strongest disease association
chronic myelogenous leukemia, BCR-ABL1 positive
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
12 approved · 3 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
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.
View supporting evidenceHide supporting evidence
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
Excitatory neurotransmission
- ·glutamatergic synapse
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.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Bcr/Abl fusion protein inhibitor
Appears in clinical studies involving chronic myelogenous leukemia, BCR-ABL1 positive, myelodysplastic/myeloproliferative disease, gastrointestinal stromal tumor, dermatofibrosarcoma protuberans
Bcr/Abl fusion protein inhibitor
Appears in clinical studies involving acute lymphoblastic leukemia, chronic myelogenous leukemia, BCR-ABL1 positive, chronic myelogenous leukemia, BCR-ABL1 positive, chronic myelogenous leukemia, BCR-ABL1 positive
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 1,167 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 15 total
Parkinson disease · dementia · acute lymphoblastic leukemia
breast cancer · neoplasm · chronic myelogenous leukemia, BCR-ABL1 positive
lymphoid leukemia · myeloid leukemia · neoplasm
chronic myelogenous leukemia, BCR-ABL1 positive · acute lymphoblastic leukemia · chronic myelogenous leukemia, BCR-ABL1 positive
chronic myelogenous leukemia, BCR-ABL1 positive · chronic myelogenous leukemia, BCR-ABL1 positive · blast phase chronic myelogenous leukemia, BCR-ABL1 positive
chronic myelogenous leukemia, BCR-ABL1 positive · myelodysplastic/myeloproliferative disease · gastrointestinal stromal tumor
chronic myelogenous leukemia, BCR-ABL1 positive · acute lymphoblastic leukemia · leukemia
chronic myelogenous leukemia, BCR-ABL1 positive · acute lymphoblastic leukemia · gastrointestinal stromal tumor
chronic myelogenous leukemia, BCR-ABL1 positive · myeloid leukemia
chronic myelogenous leukemia, BCR-ABL1 positive · chronic myelogenous leukemia, BCR-ABL1 positive · chronic myelogenous leukemia, BCR-ABL1 positive
Tractability
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.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
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 underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- 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.
- Label change
Label change: IMATINIB (ANDA204644)
- Label change
Label change: IMATINIB (ANDA204644)
- Label change
Label change: IMATINIB (ANDA204644)
- Label change
Label change: IMATINIB (ANDA204644)
- Label change
Label change: IMATINIB (ANDA204644)
- Label change
Label change: IMATINIB (ANDA204644)
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.