BCR

Oncogene
Breakpoint cluster region protein UniProt accession P11274

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)

Source: UniProt

Homotetramer. Interacts with PDZK1 (PubMed:15494376). May interact with CCPG1 (By similarity).

Interacts with FES/FPS, ABL1, PIK3R1 and GRB2 (PubMed:15302586, PubMed:1712671, PubMed:9407116). Interacts with HCK (PubMed:9407116). Interacts with SH2D5 (PubMed:25331951).

Interacts with DLG4 (PubMed:20962234)

Source: UniProt
Postsynaptic density, Cell projection, dendritic spine, Cell projection, axon, Synapse
Source: UniProt

The region involved in binding to ABL1 SH2-domain is rich in serine residues and needs to be Ser/Thr phosphorylated prior to SH2 binding. This region is essential for the activation of the ABL1 tyrosine kinase and transforming potential of the chimeric BCR-ABL oncogene

The DH domain is involved in interaction with CCPG1

The amino terminus contains an intrinsic kinase activity. The central Dbl homology (DH) domain functions as a 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.

The C-terminus is a Rho-GAP domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique structure having two opposing regulatory activities toward small GTP-binding proteins

Source: UniProt
  • Leukemia, chronic myeloid (CML)

    A clonal myeloproliferative disorder of a pluripotent stem cell with a specific cytogenetic abnormality, the Philadelphia chromosome (Ph), involving myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T-lymphoid cells, but not marrow fibroblasts.

  • Unknown disease
Source: UniProt
  • Signaling by cytosolic FGFR1 fusion mutants
  • Signaling by FGFR1 in disease
  • RHOA GTPase cycle
  • RHOB GTPase cycle
  • RHOC GTPase cycle
  • CDC42 GTPase cycle
  • RAC1 GTPase cycle
  • RAC2 GTPase cycle
  • RAC3 GTPase cycle
Source: Reactome via UniProt

Mutations

Cancer Type Mutation Percentage
Central Nervous System Astrocytoma Grade Iv 0.47%
Lung Adenocarcinoma 1.40%
Lung Small Cell Carcinoma 0.89%
Lung Squamous Cell Carcinoma 1.36%
Oesophagus Adenocarcinoma 0.62%
Oesophagus Squamous Cell Carcinoma 1.41%
Pancreas Ductal Carcinoma 0.49%

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to BCR, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 2

NCT ID Condition Brief Title Phase Status
NCT00002790 Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes Prevention of Graft-Versus-Host Disease in Patients With Hematologic Malignancies Who Are Receiving a Bone Marrow Transplant PHASE1, PHASE2 WITHDRAWN
NCT00145613 Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Secondary AML, Myelodysplastic Syndrome (MDS), Secondary MDS, Chronic Myeloid Leukemia, Juvenile Myelomonocytic Leukemia (JMML), Paroxysmal Nocturnal Hemoglobinuria (PNH), Lymphoma, Non-Hodgkin, Hodgkin Disease Haploidentical Stem Cell Transplant for Treatment Refractory Hematological Malignancies PHASE2 COMPLETED
NCT00860574 Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia, Childhood Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes, Untreated Adult Acute Lymphoblastic Leukemia, Untreated Childhood Acute Lymphoblastic Leukemia Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia PHASE2 COMPLETED
NCT00750659 Chronic Myeloid Leukemia, Acute Lymphoblastic Leukemia, Stem Cell Transplantation Nilotinib Pre and Post Allogeneic Stem Cell Transplantation PHASE2 COMPLETED
NCT00152139 Acute Lymphoblastic Leukemias, Acute Myelocytic Leukemia, Chronic Myeloid Leukemia, Juvenile Myelomonocytic Leukemia, Myelodysplastic Syndrome, Hemoglobinuria, Paroxysmal, Non-Hodgkin Lymphoma Stem Cell Transplantation for Patients With Hematologic Malignancies PHASE3 COMPLETED
NCT03932669 Ataxia, Cerebellar, Ataxia, Progressive Effect of Nilotinib in Cerebellar Ataxia Patients PHASE2 COMPLETED
NCT07354074 Chronic Myelogenous Leukemia, Leukemia, Myelogenous, Chronic, Philadelphia Chromosome Positive Study to Determine the Efficacy and Safety of Asciminib in Pediatric Patients With Ph+ CML-CP PHASE2 RECRUITING
NCT01076270 Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Atypical Chronic Myeloid Leukemia, BCR-ABL Negative, Blastic Phase Chronic Myelogenous Leukemia, Chronic Phase Chronic Myelogenous Leukemia, de Novo Myelodysplastic Syndromes, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Nodal Marginal Zone B-cell Lymphoma, Noncontiguous Stage II Adult Burkitt Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma, Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma, Noncontiguous Stage II Adult Lymphoblastic Lymphoma, Noncontiguous Stage II Grade 1 Follicular Lymphoma, Noncontiguous Stage II Grade 2 Follicular Lymphoma, Noncontiguous Stage II Grade 3 Follicular Lymphoma, Noncontiguous Stage II Mantle Cell Lymphoma, Noncontiguous Stage II Marginal Zone Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Refractory Multiple Myeloma, Relapsing Chronic Myelogenous Leukemia, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes, Splenic Marginal Zone Lymphoma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Adult Burkitt Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Mixed Cell Lymphoma, Stage III Adult Diffuse Small Cleaved Cell Lymphoma, Stage III Adult Hodgkin Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Chronic Lymphocytic Leukemia, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Multiple Myeloma, Stage III Small Lymphocytic Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Mixed Cell Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Hodgkin Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Chronic Lymphocytic Leukemia, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Small Lymphocytic Lymphoma Plerixafor and Filgrastim For Mobilization of Donor Peripheral Blood Stem Cells Before A Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies NA TERMINATED
NCT02324686 End Stage Renal Failure on Dialysis, Atrial Fibrillation Vitamin K Supplementation in Patients on Hemodialysis PHASE2 COMPLETED
NCT03941769 Acute Myeloid Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Cord Blood Transplant Recipient, Myelodysplastic Syndrome, Myeloproliferative Neoplasm 2018-0674 - IL-7 for T-Cell Recovery Post Haplo and CB Transplant - Phase I/II PHASE1, PHASE2 COMPLETED