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FLASH GENE

Symbol

BCR

contributors: mct/npt - updated : 21-05-2017

HGNC name	breakpoint cluster region
HGNC id	1014

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	137.67 kb     23 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004327 23 splicing 6927 160 1271 - 2000 11069024 NM_021574 22 splicing 6795 130 1227 - 2000 11069024 BCR/ABL - - - 210 - - 2000 11069024 ABL-BCR - - - 40 - - 2009 19876398 increased proliferation of early progenitors and the short term stem cell capacity of stem-cells and exhibited own leukemogenic potential ABL-BCRl - - - 96 - - 2009 19876398 increased proliferation of early progenitors and the short term stem cell capacity of stem-cells and exhibited own leukemogenic potential

EXPRESSION

Rna function	BCR mRNAs are abundantly expressed in the brain
Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune spleen       highly Nervous brain       highly Homo sapiens Skin/Tegument skin       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Nervous central     highly Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a region of homology to GDP-GTP exchangers like CDC24, for Rac and Rho (Arh) proteins, (signal transduction)

HOMOLOGY

Homologene

FAMILY

CATEGORY

enzyme , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	BCR and its close relative active BCR-related (ABR) localize at excitatory synapses

basic FUNCTION	promoting the exchange of RAC or CDC42-bound GDP by GTP thereby activating them
	displaying serine/threonine kinase activity
	PCAF and BCR signalling are essential for apoptotic cell death (PCAF and BCR signalling control cooperatively pre-mature B cell apoptosis via both depletions of DFFA and BIRC2)
	ABR and BCR are the only GTPase-activating proteins to date that specifically negatively regulate Rac function in primary macrophages
	BCR and ABR cooperate in negatively regulating acute inflammatory responses
	represses the expression of PEBP1, continuously activates pERK1/2, and suppresses FOXM1 expression, resulting in proliferation of CML cells (
	BCR-ABL increases FBXO5 phosphorylation and stability to prevent SKP2 protein degradation via APC/CDH1-induced ubiquitination and to enhance proliferation of CML cells
	functional interaction between BCR-ABL and mitosis dysfunctions, due to compromised mitotic checkpoints, may have important implications for the generation of aneuploidy and CML progression
	BCR and ABR have novel roles in the regulation of synaptic Rac1 signaling, synaptic plasticity, and learning and memory, and that excessive Rac1 activity negatively affects synaptic and cognitive functions
	also acts via PPARG independent signaling
	a RAC1 GTPase-activating protein that plays a key role in neuronal development
	is involved in the regulation of neuronal development via control of the BCR GTPase-activating domain function by PTPRT

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component	proximal BCR-ABL1 signaling network shows a modular and layered organization with an inner core of three leukemia transformation-relevant adaptor protein complexes (GRB2/GAB2/SHC1 complex, CRK complex and DOK1/DOK2 complex)
	BCR-ABL1 suppresses autophagy through ATF5-mediated regulation of MTOR transcription

INTERACTION

DNA

RNA

small molecule

protein	binding of the adaptor protein GRB2 to Tyr177 of BCR-ABL1 is crucial for the leukemic transformation of cells by BCR-ABL1
	TGM2 bound to the Rac-binding pocket in the GTPase-activating domains of BCR and ABR, blocked BCR activity and, through this mechanism, increased levels of active GTP-bound Rac and EGF-stimulated membrane ruffling
	BCR-ABL fusion oncogene frequently found in chronic myeloid leukemia (CML) cells can up-regulate SKP2 expression via transcriptional activation
	directly interact with DLG4, an abundant postsynaptic scaffolding protein
	binds to DDX39B and binding of DDX39B to BCR is critical for BCR induced DNA synthesis in vascular smooth muscle cells (VSMC)
	DDX329B/BCR interaction is important for BCR induced DNA synthesis
	signaling cascades driven by the BCR and TLR9 have a newly identified meeting point at TBX21(
	HAP1 interacts with BCR on microtubules to regulate neuronal differentiation
	RICTOR positively regulates the early events of BCR signaling

cell & other

REGULATION

Other	functional involvement of LRRK1 in the balance of BCR-ABL1-mediated MAP-kinase signaling
	Janus kinase 2 regulates BCR-ABL signaling in chronic myeloid leukemia
	function of the BCR GTPase-activating domain could be modulated by protein tyrosine phosphatase receptor T (PTPRT), which is expressed principally in the brain

ASSOCIATED DISORDERS

corresponding disease(s)

BCR-ABL , DEL22Q11D

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion       BCR-JAK2 fusion result of a t(9;22)(p24;q11.2) translocation in chronic myeloid leukemia tumoral fusion       fused with FGFR1 in t(8;22) (p11;q11) in myelo proliferative disorder and with PDGFRA in t(4;22) (q12;q11) in atypical chronic myeloid leukemia tumoral fusion       with ABL1, in reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cardiovascular aquired   BCR/DDX39B interaction may be a target for inhibiting pathological VSMC proliferation cancer hemopathy   targeting ROR1 simultaneously with inhibition of B-cell receptor (BCR) signaling is more effective in killing ROR1-positive leukemia cells

ANIMAL & CELL MODELS