Gene Report

Gene: BCR     Link to MethyView
Summary
Gene symbol BCR
Alias ALL, BCR, BCR1, CML, D22S11, D22S662, FBW3, FBXW3, FLJ16453, PHL, SHFM3P1
Cytogenetic Location 22q11.23
Type KNOWN
Property protein_coding
Description Breakpoint cluster region protein (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-26) [BCR1]
External Links
   Ensembl ENSG00000186716
   OMIM 151410
   UniGene Hs.517461 Hs.551463 Hs.604560 Hs.634378
   mRNA NM_004327.3 NM_021574.2
   SwissProt P11274
 
Diseases(Cancers)
Cancer Name Acute lymphocytic leukemia
Description From cancer gene census of CGP:
 
Cancer Name Chronic myelogenous leukaemia (CML)
Description From cancer gene census of CGP: " various splicingsmain form: 160 KDa; N-term Serine-Treonine kinase domain, SH2 binding, and C-term domain which functions as a GTPase activating protein for p21rac; widely expressed; cytoplasmic localisation; protein kinase; probable role in signal transduction "
 
Cancer Name Bladder: Urothelial carcinomas
Description From COSMIC:
 
Cancer Name t(9;22)(q34;q11) in ANLL
Description "ANLL mostly M1 or M2 ANL. The chromosome anomaly t(9;22) disappear during remission, in contrast with BC-CML cases (CML in blast crisis); additional anomalies: similar to what is found in CML"
Hybrid/Mutated Gene "BCR/ABL the crucial event lies on der(22), id est 5' BCR - 3' ABL hybrid gene is the crucial one, while ABL/BCR may or may not be expressed; breakpoint in ABL is variable over a region of 200 kb, often between the two alternative exons 1b and 1a, sometimes 5' of 1b or 3' of 1a, but always 5' of exon 2;
breakpoint in BCR is either:
  • 1- in a region called M-bcr (for major breakpoint cluster region), a cluster of 5.8 kb, between exons 12 and 16, also called b1 to b5 of M- bcr; most breakpoints being either between b2 and b3, or between b3 and b4; transcript is 8.5 kb long; this results in a 210 KDa chimeric protein (P210); this is found in (most cases of) CML, and in half cases of ALL or ANLL
    HYBRID_GENE
  • 2- in a 35 kb region between exons 1 and 2, called m-bcr (minor breakpoint cluster region), -> 7 kb mRNA, resulting in a 190 KDa protein (P190); this is found in half of the cases of ALL or ANLL
  • 3- A breakpoint in the exon 19 of BCR (designed as micro-bcr) with fusion to abl sequences (a2) has been in neutrophilic CML, with presence of a larger protein (P230)."
  • Abnormal Protein "BCR/ABL P210 comprises the first 902 or 927 amino acids from BCR, P190 only the 427 N-term from BCR; BCR/ABL has a cytoplasmic localization, in contrast with ABL, mostly nuclear"
    Oncogenesis "BCR/ABL has a cytoplasmic localization role and all three BCR-ABL fusion proteins have been shown to exhibit oncogenic potential. All three hybrid proteins have increased protein kinase activity compared to ABL: 3BP1 (binding protein) binds normal ABL on SH3 domain,which prevents SH1 activation; with BCR/ABL, the first (N-terminal) exon of BCR binds to SH2, hidding SH3 which, as a consequence, cannot be bound to 3BP1; thereof, SH1 is activated; oncogenesis
    1- proliferation is induced through activation by BCR/ABL of RAS signal transduction pathway, PI3-K (phosphatidyl inositol 3' kinase) pathway, and MYC;
    2- BCR/ABL inhibits apoptosis;
    3- BCR/ABL provokes cell adhesive abnormalities."
     
    Cancer Name t(4;22)(q12;q11.2)
    Description 23 exons; alternate splicing.160-kDa protein; contains a unique serine/threonine kinase activity and at least two SH2 binding sites encoded in its first exon and a C-terminal domain that functions as a GTPase activating protein for p21(rac).
     
    Cancer Name t(9;22)(p24;q11.2)
     
    Cancer Name t(9;22)(q34;q11) in CML
    Description " all CML have a t(9;22), at least at the molecular level (BCR/ABL); phenotype and stem cell origin: multipotent progenitor: t(9;22) is found in all myeloid and B- lineage progenitors "
    Hybrid/Mutated Gene "BCR/ABL the crucial event lies on der(22), id est 5' BCR - 3' ABL hybrid gene is the crucial one, while ABL/BCR may or may not be expressed; breakpoint in ABL is variable over a region of 200 kb, often between the two alternative exons 1b and 1a, sometimes 5' of 1b or 3' of 1a, but always 5' of exon 2;
    breakpoint in BCR is either:
  • 1- in a region called M-bcr (for major breakpoint cluster region), a cluster of 5.8 kb, between exons 12 and 16, also called b1 to b5 of M- bcr; most breakpoints being either between b2 and b3, or between b3 and b4; transcript is 8.5 kb long; this results in a 210 KDa chimeric protein (P210); this is found in (most cases of) CML, and in half cases of ALL or ANLL
    HYBRID_GENE
  • 2- in a 35 kb region between exons 1 and 2, called m-bcr (minor breakpoint cluster region), -> 7 kb mRNA, resulting in a 190 KDa protein (P190); this is found in half of the cases of ALL or ANLL
  • 3- A breakpoint in the exon 19 of BCR (designed as micro-bcr) with fusion to abl sequences (a2) has been in neutrophilic CML, with presence of a larger protein (P230)."
  • Abnormal Protein "BCR/ABL P210 comprises the first 902 or 927 amino acids from BCR, P190 only the 427 N-term from BCR; BCR/ABL has a cytoplasmic localization, in contrast with ABL, mostly nuclear"
    Oncogenesis "BCR/ABL has a cytoplasmic localization role and all three BCR-ABL fusion proteins have been shown to exhibit oncogenic potential. All three hybrid proteins have increased protein kinase activity compared to ABL: 3BP1 (binding protein) binds normal ABL on SH3 domain,which prevents SH1 activation; with BCR/ABL, the first (N-terminal) exon of BCR binds to SH2, hidding SH3 which, as a consequence, cannot be bound to 3BP1; thereof, SH1 is activated; oncogenesis
    1- proliferation is induced through activation by BCR/ABL of RAS signal transduction pathway, PI3-K (phosphatidyl inositol 3' kinase) pathway, and MYC;
    2- BCR/ABL inhibits apoptosis;
    3- BCR/ABL provokes cell adhesive abnormalities."
     
    Cancer Name t(9;22)(q34;q11) in ALL
    Description " various splicingsmain form: 160 KDa; N-term Serine-Treonine kinase domain, SH2 binding, and C-term domain which functions as a GTPase activating protein for p21rac; widely expressed; cytoplasmic localisation; protein kinase; probable role in signal transduction "
    Hybrid/Mutated Gene "BCR/ABL the crucial event lies on der(22), id est 5' BCR - 3' ABL hybrid gene is the crucial one, while ABL/BCR may or may not be expressed; breakpoint in ABL is variable over a region of 200 kb, often between the two alternative exons 1b and 1a, sometimes 5' of 1b or 3' of 1a, but always 5' of exon 2;
    breakpoint in BCR is either:
  • 1- in a region called M-bcr (for major breakpoint cluster region), a cluster of 5.8 kb, between exons 12 and 16, also called b1 to b5 of M- bcr; most breakpoints being either between b2 and b3, or between b3 and b4; transcript is 8.5 kb long; this results in a 210 KDa chimeric protein (P210); this is found in (most cases of) CML, and in half cases of ALL or ANLL
    HYBRID_GENE
  • 2- in a 35 kb region between exons 1 and 2, called m-bcr (minor breakpoint cluster region), -> 7 kb mRNA, resulting in a 190 KDa protein (P190); this is found in half of the cases of ALL or ANLL
  • 3- A breakpoint in the exon 19 of BCR (designed as micro-bcr) with fusion to abl sequences (a2) has been in neutrophilic CML, with presence of a larger protein (P230)."
  • Abnormal Protein "BCR/ABL P210 comprises the first 902 or 927 amino acids from BCR, P190 only the 427 N-term from BCR; BCR/ABL has a cytoplasmic localization, in contrast with ABL, mostly nuclear"
    Oncogenesis "BCR/ABL has a cytoplasmic localization role and all three BCR-ABL fusion proteins have been shown to exhibit oncogenic potential. All three hybrid proteins have increased protein kinase activity compared to ABL: 3BP1 (binding protein) binds normal ABL on SH3 domain,which prevents SH1 activation; with BCR/ABL, the first (N-terminal) exon of BCR binds to SH2, hidding SH3 which, as a consequence, cannot be bound to 3BP1; thereof, SH1 is activated; oncogenesis
    1- proliferation is induced through activation by BCR/ABL of RAS signal transduction pathway, PI3-K (phosphatidyl inositol 3' kinase) pathway, and MYC;
    2- BCR/ABL inhibits apoptosis;
    3- BCR/ABL provokes cell adhesive abnormalities."
     
    Cancer Name t(8;22)(p11;q11)
    Description Normal function unclear; fuses to ABL in CML .
     
    Expression
    Expresstion pancreatic, whole, mammary, liver, parathyroid, head, vascular, brain, gastrointestinal, cervix, colon, esophagus, muscle, placenta, pooled, uncharacterized, synovium, cerebellum, cartilage, ovary, bone, stomach, uterus, kidney, pancreas, pituitary, skin, cerebrum, heart, lymphoreticular, peripheral, embryonic, prostate, lung, thyroid, lymph, nervous, testis, eye, genitourinary, adipose, thymus, spleen
    Related library Link
     
    Genomic Regions, Transcripts and Proteins
    Gene Structure <0...1874>, <73434...73615>, <80585...80689>, <80990...81175>, <88043...88150>, <91167...91227>, <92716...92768>, <93269...93409>, <103612...103733>, <104668...104836>, <106794...106913>, <107732...107807>, <109152...109256>, <109974...110048>, <112176...112273>, <129059...129118>, <129959...130068>, <131332...131471>, <132522...132656>, <133603...133708>, <134187...134349>, <135068...137672>
    Ensembl Transcript ENST00000359540
    Ensembl Protein ENSP00000352535
    Gene Ontology GO:0003674 ND Generated via Q9P1T7
    GO:0008150 ND Generated via P09565
    GO:0005622 IEA Generated via Q9Y2A4
    GO:0007165 IEA Generated via Q96R67
    GO:0005575 ND Generated via P09565
     
    Gene Structure <0...134>, <960...1101>, <33418...33422>, <55548...55729>, <62546...62546>, <62699...62803>, <63104...63289>, <70157...70264>, <73281...73341>, <74830...74882>, <75383...75523>, <85726...85847>, <86782...86950>, <88908...89027>, <89846...89921>, <91266...91370>, <92088...92162>, <94290...94387>, <96773...96904>, <111173...111232>, <112073...112182>, <113446...113585>, <114636...114770>, <115717...115822>, <116301...116463>, <117182...119786>
    Ensembl Transcript ENST00000334149
    Ensembl Protein ENSP00000335450
    Gene Ontology GO:0005089 IEA Generated via Q9Y2A5
    GO:0005085 IEA Generated via Q9Y2A5
    GO:0004674 NAS Generated via Q9Y2A5
    GO:0005622 IEA Generated via Q9Y2A4
    GO:0007165 IEA Generated via Q96R67
    GO:0035023 IEA Generated via Q9Y2A5
    GO:0005575 ND Generated via P09565
    GO:0005096 NAS Generated via Q5S007
    GO:0007242 NAS Generated via Q5HYD7
     
    Gene Structure <0...1874>, <73434...73615>, <80585...80689>, <80990...81175>, <91167...91227>, <92716...92768>, <93269...93409>, <103612...103733>, <104668...104836>, <106794...106913>, <107732...107807>, <109152...109256>, <109974...110048>, <112176...112273>, <114659...114790>, <129059...129118>, <129959...130068>, <131332...131471>, <132522...132656>, <133603...133708>, <134187...134349>, <135068...137672>
    Ensembl Transcript ENST00000292697
    Ensembl Protein ENSP00000292697
    Gene Ontology GO:0005622 IEA Generated via Q9Y2A4
    GO:0007242 IEA Generated via Q5HYD7
    GO:0035023 IEA Generated via Q9Y2A5
    GO:0005085 IEA Generated via Q9Y2A5
    GO:0005089 IEA Generated via Q9Y2A5
     
    Gene Structure <0...1874>, <73434...73615>, <80585...80689>, <80990...81175>, <88043...88150>, <91167...91227>, <92716...92768>, <93269...93409>, <103612...103733>, <104668...104836>, <106794...106913>, <107732...107807>, <109152...109256>, <109974...110048>, <112176...112273>, <114659...114790>, <129059...129118>, <129959...130068>, <131332...131471>, <132522...132656>, <133603...133708>, <134187...134349>, <135068...137672>
    Ensembl Transcript ENST00000305877
    Ensembl Protein ENSP00000303507
    Gene Ontology GO:0003674 ND Generated via Q9P1T7
    GO:0008150 ND Generated via P09565
    GO:0005575 ND Generated via P09565
    GO:0004674 TAS Generated via Q9Y2A5
    GO:0005089 IEA Generated via Q9Y2A5
    GO:0005085 IEA Generated via Q9Y2A5
    GO:0016301 IEA Generated via Q5T432
    GO:0005096 TAS Generated via Q5S007
    GO:0006468 TAS Generated via Q59F24
    GO:0016740 IEA Generated via Q86UN3
    GO:0035023 IEA Generated via Q9Y2A5
    GO:0007242 IEA Generated via Q5HYD7
    GO:0005622 IEA Generated via Q9Y2A4
    GO:0007165 IEA Generated via Q96R67
     
    Gene Structure <0...1874>, <73434...73615>, <80585...80689>, <80990...81099>, <93355...93409>, <103612...103733>, <104668...104836>, <106794...106913>, <107732...107807>, <109152...109256>, <109974...110048>, <112176...112273>, <114659...114790>, <129059...129118>, <129959...130068>, <131332...131471>, <132522...132656>, <133603...133708>, <134187...134349>, <135068...137672>
    Ensembl Transcript ENST00000290956
    Ensembl Protein ENSP00000290956
    Gene Ontology GO:0005622 IEA Generated via Q9Y2A4
    GO:0035023 IEA Generated via Q9Y2A5
    GO:0005089 IEA Generated via Q9Y2A5
     
    Gene Structure <0...20>, <6412...6516>, <6817...6978>, <29496...29560>, <30495...30663>, <32621...32740>, <33559...33634>, <34979...35083>, <35801...35875>, <38003...38100>, <40486...40617>, <54886...54945>, <55786...55895>, <57159...57298>, <58349...58483>, <59430...59535>, <60014...60176>, <60895...63499>
    Ensembl Transcript ENST00000347173
    Ensembl Protein ENSP00000317586
    Gene Ontology GO:0005089 IEA Generated via Q9Y2A5
    GO:0035023 IEA Generated via Q9Y2A5
    GO:0005622 IEA Generated via Q9Y2A4
     
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    DNA methylation and CGIs
    Gene MethyCancer Type Annotated cancer gene with experimental methylation data
    Link to MethyView
     
    Mutations
    Nucleotide c.1198T>C
    Amino Acid p.S400P
    Type mutation
    Tissue urinary_tract
    Source CGP
     
    Pathway
    BIOCARTA Integrin Signaling Pathway Link to BIOCARTA
     
    KEGG VEGF signaling pathway Link to KEGG
     
    KEGG Axon guidance Link to KEGG
     
    KEGG Gap junction Link to KEGG
     
    KEGG Focal adhesion Link to KEGG
     
    KEGG Apoptosis Link to KEGG
     
    KEGG Wnt signaling pathway Link to KEGG
     
    KEGG mTOR signaling pathway Link to KEGG
     
    KEGG TGF-beta signaling pathway Link to KEGG
     
    KEGG Dorso-ventral axis formation Link to KEGG
     
    KEGG GnRH signaling pathway Link to KEGG
     
    KEGG Regulation of actin cytoskeleton Link to KEGG
     
    KEGG Colorectal cancer Link to KEGG
     
    KEGG Alzheimer's disease Link to KEGG
     
    KEGG Hedgehog signaling pathway Link to KEGG
     
    KEGG Fc epsilon RI signaling pathway Link to KEGG
     
    KEGG Toll-like receptor signaling pathway Link to KEGG
     
    KEGG Circadian rhythm Link to KEGG
     
    KEGG Long-term depression Link to KEGG
     
    KEGG Long-term potentiation Link to KEGG
     
    KEGG Tight junction Link to KEGG
     
    KEGG Cell cycle Link to KEGG
     
    KEGG MAPK signaling pathway Link to KEGG
     
    KEGG Natural killer cell mediated cytotoxicity Link to KEGG
     
    KEGG T cell receptor signaling pathway Link to KEGG
     
    KEGG Adherens junction Link to KEGG
     
    KEGG Jak-STAT signaling pathway Link to KEGG
     
    KEGG Adipocytokine signaling pathway Link to KEGG
     
    KEGG Insulin signaling pathway Link to KEGG
     
    KEGG B cell receptor signaling pathway Link to KEGG
     
    BIOCARTA Inhibition of Cellular Proliferation by Gleevec Link to BIOCARTA
     
    Bibliography
    Title The function of BCR/ABL and related proto-oncogenes.
    Authors Gotoh A, Broxmeyer HE
    Citations Curr Opin Hematol 1997 Jan;4(1):3-11
    PubMedID 97196352
     
    Title Molecular insights into the Philadelphia translocation.
    Authors Heisterkamp N, Groffen J
    Citations Hematol Pathol. 1991;5(1):1-10. Review.
    PubMedID 2050600
     
    Title The molecular biology of chronic myeloid leukemia.
    Authors Deininger MWN, Goldman JM, Melo JV.
    Citations Blood 2000; 96: 3343-3356.
    PubMedID 11071626
     
    Title The BCR-ABL oncoprotein potentially interacts with the xeroderma pigmentosum group B protein.
    Authors Takeda N, Shibuya M, Maru Y.
    Citations Proc. Natl Acad Sci USA 1999; 96: 203-207.
    PubMedID 9874796
     
    Title BCR-ABL downregulates the DNA repair protein DNA-PKcs.
    Authors Deutsch E, Dugray A, Abdulkarim B, Marangoni E, Maggiorella L, Vaganay S, M'Kacher R, Rasy SD, Eschwege F, Vainchenker W, Turhan AG , Bourhis J.
    Citations Blood 2001; 97: 2084-2090.
    PubMedID 11264175
     
    Title The BCR gene and Philadelphia Chromosome-positive Leukemogenesis.
    Authors Laurent E, Talpaz M, Kantarjian H, Kurzrock R.
    Citations Cancer Res 2001; 61: 2343-2355.
    PubMedID 11289094