Open Access Articles- Top Results for BCR (gene)

BCR (gene)

SymbolsBCR ; ALL; BCR1; CML; D22S11; D22S662; PHL
External IDsOMIM151410 MGI88141 HomoloGene3192 IUPHAR: 2755 ChEMBL: 5146 GeneCards: BCR Gene
EC number2.7.11.1
RefSeq (mRNA)NM_004327NM_001081412
RefSeq (protein)NP_004318NP_001074881
Location (UCSC)Chr 22:
23.52 – 23.66 Mb
Chr 10:
75.06 – 75.18 Mb
PubMed search[1][2]
Bcr-Abl oncoprotein oligomerisation domain
File:PDB 1k1f EBI.jpg
structure of the bcr-abl oncoprotein oligomerization domain
Symbol Bcr-Abl_Oligo
Pfam PF09036
InterPro IPR015123

The breakpoint cluster region protein (BCR) also known as renal carcinoma antigen NY-REN-26 is a protein that in humans is encoded by the BCR gene. BCR is one of the two genes in the BCR-ABL complex, which is associated with the Philadelphia chromosome. Two transcript variants encoding different isoforms have been found for this gene.


Although the BCR-ABL fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The protein has serine/threonine kinase activity and is a GTPase-activating protein for RAC1 and CDC42.[1]

Clinical significance

A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the BCR gene. The translocation produces a fusion protein that is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint.[2]


The Bcr-Abl oncoprotein oligomerisation domain found at the N-terminus of BCR is essential for the oncogenicity of the BCR-ABL fusion protein. The Bcr-Abl oncoprotein oligomerisation domain consists of a short N-terminal helix (alpha-1), a flexible loop and a long C-terminal helix (alpha-2). Together these form an N-shaped structure, with the loop allowing the two helices to assume a parallel orientation. The monomeric domains associate into a dimer through the formation of an antiparallel coiled coil between the alpha-2 helices and domain swapping of two alpha-1 helices, where one alpha-1 helix swings back and packs against the alpha-2 helix from the second monomer. Two dimers then associate into a tetramer.[3]


BCR gene has been shown to interact with:

See also


  1. "Entrez Gene: Breakpoint cluster region". 
  2. "Entrez Gene: BCR breakpoint cluster region". 
  3. Zhao X, Ghaffari S, Lodish H, Malashkevich VN, Kim PS (February 2002). "Structure of the Bcr-Abl oncoprotein oligomerization domain". Nat. Struct. Biol. 9 (2): 117–20. PMID 11780146. doi:10.1038/nsb747. 
  4. 4.0 4.1 4.2 Puil L, Liu J, Gish G, Mbamalu G, Bowtell D, Pelicci PG et al. (February 1994). "Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway". EMBO J. 13 (4): 764–73. PMC 394874. PMID 8112292. 
  5. Ling X, Ma G, Sun T, Liu J, Arlinghaus RB (January 2003). "Bcr and Abl interaction: oncogenic activation of c-Abl by sequestering Bcr". Cancer Res. 63 (2): 298–303. PMID 12543778. 
  6. Pendergast AM, Muller AJ, Havlik MH, Maru Y, Witte ON (July 1991). "BCR sequences essential for transformation by the BCR-ABL oncogene bind to the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner". Cell 66 (1): 161–71. PMID 1712671. doi:10.1016/0092-8674(91)90148-R. 
  7. Hallek M, Danhauser-Riedl S, Herbst R, Warmuth M, Winkler A, Kolb HJ et al. (July 1996). "Interaction of the receptor tyrosine kinase p145c-kit with the p210bcr/abl kinase in myeloid cells". Br. J. Haematol. 94 (1): 5–16. PMID 8757502. doi:10.1046/j.1365-2141.1996.6102053.x. 
  8. 8.0 8.1 8.2 8.3 Bai RY, Jahn T, Schrem S, Munzert G, Weidner KM, Wang JY et al. (August 1998). "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene 17 (8): 941–8. PMID 9747873. doi:10.1038/sj.onc.1202024. 
  9. 9.0 9.1 Million RP, Harakawa N, Roumiantsev S, Varticovski L, Van Etten RA (June 2004). "A direct binding site for Grb2 contributes to transformation and leukemogenesis by the Tel-Abl (ETV6-Abl) tyrosine kinase". Mol. Cell. Biol. 24 (11): 4685–95. PMC 416425. PMID 15143164. doi:10.1128/MCB.24.11.4685-4695.2004. 
  10. Heaney C, Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S et al. (January 1997). "Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation". Blood 89 (1): 297–306. PMID 8978305. 
  11. Kolibaba KS, Bhat A, Heaney C, Oda T, Druker BJ (March 1999). "CRKL binding to BCR-ABL and BCR-ABL transformation". Leuk. Lymphoma 33 (1-2): 119–26. PMID 10194128. doi:10.3109/10428199909093732. 
  12. Lionberger JM, Smithgall TE (February 2000). "The c-Fes protein-tyrosine kinase suppresses cytokine-independent outgrowth of myeloid leukemia cells induced by Bcr-Abl". Cancer Res. 60 (4): 1097–103. PMID 10706130. 
  13. 13.0 13.1 13.2 Maru Y, Peters KL, Afar DE, Shibuya M, Witte ON, Smithgall TE (February 1995). "Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS". Mol. Cell. Biol. 15 (2): 835–42. PMC 231961. PMID 7529874. 
  14. Million RP, Van Etten RA (July 2000). "The Grb2 binding site is required for the induction of chronic myeloid leukemia-like disease in mice by the Bcr/Abl tyrosine kinase". Blood 96 (2): 664–70. PMID 10887132. 
  15. Ma G, Lu D, Wu Y, Liu J, Arlinghaus RB (May 1997). "Bcr phosphorylated on tyrosine 177 binds Grb2". Oncogene 14 (19): 2367–72. PMID 9178913. doi:10.1038/sj.onc.1201053. 
  16. Stanglmaier M, Warmuth M, Kleinlein I, Reis S, Hallek M (February 2003). "The interaction of the Bcr-Abl tyrosine kinase with the Src kinase Hck is mediated by multiple binding domains". Leukemia 17 (2): 283–9. PMID 12592324. doi:10.1038/sj.leu.2402778. 
  17. Lionberger JM, Wilson MB, Smithgall TE (June 2000). "Transformation of myeloid leukemia cells to cytokine independence by Bcr-Abl is suppressed by kinase-defective Hck". J. Biol. Chem. 275 (24): 18581–5. PMID 10849448. doi:10.1074/jbc.C000126200. 
  18. Radziwill G, Erdmann RA, Margelisch U, Moelling K (July 2003). "The Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to its PDZ domain". Mol. Cell. Biol. 23 (13): 4663–72. PMC 164848. PMID 12808105. doi:10.1128/MCB.23.13.4663-4672.2003. 
  19. 19.0 19.1 Salgia R, Sattler M, Pisick E, Li JL, Griffin JD (February 1996). "p210BCR/ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c-Cbl". Exp. Hematol. 24 (2): 310–3. PMID 8641358. 
  20. Salgia R, Li JL, Lo SH, Brunkhorst B, Kansas GS, Sobhany ES et al. (March 1995). "Molecular cloning of human paxillin, a focal adhesion protein phosphorylated by P210BCR/ABL". J. Biol. Chem. 270 (10): 5039–47. PMID 7534286. doi:10.1074/jbc.270.10.5039. 
  21. Skorski T, Kanakaraj P, Nieborowska-Skorska M, Ratajczak MZ, Wen SC, Zon G et al. (July 1995). "Phosphatidylinositol-3 kinase activity is regulated by BCR/ABL and is required for the growth of Philadelphia chromosome-positive cells". Blood 86 (2): 726–36. PMID 7606002. 
  22. Liedtke M, Pandey P, Kumar S, Kharbanda S, Kufe D (October 1998). "Regulation of Bcr-Abl-induced SAP kinase activity and transformation by the SHPTP1 protein tyrosine phosphatase". Oncogene 17 (15): 1889–92. PMID 9788431. doi:10.1038/sj.onc.1202117. 
  23. Park AR, Oh D, Lim SH, Choi J, Moon J, Yu DY et al. (2012). "Regulation of dendritic arborization by BCR Rac1 GTPase-activating protein, a substrate of PTPRT". J. Cell. Sci. 125 (Pt 19): 4518–31. PMID 22767509. doi:10.1242/jcs.105502. 
  24. Takeda N, Shibuya M, Maru Y (January 1999). "The BCR-ABL oncoprotein potentially interacts with the xeroderma pigmentosum group B protein". Proc. Natl. Acad. Sci. U.S.A. 96 (1): 203–7. PMC 15117. PMID 9874796. doi:10.1073/pnas.96.1.203. 

Further reading

  • Wang L, Seale J, Woodcock BE, Clark RE (2002). "e19a2-positive chronic myeloid leukaemia with BCR exon e16-deleted transcripts". Leukemia 16 (8): 1562–3. PMID 12145699. doi:10.1038/sj.leu.2402600. 

External links

This article incorporates text from the public domain Pfam and InterPro IPR015123