BCR基因

Breakpoint cluster region
Breakpoint cluster region
	PDB rendering based on 1k1f.
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB查询代码列表
	1K1F, 2AIN
标识
代号	BCR; ALL; BCR1; CML; D22S11; D22S662; PHL
扩展标识	遗传学：151410 鼠基因：88141 同源基因：3192 ChEMBL: 5146 GeneCards: BCR Gene
EC编号	2.7.11.1
基因本体论描述
分子功能	· protein serine/threonine kinase activity; · protein tyrosine kinase activity; · Rho guanyl-nucleotide exchange factor activity; · GTPase activator activity; · protein binding; · ATP binding; · phospholipid binding; · kinase activity; · enzyme binding; · Rac GTPase activator activity;
细胞成分	· cytosol; · plasma membrane;
生物过程	· protein phosphorylation; · signal transduction; · small GTPase mediated signal transduction; · brain development; · actin cytoskeleton organization; · negative regulation of cell migration; · response to lipopolysaccharide; · inner ear morphogenesis; · negative regulation of neutrophil degranulation; · protein autophosphorylation; · platelet-derived growth factor receptor signaling pathway; · negative regulation of inflammatory response; · positive regulation of phagocytosis; · neuromuscular process controlling balance; · regulation of small GTPase mediated signal transduction; · regulation of cell cycle;
	Sources: Amigo / QuickGO
直系同源体
物种	人类
Entrez	613
Ensembl	ENSG00000186716
UniProt	P11274
mRNA序列	NM_004327
蛋白序列	NP_004318
基因位置	Chr 22:; 23.52 – 23.66 Mb
PubMed查询	[1]
	查; 论; 编;

现有可用的蛋白结构：
Pfam	结构（旧版） / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum（英语：PDBsum）	结构概要

Bcr-Abl肿瘤蛋白齐聚反应结构域
Bcr-Abl肿瘤蛋白齐聚反应结构域
	Bcr-Abl肿瘤蛋白齐聚反应结构域机制
鉴定
标志	Bcr-Abl_Oligo
Pfam	PF09036（旧版）
InterPro（英语：InterPro）	IPR015123
Pfam
现有可用的蛋白结构：
Pfam	结构（旧版） / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum（英语：PDBsum）	结构概要

BCR基因（英语：BCR gene），或称断裂点簇集区（英语：breakpoint cluster region），是bcr-abl融合基因的组成部分之一，其与费城染色体的形成机制有关。

Quick Facts Bcr-Abl肿瘤蛋白齐聚反应结构域, 鉴定 ...

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Quick Facts Breakpoint cluster region, 有效结构 ...

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病理学

一个22号染色体与9号染色体的相互易位作用而产生的费城染色体，它通常在慢性粒细胞性白血病患者体内发现。22号染色体的断裂点就在BCR基因中。这个易位作用产生了一种基于BCR基因和ABL基因进行编码而成的融合蛋白，其基因就位于9号染色体的断裂点上。尽管bcr-abl融合基因已经被广泛研究，但普通的BCR基因机制仍然不明。其蛋白产生一些丝氨酸或苏氨酸蛋白激酶活动，并是一类p21rac酶活化蛋白。^[1]

Bcr-Abl肿瘤蛋白齐聚反应域（Bcr-Abl oncoprotein oligomerisation domain）位于BCR的氨基端（N-terminus），其为BCR-ABL融合蛋白的齐聚反应必不可少的基因之一。Bcr-Abl肿瘤蛋白齐聚反应域包含一个短状氨基端 α螺旋（alpha-1），一个灵活的转角（Turn）和一个长状的C型α螺旋（alpha-2）。其螺旋体转角使得两个α螺旋能够保持平行定向。这一单体分子的蛋白质结构域，通过一个反平行的卷轴螺旋（coiled coil）形成为一个蛋白质二聚体（protein dimer）。其中两个α螺旋彼此之间发生了结构域对换，其中一个α-1螺旋氨基端进行交换，并挤压另个单体上的α-2螺旋（alpha-2）。两个蛋白质二聚体随后形成一个四聚体（tetramer）^[2]。

相互机制

现今已经发现BCR基因与以下基因发生蛋白-蛋白交互作用（Protein-protein interaction）：PTPN6（英语：PTPN6）^[3]、XPB（英语：XPB）^[4]、猫肉瘤癌基因^[5]^[6]、GRB10（英语：GRB10）^[7]、CD117（英语：CD117）^[8]、Grb2（英语：Grb2）^[6]^[7]^[9]^[10]^[11]^[12]、MLLT4（英语：MLLT4）^[13]、Abl基因（英语：ABL (gene)）^[11]^[14]^[15]、HCK（英语：HCK）^[16]^[17]、SOS1（英语：SOS1）^[6]^[11]、PIK3CG（英语：PIK3CG）^[7]^[18]^[19]、CRKL（英语：CRKL）^[7]^[10]^[20]^[21]和桩蛋白^[18]^[22]。

参考

[1]
Entrez Gene: BCR breakpoint cluster region.
[2]
Zhao X, Ghaffari S, Lodish H, Malashkevich VN, Kim PS. Structure of the Bcr-Abl oncoprotein oligomerization domain. Nat. Struct. Biol. February 2002, 9 (2): 117–20. PMID 11780146. doi:10.1038/nsb747.
[3]
Liedtke, M; Pandey P, Kumar S, Kharbanda S, Kufe D. Regulation of Bcr-Abl-induced SAP kinase activity and transformation by the SHPTP1 protein tyrosine phosphatase. Oncogene (ENGLAND). Oct 1998, 17 (15): 1889–92. ISSN 0950-9232. PMID 9788431. doi:10.1038/sj.onc.1202117.
[4]
Takeda, N; Shibuya M, Maru Y. The BCR-ABL oncoprotein potentially interacts with the xeroderma pigmentosum group B protein. Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES). Jan 1999, 96 (1): 203–7. ISSN 0027-8424. PMC 15117 . PMID 9874796. doi:10.1073/pnas.96.1.203.
[5]
Lionberger, J M; Smithgall T E. The c-Fes protein-tyrosine kinase suppresses cytokine-independent outgrowth of myeloid leukemia cells induced by Bcr-Abl. Cancer Res. (UNITED STATES). Feb 2000, 60 (4): 1097–103. ISSN 0008-5472. PMID 10706130.
[6]
Maru, Y; Peters K L, Afar D E, Shibuya M, Witte O N, Smithgall T E. Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS. Mol. Cell. Biol. (UNITED STATES). Feb 1995, 15 (2): 835–42. ISSN 0270-7306. PMC 231961 . PMID 7529874.
[7]
Bai, R Y; Jahn T, Schrem S, Munzert G, Weidner K M, Wang J Y, Duyster J. The SH2-containing adapter protein GRB10 interacts with BCR-ABL. Oncogene (ENGLAND). Aug 1998, 17 (8): 941–8. ISSN 0950-9232. PMID 9747873. doi:10.1038/sj.onc.1202024.
[8]
Hallek, M; Danhauser-Riedl S, Herbst R, Warmuth M, Winkler A, Kolb H J, Druker B, Griffin J D, Emmerich B, Ullrich A. Interaction of the receptor tyrosine kinase p145c-kit with the p210bcr/abl kinase in myeloid cells. Br. J. Haematol. (ENGLAND). Jul 1996, 94 (1): 5–16. ISSN 0007-1048. PMID 8757502. doi:10.1046/j.1365-2141.1996.6102053.x.
[9]
Million, R P; Van Etten R A. The Grb2 binding site is required for the induction of chronic myeloid leukemia-like disease in mice by the Bcr/Abl tyrosine kinase. Blood (UNITED STATES). Jul 2000, 96 (2): 664–70. ISSN 0006-4971. PMID 10887132.
[10]
Million, Ryan P; Harakawa Nari, Roumiantsev Sergei, Varticovski Lyuba, Van Etten Richard A. A direct binding site for Grb2 contributes to transformation and leukemogenesis by the Tel-Abl (ETV6-Abl) tyrosine kinase. Mol. Cell. Biol. (United States). Jun 2004, 24 (11): 4685–95. ISSN 0270-7306. PMC 416425 . PMID 15143164. doi:10.1128/MCB.24.11.4685-4695.2004.
[11]
Puil, L; Liu J, Gish G, Mbamalu G, Bowtell D, Pelicci P G, Arlinghaus R, Pawson T. Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway. EMBO J. (ENGLAND). Feb 1994, 13 (4): 764–73. ISSN 0261-4189. PMC 394874 . PMID 8112292.
[12]
Ma, G; Lu D, Wu Y, Liu J, Arlinghaus R B. Bcr phosphorylated on tyrosine 177 binds Grb2. Oncogene (ENGLAND). May 1997, 14 (19): 2367–72. ISSN 0950-9232. PMID 9178913. doi:10.1038/sj.onc.1201053.
[13]
Radziwill, G; Erdmann R A, Margelisch U, Moelling K. The Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to its PDZ domain. Mol. Cell. Biol. (United States). Jul 2003, 23 (13): 4663–72. ISSN 0270-7306. PMC 164848 . PMID 12808105. doi:10.1128/MCB.23.13.4663-4672.2003.
[14]
Ling, Xiaoyang; Ma Guozhen, Sun Tong, Liu Jiaxin, Arlinghaus Ralph B. Bcr and Abl interaction: oncogenic activation of c-Abl by sequestering Bcr. Cancer Res. (United States). Jan 2003, 63 (2): 298–303. ISSN 0008-5472. PMID 12543778.
[15]
Pendergast, A M; Muller A J, Havlik M H, Maru Y, Witte O N. BCR sequences essential for transformation by the BCR-ABL oncogene bind to the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner. Cell (UNITED STATES). Jul 1991, 66 (1): 161–71. ISSN 0092-8674. PMID 1712671. doi:10.1016/0092-8674(91)90148-R.
[16]
Stanglmaier, M; Warmuth M, Kleinlein I, Reis S, Hallek M. The interaction of the Bcr-Abl tyrosine kinase with the Src kinase Hck is mediated by multiple binding domains. Leukemia (England). Feb 2003, 17 (2): 283–9. ISSN 0887-6924. PMID 12592324. doi:10.1038/sj.leu.2402778.
[17]
Lionberger, J M; Wilson M B, Smithgall T E. Transformation of myeloid leukemia cells to cytokine independence by Bcr-Abl is suppressed by kinase-defective Hck. J. Biol. Chem. (UNITED STATES). Jun 2000, 275 (24): 18581–5. ISSN 0021-9258. PMID 10849448. doi:10.1074/jbc.C000126200.
[18]
Salgia, R; Sattler M, Pisick E, Li J L, Griffin J D. p210BCR/ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c-Cbl. Exp. Hematol. (UNITED STATES). Feb 1996, 24 (2): 310–3. ISSN 0301-472X. PMID 8641358.
[19]
Skorski, T; Kanakaraj P, Nieborowska-Skorska M, Ratajczak M Z, Wen S C, Zon G, Gewirtz A M, Perussia B, Calabretta B. Phosphatidylinositol-3 kinase activity is regulated by BCR/ABL and is required for the growth of Philadelphia chromosome-positive cells. Blood (UNITED STATES). Jul 1995, 86 (2): 726–36. ISSN 0006-4971. PMID 7606002.
[20]
Heaney, C; Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S, Druker B J. Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation. Blood (UNITED STATES). Jan 1997, 89 (1): 297–306. ISSN 0006-4971. PMID 8978305.
[21]
Kolibaba, K S; Bhat A, Heaney C, Oda T, Druker B J. CRKL binding to BCR-ABL and BCR-ABL transformation. Leuk. Lymphoma (SWITZERLAND). Mar 1999, 33 (1-2): 119–26. ISSN 1042-8194. PMID 10194128. doi:10.3109/10428199909093732.
[22]
Salgia, R; Li J L, Lo S H, Brunkhorst B, Kansas G S, Sobhany E S, Sun Y, Pisick E, Hallek M, Ernst T. Molecular cloning of human paxillin, a focal adhesion protein phosphorylated by P210BCR/ABL. J. Biol. Chem. (UNITED STATES). Mar 1995, 270 (10): 5039–47. ISSN 0021-9258. PMID 7534286. doi:10.1074/jbc.270.10.5039.

外部链接

医学主题词表（MeSH）：BCR+protein,+human

延伸阅读

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

[1] [1]
Entrez Gene: BCR breakpoint cluster region.

[pmid11780146-2] [2]
Zhao X, Ghaffari S, Lodish H, Malashkevich VN, Kim PS. Structure of the Bcr-Abl oncoprotein oligomerization domain. Nat. Struct. Biol. February 2002, 9 (2): 117–20. PMID 11780146. doi:10.1038/nsb747.

[pmid9788431-3] [3]
Liedtke, M; Pandey P, Kumar S, Kharbanda S, Kufe D. Regulation of Bcr-Abl-induced SAP kinase activity and transformation by the SHPTP1 protein tyrosine phosphatase. Oncogene (ENGLAND). Oct 1998, 17 (15): 1889–92. ISSN 0950-9232. PMID 9788431. doi:10.1038/sj.onc.1202117.

[pmid9874796-4] [4]
Takeda, N; Shibuya M, Maru Y. The BCR-ABL oncoprotein potentially interacts with the xeroderma pigmentosum group B protein. Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES). Jan 1999, 96 (1): 203–7. ISSN 0027-8424. PMC 15117 . PMID 9874796. doi:10.1073/pnas.96.1.203.

[pmid10706130-5] [5]
Lionberger, J M; Smithgall T E. The c-Fes protein-tyrosine kinase suppresses cytokine-independent outgrowth of myeloid leukemia cells induced by Bcr-Abl. Cancer Res. (UNITED STATES). Feb 2000, 60 (4): 1097–103. ISSN 0008-5472. PMID 10706130.

[pmid7529874-6] [6]
Maru, Y; Peters K L, Afar D E, Shibuya M, Witte O N, Smithgall T E. Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS. Mol. Cell. Biol. (UNITED STATES). Feb 1995, 15 (2): 835–42. ISSN 0270-7306. PMC 231961 . PMID 7529874.

[pmid9747873-7] [7]
Bai, R Y; Jahn T, Schrem S, Munzert G, Weidner K M, Wang J Y, Duyster J. The SH2-containing adapter protein GRB10 interacts with BCR-ABL. Oncogene (ENGLAND). Aug 1998, 17 (8): 941–8. ISSN 0950-9232. PMID 9747873. doi:10.1038/sj.onc.1202024.

[pmid8757502-8] [8]
Hallek, M; Danhauser-Riedl S, Herbst R, Warmuth M, Winkler A, Kolb H J, Druker B, Griffin J D, Emmerich B, Ullrich A. Interaction of the receptor tyrosine kinase p145c-kit with the p210bcr/abl kinase in myeloid cells. Br. J. Haematol. (ENGLAND). Jul 1996, 94 (1): 5–16. ISSN 0007-1048. PMID 8757502. doi:10.1046/j.1365-2141.1996.6102053.x.

[pmid10887132-9] [9]
Million, R P; Van Etten R A. The Grb2 binding site is required for the induction of chronic myeloid leukemia-like disease in mice by the Bcr/Abl tyrosine kinase. Blood (UNITED STATES). Jul 2000, 96 (2): 664–70. ISSN 0006-4971. PMID 10887132.

[pmid15143164-10] [10]
Million, Ryan P; Harakawa Nari, Roumiantsev Sergei, Varticovski Lyuba, Van Etten Richard A. A direct binding site for Grb2 contributes to transformation and leukemogenesis by the Tel-Abl (ETV6-Abl) tyrosine kinase. Mol. Cell. Biol. (United States). Jun 2004, 24 (11): 4685–95. ISSN 0270-7306. PMC 416425 . PMID 15143164. doi:10.1128/MCB.24.11.4685-4695.2004.

[pmid8112292-11] [11]
Puil, L; Liu J, Gish G, Mbamalu G, Bowtell D, Pelicci P G, Arlinghaus R, Pawson T. Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway. EMBO J. (ENGLAND). Feb 1994, 13 (4): 764–73. ISSN 0261-4189. PMC 394874 . PMID 8112292.

[pmid9178913-12] [12]
Ma, G; Lu D, Wu Y, Liu J, Arlinghaus R B. Bcr phosphorylated on tyrosine 177 binds Grb2. Oncogene (ENGLAND). May 1997, 14 (19): 2367–72. ISSN 0950-9232. PMID 9178913. doi:10.1038/sj.onc.1201053.

[pmid12808105-13] [13]
Radziwill, G; Erdmann R A, Margelisch U, Moelling K. The Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to its PDZ domain. Mol. Cell. Biol. (United States). Jul 2003, 23 (13): 4663–72. ISSN 0270-7306. PMC 164848 . PMID 12808105. doi:10.1128/MCB.23.13.4663-4672.2003.

[pmid12543778-14] [14]
Ling, Xiaoyang; Ma Guozhen, Sun Tong, Liu Jiaxin, Arlinghaus Ralph B. Bcr and Abl interaction: oncogenic activation of c-Abl by sequestering Bcr. Cancer Res. (United States). Jan 2003, 63 (2): 298–303. ISSN 0008-5472. PMID 12543778.

[pmid1712671-15] [15]
Pendergast, A M; Muller A J, Havlik M H, Maru Y, Witte O N. BCR sequences essential for transformation by the BCR-ABL oncogene bind to the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner. Cell (UNITED STATES). Jul 1991, 66 (1): 161–71. ISSN 0092-8674. PMID 1712671. doi:10.1016/0092-8674(91)90148-R.

[pmid12592324-16] [16]
Stanglmaier, M; Warmuth M, Kleinlein I, Reis S, Hallek M. The interaction of the Bcr-Abl tyrosine kinase with the Src kinase Hck is mediated by multiple binding domains. Leukemia (England). Feb 2003, 17 (2): 283–9. ISSN 0887-6924. PMID 12592324. doi:10.1038/sj.leu.2402778.

[pmid10849448-17] [17]
Lionberger, J M; Wilson M B, Smithgall T E. Transformation of myeloid leukemia cells to cytokine independence by Bcr-Abl is suppressed by kinase-defective Hck. J. Biol. Chem. (UNITED STATES). Jun 2000, 275 (24): 18581–5. ISSN 0021-9258. PMID 10849448. doi:10.1074/jbc.C000126200.

[pmid8641358-18] [18]
Salgia, R; Sattler M, Pisick E, Li J L, Griffin J D. p210BCR/ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c-Cbl. Exp. Hematol. (UNITED STATES). Feb 1996, 24 (2): 310–3. ISSN 0301-472X. PMID 8641358.

[pmid7606002-19] [19]
Skorski, T; Kanakaraj P, Nieborowska-Skorska M, Ratajczak M Z, Wen S C, Zon G, Gewirtz A M, Perussia B, Calabretta B. Phosphatidylinositol-3 kinase activity is regulated by BCR/ABL and is required for the growth of Philadelphia chromosome-positive cells. Blood (UNITED STATES). Jul 1995, 86 (2): 726–36. ISSN 0006-4971. PMID 7606002.

[pmid8978305-20] [20]
Heaney, C; Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S, Druker B J. Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation. Blood (UNITED STATES). Jan 1997, 89 (1): 297–306. ISSN 0006-4971. PMID 8978305.

[pmid10194128-21] [21]
Kolibaba, K S; Bhat A, Heaney C, Oda T, Druker B J. CRKL binding to BCR-ABL and BCR-ABL transformation. Leuk. Lymphoma (SWITZERLAND). Mar 1999, 33 (1-2): 119–26. ISSN 1042-8194. PMID 10194128. doi:10.3109/10428199909093732.

[pmid7534286-22] [22]
Salgia, R; Li J L, Lo S H, Brunkhorst B, Kansas G S, Sobhany E S, Sun Y, Pisick E, Hallek M, Ernst T. Molecular cloning of human paxillin, a focal adhesion protein phosphorylated by P210BCR/ABL. J. Biol. Chem. (UNITED STATES). Mar 1995, 270 (10): 5039–47. ISSN 0021-9258. PMID 7534286. doi:10.1074/jbc.270.10.5039.

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