WordNet

the 2nd letter of the Roman alphabet (同)b
the blood group whose red cells carry the B antigen (同)type_B, group B
(genetics) a segment of DNA that is involved in producing a polypeptide chain; it can include regions preceding and following the coding DNA as well as introns between the exons; it is considered a unit of heredity; "genes were formerly called factors" (同)cistron, factor
before the Christian era; used following dates before the supposed year Christ was born; "in 200 BC" (同)B.C., before Christ
informal term for information; "give me the gen on your new line of computers"

PrepTutorEJDIC

遺伝子

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/08/04 17:33:38」(JST)

wiki en

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.

Function

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.^[3]

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.^[4]

Structure

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.^[5]

Interactions

BCR gene has been shown to interact with:

Abl gene,^[6]^[7]^[8]
CD117,^[9]
CRKL^[10]^[11]^[12]^[13]
FES,^[14]^[15]
Grb2,^[6]^[10]^[11]^[15]^[16]^[17]
GRB10,^[10]
HCK,^[18]^[19]
MLLT4,^[20]
PXN,^[21]^[22]
PIK3CG,^[10]^[21]^[23]
PTPN6,^[24]
PTPRT(PTPrho)^[25]
SOS1,^[6]^[15] and
XPB.^[26]

References

^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ "Entrez Gene: Breakpoint cluster region".
^ "Entrez Gene: BCR breakpoint cluster region".
^ 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.
^ ^a ^b ^c Puil L, Liu J, Gish G, Mbamalu G, Bowtell D, Pelicci PG, Arlinghaus R, Pawson T (February 1994). "Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway". EMBO J. 13 (4): 764–73. PMC 394874 . PMID 8112292.
^ 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.
^ 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.
^ Hallek M, Danhauser-Riedl S, Herbst R, Warmuth M, Winkler A, Kolb HJ, Druker B, Griffin JD, Emmerich B, Ullrich A (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.
^ ^a ^b ^c ^d Bai RY, Jahn T, Schrem S, Munzert G, Weidner KM, Wang JY, Duyster J (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.
^ ^a ^b 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.
^ Heaney C, Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S, Druker BJ (January 1997). "Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation". Blood. 89 (1): 297–306. PMID 8978305.
^ 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.
^ 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.
^ ^a ^b ^c 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b 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.
^ Salgia R, Li JL, Lo SH, Brunkhorst B, Kansas GS, Sobhany ES, Sun Y, Pisick E, Hallek M, Ernst T (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.
^ Skorski T, Kanakaraj P, Nieborowska-Skorska M, Ratajczak MZ, Wen SC, Zon G, Gewirtz AM, Perussia B, Calabretta B (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.
^ 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.
^ Park AR, Oh D, Lim SH, Choi J, Moon J, Yu DY, Park SG, Heisterkamp N, Kim E, Myung PK, Lee JR (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.
^ 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.

External links

BCR protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
Human BCR genome location and BCR gene details page in the UCSC Genome Browser.

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

UpToDate Contents

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1. 血液悪性腫瘍およびリンパ悪性腫瘍の遺伝的異常 genetic abnormalities in hematologic and lymphoid malignancies
2. 慢性骨髄性白血病の分子遺伝学 molecular genetics of chronic myeloid leukemia
3. 慢性骨髄性白血病の細胞生物学および分子生物学 cellular and molecular biology of chronic myeloid leukemia
4. 急性リンパ芽球性白血病における細胞遺伝学および分子遺伝学 cytogenetics and molecular genetics in acute lymphoblastic leukemia
5. 慢性骨髄性白血病の臨床症状および診断 clinical manifestations and diagnosis of chronic myeloid leukemia

English Journal

Impact of the BCR-ABL1 fusion transcripts on different responses to Imatinib and disease recurrence in Iranian patients with Chronic Myeloid Leukemia.

Rostami G1, Hamid M2, Jalaeikhoo H3.
Gene.Gene.2017 Sep 5;627:202-206. doi: 10.1016/j.gene.2017.06.018. Epub 2017 Jun 13.
PMID 28627443

BCR-ABL1-like acute lymphoblastic leukaemia: From bench to bedside.

Boer JM1, den Boer ML2.
European journal of cancer (Oxford, England : 1990).Eur J Cancer.2017 Sep;82:203-218. doi: 10.1016/j.ejca.2017.06.012. Epub 2017 Jul 12.
PMID 28709134

The clinical characteristics and prognostic significance of AID, miR-181b, and miR-155 expression in adult patients with de novo B-cell acute lymphoblastic leukemia.

Zhou G1, Cao Y1, Dong W1, Lin Y1, Wang Q2, Wu W1, Hua X1, Ling Y1, Xie X1, Hu S3, Cen J4, Gu W1.
Leukemia & lymphoma.Leuk Lymphoma.2017 Sep;58(9):1-9. doi: 10.1080/10428194.2017.1283028. Epub 2017 Jan 31.
PMID 28140712

Japanese Journal

慢性骨髄性白血病とケモカイン

臨床血液 57(2), 129-136, 2016
NAID 130005132715

Modification of Gene Expression, Proliferation, and Function of OP9 Stroma Cells by Bcr-Abl-Expressing Leukemia Cells.

PLOS ONE 10(7), 2015-07-28
NAID 120005678188

自己免疫疾患におけるT細胞-B細胞相互作用の重要性

日本臨床免疫学会会誌 38(5), 398-402, 2015
NAID 130005116549

★リンクテーブル★

リンク元	「BCR遺伝子」
関連記事	「B」「BC」

「BCR遺伝子」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Bcr-Abl oncoprotein oligomerisation domain
	structure of the bcr-abl oncoprotein oligomerization domain
Identifiers
Symbol	Bcr-Abl_Oligo
Pfam	PF09036
InterPro	IPR015123
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

BCR
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1K1F, 2AIN
Identifiers
Aliases	BCR, Bcr, 5133400C09Rik, AI561783, AI853148, mKIAA3017, ALL, BCR1, CML, D22S11, D22S662, PHL, RhoGEF and GTPase activating protein, BCR gene
External IDs	MGI: 88141 HomoloGene: 3192 GeneCards: BCR
Gene ontology
Molecular function	• transferase activity; • nucleotide binding; • guanyl-nucleotide exchange factor activity; • kinase activity; • protein serine/threonine kinase activity; • protein binding; • Rho guanyl-nucleotide exchange factor activity; • enzyme binding; • protein tyrosine kinase activity; • ATP binding; • GTPase activator activity;
Cellular component	• cytoplasm; • cytosol; • postsynaptic membrane; • membrane; • postsynaptic density of dendrite; • plasma membrane; • synapse; • protein complex; • cell junction; • extracellular exosome; • intracellular;
Biological process	• positive regulation of phagocytosis; • intracellular signal transduction; • neuromuscular process controlling balance; • phosphorylation; • regulation of cell cycle; • negative regulation of blood vessel remodeling; • protein phosphorylation; • negative regulation of cellular extravasation; • response to lipopolysaccharide; • brain development; • regulation of vascular permeability; • negative regulation of cell migration; • negative regulation of neutrophil degranulation; • inner ear morphogenesis; • protein autophosphorylation; • platelet-derived growth factor receptor signaling pathway; • regulation of Rho protein signal transduction; • regulation of small GTPase mediated signal transduction; • negative regulation of inflammatory response; • actin cytoskeleton organization; • signal transduction; • peptidyl-tyrosine phosphorylation; • renal system process; • homeostasis of number of cells; • regulation of nitrogen compound metabolic process; • definitive hemopoiesis; • negative regulation of respiratory burst; • intracellular protein transmembrane transport; • cellular response to lipopolysaccharide; • negative regulation of reactive oxygen species metabolic process; • positive regulation of GTPase activity;
	Sources:Amigo / QuickGO
Orthologs
	613
	110279
	ENSG00000186716
	ENSMUSG00000009681
	P11274
	Q6PAJ1
	NM_004327; NM_021574
	NM_001081412
	NP_004318; NP_067585
	NP_001074881
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★]

英: BCR gene
関: フィラデルフィア染色体、9番染色体

「B」

　　[★]

気管分岐部下緑
補体のalternative pathwayに関わる蛋白質

Mg2+存在下でC3, B, Dが反応してC3bBbとなり、これがC3転換酵素(C3bBb)あるいはC5転換酵素(C3bBb3b)を形成する。これらはP(properdin)と結合して活性化し、それぞれC3、C5を活性化する

「BC」

　　[★] バシトラシン bacitracin

[1] "Human PubMed Reference:".

[2] "Mouse PubMed Reference:".

[entrez-3] "Entrez Gene: Breakpoint cluster region".

[4] "Entrez Gene: BCR breakpoint cluster region".

[pmid11780146-5] 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.

[pmid8112292-6] Puil L, Liu J, Gish G, Mbamalu G, Bowtell D, Pelicci PG, Arlinghaus R, Pawson T (February 1994). "Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway". EMBO J. 13 (4): 764–73. PMC 394874 . PMID 8112292.

[pmid12543778-7] 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.

[pmid1712671-8] 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.

[pmid8757502-9] Hallek M, Danhauser-Riedl S, Herbst R, Warmuth M, Winkler A, Kolb HJ, Druker B, Griffin JD, Emmerich B, Ullrich A (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.

[pmid9747873-10] Bai RY, Jahn T, Schrem S, Munzert G, Weidner KM, Wang JY, Duyster J (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.

[pmid15143164-11] 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.

[pmid8978305-12] Heaney C, Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S, Druker BJ (January 1997). "Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation". Blood. 89 (1): 297–306. PMID 8978305.

[pmid10194128-13] 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.

[pmid10706130-14] 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.

[pmid7529874-15] 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.

[pmid10887132-16] 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.

[pmid9178913-17] 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.

[pmid12592324-18] 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.

[pmid10849448-19] 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.

[pmid12808105-20] 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.

[pmid8641358-21] 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.

[pmid7534286-22] Salgia R, Li JL, Lo SH, Brunkhorst B, Kansas GS, Sobhany ES, Sun Y, Pisick E, Hallek M, Ernst T (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.

[pmid7606002-23] Skorski T, Kanakaraj P, Nieborowska-Skorska M, Ratajczak MZ, Wen SC, Zon G, Gewirtz AM, Perussia B, Calabretta B (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.

[pmid9788431-24] 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.

[pmid22767509-25] Park AR, Oh D, Lim SH, Choi J, Moon J, Yu DY, Park SG, Heisterkamp N, Kim E, Myung PK, Lee JR (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.

[pmid9874796-26] 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.

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案内

案内

BCR gene