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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
==Overview==
{{GNF_Protein_box
'''Abelson murine leukemia viral oncogene homolog 1''' also known as '''ABL1''' is a [[protein]] that, in humans, is encoded by the ''ABL1'' [[gene]] (previous symbol ''ABL'') located on [[chromosome 9]]. c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral gene.
| image = PBB_Protein_ABL1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1ab2.
| PDB = {{PDB2|1ab2}}, {{PDB2|1abo}}, {{PDB2|1abq}}, {{PDB2|1awo}}, {{PDB2|1bbz}}, {{PDB2|1fpu}}, {{PDB2|1iep}}, {{PDB2|1ju5}}, {{PDB2|1m52}}, {{PDB2|1opj}}, {{PDB2|1opk}}, {{PDB2|1opl}}, {{PDB2|1zzp}}, {{PDB2|2abl}}, {{PDB2|2e2b}}, {{PDB2|2f4j}}, {{PDB2|2fo0}}, {{PDB2|2g1t}}, {{PDB2|2g2f}}, {{PDB2|2g2h}}, {{PDB2|2g2i}}, {{PDB2|2gqg}}, {{PDB2|2hiw}}, {{PDB2|2hyy}}, {{PDB2|2hz0}}, {{PDB2|2hz4}}, {{PDB2|2hzi}}, {{PDB2|2hzn}}, {{PDB2|2o88}}
| Name = V-abl Abelson murine leukemia viral oncogene homolog 1
| HGNCid = 76
| Symbol = ABL1
| AltSymbols =; ABL; JTK7; bcr/abl; c-ABL; p150; v-abl
| OMIM = 189980
| ECnumber = 
| Homologene = 3783
| MGIid = 87859
| GeneAtlas_image1 = PBB_GE_ABL1_202123_s_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0000287 |text = magnesium ion binding}} {{GNF_GO|id=GO:0003674 |text = molecular_function}} {{GNF_GO|id=GO:0003677 |text = DNA binding}} {{GNF_GO|id=GO:0004713 |text = protein-tyrosine kinase activity}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0008022 |text = protein C-terminus binding}} {{GNF_GO|id=GO:0016740 |text = transferase activity}} {{GNF_GO|id=GO:0030145 |text = manganese ion binding}}
| Component = {{GNF_GO|id=GO:0005575 |text = cellular_component}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005856 |text = cytoskeleton}}
| Process = {{GNF_GO|id=GO:0000074 |text = regulation of progression through cell cycle}} {{GNF_GO|id=GO:0000115 |text = S-phase-specific transcription in mitotic cell cycle}} {{GNF_GO|id=GO:0006298 |text = mismatch repair}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0007155 |text = cell adhesion}} {{GNF_GO|id=GO:0007242 |text = intracellular signaling cascade}} {{GNF_GO|id=GO:0008150 |text = biological_process}} {{GNF_GO|id=GO:0008630 |text = DNA damage response, signal transduction resulting in induction of apoptosis}} {{GNF_GO|id=GO:0018108 |text = peptidyl-tyrosine phosphorylation}} {{GNF_GO|id=GO:0030036 |text = actin cytoskeleton organization and biogenesis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 25
    | Hs_Ensembl = ENSG00000097007
    | Hs_RefseqProtein = NP_005148
    | Hs_RefseqmRNA = NM_005157
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 9
    | Hs_GenLoc_start = 132579089
    | Hs_GenLoc_end = 132752883
    | Hs_Uniprot = P00519
    | Mm_EntrezGene = 11350
    | Mm_Ensembl = ENSMUSG00000026842
    | Mm_RefseqmRNA = NM_009594
    | Mm_RefseqProtein = NP_033724
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 2
    | Mm_GenLoc_start = 31511748
    | Mm_GenLoc_end = 31626236
    | Mm_Uniprot = Q3SYK5
  }}
}}
The '''abl gene''' is associated with [[chronic myelogenous leukemia]].  The abl gene is located on the 9th [[chromosome]].  This gene is activated by being [[translocated]] within the bcr (breakpoint cluster region) [[gene]] on chromosome 22. This new abl/bcr (chimeric) gene encodes a tyrosine kinase which allows the cells to proliferate without being regulated by [[cytokines]].  This in turn allows the cell to become [[cancerous]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
The ''ABL1'' [[Oncogene#Proto-oncogene|proto-oncogene]] encodes a cytoplasmic and nuclear protein [[tyrosine kinase]] that has been implicated in processes of cell differentiation, [[cell division]], [[cell adhesion]], and stress response.  Activity of ABL1 protein is negatively regulated by its [[SH3 domain]], and deletion of the SH3 domain turns ABL1 into an [[oncogene]].  The t(9;22) translocation results in the head-to-tail [[fusion gene|fusion]] of the ''[[BCR gene|BCR]]'' and ''ABL1'' genes, leading to a [[fusion gene]] present in many cases of chronic [[myelogenous leukemia]]. The DNA-binding activity of the ubiquitously expressed ABL1 tyrosine kinase is regulated by [[CDC2]]-mediated [[phosphorylation]], suggesting a cell cycle function for ABL1.  The ''ABL1'' gene is expressed as either a 6- or a 7-kb mRNA transcript, with alternatively spliced first exons spliced to the common exons 2-11.<ref>{{cite web | title = Entrez Gene: ABL1 v-abl Abelson murine leukemia viral oncogene homolog 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=25| accessdate = }}</ref>
| section_title =  
| summary_text = The ABL1 protooncogene encodes a cytoplasmic and nuclear protein [[tyrosine kinase]] that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response.  Activity of c-Abl protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene.  The t(9;22) translocation results in the head-to-tail fusion of the BCR (MIM:151410) and ABL1 genes present in many cases of chronic myelogeneous leukemia. The DNA-binding activity of the ubiquitously expressed ABL1 tyrosine kinase is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function for ABL1.  The ABL1 gene is expressed as either a 6- or 7-kb mRNA transcript, with alternatively spliced first exons spliced to the common exons 2-11.<ref>{{cite web | title = Entrez Gene: ABL1 v-abl Abelson murine leukemia viral oncogene homolog 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=25| accessdate = }}</ref>
}}


This gene is fused with the ''bcr'' gene in a [[Philadelphia chromosome]], the characteristic abnormality in [[chronic myelogenous leukemia]] (CML) and rarely in some other [[leukemia]] forms. The ''bcr-abl'' transcript is also a ''tyrosine kinase'', which activates mediators of the [[cell cycle]] regulation system, leading to a clonal [[myeloproliferative disorder]]. The ''bcr-abl'' protein can be inhibited with the agent [[imatinib|imatinib mesylate]], which occupies the ''TK'' domain and inhibits ''bcr-abl''s influence on the cell cycle.
== Clinical significance ==
[[File:3CS9 Abl1 Nilotinib.png|250px|left|thumb|ABL1 kinase domain (blue) in complex with the second-generation [[Bcr-Abl tyrosine-kinase inhibitor]] [[nilotinib]] (red)]]
Mutations in the ''ABL1'' gene are associated with [[chronic myelogenous leukemia]] (CML).  In CML, the gene is activated by being [[Chromosomal translocation|translocated]] within the [[BCR gene|BCR]] (breakpoint cluster region) [[gene]] on chromosome 22. This new [[fusion gene]], ''BCR-ABL'', encodes an unregulated, cytoplasm-targeted tyrosine kinase that allows the cells to proliferate without being regulated by [[cytokines]]. This, in turn, allows the cell to become [[cancerous]].


==References==
This gene is a partner in a [[fusion gene]] with the ''BCR'' gene in the [[Philadelphia chromosome]], a characteristic abnormality in chronic [[myelogenous leukemia]] (CML) and rarely in some other [[leukemia]] forms. The BCR-ABL transcript encodes a [[tyrosine kinase]], which activates mediators of the [[cell cycle]] regulation system, leading to a clonal [[myeloproliferative disorder]]. The BCR-ABL protein can be inhibited by various small molecules.  One such inhibitor is [[imatinib|imatinib mesylate]], which occupies the tyrosine kinase domain and inhibits BCR-ABL's influence on the [[cell cycle]].  Second generation [[Bcr-Abl tyrosine-kinase inhibitor|BCR-ABL tyrosine-kinase inhibitor]]s are also under development
{{reflist|2}}
to inhibit BCR-ABL mutants resistant to imatinib.


==Further reading==
== See also ==
{{refbegin | 2}}
* [[BCR gene]]
* Clark, Stevens. "Publications." Research Papers 1986-1989. <http://www.humonc.wisc.edu/clark/publications_abstract1x.html>
* Dunitz, Martin. "Chronic Myeloid Leukaemia" 2001. Taylor & Francis, Limited. Published online via Ebrary.com
* Scott K Shore, Ramana V Tantravahi and E Premkumar Reddy. "Transforming pathways activated by the v-Abl tyrosine kinase" 9 Dec. 2002. <http://www.nature.com/onc/journal/v21/n56/full/1206084a.html>
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Shaul Y |title=c-Abl: activation and nuclear targets. |journal=Cell Death Differ. |volume=7 |issue= 1 |pages= 10-6 |year= 2000 |pmid= 10713716 |doi= 10.1038/sj.cdd.4400626 }}
*{{cite journal  | author=Era T |title=Bcr-Abl is a "molecular switch" for the decision for growth and differentiation in hematopoietic stem cells. |journal=Int. J. Hematol. |volume=76 |issue= 1 |pages= 35-43 |year= 2002 |pmid= 12138893 |doi=  }}
*{{cite journal  | author=Pendergast AM |title=The Abl family kinases: mechanisms of regulation and signaling. |journal=Adv. Cancer Res. |volume=85 |issue=  |pages= 51-100 |year= 2003 |pmid= 12374288 |doi=  }}
*{{cite journal  | author=Keung YK, Beaty M, Steward W, ''et al.'' |title=Chronic myelocytic leukemia with eosinophilia, t(9;12)(q34;p13), and ETV6-ABL gene rearrangement: case report and review of the literature. |journal=Cancer Genet. Cytogenet. |volume=138 |issue= 2 |pages= 139-42 |year= 2003 |pmid= 12505259 |doi=  }}
*{{cite journal  | author=Saglio G, Cilloni D |title=Abl: the prototype of oncogenic fusion proteins. |journal=Cell. Mol. Life Sci. |volume=61 |issue= 23 |pages= 2897-911 |year= 2005 |pmid= 15583852 |doi= 10.1007/s00018-004-4271-0 }}
*{{cite journal  | author=Shaul Y, Ben-Yehoyada M |title=Role of c-Abl in the DNA damage stress response. |journal=Cell Res. |volume=15 |issue= 1 |pages= 33-5 |year= 2005 |pmid= 15686624 |doi= 10.1038/sj.cr.7290261 }}
*{{cite journal  | author=Yoshida K |title=Regulation for nuclear targeting of the Abl tyrosine kinase in response to DNA damage. |journal=Adv. Exp. Med. Biol. |volume=604 |issue=  |pages= 155-65 |year= 2007 |pmid= 17695727 |doi=  }}
}}
{{refend}}


==See also==
== References ==
* [[BCR gene]]
{{reflist|2}}


==External links==
== External links ==
* {{MeshName|Genes,+abl}}
* {{MeshName|Genes,+abl}}
* {{OMIM|189980}} (ABL)
* {{OMIM|189980}} (ABL)
* {{MeshName|Abelson+Leukemia+Virus}}
* {{MeshName|Abelson+Leukemia+Virus}}
* [http://www.sdbonline.org/fly/cytoskel/abelson1.htm ''Drosophila'' ''Abl tyrosine kinase'' - The Interactive Fly]
* [http://cmkb.cellmigration.org/report.cgi?report=orth_overview&gene_id=25 ABL1] Info with links in the [http://www.cellmigration.org/index.shtml Cell Migration Gateway]
* [http://AtlasGeneticsOncology.org/Genes/ABL.html ABL1]


{{Tyrosine kinases}}
{{Tyrosine kinases}}
[[Category:Tyrosine kinases]]
[[Category:Tyrosine kinases]]
[[Category:EC 2.7.10]]
[[Category:EC 2.7.10]]
[[Category:genes]]
{{WikiDoc Sources}}

Revision as of 14:52, 2 April 2015

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Abelson murine leukemia viral oncogene homolog 1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL) located on chromosome 9. c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral gene.

Function

The ABL1 proto-oncogene encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response. Activity of ABL1 protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. The t(9;22) translocation results in the head-to-tail fusion of the BCR and ABL1 genes, leading to a fusion gene present in many cases of chronic myelogenous leukemia. The DNA-binding activity of the ubiquitously expressed ABL1 tyrosine kinase is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function for ABL1. The ABL1 gene is expressed as either a 6- or a 7-kb mRNA transcript, with alternatively spliced first exons spliced to the common exons 2-11.[1]

Clinical significance

File:3CS9 Abl1 Nilotinib.png
ABL1 kinase domain (blue) in complex with the second-generation Bcr-Abl tyrosine-kinase inhibitor nilotinib (red)

Mutations in the ABL1 gene are associated with chronic myelogenous leukemia (CML). In CML, the gene is activated by being translocated within the BCR (breakpoint cluster region) gene on chromosome 22. This new fusion gene, BCR-ABL, encodes an unregulated, cytoplasm-targeted tyrosine kinase that allows the cells to proliferate without being regulated by cytokines. This, in turn, allows the cell to become cancerous.

This gene is a partner in a fusion gene with the BCR gene in the Philadelphia chromosome, a characteristic abnormality in chronic myelogenous leukemia (CML) and rarely in some other leukemia forms. The BCR-ABL transcript encodes a tyrosine kinase, which activates mediators of the cell cycle regulation system, leading to a clonal myeloproliferative disorder. The BCR-ABL protein can be inhibited by various small molecules. One such inhibitor is imatinib mesylate, which occupies the tyrosine kinase domain and inhibits BCR-ABL's influence on the cell cycle. Second generation BCR-ABL tyrosine-kinase inhibitors are also under development to inhibit BCR-ABL mutants resistant to imatinib.

See also

References

  1. ↑ "Entrez Gene: ABL1 v-abl Abelson murine leukemia viral oncogene homolog 1".

External links

Retrieved from "https://www.wikidoc.org/index.php?title=Abl_gene&oldid=1081778"