ABL (gene)

== Structure ==

== Structure ==

The ABL1 protein is a non-receptor tyrosine kinase that contains both Src homology 3 [[SH3 domain|(SH3)]] and Src homology 2 [[SH2 domain|(SH2)]] domains, followed by a tyrosine kinase domain. These domains are involved in regulating its activity and interactions with other proteins. {{Cite journal |last=Hantschel |first=Oliver |last2=Superti-Furga |first2=Giulio |date=2004-01 |title=Regulation of the c-Abl and Bcr–Abl tyrosine kinases |url=https://www.nature.com/articles/nrm1280 |journal=Nature Reviews Molecular Cell Biology |language=en |volume=5 |issue=1 |pages=33–44 |doi=10.1038/nrm1280 |issn=1471-0080 |via=}}

The ABL1 protein is a non-receptor tyrosine kinase that contains both Src homology 3 [[SH3 domain|(SH3)]] and Src homology 2 [[SH2 domain|(SH2)]] domains, followed by a tyrosine kinase domain. These domains are involved in regulating its activity and interactions with other proteins. {{Cite journal |last=Hantschel |first=Oliver |last2=Superti-Furga |first2=Giulio |date=January 2004 |title=Regulation of the c-Abl and Bcr–Abl tyrosine kinases |url=https://www.nature.com/articles/nrm1280 |journal=Nature Reviews Molecular Cell Biology |language=en |volume=5 |issue=1 |pages=33–44 |doi=10.1038/nrm1280 |issn=1471-0080 |via=}}

ABL1 also contains signals that allow it to shuttle between the nucleus and cytoplasm, as well as regions that enable binding to the actin cytoskeleton. {{Cite journal |last=Wang |first=Jean Y. J. |date=2014-04 |title=The Capable ABL: What Is Its Biological Function? |url=https://www.tandfonline.com/doi/full/10.1128/MCB.01454-13 |journal=Molecular and Cellular Biology |language=en |volume=34 |issue=7 |pages=1188–1197 |doi=10.1128/MCB.01454-13 |issn=1098-5549}}

ABL1 also contains signals that allow it to shuttle between the nucleus and cytoplasm, as well as regions that enable binding to the actin cytoskeleton. {{Cite journal |last=Wang |first=Jean Y. J. |date=April 2014 |title=The Capable ABL: What Is Its Biological Function? |url=https://www.tandfonline.com/doi/full/10.1128/MCB.01454-13 |journal=Molecular and Cellular Biology |language=en |volume=34 |issue=7 |pages=1188–1197 |doi=10.1128/MCB.01454-13 |issn=1098-5549}}

== Function ==

== Function ==

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 (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]].

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 (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|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

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 to inhibit BCR-ABL mutants resistant to imatinib.{{cite journal | vauthors = Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL | title = Overriding imatinib resistance with a novel ABL kinase inhibitor | journal = Science | volume = 305 | issue = 5682 | pages = 399–401 | date = July 2004 | pmid = 15256671 | doi = 10.1126/science.1099480 | s2cid = 34972913 | bibcode = 2004Sci...305..399S }}

to inhibit BCR-ABL mutants resistant to imatinib.{{cite journal | vauthors = Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL | title = Overriding imatinib resistance with a novel ABL kinase inhibitor | journal = Science | volume = 305 | issue = 5682 | pages = 399–401 | date = July 2004 | pmid = 15256671 | doi = 10.1126/science.1099480 | s2cid = 34972913 | bibcode = 2004Sci...305..399S }}

== Interactions ==

== Interactions ==