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V-abl Abelson murine leukemia viral oncogene homolog 1

PDB rendering based on 1ab2.
Available structures
1ab2, 1abo, 1abq, 1awo, 1bbz, 1fpu, 1iep, 1ju5, 1m52, 1opj, 1opk, 1opl, 1zzp, 2abl, 2e2b, 2f4j, 2fo0, 2g1t, 2g2f, 2g2h, 2g2i, 2gqg, 2hiw, 2hyy, 2hz0, 2hz4, 2hzi, 2hzn, 2o88
Identifiers
Symbols ABL1; ABL; JTK7; bcr/abl; c-ABL; p150; v-abl
External IDs OMIM189980 MGI87859 HomoloGene3783 GeneCards: ABL1 Gene
RNA expression pattern
PBB GE ABL1 202123 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 25 11350
Ensembl ENSG00000097007 ENSMUSG00000026842
UniProt P00519 Q3SYK5
RefSeq (mRNA) NM_005157 NM_009594
RefSeq (protein) NP_005148 NP_033724
Location (UCSC) Chr 9:
132.58 - 132.75 Mb
Chr 2:
31.51 - 31.63 Mb
PubMed search [1] [2]

V-abl Abelson murine leukemia viral oncogene homolog 1 also known as ABL1 is a protein which in humans is encoded by the ABL1 gene located on chromosome 9.[1]

Contents

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 7-kb mRNA transcript, with alternatively spliced first exons spliced to the common exons 2-11.[2]

Clinical significance

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 which 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 with the agent imatinib mesylate, which occupies the TK domain and inhibits BCR-ABL's influence on the cell cycle.

Interactions

Abl gene has been shown to interact with RAD9A,[3] YTHDC1,[4] TrkA,[5][6] NCK1,[7][8] Retinoblastoma protein,[9][10] RAD51,[11] Catalase,[12] PSTPIP1,[13] ABI2,[14][15] DOK1,[16][17] ABL2,[14] PAG1,[18] BRCA1,[19] BCAR1,[20][21] NEDD9,[22][23] CRKL,[24][8][25] PAK2,[26] SORBS2,[27][28] Mdm2,[29] SHC1,[30][31] Ataxia telangiectasia mutated,[32][11][33] EPH receptor B2,[34] GRB10,[35][36] Spectrin, alpha 1,[37] SPTAN1,[37] Grb2,[38][8] TERF1,[33] VAV1,[39] RYBP,[40] Mammalian target of rapamycin,[41] BCR gene,[42][43][31] Cbl gene,[28][7] P73,[44][45] GPX1,[46] RFX1[47] and ABI1.[48][49][50]

See also

References

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