| This gene encodes a receptor tyrosine kinase, which belongs to the insulin receptor superfamily. This protein comprises an extracellular domain, an hydrophobic stretch corresponding to a single pass transmembrane region, and an intracellular kinase domain. It plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. This gene has been found to be rearranged, mutated, or amplified in a series of tumours including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. The chromosomal rearrangements are the most common genetic alterations in this gene, which result in creation of multiple fusion genes in tumourigenesis, including ALK (chromosome 2)/EML4 (chromosome 2), ALK/RANBP2 (chromosome 2), ALK/ATIC (chromosome 2), ALK/TFG (chromosome 3), ALK/NPM1 (chromosome 5), ALK/SQSTM1 (chromosomecatalytic activity:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.,disease:A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2,17)(p23,q25) with ALO17.,disease:A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2,11)(p23,p15) with CARS, translocation t(2,4)(p23,q21) with SEC31A.,disease:A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation t(2,5)(p23,q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin lymphomas.,function:Orphan receptor with a tyrosine-protein kinase activity. Appears to play an important role in the normal development and function of the nervous system. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif.,PTM:N-glycosylated.,similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.,similarity:Contains 1 LDL-receptor class A domain.,similarity:Contains 1 protein kinase domain.,similarity:Contains 2 MAM domains.,subunit:Homodimer. When bound to ligand.,tissue specificity:Expressed in brain and CNS. Also expressed in the small intestine and testis, but not in normal lymphoid cells., |
