SAM domain of TNK(ACK)-like non-receptor tyrosine-protein kinases
SAM (sterile alpha motif) domain of TNK-like subfamily is a putative protein-protein interaction domain. This subfamily includes TNK1 and TNK2 (also known as ACK1) non-receptor tyrosine-protein kinases. They contain a SAM domain at the N-terminus followed by a catalytic domain and a few other domains. Members of this group are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Deletion of the SAM domain resulted in reduction of Ack1 ability to undergo autophosphorylation and dramatically reduces ubiquitination of Ack1 catalyzed by HECT E3 ubiquitin ligase (Nedd4-1) during EGF-induced Ack1 degradation. It has been suggested that the lysine-rich region in SAM domain might be a major ubiquitination site. Members of this group are also associated with some cancers. Amplification of the Ack1 gene correlates with prostate and lung cancer progression, and Ack1 overexpression increases invasiveness. Oncogenecity of Tnk1 gene apparently depends on cell context; it may play a role in tumor suppression since Tnk1 knockout mice can develop spontaneous tumors.
Jiyao W et al.(2023). "The conserved domain database in 2023.",