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UBA domain found in activated Cdc42 kinase 1 (ACK1) and similar proteins ACK1, also called tyrosine kinase non-receptor protein 2, is an intracellular non-receptor tyrosine kinase that specifically interacts with Cdc42 and act as Cdc42 effectors. It forms a signaling complex with Cdc42, p130(Cas), and Crk, and mediates Cdc42-dependent cell migration and signaling to p130(Cas). Ack1 also stimulates prostate tumorigenesis in part by inhibiting the proapoptotic tumor suppressor WW domain containing oxidoreductase (Wwox). Moreover, ACK1 associates directly with the heavy chain of clathrin and further participates in trafficking, underlying an ability to increase receptor-mediated transferrin uptake. It may functions as a regulator of the guanine nucleotide exchange factor Dbl that can activate Rho family proteins. ACK1 consists of an N-terminal tyrosine kinase catalytic domain followed by an SH3 domain, a Cdc42/Rac interactive binding (CRIB) domain, a proline-rich region, and a C-terminal ubiquitin-association (UBA) domain. The proline-rich region of ACK1 is responsible for the binding to the adaptor proteins Nck, Grb2, sorting nexin protein 9 (SH3PX1), and Hck. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",