AAK1
AAK1 (AP2 associated kinase 1, also known as KIAA1048) is a serine/threonine protein kinase that phosphorylates a subunit of the AP-2 adaptor complex to regulate clathrin-mediated endocytosis. It also contributes to positive regulation of Notch signalling in mammals. Browse Assay Genie's current range of AAK1 research reagents below, or read on for the biology behind the target.
AAK1 acts in receptor-mediated endocytosis. AP-2 adaptor complexes trigger clathrin assembly, interact with membrane-bound receptors and recruit endocytic accessory factors. The AAK1 protein interacts with and phosphorylates a subunit of the AP-2 complex, which promotes binding of AP-2 to sorting signals in membrane-bound receptors and the subsequent endocytosis of those receptors. Its kinase activity is stimulated by clathrin. AAK1 is also involved in positive regulation of Notch pathway signalling in mammals.
The AAK1 gene encodes a member of the SNF1 subfamily of serine/threonine protein kinases and belongs to the protein kinase superfamily and the Ser/Thr protein kinase family. HGNC places it in the Numb-associated kinase family. UniProt records localisation at the cell membrane, in clathrin-coated pits and at the presynapse. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. The gene is also known by the aliases KIAA1048 and DKFZp686K16132, and mouse and rat each have an Aak1 ortholog.
Because many viruses exploit clathrin-mediated endocytosis, AAK1 has attracted interest in infection biology. It plays a role in the entry of hepatitis C virus and in the lifecycle of other viruses such as Ebola and Dengue, and it regulates clathrin-mediated endocytosis of the rabies virus, facilitating infection. Inhibitors of this kinase are being studied as candidate therapeutics to disrupt viral entry into target cells, including that of SARS-CoV-2.
AAK1 phosphorylates an AP-2 subunit, promoting AP-2 binding to receptor sorting signals and subsequent receptor endocytosis, making it a key regulator of this trafficking route.
By regulating endocytosis, AAK1 contributes to entry of hepatitis C, rabies, Ebola and Dengue viruses, so it is studied as a host factor in infection.
Inhibitors of AAK1 are being studied as candidate therapeutics to disrupt the entry of viruses, including SARS-CoV-2, into target cells.
AAK1 is involved in positive regulation of Notch pathway signalling in mammals, linking endocytic regulation to a core developmental pathway.
AAK1 is a serine/threonine kinase that interacts with and phosphorylates a subunit of the AP-2 complex. This promotes AP-2 binding to sorting signals in membrane receptors and drives receptor endocytosis. Clathrin stimulates its kinase activity, and it also positively regulates Notch signalling in mammals.
AAK1 stands for AP2 associated kinase 1; UniProt lists the protein as AP2-associated protein kinase 1. Aliases include KIAA1048 and DKFZp686K16132. HGNC classes it in the Numb-associated kinase family. Alternatively spliced transcript variants have been described, but their biological validity is undetermined.
Mouse and rat both carry an Aak1 ortholog, so rodent models can be used to study it; check the datasheet of any product for its validated reactivity. AAK1 is linked to viral infection, aiding entry of hepatitis C, rabies, Ebola and Dengue viruses, and is a candidate antiviral target.
Other endocytosis regulators, AP-2 complex components, Numb-associated kinases and Notch pathway proteins with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q2M2I8; product specifications from Assay Genie datasheets.