The FAM83 family of proteins are anchors for Casein Kinase 1 isoforms through the DUF1669 domain

The Casein Kinase 1 (CK1) family of Ser/Thr protein kinases are implicated in the regulation of many cellular processes, including cell cycle, circadian rhythm, Wnt and Sonic Hedgehog signalling. Regarded as constitutively active kinases, their regulation in cells is critically important but poorly understood. We report here that members of the FAM83 family of uncharacterized proteins are central regulators of CK1 isoforms in cells. The eight members of the FAM83 family (A-H) interact and co-localize with different CK1 alpha, alpha-like, delta and epsilon isoforms. We demonstrate that the interaction with CK1 isoforms is mediated through a number of residues within a conserved domain of unknown function, termed DUF1669, which characterises the FAM83 family. CK1-binding deficient mutants of FAM83 proteins interfere with the subcellular localization of CK1 isoforms as well as FAM83 proteins themselves and their cellular functions. We propose that DUF1669 be renamed the Polypeptide Anchor of CK1 (PACK1) domain.