Members of the casein kinase 1 (CK1) family of serine-threonine protein kinases are implicated in the regulation of many cellular processes, including the cell cycle, circadian rhythms, and Wnt and Hedgehog signaling. Because these kinases exhibit constitutive activity in biochemical assays, it is likely that their activity in cells is controlled by subcellular localization, interactions with inhibitory proteins, targeted degradation, or combinations of these mechanisms. We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A to FAM83H) interacted with the α and α-like isoforms of CK1; FAM83A, FAM83B, FAM83E, and FAM83H also interacted with the δ and ε isoforms of CK1. We detected no interaction between any FAM83 member and the related CK1γ1, CK1γ2, and CK1γ3 isoforms. Each FAM83 protein exhibited a distinct pattern of subcellular distribution and colocalized with the CK1 isoform(s) to which it bound. The interaction of FAM83 proteins with CK1 isoforms was mediated by the conserved domain of unknown function 1669 (DUF1669) that characterizes the FAM83 family. Mutations in FAM83 proteins that prevented them from binding to CK1 interfered with the proper subcellular localization and cellular functions of both the FAM83 proteins and their CK1 binding partners. On the basis of its function, we propose that DUF1669 be renamed the polypeptide anchor of CK1 domain.

丝氨酸-苏氨酸蛋白激酶酪蛋白激酶 1 (CK1) 家族的成员参与许多细胞过程的调节，包括细胞周期、昼夜节律以及 Wnt 和 Hedgehog 信号传导。由于这些激酶在生化测定中表现出组成型活性，因此它们在细胞中的活性很可能是由亚细胞定位、与抑制蛋白的相互作用、靶向降解或这些机制的组合控制的。我们鉴定出 FAM83 蛋白家族的成员是细胞中 CK1 的伴侣。FAM83 家族的所有八个成员（FAM83A 至 FAM83H）均与 CK1 的 α 和 α 样亚型相互作用；FAM83A、FAM83B、FAM83E 和 FAM83H 还与 CK1 的 δ 和 ε 同工型相互作用。我们没有检测到任何 FAM83 成员与相关 CK1γ1、CK1γ2 和 CK1γ3 亚型之间存在相互作用。每个 FAM83 蛋白都表现出独特的亚细胞分布模式，并与其结合的 CK1 同工型共定位。FAM83 蛋白与 CK1 同工型的相互作用是由 FAM83 家族特征的未知功能保守域 1669 (DUF1669) 介导的。FAM83 蛋白中的突变阻止它们与 CK1 结合，从而干扰了 FAM83 蛋白及其 CK1 结合配偶体的正确亚细胞定位和细胞功能。根据其功能，我们建议将DUF1669更名为CK1结构域的多肽锚。