Laboratoire de Génétique Fonctionnelle, GIGA-Research Centre, Building B34, CHU Sart-Tilman, Université de Liège, Avenue de l'Hôpital 11, 4000-Liège, Belgium; Secteur de Biochimie Métabolique Vétérinaire, Département des Sciences Fonctionnelles, Faculté de Médecine Vétérinaire, Building B42, Université de Liège, Quartier Vallée 2, Avenue de Cureghem 7A-7D, 4000-Liège, Belgium.
Laboratoire de Génétique Fonctionnelle, GIGA-Research Centre, Building B34, CHU Sart-Tilman, Université de Liège, Avenue de l'Hôpital 11, 4000-Liège, Belgium.
Adv Biol Regul. 2021 Jan;79:100760. doi: 10.1016/j.jbior.2020.100760. Epub 2020 Oct 10.
INPP5K (Inositol Polyphosphate 5-Phosphatase K, or SKIP (for Skeletal muscle and Kidney enriched Inositol Phosphatase) is a member of the phosphoinositide 5-phosphatases family. Its protein structure is comprised of a N-terminal catalytic domain which hydrolyses both PtdIns(4,5)P2 and PtdIns(3,4,5)P3, followed by a SKICH domain at the C-terminus which is responsible for protein-protein interactions and subcellular localization of INPP5K. Strikingly, INPP5K is mostly concentrated in the endoplasmic reticulum, although it is also detected at the plasma membrane, in the cytosol and the nucleus. Recently, mutations in INPP5K have been detected in patients with a rare form of autosomal recessive congenital muscular dystrophy with cataract, short stature and intellectual disability. INPP5K functions extend from control of insulin signaling, endoplasmic reticulum stress response and structural integrity, myoblast differentiation, cytoskeleton organization, cell adhesion and migration, renal osmoregulation, to cancer. The goal of this review is thus to summarize and comment recent and less recent data in the literature on INPP5K, in particular on the structure, expression, intracellular localization, interactions and functions of this specific member of the 5-phosphatases family.
INPP5K（肌醇多磷酸 5-磷酸酶 K，或 SKIP（骨骼肌和肾脏富含肌醇磷酸酶）是磷酸肌醇 5-磷酸酶家族的成员。其蛋白质结构由 N 端催化结构域组成，该结构域水解 PtdIns(4,5)P2 和 PtdIns(3,4,5)P3，然后在 C 端是 SKICH 结构域，负责蛋白质-蛋白质相互作用和 INPP5K 的亚细胞定位。值得注意的是，INPP5K 主要集中在内质网，尽管它也在质膜、细胞质和核中检测到。最近，在患有一种罕见的常染色体隐性先天性肌肉营养不良伴白内障、身材矮小和智力障碍的患者中检测到 INPP5K 突变。INPP5K 的功能从控制胰岛素信号、内质网应激反应和结构完整性、成肌细胞分化、细胞骨架组织、细胞黏附和迁移、肾脏渗透压调节，到癌症。因此，本综述的目的是总结和评论文献中关于 INPP5K 的最新和较旧的数据，特别是关于该 5-磷酸酶家族特定成员的结构、表达、细胞内定位、相互作用和功能。
