Human inositol 1,4,5-trisphosphate type-1 receptor, InsP₃R1: Structure, function, regulation of expression and chromosomal localization

We have isolated cDNA clones encoding an inositol 1,4,5-trisphosphate receptor type 1 (InsP₃R1) from human uteri and a leukaemic cell line, HL-60. Northern-blot analysis showed that approx. 10 kb of InsP₃R1 mRNA is expressed in human uteri, oviducts and HL-60 cells. The predicted amino acid sequence of human InsP₃R1 (2695 amino acids) has 99% identity with that of the mouse SI^-/SII^- splicing counterpart. Western-blot analysis with anti-(mouse InsP₃R1) antibodies showed that InsP₃R1 protein of human uteri and oviducts of approx 220 kDa is immunostained. Northern-blot analysis of HL-60 cell differentiation along the neutrophilic lineage induced by retinoic acid or dimethylsulphoxide showed an accompanying enhanced expression of InsP₃R1 mRNA. Immunohistochemical analysis of the cerebella of spinocerebellar degeneration patients showed a variable loss of Purkinje cells with an altered pattern of immunostaining. The InsP₃R1 gene (Insp3r1) was localized to the 3P25-26 region of human chromosome 3. The data presented here clearly show that InsP₃R1 exists widely in human tissues and may play critical roles in various kinds of cellular functions.