Calcineurin subunit B (CNB)

Calcineurin subunit B is the essential **regulatory subunit** of the heterodimeric serine/threonine protein phosphatase known as **calcineurin** (also called protein phosphatase 2B, PP2B)[1][3][4]. Calcineurin is composed of a catalytic subunit (calcineurin A) and the regulatory subunit B, which contains four calcium-binding EF-hand motifs and is myristoylated[1][2][3]. Calcineurin B confers **calcium sensitivity and regulatory control** to the phosphatase and is required for its activity. This enzyme plays a central role in **calcium-dependent signal transduction pathways**, particularly in immune cells, where it dephosphorylates NFAT, permitting its nuclear translocation and initiation of immune gene transcription (including interleukin 2)[4]. Calcineurin subunit B is a **clinically validated target** for immunosuppressive drugs such as cyclosporin A and tacrolimus[1][3][4]. Mutations or inhibition of calcineurin can impact immune regulation, cardiac hypertrophy, and nervous system function[3][4]. The protein is highly conserved in eukaryotes, with two isoforms in humans encoded by **PPP3R1** and **PPP3R2**[4].

Other names

Protein phosphatase 2B regulatory subunitProtein phosphatase 3 regulatory subunitPPP3R1 (human gene)PPP3R2 (human gene)CNB1 (yeast)CNBCalcium-binding regulatory subunit of calcineurin

Immunosuppressant drugs (such as cyclosporin A and tacrolimus) form complexes with immunophilin proteins (cyclophilin and FK506-binding protein, respectively), which then bind to and inhibit the activity of calcineurin by targeting both the catalytic (A) and regulatory (B) subunits. This inhibition blocks activation of NFAT (nuclear factor of activated T-cells), preventing its translocation to the nucleus and the subsequent transcription of interleukin 2[1][3][4].