Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (By similarity). Dephosphorylates and activates transcription factor NFATC1 (By similarity). Dephosphorylates and inactivates transcription factor ELK1 (By similarity). Dephosphorylates DARPP32 (By similarity). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (PubMed:26029823). May play a role in skeletal muscle fiber type specification (PubMed:12773574). H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + phosphate Binds 1 Fe(3+) ion per subunit. Binds 1 zinc ion per subunit. Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A. The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A. Forms a complex composed of a calmodulin-dependent catalytic subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding subunit (also known as calcineurin B). There are three catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded by separate genes (PPP3R1 and PPP3R2). In response to an increase in Ca(2+) intracellular levels, forms a complex composed of PPP3CB/calcineurin A, calcineurin B and calmodulin. Interacts (via calcineurin B binding domain) with regulatory subunit PPP3R1/calcineurin B. Interacts (via calmodulin-binding domain) with calmodulin; the interaction depends on calmodulin binding to Ca(2+). Interacts with SLC12A1 (By similarity). Interacts with SORL1 (PubMed:25967121). Interacts with UNC119 (PubMed:31696965). Interacts with MAP3K14/NIK (via C-terminus and kinase domain) (PubMed:26029823). Interacts with TRAF3 (PubMed:26029823). Interacts with SPATA33 (via PQIIIT motif) (By similarity). Expressed in kidney, in the thick ascending limb epithelium and in the collecting duct, but not in the distal convoluted tubule (at protein level) (PubMed:25967121, PubMed:15509543). Expressed in the brain and the bicep, tricep, soleus and gastrocnemius muscles (at protein level) (PubMed:12773574). Expressed in the salivary gland (at protein level) (PubMed:21435446). Expressed in hippocampal neuron nuclei and adjacent white matter tracts in the CA1 region of the hippocampus (at protein level) (PubMed:10200317). The poly-Pro domain may confer substrate specificity. The autoinhibitory domain prevents access to the catalytic site. The autoinhibitory segment prevents access to the substrate binding site. Possible isomerization of Pro-318 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA. Knockout mice show reduced body weight, independent of changes in muscle weight (PubMed:12773574). Reduced slow and intermediate program type muscle fibers in the biceps, triceps and soleus (PubMed:12773574). Increased expression of fast program type muscle fibers in the soleus muscle (PubMed:12773574). Unlike for protein substrates, PPP3CB activity towards synthetic phosphatase substrate p-nitrophenyl phosphate (pNPP) is increased in presence of the immunosuppressant complex FKBP12-FK506. Belongs to the PPP phosphatase family. PP-2B subfamily.