PPP3CB
Domain
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.
Function
Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (PubMed:19154138, PubMed:25720963, PubMed:26794871, PubMed:32753672). Dephosphorylates TFEB in response to lysosomal Ca(2+) release, resulting in TFEB nuclear translocation and stimulation of lysosomal biogenesis (PubMed:25720963, PubMed:32753672). Dephosphorylates and activates transcription factor NFATC1 (PubMed:19154138). Dephosphorylates and inactivates transcription factor ELK1 (PubMed:19154138). Dephosphorylates DARPP32 (PubMed:19154138). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (By similarity). May play a role in skeletal muscle fiber type specification (By similarity).
Sequence Similarities
Belongs to the PPP phosphatase family. PP-2B subfamily.
Cellular localization
- Cytoplasm
Alternative names
CALNA2, CALNB, CNA2, PPP3CB, Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform, CAM-PRP catalytic subunit, Calmodulin-dependent calcineurin A subunit beta isoform, CNA beta