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| Class:Id | ReferenceIsoform:201765 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 6 2015;chain:2-524 added on Fri February 6 2015;initiator methionine:1 for 201765 removed on Fri Nov 03 2023;initiator methionine: for 201765 added on Fri Nov 03 2023;initiator methionine: for 201765 removed on Fri Aug 15 2025;initiator methionine:1 for 201765 added on Fri Aug 15 2025 |
| _displayName | UniProt:P16298-2 PPP3CB |
| _timestamp | 2025-08-15 21:10:07 |
| chain | initiator methionine:1 chain:2-524 |
| checksum | 7661183F3C2362C8 |
| comment | 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).CATALYTIC ACTIVITY O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphateCATALYTIC ACTIVITY O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphateCOFACTOR Binds 1 Fe(3+) ion per subunit.COFACTOR Binds 1 zinc ion per subunit.ACTIVITY REGULATION Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+) (PubMed:19154138, PubMed:25720963, PubMed:26794871). 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+) (PubMed:19154138, PubMed:26794871). 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 (PubMed:19154138, PubMed:26794871). 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 (PubMed:19154138, PubMed:26794871).BIOPHYSICOCHEMICAL PROPERTIES 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) (PubMed:26794871). 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) (PubMed:26794871). In response to an increase in Ca(2+) intracellular levels, forms a complex composed of PPP3CB/calcineurin A, calcineurin B and calmodulin (PubMed:26794871). Interacts (via calcineurin B binding domain) with regulatory subunit PPP3R1/calcineurin B (PubMed:26794871). Interacts (via calmodulin-binding domain) with calmodulin; the interaction depends on calmodulin binding to Ca(2+) (PubMed:26794871). Interacts with SLC12A1 (By similarity). Interacts with SORL1 (By similarity). Interacts with UNC119 (By similarity). Interacts with MAP3K14/NIK (via C-terminus and kinase domain) (By similarity). Interacts with TRAF3 (By similarity). Interacts with SPATA33 (via PQIIIT motif) (PubMed:34446558). Interacts with IRGM; promoting its association with TFEB and TFEB dephosphorylation (PubMed:32753672).INTERACTION Additional isoforms seem to exist. Calcineurin A beta isoform consists of at least two isoenzymes that may result from alternative splicing events.DOMAIN The poly-Pro domain may confer substrate specificity.DOMAIN The autoinhibitory domain prevents access to the catalytic site.DOMAIN The autoinhibitory segment prevents access to the substrate binding site.DOMAIN 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.MISCELLANEOUS Unlike for protein substrates, PPP3CB activity towards synthetic phosphatase substrate p-nitrophenyl phosphate (pNPP) is increased in presence of the immunosuppressant complex FKBP12-FK506.SIMILARITY Belongs to the PPP phosphatase family. PP-2B subfamily. |
| created | [InstanceEdit:201796] Jassal, Bijay, 2007-09-20 |
| description | recommendedName: Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform ecNumber evidence="5 7"3.1.3.16 alternativeName: CAM-PRP catalytic subunit alternativeName: Calmodulin-dependent calcineurin A subunit beta isoform shortName evidence="14"CNA beta |
| geneName | PPP3CB CALNA2 CALNB CNA2 |
| identifier | P16298 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing Calmodulin-binding Cytoplasm Hydrolase Iron Metal-binding Phosphoprotein Protein phosphatase Proteomics identification Reference proteome Zinc |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | PPP3CB |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8989152] ENSEMBL:ENSG00000107758 PPP3CB [Homo sapiens] |
| secondaryIdentifier | PP2BB_HUMAN P16299 Q5F2F9 Q8N1F0 Q8N3W4 |
| sequenceLength | 524 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | P16298-2 |
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