ID PP2BB_RAT Reviewed; 525 AA. AC P20651; Q6LDJ7; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1991, sequence version 1. DT 27-MAR-2024, entry version 176. DE RecName: Full=Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform; DE EC=3.1.3.16 {ECO:0000250|UniProtKB:P16298}; DE AltName: Full=CAM-PRP catalytic subunit; DE AltName: Full=Calmodulin-dependent calcineurin A subunit beta isoform; DE Short=CNA beta {ECO:0000250|UniProtKB:P16298}; GN Name=Ppp3cb; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2558657; DOI=10.1016/0006-291x(89)92752-6; RA Kuno T., Takeda T., Hirai M., Ito A., Mukai H., Tanaka C.; RT "Evidence for a second isoform of the catalytic subunit of calmodulin- RT dependent protein phosphatase (calcineurin A)."; RL Biochem. Biophys. Res. Commun. 165:1352-1358(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 245-315. RX PubMed=2174876; DOI=10.1016/s0021-9258(18)45767-5; RA Wadzinski B.E., Heasley L.E., Johnson G.L.; RT "Multiplicity of protein serine-threonine phosphatases in PC12 RT pheochromocytoma and FTO-2B hepatoma cells."; RL J. Biol. Chem. 265:21504-21508(1990). RN [3] RP TISSUE SPECIFICITY. RX PubMed=23699505; DOI=10.1523/jneurosci.4288-12.2013; RA Kim S.H., Ryan T.A.; RT "Balance of calcineurin Aalpha and CDK5 activities sets release probability RT at nerve terminals."; RL J. Neurosci. 33:8937-8950(2013). RN [4] RP INTERACTION WITH SLC12A1 AND SORL1, AND TISSUE SPECIFICITY. RX PubMed=25967121; DOI=10.1681/asn.2014070728; RA Borschewski A., Himmerkus N., Boldt C., Blankenstein K.I., McCormick J.A., RA Lazelle R., Willnow T.E., Jankowski V., Plain A., Bleich M., Ellison D.H., RA Bachmann S., Mutig K.; RT "Calcineurin and sorting-related receptor with A-type repeats interact to RT regulate the renal Na(+)-K(+)-2Cl(-) cotransporter."; RL J. Am. Soc. Nephrol. 27:107-119(2016). CC -!- FUNCTION: Calcium-dependent, calmodulin-stimulated protein phosphatase CC which plays an essential role in the transduction of intracellular CC Ca(2+)-mediated signals. Dephosphorylates TFEB in response to lysosomal CC Ca(2+) release, resulting in TFEB nuclear translocation and stimulation CC of lysosomal biogenesis. Dephosphorylates and activates transcription CC factor NFATC1. Dephosphorylates and inactivates transcription factor CC ELK1. Dephosphorylates DARPP32 (By similarity). Negatively regulates CC MAP3K14/NIK signaling via inhibition of nuclear translocation of the CC transcription factors RELA and RELB (By similarity). May play a role in CC skeletal muscle fiber type specification (By similarity). CC {ECO:0000250|UniProtKB:P16298, ECO:0000250|UniProtKB:P48453}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:83421; EC=3.1.3.16; CC Evidence={ECO:0000250|UniProtKB:P16298}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:61977; EC=3.1.3.16; CC Evidence={ECO:0000250|UniProtKB:P16298}; CC -!- COFACTOR: CC Name=Fe(3+); Xref=ChEBI:CHEBI:29034; CC Evidence={ECO:0000250|UniProtKB:P16298}; CC Note=Binds 1 Fe(3+) ion per subunit. {ECO:0000250|UniProtKB:P16298}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:P16298}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P16298}; CC -!- ACTIVITY REGULATION: Activated by Ca(2+)-bound calmodulin following an CC increase in intracellular Ca(2+). At low Ca(2+) concentrations, the CC catalytic subunit (also known as calcineurin A) is inactive and is CC bound to the regulatory subunit (also known as calcineurin B) in which CC only two high-affinity binding sites are occupied by Ca(2+). In CC response to elevated calcium levels, the occupancy of the low-affinity CC sites on calcineurin B by Ca(2+) causes a conformational change of the CC C-terminal regulatory domain of calcineurin A, resulting in the CC exposure of the calmodulin-binding domain and in the partial activation CC of calcineurin A. The subsequent binding of Ca(2+)-bound calmodulin CC leads to the displacement of the autoinhibitory domain from the active CC site and possibly of the autoinhibitory segment from the substrate CC binding site which fully activates calcineurin A. CC {ECO:0000250|UniProtKB:P16298}. CC -!- SUBUNIT: Forms a complex composed of a calmodulin-dependent catalytic CC subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding CC subunit (also known as calcineurin B). There are three catalytic CC subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) CC and two regulatory subunits which are also encoded by separate genes CC (PPP3R1 and PPP3R2). In response to an increase in Ca(2+) intracellular CC levels, forms a complex composed of PPP3CB/calcineurin A, calcineurin B CC and calmodulin. Interacts (via calcineurin B binding domain) with CC regulatory subunit PPP3R1/calcineurin B. Interacts (via calmodulin- CC binding domain) with calmodulin; the interaction depends on calmodulin CC binding to Ca(2+). Interacts with SLC12A1 (PubMed:25967121). Interacts CC with SORL1 (PubMed:25967121). Interacts with UNC119 (By similarity). CC Interacts with MAP3K14/NIK (via C-terminus and kinase domain) (By CC similarity). Interacts with TRAF3 (By similarity). Interacts with CC SPATA33 (via PQIIIT motif) (By similarity). Interacts with IRGM; CC promoting its association with TFEB and TFEB dephosphorylation (By CC similarity). {ECO:0000250|UniProtKB:P16298, CC ECO:0000250|UniProtKB:P48453, ECO:0000269|PubMed:25967121}. CC -!- INTERACTION: CC P20651; Q9WVC7: Akap6; NbExp=2; IntAct=EBI-7400670, EBI-7559840; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P16298}. CC -!- TISSUE SPECIFICITY: Expressed in kidney (at protein level) CC (PubMed:25967121). Expressed in hippocampal presynaptic termini (at CC protein level) (PubMed:23699505). {ECO:0000269|PubMed:23699505, CC ECO:0000269|PubMed:25967121}. CC -!- DOMAIN: The poly-Pro domain may confer substrate specificity. CC {ECO:0000250|UniProtKB:P16298}. CC -!- DOMAIN: The autoinhibitory domain prevents access to the catalytic CC site. {ECO:0000250|UniProtKB:P16298}. CC -!- DOMAIN: The autoinhibitory segment prevents access to the substrate CC binding site. {ECO:0000250|UniProtKB:P16298}. CC -!- DOMAIN: Possible isomerization of Pro-318 within the SAPNY motif CC triggers a conformation switch which affects the organization and thus CC accessibility of the active site and the substrate binding region CC (PxIxIF motif). The trans- to cis-transition may favor calcineurin A CC activation and substrate binding. The reverse cis- to trans-transition CC may be enhanced by peptidyl-prolyl isomerases such as PPIA. CC {ECO:0000250|UniProtKB:Q08209}. CC -!- MISCELLANEOUS: Unlike for protein substrates, PPP3CB activity towards CC synthetic phosphatase substrate p-nitrophenyl phosphate (pNPP) is CC increased in presence of the immunosuppressant complex FKBP12-FK506. CC {ECO:0000250|UniProtKB:P16298}. CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-2B subfamily. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M31809; AAA40848.1; -; mRNA. DR EMBL; D90036; BAA14084.1; -; mRNA. DR EMBL; M58441; AAA41915.1; -; mRNA. DR PIR; A33794; A33794. DR RefSeq; NP_058738.1; NM_017042.2. DR AlphaFoldDB; P20651; -. DR SMR; P20651; -. DR BioGRID; 246807; 3. DR CORUM; P20651; -. DR DIP; DIP-66N; -. DR IntAct; P20651; 5. DR MINT; P20651; -. DR STRING; 10116.ENSRNOP00000074339; -. DR iPTMnet; P20651; -. DR PhosphoSitePlus; P20651; -. DR jPOST; P20651; -. DR PaxDb; 10116-ENSRNOP00000010476; -. DR GeneID; 24675; -. DR KEGG; rno:24675; -. DR UCSC; RGD:3383; rat. DR AGR; RGD:3383; -. DR CTD; 5532; -. DR RGD; 3383; Ppp3cb. DR eggNOG; KOG0375; Eukaryota. DR InParanoid; P20651; -. DR OrthoDB; 1488111at2759; -. DR PhylomeDB; P20651; -. DR Reactome; R-RNO-2025928; Calcineurin activates NFAT. DR Reactome; R-RNO-2871809; FCERI mediated Ca+2 mobilization. DR Reactome; R-RNO-4086398; Ca2+ pathway. DR Reactome; R-RNO-5607763; CLEC7A (Dectin-1) induces NFAT activation. DR PRO; PR:P20651; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005955; C:calcineurin complex; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:RGD. DR GO; GO:0045202; C:synapse; IDA:SynGO. DR GO; GO:0030315; C:T-tubule; ISO:RGD. DR GO; GO:0030018; C:Z disc; ISO:RGD. DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB. DR GO; GO:0004723; F:calcium-dependent protein serine/threonine phosphatase activity; IDA:RGD. DR GO; GO:0005516; F:calmodulin binding; IDA:RGD. DR GO; GO:0033192; F:calmodulin-dependent protein phosphatase activity; ISS:UniProtKB. DR GO; GO:0019899; F:enzyme binding; ISS:UniProtKB. DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0046983; F:protein dimerization activity; ISO:RGD. DR GO; GO:0030346; F:protein phosphatase 2B binding; ISS:UniProtKB. DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISO:RGD. DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD. DR GO; GO:0097720; P:calcineurin-mediated signaling; ISS:UniProtKB. DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; ISO:RGD. DR GO; GO:0017156; P:calcium-ion regulated exocytosis; ISS:UniProtKB. DR GO; GO:0007507; P:heart development; ISO:RGD. DR GO; GO:0031987; P:locomotion involved in locomotory behavior; ISO:RGD. DR GO; GO:0001946; P:lymphangiogenesis; ISO:RGD. DR GO; GO:0046716; P:muscle cell cellular homeostasis; IEP:RGD. DR GO; GO:0023057; P:negative regulation of signaling; ISS:UniProtKB. DR GO; GO:0001915; P:negative regulation of T cell mediated cytotoxicity; ISO:RGD. DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:UniProtKB. DR GO; GO:1905673; P:positive regulation of lysosome organization; ISO:RGD. DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:RGD. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD. DR GO; GO:0050796; P:regulation of insulin secretion; IDA:UniProtKB. DR GO; GO:1900242; P:regulation of synaptic vesicle endocytosis; ISO:RGD. DR GO; GO:0001975; P:response to amphetamine; IEP:RGD. DR GO; GO:0034097; P:response to cytokine; ISO:RGD. DR GO; GO:0048741; P:skeletal muscle fiber development; ISS:UniProtKB. DR GO; GO:0030217; P:T cell differentiation; ISO:RGD. DR GO; GO:0043029; P:T cell homeostasis; ISO:RGD. DR GO; GO:0001913; P:T cell mediated cytotoxicity; ISO:RGD. DR CDD; cd07416; MPP_PP2B; 1. DR Gene3D; 3.60.21.10; -; 1. DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH. DR InterPro; IPR029052; Metallo-depent_PP-like. DR InterPro; IPR041751; MPP_PP2B. DR InterPro; IPR043360; PP2B. DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase. DR PANTHER; PTHR45673; SERINE/THREONINE-PROTEIN PHOSPHATASE 2B CATALYTIC SUBUNIT 1-RELATED; 1. DR PANTHER; PTHR45673:SF7; SERINE_THREONINE-PROTEIN PHOSPHATASE 2B CATALYTIC SUBUNIT BETA ISOFORM; 1. DR Pfam; PF00149; Metallophos; 1. DR PRINTS; PR00114; STPHPHTASE. DR SMART; SM00156; PP2Ac; 1. DR SUPFAM; SSF56300; Metallo-dependent phosphatases; 1. DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1. PE 1: Evidence at protein level; KW Acetylation; Calmodulin-binding; Cytoplasm; Hydrolase; Iron; Metal-binding; KW Phosphoprotein; Protein phosphatase; Reference proteome; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P16298" FT CHAIN 2..525 FT /note="Serine/threonine-protein phosphatase 2B catalytic FT subunit beta isoform" FT /id="PRO_0000058827" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 65..356 FT /note="Catalytic" FT /evidence="ECO:0000250|UniProtKB:P16298" FT REGION 357..379 FT /note="Calcineurin B binding" FT /evidence="ECO:0000250|UniProtKB:P16298" FT REGION 402..416 FT /note="Calmodulin-binding" FT /evidence="ECO:0000250|UniProtKB:P16298" FT REGION 417..424 FT /note="Autoinhibitory segment" FT /evidence="ECO:0000250|UniProtKB:P16298" FT REGION 475..497 FT /note="Autoinhibitory domain" FT /evidence="ECO:0000250|UniProtKB:P16298" FT MOTIF 316..320 FT /note="SAPNY motif" FT /evidence="ECO:0000250|UniProtKB:Q08209" FT ACT_SITE 160 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:Q08209" FT BINDING 99 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000250|UniProtKB:P16298" FT BINDING 101 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000250|UniProtKB:P16298" FT BINDING 127 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000250|UniProtKB:P16298" FT BINDING 127 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P16298" FT BINDING 159 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P16298" FT BINDING 208 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P16298" FT BINDING 290 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P16298" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:P16298" FT MOD_RES 479 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P48453" SQ SEQUENCE 525 AA; 59113 MW; 5E66AF3100BE3987 CRC64; MAAPEPARAA PPPPPPPPPP LGADRVVKAV PFPPTHRLTS EEVFDMDGIP RVDVLKNHLV KEGRVDEEIA LRIINEGAAI LRREKTMIEV EAPITVCGDI HGQFFDLMKL FEVGGSPANT RYLFLGDYVD RGYFSIECVL YLWVLKILYP STLFLLRGNH ECRHLTEYFT FKQECKIKYS ERVYEACMEA FDSLPLAALL NQQFLCVHGG LSPEIHTLDD IRRLDRFKEP PAFGPMCDLL WSDPSEDFGN EKSQEHFSHN TVRGCSYFYN YPAVCEFLQN NNLLSIIRAH EAQDAGYRMY RKSQTTGFPS LITIFSAPNY LDVYNNKAAV LKYENNVMNI RQFNCSPHPY WLPNFMDVFT WSLPFVGEKV TEMLVNVLSI CSDDELMTEG EDQFDVGSAA ARKEIIRNKI RAIGKMARVF SVLREESESV LTLKGLTPTG MLPSGVLAGG RQTLQSATVE AIEAEKAIRG SSPPHRICSF EEAKGLDRIN ERMPPRKDAV QQDGFNSLNT AHTTENHGTG NHSAQ //