PP2BB_RAT
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 03-AUG-2022, entry version 167.
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 (By similarity). Dephosphorylates and activates
CC transcription factor NFATC1 (By similarity). Dephosphorylates and
CC inactivates transcription factor ELK1 (By similarity). Dephosphorylates
CC DARPP32 (By similarity). Negatively regulates MAP3K14/NIK signaling via
CC inhibition of nuclear translocation of the transcription factors RELA
CC and RELB (By similarity). May play a role in skeletal muscle fiber type
CC specification (By similarity). {ECO:0000250|UniProtKB:P16298,
CC 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).
CC {ECO:0000250|UniProtKB:P16298, ECO:0000250|UniProtKB:P48453,
CC 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.ENSRNOP00000010476; -.
DR iPTMnet; P20651; -.
DR PhosphoSitePlus; P20651; -.
DR jPOST; P20651; -.
DR PaxDb; P20651; -.
DR PRIDE; P20651; -.
DR GeneID; 24675; -.
DR KEGG; rno:24675; -.
DR UCSC; RGD:3383; rat.
DR CTD; 5532; -.
DR RGD; 3383; Ppp3cb.
DR eggNOG; KOG0375; Eukaryota.
DR InParanoid; P20651; -.
DR OrthoDB; 463522at2759; -.
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:0007420; P:brain development; IEP: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:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006470; P:protein dephosphorylation; IDA: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 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; PTHR45673; 1.
DR Pfam; PF00149; Metallophos; 1.
DR PRINTS; PR00114; STPHPHTASE.
DR SMART; SM00156; PP2Ac; 1.
DR SUPFAM; SSF56300; SSF56300; 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
