PP2BB_HUMAN
ID PP2BB_HUMAN Reviewed; 524 AA.
AC P16298; P16299; Q5F2F9; Q8N1F0; Q8N3W4;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform;
DE EC=3.1.3.16 {ECO:0000269|PubMed:19154138, ECO:0000269|PubMed:26794871};
DE AltName: Full=CAM-PRP catalytic subunit;
DE AltName: Full=Calmodulin-dependent calcineurin A subunit beta isoform;
DE Short=CNA beta {ECO:0000305|PubMed:26794871};
GN Name=PPP3CB; Synonyms=CALNA2, CALNB, CNA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=2556704; DOI=10.1073/pnas.86.23.9183;
RA Guerini D., Klee C.B.;
RT "Cloning of human calcineurin A: evidence for two isozymes and
RT identification of a polyproline structural domain.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:9183-9187(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Teratocarcinoma;
RX PubMed=1848109; DOI=10.1016/0167-4781(91)90069-x;
RA McPartlin A.E., Barker H.M., Cohen P.T.W.;
RT "Identification of a third alternatively spliced cDNA encoding the
RT catalytic subunit of protein phosphatase 2B beta.";
RL Biochim. Biophys. Acta 1088:308-310(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 2-ALA--PRO-21.
RX PubMed=19154138; DOI=10.1021/bi8019355;
RA Kilka S., Erdmann F., Migdoll A., Fischer G., Weiwad M.;
RT "The proline-rich N-terminal sequence of calcineurin Abeta determines
RT substrate binding.";
RL Biochemistry 48:1900-1910(2009).
RN [8]
RP INTERACTION WITH SPATA33.
RX PubMed=34446558; DOI=10.1073/pnas.2106673118;
RA Miyata H., Oura S., Morohoshi A., Shimada K., Mashiko D., Oyama Y.,
RA Kaneda Y., Matsumura T., Abbasi F., Ikawa M.;
RT "SPATA33 localizes calcineurin to the mitochondria and regulates sperm
RT motility in mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.23 ANGSTROMS) IN COMPLEX WITH PPP3R1; IRON AND
RP ZINC, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH
RP CALMODULIN, AND MUTAGENESIS OF LEU-352; PRO-353; MET-356; 357-ASP--GLN-524;
RP TRP-361; PHE-365; 397-SER--GLN-524; 415-MET--GLN-524; ARG-417; VAL-418;
RP PHE-419; SER-420; VAL-421; LEU-422; ARG-423 AND 451-GLN--GLN-524.
RX PubMed=26794871; DOI=10.1038/cr.2016.14;
RA Li S.J., Wang J., Ma L., Lu C., Wang J., Wu J.W., Wang Z.X.;
RT "Cooperative autoinhibition and multi-level activation mechanisms of
RT calcineurin.";
RL Cell Res. 26:336-349(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 (PubMed:19154138, PubMed:26794871).
CC Dephosphorylates and activates transcription factor NFATC1
CC (PubMed:19154138). Dephosphorylates and inactivates transcription
CC factor ELK1 (PubMed:19154138). Dephosphorylates DARPP32
CC (PubMed:19154138). 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:P48453,
CC ECO:0000269|PubMed:19154138, ECO:0000269|PubMed:26794871}.
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:0000269|PubMed:19154138, ECO:0000269|PubMed:26794871};
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:0000269|PubMed:19154138, ECO:0000269|PubMed:26794871};
CC -!- COFACTOR:
CC Name=Fe(3+); Xref=ChEBI:CHEBI:29034;
CC Evidence={ECO:0000269|PubMed:26794871};
CC Note=Binds 1 Fe(3+) ion per subunit. {ECO:0000269|PubMed:26794871};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:26794871};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:26794871};
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:0000269|PubMed:19154138, ECO:0000269|PubMed:26794871}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.69 uM for NFATC1 {ECO:0000269|PubMed:19154138};
CC KM=0.7 uM for DARPP32 {ECO:0000269|PubMed:19154138};
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 (By similarity). Interacts
CC with SORL1 (By similarity). 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) (PubMed:34446558).
CC {ECO:0000250|UniProtKB:P20651, ECO:0000250|UniProtKB:P48453,
CC ECO:0000269|PubMed:26794871, ECO:0000269|PubMed:34446558}.
CC -!- INTERACTION:
CC P16298; P14316: IRF2; NbExp=2; IntAct=EBI-1759540, EBI-2866589;
CC P16298; Q99J34: Irak1; Xeno; NbExp=2; IntAct=EBI-1759540, EBI-6117042;
CC P16298-4; Q96SQ7-1: ATOH8; NbExp=5; IntAct=EBI-26442038, EBI-26429573;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19154138}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist. Calcineurin A beta isoform
CC consists of at least two isoenzymes that may result from alternative
CC splicing events.;
CC Name=1;
CC IsoId=P16298-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P16298-2; Sequence=VSP_005096, VSP_005097;
CC Name=3;
CC IsoId=P16298-3; Sequence=VSP_043803, VSP_012617;
CC Name=4;
CC IsoId=P16298-4; Sequence=VSP_043803;
CC -!- DOMAIN: The poly-Pro domain may confer substrate specificity.
CC {ECO:0000269|PubMed:19154138}.
CC -!- DOMAIN: The autoinhibitory domain prevents access to the catalytic
CC site. {ECO:0000269|PubMed:26794871}.
CC -!- DOMAIN: The autoinhibitory segment prevents access to the substrate
CC binding site. {ECO:0000269|PubMed:26794871}.
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:0000269|PubMed:26794871}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-2B subfamily.
CC {ECO:0000305}.
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DR EMBL; M29551; AAA35706.1; -; mRNA.
DR EMBL; M29550; AAA35705.1; -; mRNA.
DR EMBL; AJ488506; CAD32694.1; -; mRNA.
DR EMBL; AL353731; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359074; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54497.1; -; Genomic_DNA.
DR EMBL; CH471083; EAW54498.1; -; Genomic_DNA.
DR EMBL; BC028049; AAH28049.1; -; mRNA.
DR CCDS; CCDS44436.1; -. [P16298-3]
DR CCDS; CCDS44437.1; -. [P16298-4]
DR CCDS; CCDS7328.1; -. [P16298-1]
DR PIR; A36222; A36222.
DR PIR; B36222; B36222.
DR RefSeq; NP_001135825.1; NM_001142353.2. [P16298-4]
DR RefSeq; NP_001135826.1; NM_001142354.2. [P16298-3]
DR RefSeq; NP_001276897.1; NM_001289968.1. [P16298-2]
DR RefSeq; NP_001276898.1; NM_001289969.1.
DR RefSeq; NP_066955.1; NM_021132.3. [P16298-1]
DR PDB; 4OR9; X-ray; 2.23 A; A=1-524.
DR PDB; 4ORA; X-ray; 2.75 A; A=1-524.
DR PDB; 4ORC; X-ray; 2.70 A; A=1-524.
DR PDBsum; 4OR9; -.
DR PDBsum; 4ORA; -.
DR PDBsum; 4ORC; -.
DR AlphaFoldDB; P16298; -.
DR SMR; P16298; -.
DR BioGRID; 111524; 83.
DR ComplexPortal; CPX-1002; Calcineurin-Calmodulin complex, beta-R2 variant.
DR ComplexPortal; CPX-1009; Calcineurin-Calmodulin complex, beta-R1 variant.
DR ComplexPortal; CPX-1116; Calcineurin-Calmodulin-AKAP5 complex, beta-R2 variant.
DR ComplexPortal; CPX-998; Calcineurin-Calmodulin-AKAP5 complex, beta-R1 variant.
DR CORUM; P16298; -.
DR DIP; DIP-52337N; -.
DR IntAct; P16298; 42.
DR MINT; P16298; -.
DR STRING; 9606.ENSP00000378306; -.
DR BindingDB; P16298; -.
DR ChEMBL; CHEMBL5278; -.
DR DEPOD; PPP3CB; -.
DR iPTMnet; P16298; -.
DR PhosphoSitePlus; P16298; -.
DR SwissPalm; P16298; -.
DR BioMuta; PPP3CB; -.
DR DMDM; 60659599; -.
DR EPD; P16298; -.
DR jPOST; P16298; -.
DR MassIVE; P16298; -.
DR MaxQB; P16298; -.
DR PaxDb; P16298; -.
DR PeptideAtlas; P16298; -.
DR PRIDE; P16298; -.
DR ProteomicsDB; 53341; -. [P16298-1]
DR ProteomicsDB; 53342; -. [P16298-2]
DR ProteomicsDB; 53343; -. [P16298-3]
DR ProteomicsDB; 53344; -. [P16298-4]
DR Antibodypedia; 1918; 214 antibodies from 35 providers.
DR DNASU; 5532; -.
DR Ensembl; ENST00000360663.10; ENSP00000353881.5; ENSG00000107758.16. [P16298-1]
DR Ensembl; ENST00000394828.6; ENSP00000378305.2; ENSG00000107758.16. [P16298-3]
DR Ensembl; ENST00000394829.6; ENSP00000378306.2; ENSG00000107758.16. [P16298-4]
DR GeneID; 5532; -.
DR KEGG; hsa:5532; -.
DR MANE-Select; ENST00000360663.10; ENSP00000353881.5; NM_021132.4; NP_066955.1.
DR UCSC; uc001jue.4; human. [P16298-1]
DR CTD; 5532; -.
DR DisGeNET; 5532; -.
DR GeneCards; PPP3CB; -.
DR HGNC; HGNC:9315; PPP3CB.
DR HPA; ENSG00000107758; Group enriched (skeletal muscle, tongue).
DR MIM; 114106; gene.
DR neXtProt; NX_P16298; -.
DR OpenTargets; ENSG00000107758; -.
DR PharmGKB; PA33679; -.
DR VEuPathDB; HostDB:ENSG00000107758; -.
DR eggNOG; KOG0375; Eukaryota.
DR GeneTree; ENSGT00940000154115; -.
DR InParanoid; P16298; -.
DR OMA; TNRRIMN; -.
DR OrthoDB; 463522at2759; -.
DR TreeFam; TF105557; -.
DR PathwayCommons; P16298; -.
DR Reactome; R-HSA-180024; DARPP-32 events.
DR Reactome; R-HSA-2025928; Calcineurin activates NFAT.
DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-HSA-4086398; Ca2+ pathway.
DR Reactome; R-HSA-5607763; CLEC7A (Dectin-1) induces NFAT activation.
DR Reactome; R-HSA-9010642; ROBO receptors bind AKAP5.
DR SignaLink; P16298; -.
DR SIGNOR; P16298; -.
DR BioGRID-ORCS; 5532; 69 hits in 1079 CRISPR screens.
DR ChiTaRS; PPP3CB; human.
DR GeneWiki; PPP3CB; -.
DR GenomeRNAi; 5532; -.
DR Pharos; P16298; Tbio.
DR PRO; PR:P16298; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P16298; protein.
DR Bgee; ENSG00000107758; Expressed in endothelial cell and 216 other tissues.
DR ExpressionAtlas; P16298; baseline and differential.
DR Genevisible; P16298; HS.
DR GO; GO:0005955; C:calcineurin complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0008287; C:protein serine/threonine phosphatase complex; IC:ComplexPortal.
DR GO; GO:0030315; C:T-tubule; IEA:Ensembl.
DR GO; GO:0030018; C:Z disc; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0033192; F:calmodulin-dependent protein phosphatase activity; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IDA:UniProtKB.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0046983; F:protein dimerization activity; IPI:UniProtKB.
DR GO; GO:0030346; F:protein phosphatase 2B binding; IDA:UniProtKB.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; NAS:UniProtKB.
DR GO; GO:0048675; P:axon extension; TAS:UniProtKB.
DR GO; GO:0097720; P:calcineurin-mediated signaling; IMP:UniProtKB.
DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IDA:UniProtKB.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; ISS:UniProtKB.
DR GO; GO:0016311; P:dephosphorylation; TAS:UniProtKB.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0007612; P:learning; TAS:UniProtKB.
DR GO; GO:0031987; P:locomotion involved in locomotory behavior; IEA:Ensembl.
DR GO; GO:0001946; P:lymphangiogenesis; IEA:Ensembl.
DR GO; GO:0007613; P:memory; TAS:UniProtKB.
DR GO; GO:1905949; P:negative regulation of calcium ion import across plasma membrane; IC:ComplexPortal.
DR GO; GO:0023057; P:negative regulation of signaling; ISS:UniProtKB.
DR GO; GO:0001915; P:negative regulation of T cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; IC:ComplexPortal.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; IC:ComplexPortal.
DR GO; GO:1905665; P:positive regulation of calcium ion import across plasma membrane; IC:ComplexPortal.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:1901387; P:positive regulation of voltage-gated calcium channel activity; IC:ComplexPortal.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0048167; P:regulation of synaptic plasticity; TAS:UniProtKB.
DR GO; GO:1900242; P:regulation of synaptic vesicle endocytosis; IEA:Ensembl.
DR GO; GO:0034097; P:response to cytokine; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR GO; GO:0048741; P:skeletal muscle fiber development; ISS:UniProtKB.
DR GO; GO:0042110; P:T cell activation; TAS:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; IEA:Ensembl.
DR GO; GO:0043029; P:T cell homeostasis; IEA:Ensembl.
DR GO; GO:0001913; P:T cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:0042098; P:T cell proliferation; NAS:UniProtKB.
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 3D-structure; Acetylation; Alternative splicing; Calmodulin-binding;
KW Cytoplasm; Hydrolase; Iron; Metal-binding; Phosphoprotein;
KW Protein phosphatase; Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..524
FT /note="Serine/threonine-protein phosphatase 2B catalytic
FT subunit beta isoform"
FT /id="PRO_0000058825"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 65..356
FT /note="Catalytic"
FT /evidence="ECO:0000305"
FT REGION 357..379
FT /note="Calcineurin B binding"
FT /evidence="ECO:0000269|PubMed:26794871"
FT REGION 401..415
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:26794871"
FT REGION 416..423
FT /note="Autoinhibitory segment"
FT /evidence="ECO:0000269|PubMed:26794871"
FT REGION 474..496
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000269|PubMed:26794871"
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:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4OR9, ECO:0007744|PDB:4ORA,
FT ECO:0007744|PDB:4ORC"
FT BINDING 101
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4OR9, ECO:0007744|PDB:4ORA,
FT ECO:0007744|PDB:4ORC"
FT BINDING 127
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4OR9, ECO:0007744|PDB:4ORC"
FT BINDING 127
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4OR9, ECO:0007744|PDB:4ORA,
FT ECO:0007744|PDB:4ORC"
FT BINDING 159
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4OR9, ECO:0007744|PDB:4ORA,
FT ECO:0007744|PDB:4ORC"
FT BINDING 208
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4OR9, ECO:0007744|PDB:4ORC"
FT BINDING 290
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4OR9, ECO:0007744|PDB:4ORA,
FT ECO:0007744|PDB:4ORC"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48453"
FT VAR_SEQ 137
FT /note="E -> EHVLGTEDISINPHNNINE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2556704"
FT /id="VSP_005096"
FT VAR_SEQ 395
FT /note="D -> DV (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1848109"
FT /id="VSP_043803"
FT VAR_SEQ 456..524
FT /note="ATVEAIEAEKAIRGFSPPHRICSFEEAKGLDRINERMPPRKDAVQQDGFNSL
FT NTAHATENHGTGNHTAQ -> GNDVMQLAVPQMDWGTPHSFANNSHNACREFLLFFSSC
FT LSS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2556704"
FT /id="VSP_005097"
FT VAR_SEQ 456..465
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:1848109"
FT /id="VSP_012617"
FT MUTAGEN 2..21
FT /note="Missing: Increases catalytic efficiency towards
FT NFATC1 and DARPP32 but not towards a peptide substrate.
FT Does not affect cytoplasmic localization and activation by
FT calmodulin."
FT /evidence="ECO:0000269|PubMed:19154138"
FT MUTAGEN 352
FT /note="L->A: Severe loss of calmodulin-mediated activation.
FT Probably prevents recognition of substrates."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 353
FT /note="P->A: Reduction of basal catalytic activity in
FT absence of calmodulin."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 356
FT /note="M->A: Modest increase in catalytic activity in
FT absence of calmodulin."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 357..524
FT /note="Missing: Loss of catalytic activity. Loss of
FT interaction with PPP3R1/calreticulin B and calmodulin."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 361
FT /note="W->A: Severe reduction of basal catalytic activity
FT in absence of calmodulin. Severe loss of calmodulin-
FT mediated activation. Probably prevents recognition of
FT substrates."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 365
FT /note="F->A: Moderate loss of calmodulin-mediated
FT activation. Probably prevents recognition of substrates."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 398..524
FT /note="Missing: Increases catalytic activity independently
FT of calmodulin. Loss of interaction with calmodulin. Does
FT not affect interaction with PPP3R1/calreticulin B."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 415..524
FT /note="Missing: Increases catalytic activity independently
FT of calmodulin. Does not affect interaction with
FT PPP3R1/calreticulin B and calmodulin."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 417
FT /note="R->A: Modest increase in catalytic activity in
FT absence of calmodulin. Does not affect interaction with
FT calmodulin."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 418
FT /note="V->A: Does not affect catalytic activity in absence
FT of calmodulin. Does not affect interaction with
FT calmodulin."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 419
FT /note="F->A: Modest increase in catalytic activity in
FT absence of calmodulin. Does not affect interaction with
FT calmodulin."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 420
FT /note="S->A: Does not affect catalytic activity in absence
FT of calmodulin. Does not affect interaction with
FT calmodulin."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 421
FT /note="V->A: Modest increase in catalytic activity in
FT absence of calmodulin. Does not affect interaction with
FT calmodulin."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 422
FT /note="L->A: Modest increase in catalytic activity in
FT absence of calmodulin. Does not affect interaction with
FT calmodulin."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 423
FT /note="R->A: Modest increase in catalytic activity in
FT absence of calmodulin. Does not affect interaction with
FT calmodulin."
FT /evidence="ECO:0000269|PubMed:26794871"
FT MUTAGEN 451..524
FT /note="Missing: Increases basal catalytic activity. Does
FT not affect interaction with PPP3R1/calreticulin B and
FT calmodulin."
FT /evidence="ECO:0000269|PubMed:26794871"
FT HELIX 21..23
FT /evidence="ECO:0007829|PDB:4ORA"
FT HELIX 40..43
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 52..60
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 67..82
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 92..97
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 104..114
FT /evidence="ECO:0007829|PDB:4OR9"
FT TURN 117..119
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 129..132
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 135..148
FT /evidence="ECO:0007829|PDB:4OR9"
FT TURN 150..152
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 163..168
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 171..178
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 181..192
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 196..200
FT /evidence="ECO:0007829|PDB:4OR9"
FT TURN 201..203
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 204..209
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 218..222
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 235..241
FT /evidence="ECO:0007829|PDB:4OR9"
FT TURN 246..249
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:4OR9"
FT TURN 261..263
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 264..269
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 271..281
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 284..288
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 296..299
FT /evidence="ECO:0007829|PDB:4OR9"
FT TURN 304..306
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 308..315
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 328..334
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 337..343
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 353..355
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 358..378
FT /evidence="ECO:0007829|PDB:4OR9"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:4ORA"
FT TURN 384..386
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 479..485
FT /evidence="ECO:0007829|PDB:4OR9"
FT HELIX 488..490
FT /evidence="ECO:0007829|PDB:4OR9"
SQ SEQUENCE 524 AA; 59024 MW; 7661183F3C2362C8 CRC64;
MAAPEPARAA PPPPPPPPPP PGADRVVKAV PFPPTHRLTS EEVFDLDGIP 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 EDQFDGSAAA RKEIIRNKIR AIGKMARVFS
VLREESESVL TLKGLTPTGM LPSGVLAGGR QTLQSATVEA IEAEKAIRGF SPPHRICSFE
EAKGLDRINE RMPPRKDAVQ QDGFNSLNTA HATENHGTGN HTAQ
