PP2BA_RAT
ID PP2BA_RAT Reviewed; 521 AA.
AC P63329; P12816; P20652; Q6LDJ8; Q9WUV7; Q9Z1I5;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Protein phosphatase 3 catalytic subunit alpha {ECO:0000312|RGD:3382};
DE EC=3.1.3.16 {ECO:0000269|PubMed:1322410, ECO:0000269|PubMed:24018048};
DE AltName: Full=CAM-PRP catalytic subunit;
DE AltName: Full=Calcineurin A alpha {ECO:0000303|PubMed:1335233};
DE AltName: Full=Calmodulin-dependent calcineurin A subunit alpha isoform {ECO:0000250|UniProtKB:P63328};
DE Short=CNA alpha {ECO:0000250|UniProtKB:P63328};
DE AltName: Full=Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform {ECO:0000250|UniProtKB:Q08209};
GN Name=Ppp3ca {ECO:0000312|RGD:3382}; Synonyms=Calna;
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] (ISOFORM 1).
RX PubMed=2551293; DOI=10.1016/0006-291x(89)91148-0;
RA Ito A., Hashimoto T., Hirai M., Takeda T., Shuntoh H., Kuno T., Tanaka C.;
RT "The complete primary structure of calcineurin A, a calmodulin binding
RT protein homologous with protein phosphatases 1 and 2A.";
RL Biochem. Biophys. Res. Commun. 163:1492-1497(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY, AND
RP ACTIVITY REGULATION.
RX PubMed=1322410; DOI=10.1016/s0021-9258(19)49628-2;
RA Perrino B.A., Fong Y.L., Brickey D.A., Saitoh Y., Ushio Y., Fukunaga K.,
RA Miyamoto E., Soderling T.R.;
RT "Characterization of the phosphatase activity of a baculovirus-expressed
RT calcineurin A isoform.";
RL J. Biol. Chem. 267:15965-15969(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-19.
RC TISSUE=Liver;
RX PubMed=1335233; DOI=10.1042/bj2880801;
RA Chang C., Takeda T., Mukai H., Shuntoh H., Kuno T., Tanaka C.;
RT "Molecular cloning and characterization of the promoter region of the
RT calcineurin A alpha gene.";
RL Biochem. J. 288:801-805(1992).
RN [4]
RP PROTEIN SEQUENCE OF 143-148, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 236-306.
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 [6]
RP INTERACTION WITH CHP1.
RX PubMed=10593895; DOI=10.1074/jbc.274.51.36125;
RA Lin X., Sikkink R.A., Rusnak F., Barber D.L.;
RT "Inhibition of calcineurin phosphatase activity by a calcineurin B
RT homologous protein.";
RL J. Biol. Chem. 274:36125-36131(1999).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=11114196; DOI=10.1073/pnas.260501097;
RA Frey N., Richardson J.A., Olson E.N.;
RT "Calsarcins, a novel family of sarcomeric calcineurin-binding proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:14632-14637(2000).
RN [8]
RP INTERACTION WITH CHP2.
RX PubMed=18815128; DOI=10.1074/jbc.m806684200;
RA Li G.D., Zhang X., Li R., Wang Y.D., Wang Y.L., Han K.J., Qian X.P.,
RA Yang C.G., Liu P., Wei Q., Chen W.F., Zhang J., Zhang Y.;
RT "CHP2 activates the calcineurin/nuclear factor of activated T cells
RT signaling pathway and enhances the oncogenic potential of HEK293 cells.";
RL J. Biol. Chem. 283:32660-32668(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [10]
RP FUNCTION, AND 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 [11]
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 1-492, FUNCTION, CATALYTIC
RP ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=24018048; DOI=10.1016/j.cellsig.2013.08.033;
RA Ye Q., Feng Y., Yin Y., Faucher F., Currie M.A., Rahman M.N., Jin J.,
RA Li S., Wei Q., Jia Z.;
RT "Structural basis of calcineurin activation by calmodulin.";
RL Cell. Signal. 25:2661-2667(2013).
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:1322410, PubMed:24018048). Many of the
CC substrates contain a PxIxIT motif and/or a LxVP motif (By similarity).
CC In response to increased Ca(2+) levels, dephosphorylates and activates
CC phosphatase SSH1 which results in cofilin dephosphorylation (By
CC similarity). In response to increased Ca(2+) levels following
CC mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L
CC translocation to the mitochondrion (By similarity). Positively
CC regulates the CACNA1B/CAV2.2-mediated Ca(2+) release probability at
CC hippocampal neuronal soma and synaptic terminals (PubMed:23699505).
CC Dephosphorylates heat shock protein HSPB1 (By similarity).
CC Dephosphorylates and activates transcription factor NFATC1 (By
CC similarity). Dephosphorylates and inactivates transcription factor ELK1
CC (By similarity). Dephosphorylates DARPP32 (By similarity). May
CC dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from
CC 14-3-3 proteins (By similarity). Required for postnatal development of
CC the nephrogenic zone and superficial glomeruli in the kidneys, cell
CC cycle homeostasis in the nephrogenic zone, and ultimately normal kidney
CC function (By similarity). Plays a role in intracellular AQP2 processing
CC and localization to the apical membrane in the kidney, may thereby be
CC required for efficient kidney filtration (By similarity). Required for
CC secretion of salivary enzymes amylase, peroxidase, lysozyme and sialic
CC acid via formation of secretory vesicles in the submandibular glands
CC (By similarity). Required for calcineurin activity and homosynaptic
CC depotentiation in the hippocampus (By similarity). Required for normal
CC differentiation and survival of keratinocytes and therefore required
CC for epidermis superstructure formation (By similarity). Positively
CC regulates osteoblastic bone formation, via promotion of osteoblast
CC differentiation (By similarity). Positively regulates osteoclast
CC differentiation, potentially via NFATC1 signaling (By similarity). May
CC play a role in skeletal muscle fiber type specification, potentially
CC via NFATC1 signaling (By similarity). Negatively regulates MAP3K14/NIK
CC signaling via inhibition of nuclear translocation of the transcription
CC factors RELA and RELB (By similarity). Required for antigen-specific T-
CC cell proliferation response (By similarity).
CC {ECO:0000250|UniProtKB:P48452, ECO:0000250|UniProtKB:P63328,
CC ECO:0000250|UniProtKB:Q08209, ECO:0000269|PubMed:1322410,
CC ECO:0000269|PubMed:23699505, ECO:0000269|PubMed:24018048}.
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; Evidence={ECO:0000269|PubMed:1322410,
CC ECO:0000269|PubMed:24018048};
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; Evidence={ECO:0000269|PubMed:1322410,
CC ECO:0000269|PubMed:24018048};
CC -!- COFACTOR:
CC Name=Fe(3+); Xref=ChEBI:CHEBI:29034;
CC Evidence={ECO:0000250|UniProtKB:Q08209};
CC Note=Binds 1 Fe(3+) ion per subunit. {ECO:0000250|UniProtKB:Q08209};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q08209};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q08209};
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)-bound calmodulin following an
CC increase in intracellular Ca(2+) (PubMed:1322410, PubMed:24018048). At
CC low Ca(2+) concentrations, the catalytic subunit (also known as
CC calcineurin A) is inactive and is bound to the regulatory subunit (also
CC known as calcineurin B) in which only two high-affinity binding sites
CC are occupied by Ca(2+) (PubMed:1322410, PubMed:24018048). In response
CC to elevated calcium levels, the occupancy of the low-affinity sites on
CC calcineurin B by Ca(2+) causes a conformational change of the C-
CC terminal regulatory domain of calcineurin A, resulting in the exposure
CC of the calmodulin-binding domain and in the partial activation of
CC calcineurin A (PubMed:1322410, PubMed:24018048). The subsequent binding
CC of Ca(2+)-bound calmodulin leads to the displacement of the
CC autoinhibitory domain from the active site and possibly of the
CC autoinhibitory segment from the substrate binding site which fully
CC activates calcineurin A (PubMed:1322410, PubMed:24018048). Inhibited by
CC immunosuppressant drug FK506 (tacrolimus) in complex with FKBP12 and
CC also by immunosuppressant drug cyclosporin A (CsA) in complex with
CC PPIA/cyclophilin A; the inhibition is Ca(2+)-dependent (By similarity).
CC {ECO:0000250|UniProtKB:P48452, ECO:0000269|PubMed:1322410,
CC ECO:0000269|PubMed:24018048}.
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) (By similarity). There are three
CC catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB,
CC and PPP3CC) and two regulatory subunits which are also encoded by
CC separate genes (PPP3R1 and PPP3R2). In response to an increase in
CC Ca(2+) intracellular levels, forms a complex composed of
CC PPP3CA/calcineurin A, calcineurin B and calmodulin (By similarity).
CC Interacts (via calcineurin B binding domain) with regulatory subunit
CC PPP3R1/calcineurin B (By similarity). Interacts (via calmodulin-binding
CC domain) with calmodulin; the interaction depends on calmodulin binding
CC to Ca(2+) (By similarity). Forms a complex composed of MYOZ2 and ACTN1
CC (By similarity). Within the complex interacts with MYOZ2 (By
CC similarity). Interacts with MYOZ1 (By similarity). Interacts with MYOZ3
CC (By similarity). Interacts with CIB1; the interaction increases upon
CC cardiomyocyte hypertrophy (By similarity). Interacts with CHP1 and CHP2
CC (PubMed:10593895, PubMed:18815128). Interacts with CRTC1. Interacts
CC with CRTC2 (By similarity). Interacts with DNM1L; the interaction
CC dephosphorylates DNM1L and promotes its translocation to mitochondria
CC (By similarity). Interacts with CMYA5; this interaction represses
CC calcineurin activity in muscle (By similarity). Interacts
CC (constitutively active form) with SYNPO2 (By similarity). Interacts
CC with scaffold protein AKAP5 (via IAIIIT motif); the interaction
CC recruits PPP3CA to the plasma membrane following L-type Ca(2+)-channel
CC activation (By similarity). Interacts with NFATC2 (By similarity).
CC Interacts with RCAN3 (By similarity). Interacts with PPIA. Interacts
CC with RCAN1 (By similarity). Interacts with UNC119 (By similarity).
CC Interacts with C16orf74 (via PxIxIT motif, when phosphorylated on 'Thr-
CC 76') (By similarity). Interacts (via N-terminus) with MAP3K14/NIK (via
CC C-terminus and kinase domain) (By similarity). Interacts with TRAF3 (By
CC similarity). Interacts with SPATA33 (via PQIIIT motif) (By similarity).
CC {ECO:0000250|UniProtKB:P48452, ECO:0000250|UniProtKB:P63328,
CC ECO:0000250|UniProtKB:Q08209, ECO:0000269|PubMed:10593895,
CC ECO:0000269|PubMed:18815128}.
CC -!- INTERACTION:
CC P63329; P22002: Cacna1c; NbExp=5; IntAct=EBI-7022944, EBI-1185084;
CC P63329; Q8VHW5: Cacng8; NbExp=6; IntAct=EBI-7022944, EBI-9086576;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q08209}. Cell
CC membrane {ECO:0000250|UniProtKB:Q08209}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q08209}. Cell membrane, sarcolemma
CC {ECO:0000269|PubMed:11114196}. Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000269|PubMed:11114196}. Cell projection, dendritic spine
CC {ECO:0000250|UniProtKB:Q08209}. Note=Colocalizes with ACTN1 and MYOZ2
CC at the Z line in heart and skeletal muscle (PubMed:11114196). Recruited
CC to the cell membrane by scaffold protein AKAP5 following L-type Ca(2+)-
CC channel activation (By similarity). {ECO:0000250|UniProtKB:Q08209,
CC ECO:0000269|PubMed:11114196}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P63329-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P63329-2; Sequence=VSP_018564;
CC -!- TISSUE SPECIFICITY: Expressed in neonatal cardiomyocytes (at protein
CC level) (PubMed:11114196). Expressed in hippocampal presynaptic termini
CC (at protein level) (PubMed:23699505). {ECO:0000269|PubMed:11114196,
CC ECO:0000269|PubMed:23699505}.
CC -!- DOMAIN: The autoinhibitory domain prevents access to the catalytic
CC site. {ECO:0000250|UniProtKB:P63328}.
CC -!- DOMAIN: The autoinhibitory segment prevents access to the substrate
CC binding site. {ECO:0000250|UniProtKB:P63328}.
CC -!- DOMAIN: Possible isomerization of Pro-309 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 -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-2B subfamily.
CC {ECO:0000305}.
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DR EMBL; D90035; BAA14083.1; -; mRNA.
DR EMBL; M29275; AAA40940.1; -; mRNA.
DR EMBL; X57115; CAA40398.2; -; mRNA.
DR EMBL; D10480; BAA01283.1; -; Genomic_DNA.
DR EMBL; M58440; AAA41914.1; -; mRNA.
DR PIR; A33264; A33264.
DR RefSeq; NP_058737.1; NM_017041.1. [P63329-1]
DR RefSeq; XP_006233425.1; XM_006233363.3. [P63329-2]
DR PDB; 4IL1; X-ray; 3.00 A; A/B/C/D=1-492.
DR PDBsum; 4IL1; -.
DR AlphaFoldDB; P63329; -.
DR BMRB; P63329; -.
DR SMR; P63329; -.
DR BioGRID; 246806; 6.
DR CORUM; P63329; -.
DR IntAct; P63329; 6.
DR MINT; P63329; -.
DR STRING; 10116.ENSRNOP00000049674; -.
DR iPTMnet; P63329; -.
DR PhosphoSitePlus; P63329; -.
DR SwissPalm; P63329; -.
DR jPOST; P63329; -.
DR PaxDb; P63329; -.
DR PRIDE; P63329; -.
DR Ensembl; ENSRNOT00000047975; ENSRNOP00000049674; ENSRNOG00000009882. [P63329-2]
DR Ensembl; ENSRNOT00000105262; ENSRNOP00000082751; ENSRNOG00000009882. [P63329-1]
DR GeneID; 24674; -.
DR KEGG; rno:24674; -.
DR CTD; 5530; -.
DR RGD; 3382; Ppp3ca.
DR eggNOG; KOG0375; Eukaryota.
DR GeneTree; ENSGT00940000156306; -.
DR HOGENOM; CLU_004962_6_0_1; -.
DR InParanoid; P63329; -.
DR OMA; MESFCCL; -.
DR OrthoDB; 463522at2759; -.
DR PhylomeDB; P63329; -.
DR BRENDA; 3.1.3.16; 5301.
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:P63329; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000009882; Expressed in Ammon's horn and 19 other tissues.
DR Genevisible; P63329; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005955; C:calcineurin complex; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; ISO:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0030018; C:Z disc; ISO:RGD.
DR GO; GO:0051117; F:ATPase binding; ISO:RGD.
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; IDA:UniProtKB.
DR GO; GO:0016018; F:cyclosporin A binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:RGD.
DR GO; GO:0046983; F:protein dimerization activity; ISO:RGD.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0097720; P:calcineurin-mediated signaling; ISO:RGD.
DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; ISO:RGD.
DR GO; GO:0006816; P:calcium ion transport; ISO:RGD.
DR GO; GO:0019722; P:calcium-mediated signaling; ISO:RGD.
DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; ISO:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IMP:BHF-UCL.
DR GO; GO:0048813; P:dendrite morphogenesis; IEA:Ensembl.
DR GO; GO:0016311; P:dephosphorylation; ISO:RGD.
DR GO; GO:0008544; P:epidermis development; ISS:UniProtKB.
DR GO; GO:0060079; P:excitatory postsynaptic potential; ISO:RGD.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0030216; P:keratinocyte differentiation; ISS:UniProtKB.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISS:UniProtKB.
DR GO; GO:0033555; P:multicellular organismal response to stress; ISO:RGD.
DR GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; IC:BHF-UCL.
DR GO; GO:0035562; P:negative regulation of chromatin binding; ISO:RGD.
DR GO; GO:0050774; P:negative regulation of dendrite morphogenesis; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IMP:BHF-UCL.
DR GO; GO:1903799; P:negative regulation of miRNA maturation; ISO:RGD.
DR GO; GO:0023057; P:negative regulation of signaling; ISS:UniProtKB.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; ISO:RGD.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISS:UniProtKB.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISO:RGD.
DR GO; GO:1903244; P:positive regulation of cardiac muscle hypertrophy in response to stress; ISO:RGD.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:1905205; P:positive regulation of connective tissue replacement; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0045807; P:positive regulation of endocytosis; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0090193; P:positive regulation of glomerulus development; ISS:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISS:UniProtKB.
DR GO; GO:0046878; P:positive regulation of saliva secretion; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; ISO:RGD.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; ISO:RGD.
DR GO; GO:0061006; P:regulation of cell proliferation involved in kidney morphogenesis; ISS:UniProtKB.
DR GO; GO:0097205; P:renal filtration; ISS:UniProtKB.
DR GO; GO:0001975; P:response to amphetamine; IEP:RGD.
DR GO; GO:0051592; P:response to calcium ion; ISS:UniProtKB.
DR GO; GO:0048741; P:skeletal muscle fiber development; ISS:UniProtKB.
DR GO; GO:0014883; P:transition between fast and slow fiber; 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 3D-structure; Acetylation; Alternative splicing; Calmodulin-binding;
KW Cell membrane; Cell projection; Cytoplasm; Direct protein sequencing;
KW Hydrolase; Iron; Membrane; Metal-binding; Nitration; Phosphoprotein;
KW Protein phosphatase; Reference proteome; Synapse; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT CHAIN 2..521
FT /note="Protein phosphatase 3 catalytic subunit alpha"
FT /id="PRO_0000058824"
FT REGION 56..340
FT /note="Catalytic"
FT /evidence="ECO:0000305"
FT REGION 327..336
FT /note="Interaction with PxIxIF motif in substrate"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT REGION 341..369
FT /note="Calcineurin B binding"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT REGION 392..406
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT REGION 407..414
FT /note="Autoinhibitory segment"
FT /evidence="ECO:0000250|UniProtKB:P16298"
FT REGION 465..487
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000269|PubMed:1322410"
FT REGION 475..521
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 307..311
FT /note="SAPNY motif"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT COMPBIAS 493..521
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 151
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 90
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 92
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 118
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 150
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 199
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 281
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT SITE 352
FT /note="Interaction with PxVP motif in substrate"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT MOD_RES 224
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P63328"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT VAR_SEQ 448..457
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1322410"
FT /id="VSP_018564"
FT HELIX 31..34
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 43..51
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 58..72
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 95..105
FT /evidence="ECO:0007829|PDB:4IL1"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 126..139
FT /evidence="ECO:0007829|PDB:4IL1"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 154..159
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 162..168
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 172..184
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:4IL1"
FT TURN 192..194
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 195..200
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 209..213
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 226..232
FT /evidence="ECO:0007829|PDB:4IL1"
FT TURN 237..240
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 247..250
FT /evidence="ECO:0007829|PDB:4IL1"
FT TURN 252..255
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 256..260
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 262..271
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 275..279
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 287..290
FT /evidence="ECO:0007829|PDB:4IL1"
FT TURN 295..297
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 299..306
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 319..325
FT /evidence="ECO:0007829|PDB:4IL1"
FT STRAND 328..334
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 344..346
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 349..366
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 473..476
FT /evidence="ECO:0007829|PDB:4IL1"
FT HELIX 478..481
FT /evidence="ECO:0007829|PDB:4IL1"
SQ SEQUENCE 521 AA; 58644 MW; 16530C27DDBF1F05 CRC64;
MSEPKAIDPK LSTTDRVVKA VPFPPSHRLT AKEVFDNDGK PRVDILKAHL MKEGRLEESV
ALRIITEGAS ILRQEKNLLD IDAPVTVCGD IHGQFFDLMK LFEVGGSPAN TRYLFLGDYV
DRGYFSIECV LYLWALKILY PKTLFLLRGN HECRHLTEYF TFKQECKIKY SERVYDACMD
AFDCLPLAAL MNQQFLCVHG GLSPEINTLD DIRKLDRFKE PPAYGPMCDI LWSDPLEDFG
NEKTQEHFTH NTVRGCSYFY SYPAVCDFLQ HNNLLSILRA HEAQDAGYRM YRKSQTTGFP
SLITIFSAPN YLDVYNNKAA VLKYENNVMN IRQFNCSPHP YWLPNFMDVF TWSLPFVGEK
VTEMLVNVLN ICSDDELGSE EDGFDGATAA ARKEVIRNKI RAIGKMARVF SVLREESESV
LTLKGLTPTG MLPSGVLSGG KQTLQSATVE AIEADEAIKG FSPQHKITSF EEAKGLDRIN
ERMPPRRDAM PSDANLNSIN KALASETNGT DSNGSNSSNI Q
