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 27-MAR-2024, entry version 165. 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). Dephosphorylates KLHL3, CC promoting the interaction between KLHL3 and WNK4 and subsequent CC degradation of WNK4 (By similarity). Negatively regulates SLC9A1 CC activity (By similarity). {ECO:0000250|UniProtKB:P48452, CC ECO:0000250|UniProtKB:P63328, ECO:0000250|UniProtKB:Q08209, CC ECO:0000269|PubMed:1322410, ECO:0000269|PubMed:23699505, CC 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}. 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; 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 GlyGen; P63329; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P63329; -. DR PhosphoSitePlus; P63329; -. DR SwissPalm; P63329; -. DR jPOST; P63329; -. DR PaxDb; 10116-ENSRNOP00000049674; -. DR Ensembl; ENSRNOT00000047975.6; ENSRNOP00000049674.6; ENSRNOG00000009882.8. [P63329-2] DR Ensembl; ENSRNOT00000105262.1; ENSRNOP00000082751.1; ENSRNOG00000009882.8. [P63329-1] DR GeneID; 24674; -. DR KEGG; rno:24674; -. DR AGR; RGD:3382; -. 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 OrthoDB; 1488111at2759; -. 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 cell types or tissues. 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; ISO: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:0005634; C:nucleus; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0098794; C:postsynapse; 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:SynGO. 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: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; ISO:RGD. 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:0110062; P:negative regulation of angiotensin-activated signaling pathway; ISO:RGD. DR GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; IC:BHF-UCL. 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:0023057; P:negative regulation of signaling; ISS:UniProtKB. 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: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:SF5; PROTEIN PHOSPHATASE 3 CATALYTIC SUBUNIT ALPHA; 1. DR PANTHER; PTHR45673; SERINE/THREONINE-PROTEIN PHOSPHATASE 2B CATALYTIC SUBUNIT 1-RELATED; 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. DR Genevisible; P63329; RN. 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 //