PP2BA_MOUSE
ID PP2BA_MOUSE Reviewed; 521 AA.
AC P63328; B2RRX2; P12816; P20652; Q3UCU1; Q64135;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Protein phosphatase 3 catalytic subunit alpha {ECO:0000312|MGI:MGI:107164};
DE EC=3.1.3.16 {ECO:0000269|PubMed:26794871, ECO:0000269|PubMed:7791792};
DE AltName: Full=CAM-PRP catalytic subunit;
DE AltName: Full=Calcineurin A alpha {ECO:0000303|PubMed:8627154};
DE AltName: Full=Calmodulin-dependent calcineurin A subunit alpha isoform {ECO:0000303|PubMed:26794871};
DE Short=CNA alpha {ECO:0000305|PubMed:26794871};
DE AltName: Full=Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform {ECO:0000250|UniProtKB:Q08209};
GN Name=Ppp3ca {ECO:0000312|MGI:MGI:107164}; Synonyms=Calna;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2162844; DOI=10.1016/s0021-9258(19)38593-x;
RA Kincaid R.L., Giri P.R., Higuchi S., Tamura J., Dixon S.C., Marietta C.A.,
RA Amorese D.A., Martin B.M.;
RT "Cloning and characterization of molecular isoforms of the catalytic
RT subunit of calcineurin using nonisotopic methods.";
RL J. Biol. Chem. 265:11312-11319(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=BALB/cJ, and C57BL/6J; TISSUE=Bone marrow;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3] {ECO:0000312|EMBL:AAI38613.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP PROTEIN SEQUENCE OF 64-73; 101-122 AND 425-459, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=C57BL/6J, and OF1; TISSUE=Brain, and Hippocampus;
RA Lubec G., Kang S.U., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 95-116.
RX PubMed=8077208; DOI=10.1016/s0021-9258(17)31686-1;
RA Becker W., Kentrup H., Klumpp S., Schultz J.E., Joost H.G.;
RT "Molecular cloning of a protein serine/threonine phosphatase containing a
RT putative regulatory tetratricopeptide repeat domain.";
RL J. Biol. Chem. 269:22586-22592(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 215-521 (ISOFORM 1).
RX PubMed=2848250; DOI=10.1073/pnas.85.23.8983;
RA Kincaid R.L., Nightingale M.S., Martin B.M.;
RT "Characterization of a cDNA clone encoding the calmodulin-binding domain of
RT mouse brain calcineurin.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:8983-8987(1988).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 467-491, FUNCTION, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF ASP-477.
RX PubMed=7791792; DOI=10.1128/mcb.15.7.3857;
RA Fruman D.A., Pai S.-Y., Burakoff S.J., Bierer B.E.;
RT "Characterization of a mutant calcineurin A alpha gene expressed by EL4
RT lymphoma cells.";
RL Mol. Cell. Biol. 15:3857-3863(1995).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=8627154; DOI=10.1084/jem.183.2.413;
RA Zhang B.W., Zimmer G., Chen J., Ladd D., Li E., Alt F.W., Wiederrecht G.,
RA Cryan J., O'Neill E.A., Seidman C.E., Abbas A.K., Seidman J.G.;
RT "T cell responses in calcineurin A alpha-deficient mice.";
RL J. Exp. Med. 183:413-420(1996).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=10200317; DOI=10.1073/pnas.96.8.4650;
RA Zhuo M., Zhang W., Son H., Mansuy I., Sobel R.A., Seidman J., Kandel E.R.;
RT "A selective role of calcineurin aalpha in synaptic depotentiation in
RT hippocampus.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:4650-4655(1999).
RN [10]
RP IDENTIFICATION IN A COMPLEX WITH ACTN1 AND MYOZ2, AND INTERACTION WITH
RP MYOZ1 AND MYOZ2.
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 [11]
RP INTERACTION WITH RCAN1.
RX PubMed=12809556; DOI=10.1042/bj20030267;
RA Genesca L., Aubareda A., Fuentes J.J., Estivill X., De La Luna S.,
RA Perez-Riba M.;
RT "Phosphorylation of calcipressin 1 increases its ability to inhibit
RT calcineurin and decreases calcipressin half-life.";
RL Biochem. J. 374:567-575(2003).
RN [12]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=12773574; DOI=10.1128/mcb.23.12.4331-4343.2003;
RA Parsons S.A., Wilkins B.J., Bueno O.F., Molkentin J.D.;
RT "Altered skeletal muscle phenotypes in calcineurin Aalpha and Abeta gene-
RT targeted mice.";
RL Mol. Cell. Biol. 23:4331-4343(2003).
RN [13]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=15509543; DOI=10.1016/s0002-9440(10)63430-x;
RA Gooch J.L., Toro J.J., Guler R.L., Barnes J.L.;
RT "Calcineurin A-alpha but not A-beta is required for normal kidney
RT development and function.";
RL Am. J. Pathol. 165:1755-1765(2004).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=16286645; DOI=10.1073/pnas.0508480102;
RA Sun L., Blair H.C., Peng Y., Zaidi N., Adebanjo O.A., Wu X.B., Wu X.Y.,
RA Iqbal J., Epstein S., Abe E., Moonga B.S., Zaidi M.;
RT "Calcineurin regulates bone formation by the osteoblast.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:17130-17135(2005).
RN [15]
RP NITRATION [LARGE SCALE ANALYSIS] AT TYR-224, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16800626; DOI=10.1021/bi060474w;
RA Sacksteder C.A., Qian W.-J., Knyushko T.V., Wang H., Chin M.H., Lacan G.,
RA Melega W.P., Camp D.G. II, Smith R.D., Smith D.J., Squier T.C.,
RA Bigelow D.J.;
RT "Endogenously nitrated proteins in mouse brain: links to neurodegenerative
RT disease.";
RL Biochemistry 45:8009-8022(2006).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16735444; DOI=10.1242/jcs.02971;
RA Gooch J.L., Guler R.L., Barnes J.L., Toro J.J.;
RT "Loss of calcineurin Aalpha results in altered trafficking of AQP2 and in
RT nephrogenic diabetes insipidus.";
RL J. Cell Sci. 119:2468-2476(2006).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=16968888; DOI=10.1152/ajprenal.00415.2005;
RA Sun L., Peng Y., Zaidi N., Zhu L.L., Iqbal J., Yamoah K., Wang X., Liu P.,
RA Abe E., Moonga B.S., Epstein S., Zaidi M.;
RT "Evidence that calcineurin is required for the genesis of bone-resorbing
RT osteoclasts.";
RL Am. J. Physiol. 292:F285-F291(2007).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-492, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [19]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19626032; DOI=10.1038/jid.2009.222;
RA Pena J.A., Losi-Sasaki J.L., Gooch J.L.;
RT "Loss of calcineurin Aalpha alters keratinocyte survival and
RT differentiation.";
RL J. Invest. Dermatol. 130:135-140(2010).
RN [20]
RP INTERACTION WITH CIB1.
RX PubMed=20639889; DOI=10.1038/nm.2181;
RA Heineke J., Auger-Messier M., Correll R.N., Xu J., Benard M.J., Yuan W.,
RA Drexler H., Parise L.V., Molkentin J.D.;
RT "CIB1 is a regulator of pathological cardiac hypertrophy.";
RL Nat. Med. 16:872-879(2010).
RN [21]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=21435446; DOI=10.1016/j.ajpath.2010.12.054;
RA Reddy R.N., Pena J.A., Roberts B.R., Williams S.R., Price S.R., Gooch J.L.;
RT "Rescue of calcineurin Aalpha(-/-) mice reveals a novel role for the alpha
RT isoform in the salivary gland.";
RL Am. J. Pathol. 178:1605-1613(2011).
RN [22]
RP INTERACTION WITH CMYA5.
RX PubMed=21427212; DOI=10.1096/fj.10-169219;
RA Kielbasa O.M., Reynolds J.G., Wu C.L., Snyder C.M., Cho M.Y., Weiler H.,
RA Kandarian S., Naya F.J.;
RT "Myospryn is a calcineurin-interacting protein that negatively modulates
RT slow-fiber-type transformation and skeletal muscle regeneration.";
RL FASEB J. 25:2276-2286(2011).
RN [23]
RP FUNCTION, AND INTERACTION WITH MAP3K14 AND TRAF3.
RX PubMed=26029823; DOI=10.1038/srep10758;
RA Shinzawa M., Konno H., Qin J., Akiyama N., Miyauchi M., Ohashi H.,
RA Miyamoto-Sato E., Yanagawa H., Akiyama T., Inoue J.;
RT "Catalytic subunits of the phosphatase calcineurin interact with NF-kappaB-
RT inducing kinase (NIK) and attenuate NIK-dependent gene expression.";
RL Sci. Rep. 5:10758-10758(2015).
RN [24]
RP INTERACTION WITH CRTC1 AND CRTC2.
RX PubMed=30611118; DOI=10.1016/j.isci.2018.12.012;
RA Sonntag T., Ostojic J., Vaughan J.M., Moresco J.J., Yoon Y.S.,
RA Yates J.R. III, Montminy M.;
RT "Mitogenic Signals Stimulate the CREB Coactivator CRTC3 through PP2A
RT Recruitment.";
RL IScience 11:134-145(2018).
RN [25]
RP INTERACTION WITH UNC119.
RX PubMed=31696965; DOI=10.15252/embj.2018101409;
RA Chaya T., Tsutsumi R., Varner L.R., Maeda Y., Yoshida S., Furukawa T.;
RT "Cul3-Klhl18 ubiquitin ligase modulates rod transducin translocation during
RT light-dark adaptation.";
RL EMBO J. 2019:E101409-E101409(2019).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (3.11 ANGSTROMS) IN COMPLEX WITH PPP3R1; IRON AND
RP ZINC, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP 348-ALA--GLN-521; 389-ASP--GLN-521; 406-MET--GLN-521 AND 442-GLN--GLN-521.
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:7791792, PubMed:26794871). 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 (By similarity).
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 (PubMed:15509543). Plays a role in intracellular AQP2
CC processing and localization to the apical membrane in the kidney, may
CC thereby be required for efficient kidney filtration (PubMed:16735444).
CC Required for secretion of salivary enzymes amylase, peroxidase,
CC lysozyme and sialic acid via formation of secretory vesicles in the
CC submandibular glands (PubMed:21435446). Required for calcineurin
CC activity and homosynaptic depotentiation in the hippocampus
CC (PubMed:10200317). Required for normal differentiation and survival of
CC keratinocytes and therefore required for epidermis superstructure
CC formation (PubMed:19626032). Positively regulates osteoblastic bone
CC formation, via promotion of osteoblast differentiation
CC (PubMed:16286645). Positively regulates osteoclast differentiation,
CC potentially via NFATC1 signaling (PubMed:16968888). May play a role in
CC skeletal muscle fiber type specification, potentially via NFATC1
CC signaling (PubMed:12773574). Negatively regulates MAP3K14/NIK signaling
CC via inhibition of nuclear translocation of the transcription factors
CC RELA and RELB (PubMed:26029823). Required for antigen-specific T-cell
CC proliferation response (PubMed:8627154). {ECO:0000250|UniProtKB:P48452,
CC ECO:0000250|UniProtKB:P63329, ECO:0000250|UniProtKB:Q08209,
CC ECO:0000269|PubMed:10200317, ECO:0000269|PubMed:12773574,
CC ECO:0000269|PubMed:15509543, ECO:0000269|PubMed:16286645,
CC ECO:0000269|PubMed:16735444, ECO:0000269|PubMed:16968888,
CC ECO:0000269|PubMed:19626032, ECO:0000269|PubMed:21435446,
CC ECO:0000269|PubMed:26029823, ECO:0000269|PubMed:26794871,
CC ECO:0000269|PubMed:7791792, ECO:0000269|PubMed:8627154}.
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:26794871, ECO:0000269|PubMed:7791792};
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:26794871, ECO:0000269|PubMed:7791792};
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+) (PubMed:26794871). At low Ca(2+)
CC concentrations, the catalytic subunit (also known as calcineurin A) is
CC inactive and is bound to the regulatory subunit (also known as
CC calcineurin B) in which only two high-affinity binding sites are
CC occupied by Ca(2+) (PubMed:26794871). In response to elevated calcium
CC levels, the occupancy of the low-affinity sites on calcineurin B by
CC Ca(2+) causes a conformational change of the C-terminal regulatory
CC domain of calcineurin A, resulting in the exposure of the calmodulin-
CC binding domain and in the partial activation of calcineurin A
CC (PubMed:26794871). 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 (PubMed:26794871).
CC Inhibited by immunosuppressant drug FK506 (tacrolimus) in complex with
CC FKBP12 and also by immunosuppressant drug cyclosporin A (CsA) in
CC complex with PPIA/cyclophilin A; the inhibition is Ca(2+)-dependent (By
CC similarity). {ECO:0000250|UniProtKB:P48452,
CC ECO:0000269|PubMed:26794871}.
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) (PubMed:26794871). There are
CC three catalytic subunits, each encoded by a separate gene (PPP3CA,
CC PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded
CC by 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 (PubMed:26794871). Interacts (via calmodulin-
CC binding domain) with calmodulin; the interaction depends on calmodulin
CC binding to Ca(2+) (By similarity). Forms a complex composed of MYOZ2
CC and ACTN1 (PubMed:11114196). Within the complex interacts with MYOZ2
CC (PubMed:11114196). Interacts with MYOZ1 (PubMed:11114196). Interacts
CC with MYOZ3 (By similarity). Interacts with CIB1; the interaction
CC increases upon cardiomyocyte hypertrophy (PubMed:20639889). Interacts
CC with CHP1 and CHP2 (By similarity). Interacts with CRTC1
CC (PubMed:30611118). Interacts with CRTC2 (PubMed:30611118). Interacts
CC with DNM1L; the interaction dephosphorylates DNM1L and promotes its
CC translocation to mitochondria (By similarity). Interacts with CMYA5;
CC this interaction represses calcineurin activity in muscle
CC (PubMed:21427212). Interacts (constitutively active form) with SYNPO2
CC (By similarity). Interacts with scaffold protein AKAP5 (via IAIIIT
CC motif); the interaction recruits PPP3CA to the plasma membrane
CC following L-type Ca(2+)-channel activation (By similarity). Interacts
CC with NFATC2 (By similarity). Interacts with RCAN3 (By similarity).
CC Interacts with PPIA (By similarity). Interacts with RCAN1
CC (PubMed:12809556). Interacts with UNC119 (PubMed:31696965). Interacts
CC with C16orf74 (via PxIxIT motif, when phosphorylated on 'Thr-79') (By
CC similarity). Interacts (via N-terminus) with MAP3K14/NIK (via C-
CC terminus and kinase domain) (PubMed:26029823). Interacts with TRAF3
CC (PubMed:26029823). Interacts with SPATA33 (via PQIIIT motif) (By
CC similarity). {ECO:0000250|UniProtKB:P48452,
CC ECO:0000250|UniProtKB:P63329, ECO:0000250|UniProtKB:Q08209,
CC ECO:0000269|PubMed:11114196, ECO:0000269|PubMed:12809556,
CC ECO:0000269|PubMed:20639889, ECO:0000269|PubMed:21427212,
CC ECO:0000269|PubMed:26029823, ECO:0000269|PubMed:26794871,
CC ECO:0000269|PubMed:30611118, ECO:0000269|PubMed:31696965}.
CC -!- INTERACTION:
CC P63328; Q3U182: Crtc2; NbExp=2; IntAct=EBI-397208, EBI-8018890;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16286645,
CC ECO:0000269|PubMed:16968888}. Cell membrane
CC {ECO:0000250|UniProtKB:Q08209}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q08209}. Cell membrane, sarcolemma
CC {ECO:0000250|UniProtKB:P63329}. Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000250|UniProtKB:P63329}. 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. Recruited to the cell
CC membrane by scaffold protein AKAP5 following L-type Ca(2+)-channel
CC activation. {ECO:0000250|UniProtKB:P63329,
CC ECO:0000250|UniProtKB:Q08209}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P63328-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P63328-2; Sequence=VSP_018563;
CC -!- TISSUE SPECIFICITY: Expressed in the kidney (at protein level)
CC (PubMed:15509543). Expressed in the salivary gland (at protein level)
CC (PubMed:21435446). Expressed in osteoblasts and bone marrow (at protein
CC level) (PubMed:16286645). Expressed in the brain and the bicep, tricep,
CC soleus and gastrocnemius muscles (at protein level) (PubMed:12773574).
CC Abundantly expressed in the dentate gyrus and the CA1 and CA3 regions
CC of the hippocampus (at protein level) (PubMed:10200317). Expressed in
CC T-lymphocytes (at protein level) (PubMed:8627154). Expressed in
CC embryonic stem cells (PubMed:8627154). {ECO:0000269|PubMed:10200317,
CC ECO:0000269|PubMed:12773574, ECO:0000269|PubMed:15509543,
CC ECO:0000269|PubMed:16286645, ECO:0000269|PubMed:21435446,
CC ECO:0000269|PubMed:8627154}.
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-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 -!- DISRUPTION PHENOTYPE: Knockout mice are significantly smaller at
CC postnatal day 18 (P18), including significantly reduced weights of the
CC liver and kidneys (PubMed:15509543, PubMed:16735444). Decreased blood
CC glucose levels (PubMed:16735444). Decreased lumber spine, tibia, and
CC total body bone mass density evident at 6 weeks of age, evidence of
CC decreased density in the lumber spine as early as 3 weeks of age
CC (PubMed:16286645). No change in overall muscle weight
CC (PubMed:12773574). Decreased femur length, reduced cortical trabecular
CC bone thickness (PubMed:16286645). Significantly reduced number of
CC differentiated osteoclasts (PubMed:16968888). Reduced mitochondrial
CC oxidative capacity in slow and intermediate muscle fiber types
CC (PubMed:12773574). Reduced slow and intermediate program type muscle
CC fibers in the biceps and triceps (PubMed:12773574). Decreased number of
CC slow program type muscle fibers and NFAT activity in the soleus
CC (PubMed:12773574). Kidney size and development is normal at P4, however
CC by P18 kidneys show an obvious delay in maturation, displaying a
CC decreased overall mass, poorly defined medullary rays and decreased
CC cortical mass (PubMed:15509543). Upon examination the outer strip of
CC the medulla and cortical regions of the kidneys are significantly
CC decreased (PubMed:15509543). In the cortex there is a persistence of
CC poorly developed surface glomeruli due to attenuation of mesangial
CC cells numbers and a lack of maturation of tubules in the nephrogenic
CC zone (PubMed:15509543). Reduced proliferation and increased apoptosis
CC of cells within the nephrogenic zone at P18, potentially as a result of
CC increased p27 expression (PubMed:15509543). Impaired kidney function
CC evident by increased kidney collagen deposition, serum creatinine
CC levels and decreased urine creatinine concentration from P4 onwards
CC (PubMed:15509543, PubMed:16735444). Loss of AQP2 phosphorylation in
CC response to vasopressin and decreased localization to the apical
CC membrane of inner medullary collecting duct cells (PubMed:16735444).
CC Most mice die between P21 and P28 as a result of progressive kidney
CC failure (PubMed:15509543). Increased salivary osmolality despite normal
CC electrolyte composition and protein content (PubMed:21435446).
CC Decreased activity of amylase, peroxidase, lysozyme and sialic acid in
CC the saliva (PubMed:21435446). Decreased number of secretory vesicles,
CC mucosal acini cell size and protein content of serosal acini in the
CC submandibular glands (PubMed:21435446). Decreased activity of
CC calcineurin in the salivary glands (PubMed:21435446). Decreased
CC thickness of the epidermal stratum spinosum, a thickened corneum and
CC increased sloughing-off of keratinocytes in newborn mice
CC (PubMed:19626032). Decreased thickness of the stratum spinosum is still
CC evident at 4 weeks of age along with decreased skin elasticity
CC (PubMed:19626032). Increased apoptosis in the supra-basal layers and
CC the stratum spinosum of the epidermis (PubMed:19626032). Decrease in
CC NFATc activity in basal epidermal cells and impaired differentiation of
CC epidermal keratinocytes as shown by aberrant expression of the
CC differentiation markers KRT14, KRT10 and IVL (PubMed:19626032).
CC Decreased calcineurin activity in the brain and significant reduction
CC in homosynaptic depotentiation (PubMed:10200317). Decreased calcineurin
CC activity in T-lymphocytes and loss of T-lymphocyte proliferation in
CC response to antigen stimulation (PubMed:8627154).
CC {ECO:0000269|PubMed:10200317, ECO:0000269|PubMed:12773574,
CC ECO:0000269|PubMed:15509543, ECO:0000269|PubMed:16286645,
CC ECO:0000269|PubMed:16735444, ECO:0000269|PubMed:16968888,
CC ECO:0000269|PubMed:19626032, ECO:0000269|PubMed:21435446,
CC ECO:0000269|PubMed:8627154}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-2B subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; J05479; AAA37359.1; -; mRNA.
DR EMBL; BC138612; AAI38613.1; -; mRNA.
DR EMBL; AK146387; BAE27131.1; -; mRNA.
DR EMBL; AK150393; BAE29521.1; -; mRNA.
DR EMBL; J04134; AAA37432.1; -; mRNA.
DR EMBL; S78668; AAB34675.1; -; mRNA.
DR CCDS; CCDS17860.1; -. [P63328-1]
DR CCDS; CCDS80027.1; -. [P63328-2]
DR PIR; A42232; A31257.
DR RefSeq; NP_001280551.1; NM_001293622.1. [P63328-2]
DR RefSeq; NP_032939.1; NM_008913.5. [P63328-1]
DR PDB; 4ORB; X-ray; 3.11 A; A=1-521.
DR PDBsum; 4ORB; -.
DR AlphaFoldDB; P63328; -.
DR BMRB; P63328; -.
DR SMR; P63328; -.
DR BioGRID; 202344; 41.
DR ComplexPortal; CPX-1010; Calcineurin-Calmodulin complex, alpha-R1 variant.
DR ComplexPortal; CPX-1049; Calcineurin-Calmodulin complex, alpha-R2 variant.
DR ComplexPortal; CPX-1115; Calcineurin-Calmodulin-AKAP5 complex, alpha-R2 variant.
DR ComplexPortal; CPX-881; Calcineurin-Calmodulin-AKAP5 complex, alpha-R1 variant.
DR DIP; DIP-31543N; -.
DR IntAct; P63328; 14.
DR MINT; P63328; -.
DR STRING; 10090.ENSMUSP00000053101; -.
DR iPTMnet; P63328; -.
DR PhosphoSitePlus; P63328; -.
DR SwissPalm; P63328; -.
DR EPD; P63328; -.
DR MaxQB; P63328; -.
DR PaxDb; P63328; -.
DR PeptideAtlas; P63328; -.
DR PRIDE; P63328; -.
DR ProteomicsDB; 289791; -. [P63328-1]
DR ProteomicsDB; 289792; -. [P63328-2]
DR Antibodypedia; 2193; 608 antibodies from 44 providers.
DR DNASU; 19055; -.
DR Ensembl; ENSMUST00000056758; ENSMUSP00000053101; ENSMUSG00000028161. [P63328-1]
DR Ensembl; ENSMUST00000070198; ENSMUSP00000071040; ENSMUSG00000028161. [P63328-2]
DR GeneID; 19055; -.
DR KEGG; mmu:19055; -.
DR UCSC; uc008rmg.2; mouse. [P63328-1]
DR UCSC; uc008rmh.2; mouse. [P63328-2]
DR CTD; 5530; -.
DR MGI; MGI:107164; Ppp3ca.
DR VEuPathDB; HostDB:ENSMUSG00000028161; -.
DR eggNOG; KOG0375; Eukaryota.
DR GeneTree; ENSGT00940000156306; -.
DR HOGENOM; CLU_004962_6_0_1; -.
DR InParanoid; P63328; -.
DR OMA; MESFCCL; -.
DR OrthoDB; 463522at2759; -.
DR PhylomeDB; P63328; -.
DR TreeFam; TF105557; -.
DR Reactome; R-MMU-2025928; Calcineurin activates NFAT.
DR Reactome; R-MMU-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-MMU-4086398; Ca2+ pathway.
DR Reactome; R-MMU-5607763; CLEC7A (Dectin-1) induces NFAT activation.
DR BioGRID-ORCS; 19055; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Ppp3ca; mouse.
DR PRO; PR:P63328; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P63328; protein.
DR Bgee; ENSMUSG00000028161; Expressed in caudate-putamen and 265 other tissues.
DR ExpressionAtlas; P63328; baseline and differential.
DR Genevisible; P63328; MM.
DR GO; GO:0005955; C:calcineurin complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IMP:SynGO.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0008287; C:protein serine/threonine phosphatase complex; IC:ComplexPortal.
DR GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IMP:SynGO.
DR GO; GO:0036057; C:slit diaphragm; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0030018; C:Z disc; IDA:MGI.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0004723; F:calcium-dependent protein serine/threonine phosphatase activity; ISO:MGI.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0033192; F:calmodulin-dependent protein phosphatase activity; IDA:UniProtKB.
DR GO; GO:0016018; F:cyclosporin A binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
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:MGI.
DR GO; GO:0046983; F:protein dimerization activity; ISO:MGI.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0097720; P:calcineurin-mediated signaling; ISO:MGI.
DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IDA:MGI.
DR GO; GO:0006816; P:calcium ion transport; IMP:MGI.
DR GO; GO:0019722; P:calcium-mediated signaling; IGI:MGI.
DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; IGI:MGI.
DR GO; GO:0071333; P:cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:MGI.
DR GO; GO:0016311; P:dephosphorylation; IDA:MGI.
DR GO; GO:0008544; P:epidermis development; IMP:UniProtKB.
DR GO; GO:0060079; P:excitatory postsynaptic potential; IGI:MGI.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:MGI.
DR GO; GO:0030216; P:keratinocyte differentiation; IMP:UniProtKB.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IMP:UniProtKB.
DR GO; GO:0033555; P:multicellular organismal response to stress; IDA:MGI.
DR GO; GO:1905949; P:negative regulation of calcium ion import across plasma membrane; IC:ComplexPortal.
DR GO; GO:0035562; P:negative regulation of chromatin binding; IMP:MGI.
DR GO; GO:0050774; P:negative regulation of dendrite morphogenesis; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0046676; P:negative regulation of insulin secretion; ISO:MGI.
DR GO; GO:1903799; P:negative regulation of miRNA maturation; IDA:BHF-UCL.
DR GO; GO:0023057; P:negative regulation of signaling; IMP:UniProtKB.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; IC:ComplexPortal.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; ISO:MGI.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IMP:UniProtKB.
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:0010613; P:positive regulation of cardiac muscle hypertrophy; IGI:BHF-UCL.
DR GO; GO:1903244; P:positive regulation of cardiac muscle hypertrophy in response to stress; IDA:BHF-UCL.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:1905205; P:positive regulation of connective tissue replacement; IGI:BHF-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0045807; P:positive regulation of endocytosis; IMP:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0090193; P:positive regulation of glomerulus development; IMP:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:UniProtKB.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IMP:UniProtKB.
DR GO; GO:0046878; P:positive regulation of saliva secretion; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:1901387; P:positive regulation of voltage-gated calcium channel activity; IC:ComplexPortal.
DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; IMP:SynGO.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IDA:MGI.
DR GO; GO:0061006; P:regulation of cell proliferation involved in kidney morphogenesis; IMP:UniProtKB.
DR GO; GO:0097205; P:renal filtration; IMP:UniProtKB.
DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl.
DR GO; GO:0051592; P:response to calcium ion; ISS:UniProtKB.
DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:UniProtKB.
DR GO; GO:0014883; P:transition between fast and slow fiber; IDA:MGI.
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_0000058823"
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:0000269|PubMed:26794871"
FT REGION 392..406
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:26794871"
FT REGION 407..414
FT /note="Autoinhibitory segment"
FT /evidence="ECO:0000269|PubMed:26794871"
FT REGION 465..487
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000269|PubMed:26794871"
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:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4ORB"
FT BINDING 92
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4ORB"
FT BINDING 118
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4ORB"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4ORB"
FT BINDING 150
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4ORB"
FT BINDING 199
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4ORB"
FT BINDING 281
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26794871,
FT ECO:0007744|PDB:4ORB"
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:0007744|PubMed:16800626"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63329"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 448..457
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018563"
FT MUTAGEN 348..521
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 389..521
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 406..521
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 442..521
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 MUTAGEN 477
FT /note="D->N: Greatly reduces inhibition of calcineurin
FT phosphatase activity."
FT /evidence="ECO:0000269|PubMed:7791792"
FT HELIX 31..34
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 43..51
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 58..72
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 95..105
FT /evidence="ECO:0007829|PDB:4ORB"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 126..139
FT /evidence="ECO:0007829|PDB:4ORB"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 154..159
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 161..169
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 172..182
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:4ORB"
FT TURN 192..194
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 195..200
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 209..213
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 226..232
FT /evidence="ECO:0007829|PDB:4ORB"
FT TURN 237..240
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:4ORB"
FT TURN 252..254
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 255..260
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 262..271
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 275..279
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 286..290
FT /evidence="ECO:0007829|PDB:4ORB"
FT TURN 295..297
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 298..306
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 318..325
FT /evidence="ECO:0007829|PDB:4ORB"
FT STRAND 328..334
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 344..346
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 349..369
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 470..476
FT /evidence="ECO:0007829|PDB:4ORB"
FT HELIX 478..481
FT /evidence="ECO:0007829|PDB:4ORB"
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
