PP2BA_HUMAN
ID PP2BA_HUMAN Reviewed; 521 AA.
AC Q08209; A1A441; A8K3B7; A8W6Z7; A8W6Z8; B5BUA2; Q8TAW9;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 224.
DE RecName: Full=Protein phosphatase 3 catalytic subunit alpha {ECO:0000312|HGNC:HGNC:9314};
DE EC=3.1.3.16 {ECO:0000269|PubMed:15671020, ECO:0000269|PubMed:18838687, ECO:0000269|PubMed:19154138, ECO:0000269|PubMed:23468591, ECO:0000305|PubMed:26248042};
DE AltName: Full=CAM-PRP catalytic subunit;
DE AltName: Full=Calcineurin A alpha {ECO:0000303|PubMed:8392375};
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:0000312|HGNC:HGNC:9314};
GN Name=PPP3CA {ECO:0000312|HGNC:HGNC:9314}; Synonyms=CALNA, CNA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8392375; DOI=10.1016/0167-4889(93)90117-8;
RA Muramatsu T., Kincaid R.L.;
RT "Molecular cloning of a full-length cDNA encoding the catalytic subunit of
RT human calmodulin-dependent protein phosphatase (calcineurin A alpha).";
RL Biochim. Biophys. Acta 1178:117-120(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), AND ALTERNATIVE SPLICING.
RX PubMed=20590401; DOI=10.3109/10826084.2010.482449;
RA Chiocco M.J., Zhu X., Walther D., Pletnikova O., Troncoso J.C., Uhl G.R.,
RA Liu Q.R.;
RT "Fine mapping of calcineurin (PPP3CA) gene reveals novel alternative
RT splicing patterns, association of 5'UTR trinucleotide repeat with addiction
RT vulnerability, and differential isoform expression in Alzheimer's
RT disease.";
RL Subst. Use Misuse 45:1809-1826(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RX PubMed=21647268;
RA Landreville S., Lupien C.B., Vigneault F., Gaudreault M., Mathieu M.,
RA Rousseau A.P., Guerin S.L., Salesse C.;
RT "Identification of differentially expressed genes in uveal melanoma using
RT suppressive subtractive hybridization.";
RL Mol. Vis. 17:1324-1333(2011).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Pancreas;
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 [10]
RP INTERACTION WITH 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 MYOZ3.
RX PubMed=11842093; DOI=10.1074/jbc.m200712200;
RA Frey N., Olson E.N.;
RT "Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin
RT family, interacts with multiple Z-disc proteins.";
RL J. Biol. Chem. 277:13998-14004(2002).
RN [12]
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 [13]
RP INTERACTION WITH CRTC2.
RX PubMed=15454081; DOI=10.1016/j.cell.2004.09.015;
RA Screaton R.A., Conkright M.D., Katoh Y., Best J.L., Canettieri G.,
RA Jeffries S., Guzman E., Niessen S., Yates J.R. III, Takemori H.,
RA Okamoto M., Montminy M.;
RT "The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive
RT coincidence detector.";
RL Cell 119:61-74(2004).
RN [14]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15671020; DOI=10.1074/jbc.m411494200;
RA Wang Y., Shibasaki F., Mizuno K.;
RT "Calcium signal-induced cofilin dephosphorylation is mediated by Slingshot
RT via calcineurin.";
RL J. Biol. Chem. 280:12683-12689(2005).
RN [15]
RP INTERACTION WITH SYNPO2.
RX PubMed=17923693; DOI=10.1128/mcb.00950-07;
RA Faul C., Dhume A., Schecter A.D., Mundel P.;
RT "Protein kinase A, Ca2+/calmodulin-dependent kinase II, and calcineurin
RT regulate the intracellular trafficking of myopodin between the Z-disc and
RT the nucleus of cardiac myocytes.";
RL Mol. Cell. Biol. 27:8215-8227(2007).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH DMN1L.
RX PubMed=18838687; DOI=10.1073/pnas.0808249105;
RA Cereghetti G.M., Stangherlin A., Martins de Brito O., Chang C.R.,
RA Blackstone C., Bernardi P., Scorrano L.;
RT "Dephosphorylation by calcineurin regulates translocation of Drp1 to
RT mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:15803-15808(2008).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19154138; DOI=10.1021/bi8019355;
RA Kilka S., Erdmann F., Migdoll A., Fischer G., Weiwad M.;
RT "The proline-rich N-terminal sequence of calcineurin Abeta determines
RT substrate binding.";
RL Biochemistry 48:1900-1910(2009).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-492, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP INVOLVEMENT IN IECEE1, AND VARIANTS IECEE1 ARG-92; GLN-281; LYS-282;
RP 445-GLN--GLN-521 DEL AND THR-447.
RX PubMed=28942967; DOI=10.1016/j.ajhg.2017.08.013;
RA Myers C.T., Stong N., Mountier E.I., Helbig K.L., Freytag S.,
RA Sullivan J.E., Ben Zeev B., Nissenkorn A., Tzadok M., Heimer G.,
RA Shinde D.N., Rezazadeh A., Regan B.M., Oliver K.L., Ernst M.E., Lippa N.C.,
RA Mulhern M.S., Ren Z., Poduri A., Andrade D.M., Bird L.M., Bahlo M.,
RA Berkovic S.F., Lowenstein D.H., Scheffer I.E., Sadleir L.G.,
RA Goldstein D.B., Mefford H.C., Heinzen E.L.;
RT "De Novo Mutations in PPP3CA Cause Severe Neurodevelopmental Disease with
RT Seizures.";
RL Am. J. Hum. Genet. 101:516-524(2017).
RN [22]
RP TISSUE SPECIFICITY.
RX PubMed=29043977; DOI=10.7554/elife.27356;
RA Mishra A., Oules B., Pisco A.O., Ly T., Liakath-Ali K., Walko G.,
RA Viswanathan P., Tihy M., Nijjher J., Dunn S.J., Lamond A.I., Watt F.M.;
RT "A protein phosphatase network controls the temporal and spatial dynamics
RT of differentiation commitment in human epidermis.";
RL Elife 6:0-0(2017).
RN [23]
RP INTERACTION WITH C16ORF74, AND SUBCELLULAR LOCATION.
RX PubMed=28881575; DOI=10.18632/oncotarget.10912;
RA Nakamura T., Katagiri T., Sato S., Kushibiki T., Hontani K., Tsuchikawa T.,
RA Hirano S., Nakamura Y.;
RT "Overexpression of C16orf74 is involved in aggressive pancreatic cancers.";
RL Oncotarget 8:50460-50475(2017).
RN [24]
RP FUNCTION, AND 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 FUNCTION.
RX PubMed=33691586; DOI=10.1080/15548627.2021.1896925;
RA Mohamud Y., Tang H., Xue Y.C., Liu H., Ng C.S., Bahreyni A., Luo H.;
RT "Coxsackievirus B3 targets TFEB to disrupt lysosomal function.";
RL Autophagy 10:1-15(2021).
RN [26]
RP INTERACTION WITH SPATA33.
RX PubMed=34446558; DOI=10.1073/pnas.2106673118;
RA Miyata H., Oura S., Morohoshi A., Shimada K., Mashiko D., Oyama Y.,
RA Kaneda Y., Matsumura T., Abbasi F., Ikawa M.;
RT "SPATA33 localizes calcineurin to the mitochondria and regulates sperm
RT motility in mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH PPP3R1; IRON AND
RP ZINC, AND ACTIVE SITE.
RX PubMed=8524402; DOI=10.1038/378641a0;
RA Kissinger C.R., Parge H.E., Knighton D.R., Lewis C.T., Pelletier L.A.,
RA Tempczyk A., Kalish V.J., Tucker K.D., Showalter R.E., Moomaw E.W.,
RA Gastinel L.N., Habuka N., Chen X., Maldonado F., Barker J.E., Bacquet R.,
RA Villafranca J.E.;
RT "Crystal structures of human calcineurin and the human FKBP12-FK506-
RT calcineurin complex.";
RL Nature 378:641-644(1995).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 1-372 IN COMPLEX WITH PPIA;
RP PPP3R1; IRON AND ZINC.
RX PubMed=12218175; DOI=10.1073/pnas.192206699;
RA Huai Q., Kim H.Y., Liu Y., Zhao Y., Mondragon A., Liu J.O., Ke H.;
RT "Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but
RT distinct recognition of immunophilin-drug complexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:12037-12042(2002).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 20-392 IN COMPLEX WITH PPIA AND
RP PPP3R1.
RX PubMed=12357034; DOI=10.1073/pnas.212504399;
RA Jin L., Harrison S.C.;
RT "Crystal structure of human calcineurin complexed with cyclosporin A and
RT human cyclophilin.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13522-13526(2002).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-380 IN COMPLEX WITH SUBSTRATE
RP PEPTIDE; PPP3R1; IRON AND ZINC, AND FUNCTION.
RX PubMed=17498738; DOI=10.1016/j.jmb.2007.04.032;
RA Li H., Zhang L., Rao A., Harrison S.C., Hogan P.G.;
RT "Structure of calcineurin in complex with PVIVIT peptide: portrait of a
RT low-affinity signalling interaction.";
RL J. Mol. Biol. 369:1296-1306(2007).
RN [31]
RP STRUCTURE BY NMR OF 21-347 IN COMPLEX WITH PEPTIDE SUBSTRATE, AND FUNCTION.
RX PubMed=17502104; DOI=10.1016/j.str.2007.03.015;
RA Takeuchi K., Roehrl M.H., Sun Z.Y., Wagner G.;
RT "Structure of the calcineurin-NFAT complex: defining a T cell activation
RT switch using solution NMR and crystal coordinates.";
RL Structure 15:587-597(2007).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 389-413 IN COMPLEX WITH CALM1.
RX PubMed=18384083; DOI=10.1002/prot.22032;
RA Ye Q., Wang H., Zheng J., Wei Q., Jia Z.;
RT "The complex structure of calmodulin bound to a calcineurin peptide.";
RL Proteins 73:19-27(2008).
RN [33]
RP STRUCTURE BY NMR OF 391-414 IN COMPLEX WITH CALM1.
RA Chyan C., Huang J., Irene D., Lin T.;
RT "Structure of Calmodulin complexed with the Calmodulin Binding Domain of
RT Calcineurin.";
RL Submitted (JAN-2008) to the PDB data bank.
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 395-411 IN COMPLEX WITH CALM1.
RX PubMed=19404396; DOI=10.1371/journal.pone.0005402;
RA Majava V., Kursula P.;
RT "Domain swapping and different oligomeric States for the complex between
RT calmodulin and the calmodulin-binding domain of calcineurin a.";
RL PLoS ONE 4:E5402-E5402(2009).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 14-370 IN COMPLEX WITH PPP3R1;
RP AKAP5 PEPTIDE; IRON AND ZINC, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22343722; DOI=10.1038/nsmb.2238;
RA Li H., Pink M.D., Murphy J.G., Stein A., Dell'Acqua M.L., Hogan P.G.;
RT "Balanced interactions of calcineurin with AKAP79 regulate Ca2+-
RT calcineurin-NFAT signaling.";
RL Nat. Struct. Mol. Biol. 19:337-345(2012).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-370 IN COMPLEX WITH PPP3R1 AND
RP AFRICAN SWINE FEVER VIRUS MAL-047/A238L, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23468591; DOI=10.1371/journal.pbio.1001492;
RA Grigoriu S., Bond R., Cossio P., Chen J.A., Ly N., Hummer G., Page R.,
RA Cyert M.S., Peti W.;
RT "The molecular mechanism of substrate engagement and immunosuppressant
RT inhibition of calcineurin.";
RL PLoS Biol. 11:E1001492-E1001492(2013).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 391-414 IN COMPLEX WITH CALM1.
RX PubMed=25144868; DOI=10.1021/bi5004734;
RA Dunlap T.B., Guo H.F., Cook E.C., Holbrook E., Rumi-Masante J.,
RA Lester T.E., Colbert C.L., Vander Kooi C.W., Creamer T.P.;
RT "Stoichiometry of the calcineurin regulatory domain-calmodulin complex.";
RL Biochemistry 53:5779-5790(2014).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (3.35 ANGSTROMS) OF 2-346 IN COMPLEX WITH IRON AND
RP ZINC, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH
RP RCAN3 AND NFATC2, MOTIF, AND MUTAGENESIS OF TYR-288; TYR-341 AND
RP 328-VAL--ARG-332.
RX PubMed=26248042; DOI=10.1371/journal.pone.0134569;
RA Guasch A., Aranguren-Ibanez A., Perez-Luque R., Aparicio D.,
RA Martinez-Hoyer S., Mulero M.C., Serrano-Candelas E., Perez-Riba M.,
RA Fita I.;
RT "Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl
RT Isomerization.";
RL PLoS ONE 10:E0134569-E0134569(2015).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1-370 IN COMPLEX WITH PPP3R1;
RP PEPTIDE SUBSTRATE; IRON AND ZINC, AND FUNCTION.
RX PubMed=27974827; DOI=10.1038/srep38920;
RA Sheftic S.R., Page R., Peti W.;
RT "Investigating the human Calcineurin Interaction Network using the piLxVP
RT SLiM.";
RL Sci. Rep. 6:38920-38920(2016).
RN [40]
RP VARIANTS ACCIID LEU-470 AND THR-473, INVOLVEMENT IN ACCIID, AND VARIANTS
RP IECEE1 ARG-92; ILE-150 AND GLU-234.
RX PubMed=29432562; DOI=10.1093/hmg/ddy052;
RA Mizuguchi T., Nakashima M., Kato M., Okamoto N., Kurahashi H.,
RA Ekhilevitch N., Shiina M., Nishimura G., Shibata T., Matsuo M., Ikeda T.,
RA Ogata K., Tsuchida N., Mitsuhashi S., Miyatake S., Takata A., Miyake N.,
RA Hata K., Kaname T., Matsubara Y., Saitsu H., Matsumoto N.;
RT "Loss-of-function and gain-of-function mutations in PPP3CA cause two
RT distinct disorders.";
RL Hum. Mol. Genet. 27:1421-1433(2018).
RN [41]
RP VARIANT IECEE1 442-GLN--GLN-521 DEL, CHARACTERIZATION OF VARIANT IECEE1
RP 442-GLN--GLN-521 DEL, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=30254215; DOI=10.1038/s41431-018-0254-8;
RA Rydzanicz M., Wachowska M., Cook E.C., Lisowski P., Kuzniewska B.,
RA Szymanska K., Diecke S., Prigione A., Szczaluba K., Szybinska A.,
RA Koppolu A., Murcia Pienkowski V., Kosinska J., Wiweger M., Kostrzewa G.,
RA Brzozowska M., Domanska-Pakiela D., Jurkiewicz E., Stawinski P.,
RA Gromadka A., Zielenkiewicz P., Demkow U., Dziembowska M., Kuznicki J.,
RA Creamer T.P., Ploski R.;
RT "Novel calcineurin A (PPP3CA) variant associated with epilepsy,
RT constitutive enzyme activation and downregulation of protein expression.";
RL Eur. J. Hum. Genet. 27:61-69(2019).
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:15671020, PubMed:18838687,
CC PubMed:19154138, PubMed:23468591, PubMed:30254215). Many of the
CC substrates contain a PxIxIT motif and/or a LxVP motif (PubMed:17498738,
CC PubMed:17502104, PubMed:22343722, PubMed:23468591, PubMed:27974827). In
CC response to increased Ca(2+) levels, dephosphorylates and activates
CC phosphatase SSH1 which results in cofilin dephosphorylation
CC (PubMed:15671020). In response to increased Ca(2+) levels following
CC mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L
CC translocation to the mitochondrion (PubMed:18838687). 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
CC (PubMed:19154138). In response to increased Ca(2+) levels, regulates
CC NFAT-mediated transcription probably by dephosphorylating NFAT and
CC promoting its nuclear translocation (PubMed:26248042). Dephosphorylates
CC and inactivates transcription factor ELK1 (PubMed:19154138).
CC Dephosphorylates DARPP32 (PubMed:19154138). May dephosphorylate CRTC2
CC at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins
CC (PubMed:30611118). Dephosphorylates transcription factor TFEB at 'Ser-
CC 211' following Coxsackievirus B3 infection, promoting nuclear
CC translocation (PubMed:33691586). 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:P63329, ECO:0000269|PubMed:15671020,
CC ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:17502104,
CC ECO:0000269|PubMed:18838687, ECO:0000269|PubMed:19154138,
CC ECO:0000269|PubMed:22343722, ECO:0000269|PubMed:23468591,
CC ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827,
CC ECO:0000269|PubMed:30254215, ECO:0000269|PubMed:30611118,
CC ECO:0000269|PubMed:33691586}.
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:15671020, ECO:0000269|PubMed:18838687,
CC ECO:0000269|PubMed:19154138, ECO:0000269|PubMed:23468591,
CC ECO:0000305|PubMed:26248042};
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:15671020, ECO:0000269|PubMed:18838687,
CC ECO:0000269|PubMed:19154138, ECO:0000269|PubMed:23468591,
CC ECO:0000305|PubMed:26248042};
CC -!- COFACTOR:
CC Name=Fe(3+); Xref=ChEBI:CHEBI:29034;
CC Evidence={ECO:0000269|PubMed:12218175, ECO:0000269|PubMed:17498738,
CC ECO:0000269|PubMed:22343722, ECO:0000269|PubMed:26248042,
CC ECO:0000269|PubMed:27974827, ECO:0000269|PubMed:8524402};
CC Note=Binds 1 Fe(3+) ion per subunit. {ECO:0000269|PubMed:12218175,
CC ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:22343722,
CC ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827,
CC ECO:0000269|PubMed:8524402};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:12218175, ECO:0000269|PubMed:17498738,
CC ECO:0000269|PubMed:22343722, ECO:0000269|PubMed:26248042,
CC ECO:0000269|PubMed:27974827, ECO:0000269|PubMed:8524402};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:12218175,
CC ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:22343722,
CC ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827,
CC ECO:0000269|PubMed:8524402};
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)-bound calmodulin following an
CC increase in intracellular Ca(2+). At low Ca(2+) concentrations, the
CC catalytic subunit (also known as calcineurin A) is inactive and is
CC bound to the regulatory subunit (also known as calcineurin B) in which
CC only two high-affinity binding sites are occupied by Ca(2+). In
CC response to elevated calcium levels, the occupancy of the low-affinity
CC sites on calcineurin B by Ca(2+) causes a conformational change of the
CC C-terminal regulatory domain of calcineurin A, resulting in the
CC exposure of the calmodulin-binding domain and in the partial activation
CC of calcineurin A. The subsequent binding of Ca(2+)-bound calmodulin
CC leads to the displacement of the autoinhibitory domain from the active
CC site and possibly of the autoinhibitory segment from the substrate
CC binding site which fully activates calcineurin A. 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
CC (PubMed:26248042). {ECO:0000250|UniProtKB:P16298,
CC ECO:0000269|PubMed:26248042}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.04 uM for NFATC1 {ECO:0000269|PubMed:19154138};
CC KM=2.22 uM for DARPP32 {ECO:0000269|PubMed:19154138};
CC -!- SUBUNIT: Forms a complex composed of a calmodulin-dependent catalytic
CC subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding
CC subunit (also known as calcineurin B) (PubMed:8524402, PubMed:12218175,
CC PubMed:12357034, PubMed:17498738, PubMed:22343722, PubMed:23468591,
CC PubMed:27974827). There are three catalytic subunits, each encoded by a
CC separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits
CC which are also encoded by separate genes (PPP3R1 and PPP3R2). In
CC response to an increase in Ca(2+) intracellular levels, forms a complex
CC composed of PPP3CA/calcineurin A, calcineurin B and calmodulin (By
CC similarity). Interacts (via calcineurin B binding domain) with
CC regulatory subunit PPP3R1/calcineurin B (PubMed:8524402,
CC PubMed:12218175, PubMed:12357034, PubMed:17498738, PubMed:22343722,
CC PubMed:23468591, PubMed:27974827). Interacts (via calmodulin-binding
CC domain) with CALM1/calmodulin; the interaction depends on calmodulin
CC binding to Ca(2+) (PubMed:18384083, Ref.33, PubMed:19404396,
CC PubMed:25144868). Forms a complex composed of MYOZ2 and ACTN1 (By
CC similarity). Within the complex interacts with MYOZ2 (PubMed:11114196).
CC Interacts with MYOZ1 (PubMed:11114196). Interacts with MYOZ3
CC (PubMed:11842093). Interacts with CIB1; the interaction increases upon
CC cardiomyocyte hypertrophy (By similarity). Interacts with CHP1 and CHP2
CC (By similarity). Interacts with CRTC1 (PubMed:30611118). Interacts with
CC CRTC2 (PubMed:15454081, PubMed:30611118). Interacts with DNM1L; the
CC interaction dephosphorylates DNM1L and promotes its translocation to
CC mitochondria (PubMed:18838687). Interacts with CMYA5; this interaction
CC represses calcineurin activity in muscle (By similarity). Interacts
CC (constitutively active form) with SYNPO2 (PubMed:17923693). 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 (PubMed:22343722). Interacts with NFATC2 (PubMed:26248042).
CC Interacts with RCAN3 (PubMed:26248042). Interacts with PPIA
CC (PubMed:12218175, PubMed:12357034). Interacts with RCAN1
CC (PubMed:12809556). Interacts with UNC119 (By similarity). Interacts
CC with C16orf74 (via PxIxIT motif, when phosphorylated on 'Thr-44')
CC (PubMed:28881575). Interacts (via N-terminus) with MAP3K14/NIK (via C-
CC terminus and kinase domain) (By similarity). Interacts with TRAF3 (By
CC similarity). Interacts with SPATA33 (via PQIIIT motif)
CC (PubMed:34446558). {ECO:0000250|UniProtKB:P48452,
CC ECO:0000250|UniProtKB:P63328, ECO:0000250|UniProtKB:P63329,
CC ECO:0000269|PubMed:11114196, ECO:0000269|PubMed:11842093,
CC ECO:0000269|PubMed:12218175, ECO:0000269|PubMed:12357034,
CC ECO:0000269|PubMed:12809556, ECO:0000269|PubMed:15454081,
CC ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:17923693,
CC ECO:0000269|PubMed:18384083, ECO:0000269|PubMed:18838687,
CC ECO:0000269|PubMed:19404396, ECO:0000269|PubMed:22343722,
CC ECO:0000269|PubMed:23468591, ECO:0000269|PubMed:25144868,
CC ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827,
CC ECO:0000269|PubMed:28881575, ECO:0000269|PubMed:30611118,
CC ECO:0000269|PubMed:34446558, ECO:0000269|PubMed:8524402,
CC ECO:0000269|Ref.33}.
CC -!- INTERACTION:
CC Q08209; R4GN89: C16orf74; NbExp=3; IntAct=EBI-352922, EBI-10225238;
CC Q08209; P62993: GRB2; NbExp=3; IntAct=EBI-352922, EBI-401755;
CC Q08209; P63098: PPP3R1; NbExp=6; IntAct=EBI-352922, EBI-915984;
CC Q08209; P54578: USP14; NbExp=3; IntAct=EBI-352922, EBI-1048016;
CC Q08209; Q8VHW5: Cacng8; Xeno; NbExp=2; IntAct=EBI-352922, EBI-9086576;
CC Q08209-1; P24588: AKAP5; NbExp=6; IntAct=EBI-15637215, EBI-703640;
CC Q08209-1; O95644: NFATC1; NbExp=4; IntAct=EBI-15637215, EBI-6907210;
CC Q08209-1; Q13469: NFATC2; NbExp=2; IntAct=EBI-15637215, EBI-716258;
CC Q08209-1; P63098: PPP3R1; NbExp=7; IntAct=EBI-15637215, EBI-915984;
CC Q08209-1; P46939: UTRN; NbExp=3; IntAct=EBI-15637215, EBI-295856;
CC Q08209-1; O36972: A238L; Xeno; NbExp=2; IntAct=EBI-15637215, EBI-16039701;
CC Q08209-2; Q9NYB9-2: ABI2; NbExp=3; IntAct=EBI-11959013, EBI-11096309;
CC Q08209-2; P24588: AKAP5; NbExp=3; IntAct=EBI-11959013, EBI-703640;
CC Q08209-2; P49418: AMPH; NbExp=3; IntAct=EBI-11959013, EBI-7121510;
CC Q08209-2; Q9H993: ARMT1; NbExp=4; IntAct=EBI-11959013, EBI-1046033;
CC Q08209-2; Q96GX8: C16orf74; NbExp=3; IntAct=EBI-11959013, EBI-745814;
CC Q08209-2; Q96KS9: FAM167A; NbExp=3; IntAct=EBI-11959013, EBI-10290462;
CC Q08209-2; P27987: ITPKB; NbExp=3; IntAct=EBI-11959013, EBI-751388;
CC Q08209-2; P63098: PPP3R1; NbExp=13; IntAct=EBI-11959013, EBI-915984;
CC Q08209-2; Q9UPX8-4: SHANK2; NbExp=3; IntAct=EBI-11959013, EBI-11959011;
CC Q08209-2; P00441: SOD1; NbExp=3; IntAct=EBI-11959013, EBI-990792;
CC Q08209-2; Q8IZW8: TNS4; NbExp=5; IntAct=EBI-11959013, EBI-7543499;
CC Q08209-2; Q6ZMU5: TRIM72; NbExp=3; IntAct=EBI-11959013, EBI-2341648;
CC Q08209-2; Q13432: UNC119; NbExp=5; IntAct=EBI-11959013, EBI-711260;
CC Q08209-2; Q96EJ4; NbExp=3; IntAct=EBI-11959013, EBI-750454;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19154138,
CC ECO:0000269|PubMed:22343722}. Cell membrane
CC {ECO:0000269|PubMed:22343722, ECO:0000269|PubMed:28881575}; Peripheral
CC membrane protein {ECO:0000269|PubMed:22343722}. Cell membrane,
CC sarcolemma {ECO:0000250|UniProtKB:P63329}. Cytoplasm, myofibril,
CC sarcomere, Z line {ECO:0000250|UniProtKB:P63329}. Cell projection,
CC dendritic spine {ECO:0000269|PubMed:22343722}. Note=Colocalizes with
CC ACTN1 and MYOZ2 at the Z line in heart and skeletal muscle (By
CC similarity). Recruited to the cell membrane by scaffold protein AKAP5
CC following L-type Ca(2+)-channel activation (PubMed:22343722).
CC {ECO:0000250|UniProtKB:P63329, ECO:0000269|PubMed:22343722}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q08209-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q08209-2; Sequence=VSP_018562;
CC Name=3;
CC IsoId=Q08209-3; Sequence=VSP_043378, VSP_018562;
CC Name=4;
CC IsoId=Q08209-4; Sequence=VSP_047755;
CC Name=5;
CC IsoId=Q08209-5; Sequence=VSP_054467;
CC -!- TISSUE SPECIFICITY: Expressed in keratinocytes (at protein level)
CC (PubMed:29043977). Expressed in lymphoblasts (at protein level)
CC (PubMed:30254215). {ECO:0000269|PubMed:29043977,
CC ECO:0000269|PubMed:30254215}.
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:0000269|PubMed:26248042}.
CC -!- DISEASE: Epileptic encephalopathy, infantile or early childhood, 1
CC (IECEE1) [MIM:617711]: A form of epileptic encephalopathy, a
CC heterogeneous group of severe childhood onset epilepsies characterized
CC by refractory seizures, neurodevelopmental impairment, and poor
CC prognosis. Development is normal prior to seizure onset, after which
CC cognitive and motor delays become apparent. IECEE1 is an autosomal
CC dominant condition with onset of seizures between the first weeks and
CC first years of life. {ECO:0000269|PubMed:28942967,
CC ECO:0000269|PubMed:29432562, ECO:0000269|PubMed:30254215}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Arthrogryposis, cleft palate, craniosynostosis, and impaired
CC intellectual development (ACCIID) [MIM:618265]: An autosomal dominant
CC disease characterized by moderate to severe intellectual disability,
CC craniosynostosis, cleft palate, micrognathia, arthrogryposis, and short
CC stature. Some patients may present bone abnormalities and generalized
CC seizures. {ECO:0000269|PubMed:29432562}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Although African swine fever virus infects pigs and not
CC humans, human PPP3CA has been used for the crystallization. PPP3CA
CC interacts with African swine fever virus Mal-047/A238L (via PKIIIT and
CC FLCVK motifs); the interaction does not block catalytic activity per se
CC but inhibits PPP3CA function by blocking the access to the two
CC substrate recognition sites. {ECO:0000269|PubMed:23468591}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-2B subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Calcineurin entry;
CC URL="https://en.wikipedia.org/wiki/Calcineurin";
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; L14778; AAA02631.1; -; mRNA.
DR EMBL; EU192652; ABW74484.1; -; mRNA.
DR EMBL; EU192653; ABW74485.1; -; mRNA.
DR EMBL; AY904364; AAY17314.1; -; mRNA.
DR EMBL; AK290532; BAF83221.1; -; mRNA.
DR EMBL; AL353950; CAB89253.1; -; mRNA.
DR EMBL; AB451338; BAG70152.1; -; mRNA.
DR EMBL; AB451487; BAG70301.1; -; mRNA.
DR EMBL; AC092671; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001816; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001870; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001939; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471057; EAX06125.1; -; Genomic_DNA.
DR EMBL; CH471057; EAX06124.1; -; Genomic_DNA.
DR EMBL; BC025714; AAH25714.1; -; mRNA.
DR CCDS; CCDS34037.1; -. [Q08209-1]
DR CCDS; CCDS47113.1; -. [Q08209-3]
DR CCDS; CCDS47114.1; -. [Q08209-2]
DR PIR; S35067; S35067.
DR RefSeq; NP_000935.1; NM_000944.4. [Q08209-1]
DR RefSeq; NP_001124163.1; NM_001130691.1. [Q08209-2]
DR RefSeq; NP_001124164.1; NM_001130692.1. [Q08209-3]
DR PDB; 1AUI; X-ray; 2.10 A; A=1-521.
DR PDB; 1M63; X-ray; 2.80 A; A/E=1-372.
DR PDB; 1MF8; X-ray; 3.10 A; A=20-392.
DR PDB; 2JOG; NMR; -; A=21-347.
DR PDB; 2JZI; NMR; -; B=391-414.
DR PDB; 2P6B; X-ray; 2.30 A; A/C=1-380.
DR PDB; 2R28; X-ray; 1.86 A; C/D=389-413.
DR PDB; 2W73; X-ray; 1.45 A; K/L/M/O=395-411.
DR PDB; 3LL8; X-ray; 2.00 A; A/C=14-370.
DR PDB; 4F0Z; X-ray; 1.70 A; A=1-370.
DR PDB; 4Q5U; X-ray; 1.95 A; C=391-414.
DR PDB; 5C1V; X-ray; 3.35 A; A/B=2-346.
DR PDB; 5SVE; X-ray; 2.60 A; A=1-370.
DR PDB; 6NUC; X-ray; 1.90 A; A=1-370.
DR PDB; 6NUF; X-ray; 1.90 A; A=1-370.
DR PDB; 6NUU; X-ray; 2.30 A; A=1-370.
DR PDB; 6UUQ; X-ray; 1.85 A; A=26-339.
DR PDBsum; 1AUI; -.
DR PDBsum; 1M63; -.
DR PDBsum; 1MF8; -.
DR PDBsum; 2JOG; -.
DR PDBsum; 2JZI; -.
DR PDBsum; 2P6B; -.
DR PDBsum; 2R28; -.
DR PDBsum; 2W73; -.
DR PDBsum; 3LL8; -.
DR PDBsum; 4F0Z; -.
DR PDBsum; 4Q5U; -.
DR PDBsum; 5C1V; -.
DR PDBsum; 5SVE; -.
DR PDBsum; 6NUC; -.
DR PDBsum; 6NUF; -.
DR PDBsum; 6NUU; -.
DR PDBsum; 6UUQ; -.
DR AlphaFoldDB; Q08209; -.
DR BMRB; Q08209; -.
DR SMR; Q08209; -.
DR BioGRID; 111522; 109.
DR ComplexPortal; CPX-1003; Calcineurin-Calmodulin complex, alpha-R1 variant.
DR ComplexPortal; CPX-1048; Calcineurin-Calmodulin complex, alpha-R2 variant.
DR ComplexPortal; CPX-1114; Calcineurin-Calmodulin-AKAP5 complex, alpha-R2 variant.
DR ComplexPortal; CPX-674; Calcineurin-Calmodulin-AKAP5 complex, alpha-R1 variant.
DR CORUM; Q08209; -.
DR DIP; DIP-6095N; -.
DR ELM; Q08209; -.
DR IntAct; Q08209; 64.
DR MINT; Q08209; -.
DR STRING; 9606.ENSP00000378323; -.
DR BindingDB; Q08209; -.
DR ChEMBL; CHEMBL4445; -.
DR DrugBank; DB08231; Myristic acid.
DR DrugCentral; Q08209; -.
DR DEPOD; PPP3CA; -.
DR iPTMnet; Q08209; -.
DR MetOSite; Q08209; -.
DR PhosphoSitePlus; Q08209; -.
DR SwissPalm; Q08209; -.
DR BioMuta; PPP3CA; -.
DR DMDM; 1352673; -.
DR EPD; Q08209; -.
DR jPOST; Q08209; -.
DR MassIVE; Q08209; -.
DR MaxQB; Q08209; -.
DR PaxDb; Q08209; -.
DR PeptideAtlas; Q08209; -.
DR PRIDE; Q08209; -.
DR ProteomicsDB; 2488; -.
DR ProteomicsDB; 58579; -. [Q08209-1]
DR ProteomicsDB; 58580; -. [Q08209-2]
DR ProteomicsDB; 58581; -. [Q08209-3]
DR ProteomicsDB; 88; -.
DR Antibodypedia; 2193; 608 antibodies from 44 providers.
DR DNASU; 5530; -.
DR Ensembl; ENST00000323055.10; ENSP00000320580.6; ENSG00000138814.17. [Q08209-3]
DR Ensembl; ENST00000394853.8; ENSP00000378322.4; ENSG00000138814.17. [Q08209-2]
DR Ensembl; ENST00000394854.8; ENSP00000378323.3; ENSG00000138814.17. [Q08209-1]
DR Ensembl; ENST00000512215.5; ENSP00000422781.1; ENSG00000138814.17. [Q08209-4]
DR GeneID; 5530; -.
DR KEGG; hsa:5530; -.
DR MANE-Select; ENST00000394854.8; ENSP00000378323.3; NM_000944.5; NP_000935.1.
DR UCSC; uc003hvu.3; human. [Q08209-1]
DR CTD; 5530; -.
DR DisGeNET; 5530; -.
DR GeneCards; PPP3CA; -.
DR HGNC; HGNC:9314; PPP3CA.
DR HPA; ENSG00000138814; Tissue enhanced (brain).
DR MalaCards; PPP3CA; -.
DR MIM; 114105; gene.
DR MIM; 617711; phenotype.
DR MIM; 618265; phenotype.
DR neXtProt; NX_Q08209; -.
DR OpenTargets; ENSG00000138814; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR Orphanet; 565858; Craniosynostosis-microretrognathia-severe intellectual disability syndrome.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR PharmGKB; PA33678; -.
DR VEuPathDB; HostDB:ENSG00000138814; -.
DR eggNOG; KOG0375; Eukaryota.
DR GeneTree; ENSGT00940000156306; -.
DR HOGENOM; CLU_962966_0_0_1; -.
DR InParanoid; Q08209; -.
DR OMA; MESFCCL; -.
DR PhylomeDB; Q08209; -.
DR TreeFam; TF105557; -.
DR BRENDA; 3.1.3.16; 2681.
DR PathwayCommons; Q08209; -.
DR Reactome; R-HSA-180024; DARPP-32 events.
DR Reactome; R-HSA-2025928; Calcineurin activates NFAT.
DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-HSA-4086398; Ca2+ pathway.
DR Reactome; R-HSA-5607763; CLEC7A (Dectin-1) induces NFAT activation.
DR SignaLink; Q08209; -.
DR SIGNOR; Q08209; -.
DR BioGRID-ORCS; 5530; 6 hits in 1083 CRISPR screens.
DR ChiTaRS; PPP3CA; human.
DR EvolutionaryTrace; Q08209; -.
DR GeneWiki; PPP3CA; -.
DR GenomeRNAi; 5530; -.
DR Pharos; Q08209; Tchem.
DR PRO; PR:Q08209; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q08209; protein.
DR Bgee; ENSG00000138814; Expressed in Brodmann (1909) area 23 and 207 other tissues.
DR ExpressionAtlas; Q08209; baseline and differential.
DR Genevisible; Q08209; HS.
DR GO; GO:0005955; C:calcineurin complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043197; C:dendritic spine; IDA:UniProtKB.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IC:ARUK-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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; IEA:Ensembl.
DR GO; GO:0036057; C:slit diaphragm; IEA:Ensembl.
DR GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell.
DR GO; GO:0051117; F:ATPase binding; IPI:ARUK-UCL.
DR GO; GO:0005509; F:calcium ion binding; NAS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0033192; F:calmodulin-dependent protein phosphatase activity; IDA:UniProtKB.
DR GO; GO:0016018; F:cyclosporin A binding; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IDA:UniProtKB.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0046983; F:protein dimerization activity; IPI:UniProtKB.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IMP:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
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; IMP:UniProtKB.
DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IDA:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; IEA:Ensembl.
DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; IEA:Ensembl.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0048813; P:dendrite morphogenesis; IEA:Ensembl.
DR GO; GO:0016311; P:dephosphorylation; TAS:UniProtKB.
DR GO; GO:0008544; P:epidermis development; ISS:UniProtKB.
DR GO; GO:0060079; P:excitatory postsynaptic potential; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IEA:Ensembl.
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; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0050774; P:negative regulation of dendrite morphogenesis; IEA:Ensembl.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:1903799; P:negative regulation of miRNA maturation; IEA:Ensembl.
DR GO; GO:0023057; P:negative regulation of signaling; ISS:UniProtKB.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; IC:ComplexPortal.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; IMP:UniProtKB.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISS: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:1903244; P:positive regulation of cardiac muscle hypertrophy in response to stress; IEA:Ensembl.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:ARUK-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:ARUK-UCL.
DR GO; GO:1905205; P:positive regulation of connective tissue replacement; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR GO; GO:0045807; P:positive regulation of endocytosis; IEA:Ensembl.
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; IDA:BHF-UCL.
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; IEA:Ensembl.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0051592; P:response to calcium ion; IDA:UniProtKB.
DR GO; GO:0048741; P:skeletal muscle fiber development; ISS:UniProtKB.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; TAS:BHF-UCL.
DR GO; GO:0042110; P:T cell activation; TAS:UniProtKB.
DR GO; GO:0014883; P:transition between fast and slow fiber; IEA:Ensembl.
DR GO; GO:0042060; P:wound healing; TAS:BHF-UCL.
DR CDD; cd07416; MPP_PP2B; 1.
DR DisProt; DP00092; -.
DR Gene3D; 3.60.21.10; -; 1.
DR IDEAL; IID00069; -.
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; Craniosynostosis; Cytoplasm;
KW Disease variant; Dwarfism; Epilepsy; Hydrolase; Intellectual disability;
KW Iron; Membrane; Metal-binding; Nitration; Phosphoprotein;
KW Protein phosphatase; Reference proteome; Synapse; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..521
FT /note="Protein phosphatase 3 catalytic subunit alpha"
FT /id="PRO_0000058822"
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:0000269|PubMed:17498738,
FT ECO:0000269|PubMed:17502104, ECO:0000269|PubMed:22343722,
FT ECO:0000269|PubMed:23468591, ECO:0000269|PubMed:26248042"
FT REGION 341..369
FT /note="Calcineurin B binding"
FT /evidence="ECO:0000269|PubMed:12218175,
FT ECO:0000269|PubMed:12357034, ECO:0000269|PubMed:17498738,
FT ECO:0000269|PubMed:23468591, ECO:0000269|PubMed:27974827,
FT ECO:0000269|PubMed:8524402"
FT REGION 392..406
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:18384083,
FT ECO:0000269|PubMed:19404396, ECO:0000269|PubMed:25144868,
FT ECO:0000269|Ref.33"
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:8524402"
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:0000305|PubMed:26248042"
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:0000305|PubMed:8524402"
FT BINDING 90
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:12218175,
FT ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:22343722,
FT ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827,
FT ECO:0000269|PubMed:8524402, ECO:0007744|PDB:1AUI,
FT ECO:0007744|PDB:1M63, ECO:0007744|PDB:2P6B,
FT ECO:0007744|PDB:3LL8, ECO:0007744|PDB:5C1V,
FT ECO:0007744|PDB:5SVE"
FT BINDING 92
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:12218175,
FT ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:22343722,
FT ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827,
FT ECO:0000269|PubMed:8524402, ECO:0007744|PDB:1AUI,
FT ECO:0007744|PDB:1M63, ECO:0007744|PDB:2P6B,
FT ECO:0007744|PDB:3LL8, ECO:0007744|PDB:5C1V,
FT ECO:0007744|PDB:5SVE"
FT BINDING 118
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:12218175,
FT ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:22343722,
FT ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827,
FT ECO:0000269|PubMed:8524402, ECO:0007744|PDB:1AUI,
FT ECO:0007744|PDB:1M63, ECO:0007744|PDB:2P6B,
FT ECO:0007744|PDB:3LL8, ECO:0007744|PDB:5C1V,
FT ECO:0007744|PDB:5SVE"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:12218175,
FT ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:22343722,
FT ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827,
FT ECO:0000269|PubMed:8524402, ECO:0007744|PDB:1AUI,
FT ECO:0007744|PDB:1M63, ECO:0007744|PDB:2P6B,
FT ECO:0007744|PDB:3LL8, ECO:0007744|PDB:5C1V,
FT ECO:0007744|PDB:5SVE"
FT BINDING 150
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:12218175,
FT ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:22343722,
FT ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827,
FT ECO:0000269|PubMed:8524402, ECO:0007744|PDB:1AUI,
FT ECO:0007744|PDB:1M63, ECO:0007744|PDB:2P6B,
FT ECO:0007744|PDB:3LL8, ECO:0007744|PDB:5C1V,
FT ECO:0007744|PDB:5SVE"
FT BINDING 199
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:12218175,
FT ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:22343722,
FT ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827,
FT ECO:0000269|PubMed:8524402, ECO:0007744|PDB:1AUI,
FT ECO:0007744|PDB:1M63, ECO:0007744|PDB:2P6B,
FT ECO:0007744|PDB:3LL8, ECO:0007744|PDB:5C1V,
FT ECO:0007744|PDB:5SVE"
FT BINDING 281
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:12218175,
FT ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:22343722,
FT ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827,
FT ECO:0000269|PubMed:8524402, ECO:0007744|PDB:1AUI,
FT ECO:0007744|PDB:1M63, ECO:0007744|PDB:2P6B,
FT ECO:0007744|PDB:3LL8, ECO:0007744|PDB:5C1V,
FT ECO:0007744|PDB:5SVE"
FT SITE 352
FT /note="Interaction with PxVP motif in substrate"
FT /evidence="ECO:0000269|PubMed:23468591,
FT ECO:0000269|PubMed:27974827"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 224
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P63328"
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:23186163"
FT VAR_SEQ 20..86
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:21647268"
FT /id="VSP_054467"
FT VAR_SEQ 87..318
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:20590401"
FT /id="VSP_047755"
FT VAR_SEQ 318..359
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:20590401"
FT /id="VSP_043378"
FT VAR_SEQ 448..457
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:20590401"
FT /id="VSP_018562"
FT VARIANT 92
FT /note="H -> R (in IECEE1; dbSNP:rs1553925558)"
FT /evidence="ECO:0000269|PubMed:28942967,
FT ECO:0000269|PubMed:29432562"
FT /id="VAR_080348"
FT VARIANT 150
FT /note="N -> I (in IECEE1)"
FT /evidence="ECO:0000269|PubMed:29432562"
FT /id="VAR_081900"
FT VARIANT 234
FT /note="D -> E (in IECEE1)"
FT /evidence="ECO:0000269|PubMed:29432562"
FT /id="VAR_081901"
FT VARIANT 281
FT /note="H -> Q (in IECEE1; dbSNP:rs199706529)"
FT /evidence="ECO:0000269|PubMed:28942967"
FT /id="VAR_080349"
FT VARIANT 282
FT /note="E -> K (in IECEE1; dbSNP:rs1553923787)"
FT /evidence="ECO:0000269|PubMed:28942967"
FT /id="VAR_080350"
FT VARIANT 442..521
FT /note="Missing (in IECEE1; results in constitutive
FT phosphatase activity in the absence of calmodulin)"
FT /evidence="ECO:0000269|PubMed:30254215"
FT /id="VAR_085829"
FT VARIANT 445..521
FT /note="Missing (in IECEE1)"
FT /evidence="ECO:0000269|PubMed:28942967"
FT /id="VAR_080351"
FT VARIANT 447
FT /note="A -> T (in IECEE1; unknown pathological
FT significance; dbSNP:rs1553920374)"
FT /evidence="ECO:0000269|PubMed:28942967"
FT /id="VAR_080352"
FT VARIANT 470
FT /note="F -> L (in ACCIID; dbSNP:rs1560567347)"
FT /evidence="ECO:0000269|PubMed:29432562"
FT /id="VAR_081902"
FT VARIANT 473
FT /note="A -> T (in ACCIID; dbSNP:rs1560567337)"
FT /evidence="ECO:0000269|PubMed:29432562"
FT /id="VAR_081903"
FT MUTAGEN 288
FT /note="Y->F: Partial loss of Ca(2+)-mediated transcription
FT factor NFAT activation; when associated with F-341."
FT /evidence="ECO:0000269|PubMed:26248042"
FT MUTAGEN 288
FT /note="Y->N,A: Loss of Ca(2+)-mediated transcription factor
FT NFAT activation; when associated with F-341."
FT /evidence="ECO:0000269|PubMed:26248042"
FT MUTAGEN 328..332
FT /note="Missing: Loss of Ca(2+)-mediated transcription
FT factor NFAT activation; when associated with F-341."
FT /evidence="ECO:0000269|PubMed:26248042"
FT MUTAGEN 341
FT /note="Y->F: Resistant to cyclosporin A-mediated
FT inhibition. Loss of Ca(2+)-mediated transcription factor
FT NFAT activation; when associated with N-288, A-228 or 328-
FT V--R-332 DEL. Partial loss in Ca(2+)-mediated transcription
FT factor NFAT activation; when associated with F-288."
FT /evidence="ECO:0000269|PubMed:26248042"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:6NUC"
FT HELIX 31..34
FT /evidence="ECO:0007829|PDB:4F0Z"
FT HELIX 43..51
FT /evidence="ECO:0007829|PDB:4F0Z"
FT HELIX 58..73
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:4F0Z"
FT HELIX 95..105
FT /evidence="ECO:0007829|PDB:4F0Z"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:6UUQ"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:4F0Z"
FT HELIX 126..139
FT /evidence="ECO:0007829|PDB:4F0Z"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:4F0Z"
FT HELIX 154..159
FT /evidence="ECO:0007829|PDB:4F0Z"
FT HELIX 162..169
FT /evidence="ECO:0007829|PDB:4F0Z"
FT HELIX 172..183
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:4F0Z"
FT TURN 192..194
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 195..200
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:2JOG"
FT HELIX 210..213
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:4F0Z"
FT HELIX 226..232
FT /evidence="ECO:0007829|PDB:4F0Z"
FT TURN 237..240
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 247..250
FT /evidence="ECO:0007829|PDB:4F0Z"
FT TURN 252..254
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 255..260
FT /evidence="ECO:0007829|PDB:4F0Z"
FT HELIX 262..271
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 276..279
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 287..290
FT /evidence="ECO:0007829|PDB:4F0Z"
FT TURN 295..297
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 298..306
FT /evidence="ECO:0007829|PDB:4F0Z"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 319..325
FT /evidence="ECO:0007829|PDB:4F0Z"
FT STRAND 328..334
FT /evidence="ECO:0007829|PDB:4F0Z"
FT HELIX 344..346
FT /evidence="ECO:0007829|PDB:4F0Z"
FT HELIX 349..369
FT /evidence="ECO:0007829|PDB:4F0Z"
FT HELIX 396..409
FT /evidence="ECO:0007829|PDB:2W73"
FT HELIX 470..477
FT /evidence="ECO:0007829|PDB:1AUI"
FT HELIX 478..481
FT /evidence="ECO:0007829|PDB:1AUI"
SQ SEQUENCE 521 AA; 58688 MW; 16480D62DDBF1F40 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 SYPAVCEFLQ HNNLLSILRA HEAQDAGYRM YRKSQTTGFP
SLITIFSAPN YLDVYNNKAA VLKYENNVMN IRQFNCSPHP YWLPNFMDVF TWSLPFVGEK
VTEMLVNVLN ICSDDELGSE EDGFDGATAA ARKEVIRNKI RAIGKMARVF SVLREESESV
LTLKGLTPTG MLPSGVLSGG KQTLQSATVE AIEADEAIKG FSPQHKITSF EEAKGLDRIN
ERMPPRRDAM PSDANLNSIN KALTSETNGT DSNGSNSSNI Q
