PP2BC_MOUSE
ID PP2BC_MOUSE Reviewed; 513 AA.
AC P48455; Q3V074;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform;
DE EC=3.1.3.16 {ECO:0000250|UniProtKB:P48454};
DE AltName: Full=CAM-PRP catalytic subunit;
DE AltName: Full=Calcineurin, testis-specific catalytic subunit;
DE AltName: Full=Calmodulin-dependent calcineurin A subunit gamma isoform;
GN Name=Ppp3cc; Synonyms=Calnc;
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], AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=1309945; DOI=10.1073/pnas.89.2.529;
RA Muramatsu T., Giri P.R., Higuchi S., Kincaid R.L.;
RT "Molecular cloning of a calmodulin-dependent phosphatase from murine
RT testis: identification of a developmentally expressed nonneural
RT isoenzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:529-533(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE21630.1};
RC TISSUE=Testis {ECO:0000312|EMBL:BAE21630.1};
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:AAI41080.1};
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 [5]
RP TISSUE SPECIFICITY.
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
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 [7]
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 [8]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH SPATA33 AND
RP VDAC2.
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).
CC -!- FUNCTION: Calcium-dependent, calmodulin-stimulated protein phosphatase
CC which plays an essential role in the transduction of intracellular
CC Ca(2+)-mediated signals. Dephosphorylates and activates transcription
CC factor NFATC1. Dephosphorylates and inactivates transcription factor
CC ELK1. Dephosphorylates DARPP32. {ECO:0000250|UniProtKB:P48454}.
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:0000250|UniProtKB:P48454};
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:0000250|UniProtKB:P48454};
CC -!- COFACTOR:
CC Name=Fe(3+); Xref=ChEBI:CHEBI:29034;
CC Evidence={ECO:0000250|UniProtKB:P16298};
CC Note=Binds 1 Fe(3+) ion per subunit. {ECO:0000250|UniProtKB:P16298};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P16298};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P16298};
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)-bound calmodulin following an
CC increase in intracellular Ca(2+). At low Ca(2+) concentrations, the
CC catalytic subunit (also known as calcineurin A) is inactive and is
CC bound to the regulatory subunit (also known as calcineurin B) in which
CC only two high-affinity binding sites are occupied by Ca(2+). In
CC response to elevated calcium levels, the occupancy of the low-affinity
CC sites on calcineurin B by Ca(2+) causes a conformational change of the
CC C-terminal regulatory domain of calcineurin A, resulting in the
CC exposure of the calmodulin-binding domain and in the partial activation
CC of calcineurin A. The subsequent binding of Ca(2+)-bound calmodulin
CC leads to the displacement of the autoinhibitory domain from the active
CC site and possibly of the autoinhibitory segment from the substrate
CC binding site which fully activates calcineurin A.
CC {ECO:0000250|UniProtKB:P16298}.
CC -!- SUBUNIT: Forms a complex composed of a calmodulin-dependent catalytic
CC subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding
CC subunit (also known as calcineurin B). There are three catalytic
CC subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC)
CC and two regulatory subunits which are also encoded by separate genes
CC (PPP3R1 and PPP3R2). In response to an increase in Ca(2+) intracellular
CC levels, forms a complex composed of PPP3CC/calcineurin A, calcineurin B
CC and calmodulin. Interacts (via calmodulin-binding domain) with
CC calmodulin; the interaction depends on calmodulin binding to Ca(2+) (By
CC similarity). Interacts with UNC119 (PubMed:31696965). Interacts with
CC SPATA33 (via PQIIIT motif) (PubMed:34446558). Interacts with VDAC2 in a
CC SPATA33-dependent manner (PubMed:34446558).
CC {ECO:0000250|UniProtKB:P16298, ECO:0000250|UniProtKB:P48454,
CC ECO:0000269|PubMed:31696965, ECO:0000269|PubMed:34446558}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:34446558}.
CC Note=Localizes in the mitochondria in a SPATA33-dependent manner.
CC {ECO:0000269|PubMed:34446558}.
CC -!- TISSUE SPECIFICITY: Expressed in osteoblasts and bone marrow (at
CC protein level) (PubMed:16286645). Expressed in the testis
CC (PubMed:1309945, PubMed:34446558). Expressed in the sperm midpiece in a
CC SPATA33-dependent manner (at protein level) (PubMed:34446558).
CC {ECO:0000269|PubMed:1309945, ECO:0000269|PubMed:16286645,
CC ECO:0000269|PubMed:34446558}.
CC -!- DOMAIN: The autoinhibitory domain prevents access to the catalytic
CC site. {ECO:0000250|UniProtKB:P16298}.
CC -!- DOMAIN: The autoinhibitory segment prevents access to the substrate
CC binding site. {ECO:0000250|UniProtKB:P16298}.
CC -!- DOMAIN: Possible isomerization of Pro-305 within the SAPNY motif
CC triggers a conformation switch which affects the organization and thus
CC accessibility of the active site and the substrate binding region
CC (PxIxIF motif). The trans- to cis-transition may favor calcineurin A
CC activation and substrate binding. The reverse cis- to trans-transition
CC may be enhanced by peptidyl-prolyl isomerases such as PPIA.
CC {ECO:0000250|UniProtKB:Q08209}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-2B subfamily.
CC {ECO:0000305}.
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DR EMBL; M81475; AAA39968.1; -; mRNA.
DR EMBL; AK133393; BAE21630.1; -; mRNA.
DR EMBL; CH466535; EDL35914.1; -; Genomic_DNA.
DR EMBL; BC141079; AAI41080.1; -; mRNA.
DR CCDS; CCDS36968.1; -.
DR PIR; A38193; A38193.
DR RefSeq; NP_032941.1; NM_008915.3.
DR AlphaFoldDB; P48455; -.
DR SMR; P48455; -.
DR BioGRID; 202346; 5.
DR ComplexPortal; CPX-1007; Calcineurin-Calmodulin complex, gamma-R1 variant.
DR ComplexPortal; CPX-1051; Calcineurin-Calmodulin complex, gamma-R2 variant.
DR ComplexPortal; CPX-1113; Calcineurin-Calmodulin-AKAP5 complex, gamma-R1 variant.
DR ComplexPortal; CPX-1119; Calcineurin-Calmodulin-AKAP5 complex, gamma-R2 variant.
DR IntAct; P48455; 1.
DR STRING; 10090.ENSMUSP00000077532; -.
DR iPTMnet; P48455; -.
DR PhosphoSitePlus; P48455; -.
DR EPD; P48455; -.
DR PaxDb; P48455; -.
DR PeptideAtlas; P48455; -.
DR PRIDE; P48455; -.
DR ProteomicsDB; 291779; -.
DR Antibodypedia; 9535; 232 antibodies from 30 providers.
DR DNASU; 19057; -.
DR Ensembl; ENSMUST00000078434; ENSMUSP00000077532; ENSMUSG00000022092.
DR GeneID; 19057; -.
DR KEGG; mmu:19057; -.
DR UCSC; uc007unp.2; mouse.
DR CTD; 5533; -.
DR MGI; MGI:107162; Ppp3cc.
DR VEuPathDB; HostDB:ENSMUSG00000022092; -.
DR eggNOG; KOG0375; Eukaryota.
DR GeneTree; ENSGT00940000154115; -.
DR HOGENOM; CLU_004962_6_0_1; -.
DR InParanoid; P48455; -.
DR PhylomeDB; P48455; -.
DR TreeFam; TF105557; -.
DR Reactome; R-MMU-111447; Activation of BAD and translocation to mitochondria.
DR BioGRID-ORCS; 19057; 3 hits in 59 CRISPR screens.
DR ChiTaRS; Ppp3cc; mouse.
DR PRO; PR:P48455; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P48455; protein.
DR Bgee; ENSMUSG00000022092; Expressed in spermatocyte and 229 other tissues.
DR ExpressionAtlas; P48455; baseline and differential.
DR Genevisible; P48455; MM.
DR GO; GO:0005955; C:calcineurin complex; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IC:ComplexPortal.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0098793; C:presynapse; ISO:MGI.
DR GO; GO:0099523; C:presynaptic cytosol; IDA:SynGO.
DR GO; GO:0008287; C:protein serine/threonine phosphatase complex; IC:ComplexPortal.
DR GO; GO:0036126; C:sperm flagellum; IDA:MGI.
DR GO; GO:0097225; C:sperm midpiece; IDA:UniProtKB.
DR GO; GO:0097226; C:sperm mitochondrial sheath; IDA:MGI.
DR GO; GO:0004723; F:calcium-dependent protein serine/threonine phosphatase activity; IDA:MGI.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0033192; F:calmodulin-dependent protein phosphatase activity; 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:0097720; P:calcineurin-mediated signaling; IBA:GO_Central.
DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; ISO:MGI.
DR GO; GO:1905949; P:negative regulation of calcium ion import across plasma membrane; IC:ComplexPortal.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; IC:ComplexPortal.
DR GO; GO:0007341; P:penetration of zona pellucida; IMP:MGI.
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:1900244; P:positive regulation of synaptic vesicle endocytosis; ISO:MGI.
DR GO; GO:1901387; P:positive regulation of voltage-gated calcium channel activity; IC:ComplexPortal.
DR GO; GO:0006470; P:protein dephosphorylation; ISO:MGI.
DR GO; GO:1900242; P:regulation of synaptic vesicle endocytosis; ISO: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 Calmodulin-binding; Hydrolase; Iron; Metal-binding; Mitochondrion;
KW Protein phosphatase; Reference proteome; Zinc.
FT CHAIN 1..513
FT /note="Serine/threonine-protein phosphatase 2B catalytic
FT subunit gamma isoform"
FT /id="PRO_0000058829"
FT REGION 52..343
FT /note="Catalytic"
FT /evidence="ECO:0000305"
FT REGION 344..366
FT /note="Calcineurin B binding"
FT /evidence="ECO:0000250|UniProtKB:P16298"
FT REGION 385..399
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:P16298"
FT REGION 400..407
FT /note="Autoinhibitory segment"
FT /evidence="ECO:0000250|UniProtKB:P16298"
FT REGION 458..480
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250|UniProtKB:P16298"
FT REGION 472..513
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 303..307
FT /note="SAPNY motif"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT ACT_SITE 147
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 86
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P16298"
FT BINDING 88
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P16298"
FT BINDING 114
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P16298"
FT BINDING 114
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P16298"
FT BINDING 146
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P16298"
FT BINDING 195
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P16298"
FT BINDING 277
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P16298"
SQ SEQUENCE 513 AA; 58699 MW; 521CB2B1DD9E03A0 CRC64;
MSVRRPQFST TERVIKAVPF PPTRRLTLKE VFENGKPKMD LLKNHLVKEG RVEEEVALKI
INDGAAILKQ EKTMIEVEAP ITVCGDVHGQ FFDLMKLFEV GGSPSNTRYL FLGDYVDRGY
FSIECVLYLW SLKINHPKTL FLLRGNHECR HLTEYFTFKQ ECRIKYSEMV YDACMHTFDC
LPLAALLNQQ FLCVHGGMSP EITCLEDIRK LDRFSEPPAF GPVCDLLWSD PLEDYGSEKT
LEHYTHNTVR GCSYFFSYPA VCEFLQNNSL LSIIRAHEAQ DAGYRMYRKN QATGFPSLIT
IFSAPNYLDV YNNKAAVLKY ENNVMNIRQF NCSPHPYWLP NFMDVFTWSL PFVGEKVTEM
LVNILNICSD EEMNVTDEEG ATTGRKEVIK NKIRAIGKMA RVFTVLREES ENVLTLKGLT
PTGTLPLGVL SGGKQTIETA KQEAAEEREA IRGFTIAHRI RSFEEARGLD RINERMPPRK
EASYHHDAGR MHSHSHPPHP QASRRTDHGK KAL
