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P63328

- PP2BA_MOUSE

UniProt

P63328 - PP2BA_MOUSE

Protein

Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform

Gene

Ppp3ca

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 111 (01 Oct 2014)
      Sequence version 1 (11 Oct 2004)
      Previous versions | rss
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    Functioni

    Calcium-dependent, calmodulin-stimulated protein phosphatase. Many of the substrates contain a PxIxIT motif. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L and HSPB1 By similarity. Dephosphorylates SSH1.By similarity1 Publication

    Catalytic activityi

    [a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

    Cofactori

    Binds 1 Fe3+ ion per subunit.By similarity
    Binds 1 zinc ion per subunit.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi90 – 901IronBy similarity
    Metal bindingi92 – 921IronBy similarity
    Metal bindingi118 – 1181IronBy similarity
    Metal bindingi118 – 1181ZincBy similarity
    Metal bindingi150 – 1501ZincBy similarity
    Active sitei151 – 1511Proton donorBy similarity
    Metal bindingi199 – 1991ZincBy similarity
    Metal bindingi281 – 2811ZincBy similarity

    GO - Molecular functioni

    1. calcium-dependent protein serine/threonine phosphatase activity Source: Reactome
    2. calmodulin-dependent protein phosphatase activity Source: UniProtKB
    3. drug binding Source: Ensembl
    4. metal ion binding Source: UniProtKB-KW
    5. phosphoprotein phosphatase activity Source: MGI
    6. protein binding Source: BHF-UCL

    GO - Biological processi

    1. calcineurin-NFAT signaling cascade Source: MGI
    2. calcium ion transport Source: MGI
    3. calcium-mediated signaling Source: MGI
    4. cellular response to drug Source: Ensembl
    5. cellular response to glucose stimulus Source: Ensembl
    6. dephosphorylation Source: MGI
    7. G1/S transition of mitotic cell cycle Source: MGI
    8. multicellular organismal response to stress Source: MGI
    9. negative regulation of insulin secretion Source: Ensembl
    10. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    11. protein dephosphorylation Source: MGI
    12. protein import into nucleus Source: MGI
    13. regulation of excitatory postsynaptic membrane potential Source: MGI
    14. regulation of synaptic transmission Source: MGI
    15. response to amphetamine Source: Ensembl
    16. response to calcium ion Source: UniProtKB
    17. skeletal muscle fiber development Source: MGI
    18. transition between fast and slow fiber Source: MGI

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Ligandi

    Calmodulin-binding, Iron, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_188202. FCERI mediated Ca+2 mobilization.
    REACT_203795. DARPP-32 events.
    REACT_221970. Ca2+ pathway.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform (EC:3.1.3.16)
    Alternative name(s):
    CAM-PRP catalytic subunit
    Calmodulin-dependent calcineurin A subunit alpha isoform
    Gene namesi
    Name:Ppp3ca
    Synonyms:Calna
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 3

    Organism-specific databases

    MGIiMGI:107164. Ppp3ca.

    Subcellular locationi

    Cell membrane. Cell membranesarcolemma. Nucleus
    Note: Colocalizes with ACTN1 and MYOZ2 at the Z line in heart and skeletal muscle.

    GO - Cellular componenti

    1. calcineurin complex Source: MGI
    2. cytosol Source: MGI
    3. mitochondrion Source: MGI
    4. nucleus Source: MGI
    5. sarcolemma Source: UniProtKB-SubCell
    6. Z disc Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi477 – 4771D → N: Greatly reduces inhibition of calcineurin phosphatase activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 521520Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoformPRO_0000058823Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserineBy similarity
    Modified residuei224 – 2241Nitrated tyrosine1 Publication

    Keywords - PTMi

    Acetylation, Nitration

    Proteomic databases

    MaxQBiP63328.
    PaxDbiP63328.
    PRIDEiP63328.

    PTM databases

    PhosphoSiteiP63328.

    Expressioni

    Gene expression databases

    ArrayExpressiP63328.
    BgeeiP63328.
    GenevestigatoriP63328.

    Interactioni

    Subunit structurei

    Composed of two components (A and B), the A component is the catalytic subunit and the B component confers calcium sensitivity. Interacts with CRTC2, MYOZ1, MYOZ2 and MYOZ3. Interacts with DNM1L; the interaction dephosphorylates DNM1L and regulates its translocation to mitochondria. Interacts with CHP1 and CHP2 By similarity. Interacts with CMYA5; this interaction represses calcineurin activity in muscle. Interacts with CIB1; the interaction increases upon cardiomyocytes hypertrophy.By similarity2 Publications

    Protein-protein interaction databases

    BioGridi202344. 8 interactions.
    DIPiDIP-31543N.
    IntActiP63328. 8 interactions.
    MINTiMINT-135995.

    Structurei

    3D structure databases

    ProteinModelPortaliP63328.
    SMRiP63328. Positions 1-411.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni2 – 301300CatalyticAdd
    BLAST
    Regioni247 – 2537Calcineurin B binding-site 1Sequence Analysis
    Regioni296 – 3016Calcineurin B binding-site 2Sequence Analysis
    Regioni392 – 41423Calmodulin-bindingSequence AnalysisAdd
    BLAST
    Regioni465 – 48723Inhibitory domainAdd
    BLAST

    Sequence similaritiesi

    Belongs to the PPP phosphatase family. PP-2B subfamily.Curated

    Phylogenomic databases

    eggNOGiCOG0639.
    GeneTreeiENSGT00530000063087.
    HOGENOMiHOG000172699.
    HOVERGENiHBG002819.
    InParanoidiP63328.
    KOiK04348.
    OMAiMFWSPED.
    OrthoDBiEOG7BZVSC.
    PhylomeDBiP63328.
    TreeFamiTF105557.

    Family and domain databases

    Gene3Di3.60.21.10. 1 hit.
    InterProiIPR004843. Calcineurin-like_PHP_apaH.
    IPR029052. Metallo-depent_PP-like.
    IPR006186. Ser/Thr-sp_prot-phosphatase.
    [Graphical view]
    PfamiPF00149. Metallophos. 1 hit.
    [Graphical view]
    PRINTSiPR00114. STPHPHTASE.
    SMARTiSM00156. PP2Ac. 1 hit.
    [Graphical view]
    SUPFAMiSSF56300. SSF56300. 1 hit.
    PROSITEiPS00125. SER_THR_PHOSPHATASE. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P63328-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSEPKAIDPK LSTTDRVVKA VPFPPSHRLT AKEVFDNDGK PRVDILKAHL    50
    MKEGRLEESV ALRIITEGAS ILRQEKNLLD IDAPVTVCGD IHGQFFDLMK 100
    LFEVGGSPAN TRYLFLGDYV DRGYFSIECV LYLWALKILY PKTLFLLRGN 150
    HECRHLTEYF TFKQECKIKY SERVYDACMD AFDCLPLAAL MNQQFLCVHG 200
    GLSPEINTLD DIRKLDRFKE PPAYGPMCDI LWSDPLEDFG NEKTQEHFTH 250
    NTVRGCSYFY SYPAVCDFLQ HNNLLSILRA HEAQDAGYRM YRKSQTTGFP 300
    SLITIFSAPN YLDVYNNKAA VLKYENNVMN IRQFNCSPHP YWLPNFMDVF 350
    TWSLPFVGEK VTEMLVNVLN ICSDDELGSE EDGFDGATAA ARKEVIRNKI 400
    RAIGKMARVF SVLREESESV LTLKGLTPTG MLPSGVLSGG KQTLQSATVE 450
    AIEADEAIKG FSPQHKITSF EEAKGLDRIN ERMPPRRDAM PSDANLNSIN 500
    KALASETNGT DSNGSNSSNI Q 521
    Length:521
    Mass (Da):58,644
    Last modified:October 11, 2004 - v1
    Checksum:i16530C27DDBF1F05
    GO
    Isoform 2 (identifier: P63328-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         448-457: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:511
    Mass (Da):57,615
    Checksum:i01428D70D67450BD
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei448 – 45710Missing in isoform 2. 1 PublicationVSP_018563

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J05479 mRNA. Translation: AAA37359.1.
    AK146387 mRNA. Translation: BAE27131.1.
    AK150393 mRNA. Translation: BAE29521.1.
    J04134 mRNA. Translation: AAA37432.1.
    S78668 mRNA. Translation: AAB34675.1.
    CCDSiCCDS17860.1. [P63328-1]
    PIRiA42232. A31257.
    RefSeqiNP_032939.1. NM_008913.5. [P63328-1]
    UniGeneiMm.331389.

    Genome annotation databases

    EnsembliENSMUST00000056758; ENSMUSP00000053101; ENSMUSG00000028161. [P63328-1]
    ENSMUST00000070198; ENSMUSP00000071040; ENSMUSG00000028161. [P63328-2]
    GeneIDi19055.
    KEGGimmu:19055.
    UCSCiuc008rmg.1. mouse. [P63328-1]
    uc008rmh.1. mouse. [P63328-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J05479 mRNA. Translation: AAA37359.1 .
    AK146387 mRNA. Translation: BAE27131.1 .
    AK150393 mRNA. Translation: BAE29521.1 .
    J04134 mRNA. Translation: AAA37432.1 .
    S78668 mRNA. Translation: AAB34675.1 .
    CCDSi CCDS17860.1. [P63328-1 ]
    PIRi A42232. A31257.
    RefSeqi NP_032939.1. NM_008913.5. [P63328-1 ]
    UniGenei Mm.331389.

    3D structure databases

    ProteinModelPortali P63328.
    SMRi P63328. Positions 1-411.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202344. 8 interactions.
    DIPi DIP-31543N.
    IntActi P63328. 8 interactions.
    MINTi MINT-135995.

    PTM databases

    PhosphoSitei P63328.

    Proteomic databases

    MaxQBi P63328.
    PaxDbi P63328.
    PRIDEi P63328.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000056758 ; ENSMUSP00000053101 ; ENSMUSG00000028161 . [P63328-1 ]
    ENSMUST00000070198 ; ENSMUSP00000071040 ; ENSMUSG00000028161 . [P63328-2 ]
    GeneIDi 19055.
    KEGGi mmu:19055.
    UCSCi uc008rmg.1. mouse. [P63328-1 ]
    uc008rmh.1. mouse. [P63328-2 ]

    Organism-specific databases

    CTDi 5530.
    MGIi MGI:107164. Ppp3ca.

    Phylogenomic databases

    eggNOGi COG0639.
    GeneTreei ENSGT00530000063087.
    HOGENOMi HOG000172699.
    HOVERGENi HBG002819.
    InParanoidi P63328.
    KOi K04348.
    OMAi MFWSPED.
    OrthoDBi EOG7BZVSC.
    PhylomeDBi P63328.
    TreeFami TF105557.

    Enzyme and pathway databases

    Reactomei REACT_188202. FCERI mediated Ca+2 mobilization.
    REACT_203795. DARPP-32 events.
    REACT_221970. Ca2+ pathway.

    Miscellaneous databases

    ChiTaRSi PPP3CA. mouse.
    NextBioi 295542.
    PROi P63328.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P63328.
    Bgeei P63328.
    Genevestigatori P63328.

    Family and domain databases

    Gene3Di 3.60.21.10. 1 hit.
    InterProi IPR004843. Calcineurin-like_PHP_apaH.
    IPR029052. Metallo-depent_PP-like.
    IPR006186. Ser/Thr-sp_prot-phosphatase.
    [Graphical view ]
    Pfami PF00149. Metallophos. 1 hit.
    [Graphical view ]
    PRINTSi PR00114. STPHPHTASE.
    SMARTi SM00156. PP2Ac. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56300. SSF56300. 1 hit.
    PROSITEi PS00125. SER_THR_PHOSPHATASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and characterization of molecular isoforms of the catalytic subunit of calcineurin using nonisotopic methods."
      Kincaid R.L., Giri P.R., Higuchi S., Tamura J., Dixon S.C., Marietta C.A., Amorese D.A., Martin B.M.
      J. Biol. Chem. 265:11312-11319(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Strain: BALB/c and C57BL/6J.
      Tissue: Bone marrow.
    3. Lubec G., Kang S.U., Sunyer B., Chen W.-Q.
      Submitted (JAN-2009) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 64-73; 101-122 AND 425-459, IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: C57BL/6 and OF1.
      Tissue: Brain and Hippocampus.
    4. "Molecular cloning of a protein serine/threonine phosphatase containing a putative regulatory tetratricopeptide repeat domain."
      Becker W., Kentrup H., Klumpp S., Schultz J.E., Joost H.G.
      J. Biol. Chem. 269:22586-22592(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 95-116.
    5. "Characterization of a cDNA clone encoding the calmodulin-binding domain of mouse brain calcineurin."
      Kincaid R.L., Nightingale M.S., Martin B.M.
      Proc. Natl. Acad. Sci. U.S.A. 85:8983-8987(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 215-521 (ISOFORM 1).
    6. "Characterization of a mutant calcineurin A alpha gene expressed by EL4 lymphoma cells."
      Fruman D.A., Pai S.-Y., Burakoff S.J., Bierer B.E.
      Mol. Cell. Biol. 15:3857-3863(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 467-491, MUTAGENESIS OF ASP-477.
    7. "Dephosphorylation of the small heat shock protein hsp25 by calcium/calmodulin-dependent (type 2B) protein phosphatase."
      Gaestel M., Benndorf R., Hayess K., Priemer E., Engel K.
      J. Biol. Chem. 267:21607-21611(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. "Calsarcins, a novel family of sarcomeric calcineurin-binding proteins."
      Frey N., Richardson J.A., Olson E.N.
      Proc. Natl. Acad. Sci. U.S.A. 97:14632-14637(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    9. Cited for: NITRATION [LARGE SCALE ANALYSIS] AT TYR-224, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Brain.
    10. Cited for: INTERACTION WITH CIB1, SUBCELLULAR LOCATION.
    11. "Myospryn is a calcineurin-interacting protein that negatively modulates slow-fiber-type transformation and skeletal muscle regeneration."
      Kielbasa O.M., Reynolds J.G., Wu C.L., Snyder C.M., Cho M.Y., Weiler H., Kandarian S., Naya F.J.
      FASEB J. 25:2276-2286(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CMYA5.

    Entry informationi

    Entry nameiPP2BA_MOUSE
    AccessioniPrimary (citable) accession number: P63328
    Secondary accession number(s): P12816
    , P20652, Q3UCU1, Q64135
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 11, 2004
    Last sequence update: October 11, 2004
    Last modified: October 1, 2014
    This is version 111 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3