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P63328 (PP2BA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Ppp3ca
Synonyms:Calna
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length521 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7

Catalytic activity

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

Cofactor

Binds 1 Fe3+ ion per subunit By similarity.

Binds 1 zinc ion per subunit By similarity.

Subunit structure

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. Ref.10 Ref.11

Subcellular location

Cell membrane. Cell membranesarcolemma. Nucleus. Note: Colocalizes with ACTN1 and MYOZ2 at the Z line in heart and skeletal muscle. Ref.8 Ref.10

Sequence similarities

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

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   LigandCalmodulin-binding
Iron
Metal-binding
Zinc
   Molecular functionHydrolase
Protein phosphatase
   PTMAcetylation
Nitration
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from mutant phenotype PubMed 12660151. Source: MGI

calcineurin-NFAT signaling cascade

Inferred from direct assay PubMed 19188439Ref.11. Source: MGI

calcium ion transport

Inferred from mutant phenotype PubMed 12660151. Source: MGI

calcium-mediated signaling

Inferred from genetic interaction PubMed 19560418. Source: MGI

cellular response to drug

Inferred from electronic annotation. Source: Ensembl

cellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

dephosphorylation

Inferred from direct assay PubMed 12574411PubMed 16024798. Source: MGI

multicellular organismal response to stress

Inferred from direct assay PubMed 11782539. Source: MGI

negative regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 17229811. Source: MGI

protein dephosphorylation

Inferred from mutant phenotype PubMed 19560418. Source: MGI

protein import into nucleus

Inferred from direct assay PubMed 11782539. Source: MGI

regulation of excitatory postsynaptic membrane potential

Inferred from genetic interaction PubMed 17428973. Source: MGI

regulation of synaptic transmission

Inferred from mutant phenotype PubMed 15590926. Source: MGI

response to amphetamine

Inferred from electronic annotation. Source: Ensembl

response to calcium ion

Inferred from sequence or structural similarity. Source: UniProtKB

skeletal muscle fiber development

Inferred from mutant phenotype PubMed 16024798. Source: MGI

transition between fast and slow fiber

Inferred from direct assay Ref.11. Source: MGI

   Cellular_componentZ disc

Inferred from direct assay PubMed 15665106. Source: MGI

calcineurin complex

Inferred from direct assay PubMed 12617961. Source: MGI

cytosol

Inferred from direct assay PubMed 12617961. Source: MGI

mitochondrion

Inferred from direct assay PubMed 12617961. Source: MGI

nucleus

Inferred from direct assay PubMed 12617961. Source: MGI

sarcolemma

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncalcium-dependent protein serine/threonine phosphatase activity

Traceable author statement. Source: Reactome

calmodulin-dependent protein phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

drug binding

Inferred from electronic annotation. Source: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

phosphoprotein phosphatase activity

Inferred from direct assay PubMed 16024798. Source: MGI

protein binding

Inferred from physical interaction Ref.10. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P63328-1)

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.
Isoform 2 (identifier: P63328-2)

The sequence of this isoform differs from the canonical sequence as follows:
     448-457: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 521520Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform
PRO_0000058823

Regions

Region2 – 301300Catalytic
Region247 – 2537Calcineurin B binding-site 1 Potential
Region296 – 3016Calcineurin B binding-site 2 Potential
Region392 – 41423Calmodulin-binding Potential
Region465 – 48723Inhibitory domain

Sites

Active site1511Proton donor By similarity
Metal binding901Iron By similarity
Metal binding921Iron By similarity
Metal binding1181Iron By similarity
Metal binding1181Zinc By similarity
Metal binding1501Zinc By similarity
Metal binding1991Zinc By similarity
Metal binding2811Zinc By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue2241Nitrated tyrosine Ref.9

Natural variations

Alternative sequence448 – 45710Missing in isoform 2.
VSP_018563

Experimental info

Mutagenesis4771D → N: Greatly reduces inhibition of calcineurin phosphatase activity. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: 16530C27DDBF1F05

FASTA52158,644
        10         20         30         40         50         60 
MSEPKAIDPK LSTTDRVVKA VPFPPSHRLT AKEVFDNDGK PRVDILKAHL MKEGRLEESV 

        70         80         90        100        110        120 
ALRIITEGAS ILRQEKNLLD IDAPVTVCGD IHGQFFDLMK LFEVGGSPAN TRYLFLGDYV 

       130        140        150        160        170        180 
DRGYFSIECV LYLWALKILY PKTLFLLRGN HECRHLTEYF TFKQECKIKY SERVYDACMD 

       190        200        210        220        230        240 
AFDCLPLAAL MNQQFLCVHG GLSPEINTLD DIRKLDRFKE PPAYGPMCDI LWSDPLEDFG 

       250        260        270        280        290        300 
NEKTQEHFTH NTVRGCSYFY SYPAVCDFLQ HNNLLSILRA HEAQDAGYRM YRKSQTTGFP 

       310        320        330        340        350        360 
SLITIFSAPN YLDVYNNKAA VLKYENNVMN IRQFNCSPHP YWLPNFMDVF TWSLPFVGEK 

       370        380        390        400        410        420 
VTEMLVNVLN ICSDDELGSE EDGFDGATAA ARKEVIRNKI RAIGKMARVF SVLREESESV 

       430        440        450        460        470        480 
LTLKGLTPTG MLPSGVLSGG KQTLQSATVE AIEADEAIKG FSPQHKITSF EEAKGLDRIN 

       490        500        510        520 
ERMPPRRDAM PSDANLNSIN KALASETNGT DSNGSNSSNI Q 

« Hide

Isoform 2 [UniParc].

Checksum: 01428D70D67450BD
Show »

FASTA51157,615

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Endogenously nitrated proteins in mouse brain: links to neurodegenerative disease."
Sacksteder C.A., Qian W.-J., Knyushko T.V., Wang H., Chin M.H., Lacan G., Melega W.P., Camp D.G. II, Smith R.D., Smith D.J., Squier T.C., Bigelow D.J.
Biochemistry 45:8009-8022(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NITRATION [LARGE SCALE ANALYSIS] AT TYR-224, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain.
[10]"CIB1 is a regulator of pathological cardiac hypertrophy."
Heineke J., Auger-Messier M., Correll R.N., Xu J., Benard M.J., Yuan W., Drexler H., Parise L.V., Molkentin J.D.
Nat. Med. 16:872-879(2010) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS17860.1. [P63328-1]
PIRA31257. A42232.
RefSeqNP_032939.1. NM_008913.4. [P63328-1]
XP_006501199.1. XM_006501136.1. [P63328-2]
UniGeneMm.331389.

3D structure databases

ProteinModelPortalP63328.
SMRP63328. Positions 1-411.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202344. 8 interactions.
DIPDIP-31543N.
IntActP63328. 8 interactions.
MINTMINT-135995.

PTM databases

PhosphoSiteP63328.

Proteomic databases

MaxQBP63328.
PaxDbP63328.
PRIDEP63328.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000056758; ENSMUSP00000053101; ENSMUSG00000028161. [P63328-1]
ENSMUST00000070198; ENSMUSP00000071040; ENSMUSG00000028161. [P63328-2]
GeneID19055.
KEGGmmu:19055.
UCSCuc008rmg.1. mouse. [P63328-1]
uc008rmh.1. mouse. [P63328-2]

Organism-specific databases

CTD5530.
MGIMGI:107164. Ppp3ca.

Phylogenomic databases

eggNOGCOG0639.
GeneTreeENSGT00530000063087.
HOGENOMHOG000172699.
HOVERGENHBG002819.
InParanoidP63328.
KOK04348.
OMAMFWSPED.
OrthoDBEOG7BZVSC.
PhylomeDBP63328.
TreeFamTF105557.

Enzyme and pathway databases

ReactomeREACT_118809. Calcineurin Dephosphorylates Nfatc2.

Gene expression databases

ArrayExpressP63328.
BgeeP63328.
GenevestigatorP63328.

Family and domain databases

Gene3D3.60.21.10. 1 hit.
InterProIPR004843. Calcineurin-like_PHP_apaH.
IPR029052. Metallo-depent_PP-like.
IPR006186. Ser/Thr-sp_prot-phosphatase.
[Graphical view]
PfamPF00149. Metallophos. 1 hit.
[Graphical view]
PRINTSPR00114. STPHPHTASE.
SMARTSM00156. PP2Ac. 1 hit.
[Graphical view]
SUPFAMSSF56300. SSF56300. 1 hit.
PROSITEPS00125. SER_THR_PHOSPHATASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPPP3CA. mouse.
NextBio295542.
PROP63328.
SOURCESearch...

Entry information

Entry namePP2BA_MOUSE
AccessionPrimary (citable) accession number: P63328
Secondary accession number(s): P12816 expand/collapse secondary AC list , P20652, Q3UCU1, Q64135
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: July 9, 2014
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot