P63328 (PP2BA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Ppp3ca
Synonyms:	Calna

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	521 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Calcium-dependent, calmodulin-stimulated protein phosphatase. 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 phosphoprotein + H2O = a protein + 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 By similarity.
Subcellular location	Nucleus. Note: Colocalizes with ACTN1 and MYOZ2 at the Z line in heart and skeletal muscle. Ref.8
Sequence similarities	Belongs to the PPP phosphatase family. PP-2B subfamily.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Calmodulin-binding Iron Metal-binding Zinc
Molecular function	Hydrolase Protein phosphatase
PTM	Nitration Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	G1/S transition of mitotic cell cycle Inferred from mutant phenotype. Source: MGI calcium ion transport Inferred from mutant phenotype. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction. Source: MGI protein import into nucleus Inferred from direct assay. Source: MGI regulation of excitatory postsynaptic membrane potential Inferred from genetic interaction. Source: MGI regulation of synaptic transmission Inferred from mutant phenotype. Source: MGI response to stress Inferred from direct assay. Source: MGI skeletal muscle fiber development Inferred from mutant phenotype. Source: MGI
Cellular component	Z disc Inferred from direct assay. Source: MGI calcineurin complex Inferred from direct assay. Source: MGI cytosol Inferred from direct assay. Source: MGI microsome Inferred from direct assay. Source: MGI mitochondrion Inferred from direct assay. Source: MGI nucleus Inferred from direct assay. Source: MGI
Molecular function	calmodulin binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 521	521	Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform		PRO_0000058823
Regions
	Region	1 – 301	301	Catalytic
	Region	247 – 253	7	Calcineurin B binding-site 1 Potential
	Region	296 – 301	6	Calcineurin B binding-site 2 Potential
	Region	392 – 414	23	Calmodulin-binding Potential
	Region	465 – 487	23	Inhibitory domain
Sites
	Active site	151	1	Proton donor By similarity
	Metal binding	90	1	Iron By similarity
	Metal binding	92	1	Iron By similarity
	Metal binding	118	1	Iron By similarity
	Metal binding	118	1	Zinc By similarity
	Metal binding	150	1	Zinc By similarity
	Metal binding	199	1	Zinc By similarity
	Metal binding	281	1	Zinc By similarity
Amino acid modifications
	Modified residue	224	1	Nitrated tyrosine Ref.9
	Modified residue	469	1	Phosphoserine Ref.10
Natural variations
	Alternative sequence	448 – 457	10	Missing in isoform 2.		VSP_018563
Experimental info
	Mutagenesis	477	1	D → N: Greatly reduces inhibition of calcineurin phosphatase activity. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 11, 2004. Version 1. Checksum: 16530C27DDBF1F05	FASTA	521	58,644
	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
	Isoform 2 [UniParc]. Checksum: 01428D70D67450BD	FASTA	511	57,615
	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 KQTLQSAIKG FSPQHKITSF EEAKGLDRIN ERMPPRRDAM 490 500 510 PSDANLNSIN KALASETNGT DSNGSNSSNI Q

References

	« Hide 'large scale' referencesShow '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: 2162844] [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: 16141072] [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, 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: 8077208] [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: 2848250] [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: 7791792] [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: 1328240] [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: 11114196] [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: 16800626] [Abstract] Cited for: NITRATION [LARGE SCALE ANALYSIS] AT TYR-224, MASS SPECTROMETRY. Tissue: Brain.
[10]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed: 17114649] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469, MASS SPECTROMETRY. Tissue: Brain cortex.
+	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.
IPI	IPI00121545. IPI00756703.
PIR	A31257. A42232.
RefSeq	NP_032939.1. NM_008913.4.
UniGene	Mm.331389.
3D structure databases
ProteinModelPortal	P63328.
SMR	P63328. Positions 1-372.
ModBase	Search...
Protein-protein interaction databases
IntAct	P63328. 6 interactions.
MINT	MINT-135995.
STRING	P63328.
PTM databases
PhosphoSite	P63328.
Proteomic databases
PRIDE	P63328.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000056758; ENSMUSP00000053101; ENSMUSG00000028161. ENSMUST00000070198; ENSMUSP00000071040; ENSMUSG00000028161.
GeneID	19055.
KEGG	mmu:19055.
UCSC	uc008rmh.1. mouse.
Organism-specific databases
CTD	5530.
MGI	MGI:107164. Ppp3ca.
Phylogenomic databases
eggNOG	roNOG11256.
GeneTree	ENSGT00530000063087.
HOGENOM	HBG716770.
HOVERGEN	HBG002819.
InParanoid	P63328.
OMA	SVWPAGP.
OrthoDB	EOG4PVNZK.
PhylomeDB	P63328.
Gene expression databases
ArrayExpress	P63328.
Bgee	P63328.
Genevestigator	P63328.
GermOnline	ENSMUSG00000028161. Mus musculus.
Family and domain databases
InterPro	IPR004843. Metallo_PEstase_dom. IPR006186. Ser/Thr-sp_prot-phosphatase. [Graphical view]
KO	K04348.
Pfam	PF00149. Metallophos. 1 hit. [Graphical view]
PRINTS	PR00114. STPHPHTASE.
SMART	SM00156. PP2Ac. 1 hit. [Graphical view]
PROSITE	PS00125. SER_THR_PHOSPHATASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	295542.
SOURCE	Search...

Entry information

Entry name

PP2BA_MOUSE

Accession

Primary (citable) accession number: P63328
Secondary accession number(s): P12816 , P20652, Q3UCU1, Q64135

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 11, 2004
Last modified:	November 16, 2011
This is version 81 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program