P63329 (PP2BA_RAT) 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

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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, HSPB1 and SSH1 By similarity. Ref.2
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. Interacts with CHP1 and CHP2. Interacts with CMYA5; this interaction represses calcineurin activity in muscle By similarity. Ref.6 Ref.7
Subcellular location	Nucleus By similarity. Note: Colocalizes with ACTN1 and MYOZ2 at the Z line in heart and skeletal muscle By similarity.
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	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G1/S transition of mitotic cell cycle Inferred from electronic annotation. Source: Compara calcineurin-NFAT signaling cascade Inferred from electronic annotation. Source: Compara calcium ion transport Inferred from electronic annotation. Source: Compara cellular response to drug Inferred from electronic annotation. Source: Compara cellular response to glucose stimulus Inferred from mutant phenotype PubMed 19965390. Source: BHF-UCL negative regulation of calcium ion-dependent exocytosis Inferred by curator PubMed 19965390. Source: BHF-UCL negative regulation of insulin secretion Inferred from mutant phenotype PubMed 19965390. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara protein dephosphorylation Inferred from direct assay PubMed 12135494Ref.2. Source: RGD protein import into nucleus Inferred from electronic annotation. Source: Compara regulation of excitatory postsynaptic membrane potential Inferred from electronic annotation. Source: Compara regulation of synaptic transmission Inferred from electronic annotation. Source: Compara response to amphetamine Inferred from expression pattern PubMed 11954050. Source: RGD response to calcium ion Inferred from sequence or structural similarity. Source: UniProtKB response to stress Inferred from electronic annotation. Source: Compara skeletal muscle fiber development Inferred from electronic annotation. Source: Compara transition between fast and slow fiber Inferred from electronic annotation. Source: Compara
Cellular_component	Z disc Inferred from electronic annotation. Source: Compara calcineurin complex Inferred from direct assay PubMed 12135494. Source: RGD cytosol Inferred from direct assay PubMed 16150427. Source: RGD membrane Inferred from direct assay PubMed 16150427. Source: RGD mitochondrion Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calmodulin binding Inferred from direct assay PubMed 12135494. Source: RGD calmodulin-dependent protein phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB drug binding Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein heterodimerization activity Inferred from direct assay PubMed 12135494. Source: RGD
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P63329-1)

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: P63329-2)

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

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_0000058824
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	469	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	448 – 457	10	Missing in isoform 2.		VSP_018564

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

[1]	"The complete primary structure of calcineurin A, a calmodulin binding protein homologous with protein phosphatases 1 and 2A." Ito A., Hashimoto T., Hirai M., Takeda T., Shuntoh H., Kuno T., Tanaka C. Biochem. Biophys. Res. Commun. 163:1492-1497(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Characterization of the phosphatase activity of a baculovirus-expressed calcineurin A isoform." Perrino B.A., Fong Y.L., Brickey D.A., Saitoh Y., Ushio Y., Fukunaga K., Miyamoto E., Soderling T.R. J. Biol. Chem. 267:15965-15969(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION.
[3]	"Molecular cloning and characterization of the promoter region of the calcineurin A alpha gene." Chang C., Takeda T., Mukai H., Shuntoh H., Kuno T., Tanaka C. Biochem. J. 288:801-805(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-19. Tissue: Liver.
[4]	Lubec G., Kang S.U. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 143-148, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Brain.
[5]	"Multiplicity of protein serine-threonine phosphatases in PC12 pheochromocytoma and FTO-2B hepatoma cells." Wadzinski B.E., Heasley L.E., Johnson G.L. J. Biol. Chem. 265:21504-21508(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 236-306.
[6]	"Inhibition of calcineurin phosphatase activity by a calcineurin B homologous protein." Lin X., Sikkink R.A., Rusnak F., Barber D.L. J. Biol. Chem. 274:36125-36131(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CHP1.
[7]	"CHP2 activates the calcineurin/nuclear factor of activated T cells signaling pathway and enhances the oncogenic potential of HEK293 cells." Li G.D., Zhang X., Li R., Wang Y.D., Wang Y.L., Han K.J., Qian X.P., Yang C.G., Liu P., Wei Q., Chen W.F., Zhang J., Zhang Y. J. Biol. Chem. 283:32660-32668(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CHP2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D90035 mRNA. Translation: BAA14083.1. M29275 mRNA. Translation: AAA40940.1. X57115 mRNA. Translation: CAA40398.2. D10480 Genomic DNA. Translation: BAA01283.1. M58440 mRNA. Translation: AAA41914.1.
IPI	IPI00201410. IPI00559849.
PIR	A33264.
RefSeq	NP_058737.1. NM_017041.1.
UniGene	Rn.6866.
3D structure databases
ProteinModelPortal	P63329.
SMR	P63329. Positions 1-411.
ModBase	Search...
PTM databases
PhosphoSite	P63329.
Proteomic databases
PaxDb	P63329.
PRIDE	P63329.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000047975; ENSRNOP00000049674; ENSRNOG00000009882.
GeneID	24674.
KEGG	rno:24674.
Organism-specific databases
CTD	5530.
RGD	3382. Ppp3ca.
Phylogenomic databases
eggNOG	COG0639.
GeneTree	ENSGT00530000063087.
HOGENOM	HOG000172699.
HOVERGEN	HBG002819.
InParanoid	P63329.
KO	K04348.
OrthoDB	EOG4PVNZK.
Enzyme and pathway databases
Reactome	REACT_111984. Signal Transduction.
Gene expression databases
ArrayExpress	P63329.
Genevestigator	P63329.
GermOnline	ENSRNOG00000009882. Rattus norvegicus.
Family and domain databases
InterPro	IPR004843. Metallo_PEstase_dom. IPR006186. Ser/Thr-sp_prot-phosphatase. [Graphical view]
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.

Entry information

Entry name

PP2BA_RAT

Accession

Primary (citable) accession number: P63329
Secondary accession number(s): P12816 , P20652, Q6LDJ8, Q9WUV7, Q9Z1I5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 11, 2004
Last modified:	May 1, 2013
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program