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UniProtKB - P63329 (PP2BA_RAT)

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Protein

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

Gene

Ppp3ca

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca2+-mediated signals (PubMed:1322410, PubMed:24018048). Many of the substrates contain a PxIxIT motif and/or a LxVP motif (By similarity). In response to increased Ca2+ levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (By similarity). In response to increased Ca2+ levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion (By similarity). Dephosphorylates heat shock protein HSPB1 (By similarity). Dephosphorylates and activates transcription factor NFATC1 (By similarity). Dephosphorylates and inactivates transcription factor ELK1 (By similarity). Dephosphorylates DARPP32 (By similarity).By similarity2 Publications

Catalytic activityi

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.2 Publications

Cofactori

Protein has several cofactor binding sites:
  • Fe3+By similarityNote: Binds 1 Fe3+ ion per subunit.By similarity
  • Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

Activated by Ca2+-bound calmodulin following an increase in intracellular Ca2+ (PubMed:1322410, PubMed:24018048). At low Ca2+ concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca2+ (PubMed:1322410, PubMed:24018048). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca2+ causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A (PubMed:1322410, PubMed:24018048). The subsequent binding of Ca2+-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A (PubMed:1322410, PubMed:24018048). Inhibited by immunosuppressant drug FK506 (tacrolimus) in complex with FKBP12 and also by immunosuppressant drug cyclosporin A (CsA) in complex with PPIA/cyclophilin A; the inhibition is Ca2+-dependent (By similarity).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi90IronBy similarity1
Metal bindingi92Iron; via tele nitrogenBy similarity1
Metal bindingi118IronBy similarity1
Metal bindingi118ZincBy similarity1
Metal bindingi150ZincBy similarity1
Active sitei151Proton donorBy similarity1
Metal bindingi199Zinc; via tele nitrogenBy similarity1
Metal bindingi281Zinc; via pros nitrogenBy similarity1

GO - Molecular functioni

  • calcium-dependent protein serine/threonine phosphatase activity Source: RGD
  • calmodulin binding Source: RGD
  • calmodulin-dependent protein phosphatase activity Source: UniProtKB
  • cyclosporin A binding Source: Ensembl
  • enzyme binding Source: Ensembl
  • metal ion binding Source: UniProtKB-KW
  • phosphoprotein phosphatase activity Source: RGD
  • protein heterodimerization activity Source: RGD
  • protein serine/threonine phosphatase activity Source: RGD
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionCalmodulin-binding, Hydrolase, Protein phosphatase
LigandIron, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.1.3.16 5301
ReactomeiR-RNO-2871809 FCERI mediated Ca+2 mobilization
R-RNO-4086398 Ca2+ pathway
R-RNO-5607763 CLEC7A (Dectin-1) induces NFAT activation

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform (EC:3.1.3.162 Publications)
Alternative name(s):
CAM-PRP catalytic subunit
Calmodulin-dependent calcineurin A subunit alpha isoform
Gene namesi
Name:Ppp3ca
Synonyms:Calna
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus
Proteomesi
  • UP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi3382 Ppp3ca

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000588242 – 521Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoformAdd BLAST520

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei224Nitrated tyrosineBy similarity1
Modified residuei469PhosphoserineCombined sources1
Modified residuei492PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Nitration, Phosphoprotein

Proteomic databases

PaxDbiP63329
PRIDEiP63329

PTM databases

iPTMnetiP63329
PhosphoSitePlusiP63329
SwissPalmiP63329

Expressioni

Tissue specificityi

Expressed in neonatal cardiomyocytes (at protein level).1 Publication

Gene expression databases

BgeeiENSRNOG00000009882
GenevisibleiP63329 RN

Interactioni

Subunit structurei

Forms a complex composed of a calmodulin-dependent catalytic subunit (also known as calcineurin A) and a regulatory Ca2+-binding subunit (also known as calcineurin B) (By similarity). There are three catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded by separate genes (PPP3R1 and PPP3R2). In response to an increase in Ca2+ intracellular levels, forms a complex composed of PPP3CA/calcineurin A, calcineurin B and calmodulin (By similarity). Interacts (via calcineurin B binding domain) with regulatory subunit PPP3R1/calcineurin B (By similarity). Interacts (via calmodulin-binding domain) with calmodulin; the interaction depends on calmodulin binding to Ca2+ (By similarity). Forms a complex composed of MYOZ2 and ACTN1 (By similarity). Within the complex interacts with MYOZ2 (By similarity). Interacts with MYOZ1 (By similarity). Interacts with MYOZ3 (By similarity). Interacts with CIB1; the interaction increases upon cardiomyocyte hypertrophy (By similarity). Interacts with CHP1 and CHP2 (PubMed:10593895, PubMed:18815128). Interacts with CRTC2 (By similarity). Interacts with DNM1L; the interaction dephosphorylates DNM1L and promotes its translocation to mitochondria (By similarity). Interacts with CMYA5; this interaction represses calcineurin activity in muscle (By similarity). Interacts (constitutively active form) with SYNPO2 (By similarity). Interacts with scaffold protein AKAP5 (via IAIIIT motif); the interaction recruits PPP3CA to the plasma membrane following L-type Ca2+-channel activation (By similarity). Interacts with NFATC2 (By similarity). Interacts with RCAN3 (By similarity). Interacts with PPIA. Interacts with RCAN1 (By similarity).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei352Interaction with PxVP motif in substrateBy similarity1

Binary interactionsi

Show more details

GO - Molecular functioni

  • calmodulin binding Source: RGD
  • enzyme binding Source: Ensembl
  • protein heterodimerization activity Source: RGD
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi246806, 4 interactors
CORUMiP63329
IntActiP63329, 4 interactors
MINTiP63329
STRINGi10116.ENSRNOP00000049674

Structurei

Secondary structure

1521
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi31 – 34Combined sources4
Helixi43 – 51Combined sources9
Helixi58 – 72Combined sources15
Beta strandi77 – 81Combined sources5
Beta strandi83 – 88Combined sources6
Helixi95 – 105Combined sources11
Turni108 – 110Combined sources3
Beta strandi113 – 115Combined sources3
Beta strandi120 – 123Combined sources4
Helixi126 – 139Combined sources14
Turni141 – 143Combined sources3
Beta strandi144 – 146Combined sources3
Helixi154 – 159Combined sources6
Helixi162 – 168Combined sources7
Helixi172 – 184Combined sources13
Beta strandi188 – 191Combined sources4
Turni192 – 194Combined sources3
Beta strandi195 – 200Combined sources6
Helixi209 – 213Combined sources5
Beta strandi218 – 220Combined sources3
Beta strandi223 – 225Combined sources3
Helixi226 – 232Combined sources7
Turni237 – 240Combined sources4
Beta strandi247 – 250Combined sources4
Turni252 – 255Combined sources4
Beta strandi256 – 260Combined sources5
Helixi262 – 271Combined sources10
Beta strandi275 – 279Combined sources5
Beta strandi287 – 290Combined sources4
Turni295 – 297Combined sources3
Beta strandi299 – 306Combined sources8
Helixi311 – 313Combined sources3
Beta strandi319 – 325Combined sources7
Beta strandi328 – 334Combined sources7
Helixi344 – 346Combined sources3
Helixi349 – 366Combined sources18
Helixi473 – 476Combined sources4
Helixi478 – 481Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4IL1X-ray3.00A/B/C/D1-492[»]
ProteinModelPortaliP63329
SMRiP63329
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni56 – 340CatalyticCuratedAdd BLAST285
Regioni327 – 336Interaction with PxIxIF motif in substrateBy similarity10
Regioni341 – 369Calcineurin B bindingBy similarityAdd BLAST29
Regioni392 – 406Calmodulin-bindingBy similarityAdd BLAST15
Regioni407 – 414Autoinhibitory segmentBy similarity8
Regioni465 – 487Autoinhibitory domain1 PublicationAdd BLAST23

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi307 – 311SAPNY motifBy similarity5

Domaini

The autoinhibitory domain prevents access to the catalytic site.By similarity
The autoinhibitory segment prevents access to the substrate binding site.By similarity
Possible isomerization of Pro-309 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA.By similarity

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0375 Eukaryota
COG0639 LUCA
GeneTreeiENSGT00530000063087
HOGENOMiHOG000172699
HOVERGENiHBG002819
InParanoidiP63329
KOiK04348
OMAiLWSLKIW
OrthoDBiEOG091G094R
PhylomeDBiP63329

Family and domain databases

Gene3Di3.60.21.10, 1 hit
InterProiView protein in InterPro
IPR004843 Calcineurin-like_PHP_ApaH
IPR029052 Metallo-depent_PP-like
IPR006186 Ser/Thr-sp_prot-phosphatase
PfamiView protein in Pfam
PF00149 Metallophos, 1 hit
PRINTSiPR00114 STPHPHTASE
SMARTiView protein in SMART
SM00156 PP2Ac, 1 hit
PROSITEiView protein in PROSITE
PS00125 SER_THR_PHOSPHATASE, 1 hit

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. AlignAdd to basket

Isoform 1 (identifier: P63329-1) [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

        10         20         30         40         50
MSEPKAIDPK LSTTDRVVKA VPFPPSHRLT AKEVFDNDGK PRVDILKAHL 
        60         70         80         90        100
MKEGRLEESV ALRIITEGAS ILRQEKNLLD IDAPVTVCGD IHGQFFDLMK 
       110        120        130        140        150
LFEVGGSPAN TRYLFLGDYV DRGYFSIECV LYLWALKILY PKTLFLLRGN 
       160        170        180        190        200
HECRHLTEYF TFKQECKIKY SERVYDACMD AFDCLPLAAL MNQQFLCVHG 
       210        220        230        240        250
GLSPEINTLD DIRKLDRFKE PPAYGPMCDI LWSDPLEDFG NEKTQEHFTH 
       260        270        280        290        300
NTVRGCSYFY SYPAVCDFLQ HNNLLSILRA HEAQDAGYRM YRKSQTTGFP 
       310        320        330        340        350
SLITIFSAPN YLDVYNNKAA VLKYENNVMN IRQFNCSPHP YWLPNFMDVF 
       360        370        380        390        400
TWSLPFVGEK VTEMLVNVLN ICSDDELGSE EDGFDGATAA ARKEVIRNKI 
       410        420        430        440        450
RAIGKMARVF SVLREESESV LTLKGLTPTG MLPSGVLSGG KQTLQSATVE 
       460        470        480        490        500
AIEADEAIKG FSPQHKITSF EEAKGLDRIN ERMPPRRDAM PSDANLNSIN 
       510        520 
KALASETNGT DSNGSNSSNI Q
Length:521
Mass (Da):58,644
Last modified:October 11, 2004 - v1
Checksum:i16530C27DDBF1F05
GO
Isoform 2 (identifier: P63329-2) [UniParc]FASTAAdd to basket

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

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

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_018564448 – 457Missing in isoform 2. 1 Publication10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
PIRiA33264
RefSeqiNP_058737.1, NM_017041.1 [P63329-1]
XP_006233425.1, XM_006233363.3 [P63329-2]
UniGeneiRn.228648
Rn.6866

Genome annotation databases

EnsembliENSRNOT00000047975; ENSRNOP00000049674; ENSRNOG00000009882 [P63329-1]
GeneIDi24674
KEGGirno:24674

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPP2BA_RAT
AccessioniPrimary (citable) accession number: P63329
Secondary accession number(s): P12816
, P20652, Q6LDJ8, Q9WUV7, Q9Z1I5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: June 20, 2018
This is version 129 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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