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Protein

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

Gene

PPP3CA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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, HSPB1 and SSH1.3 Publications

Catalytic activityi

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

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi90Iron1
Metal bindingi92Iron1
Metal bindingi118Iron1
Metal bindingi118Zinc1
Metal bindingi150Zinc1
Active sitei151Proton donorBy similarity1
Metal bindingi199Zinc1
Metal bindingi281Zinc1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • calmodulin binding Source: UniProtKB
  • calmodulin-dependent protein phosphatase activity Source: UniProtKB
  • drug binding Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • protein dimerization activity Source: UniProtKB
  • protein serine/threonine phosphatase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Ligandi

Calmodulin-binding, Iron, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS06568-MONOMER.
ReactomeiR-HSA-180024. DARPP-32 events.
R-HSA-2871809. FCERI mediated Ca+2 mobilization.
R-HSA-4086398. Ca2+ pathway.
R-HSA-5607763. CLEC7A (Dectin-1) induces NFAT activation.
SIGNORiQ08209.

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, CNA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:9314. PPP3CA.

Subcellular locationi

GO - Cellular componenti

  • calcineurin complex Source: UniProtKB
  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • mitochondrion Source: Ensembl
  • nucleoplasm Source: HPA
  • postsynapse Source: GOC
  • sarcolemma Source: UniProtKB-SubCell
  • Z disc Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi5530.
OpenTargetsiENSG00000138814.
PharmGKBiPA33678.

Chemistry databases

ChEMBLiCHEMBL4445.

Polymorphism and mutation databases

BioMutaiPPP3CA.
DMDMi1352673.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000588222 – 521Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoformAdd BLAST520

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei224Nitrated tyrosineBy similarity1
Modified residuei469PhosphoserineBy similarity1
Modified residuei492PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Nitration, Phosphoprotein

Proteomic databases

EPDiQ08209.
MaxQBiQ08209.
PaxDbiQ08209.
PeptideAtlasiQ08209.
PRIDEiQ08209.

PTM databases

DEPODiQ08209.
iPTMnetiQ08209.
PhosphoSitePlusiQ08209.
SwissPalmiQ08209.

Miscellaneous databases

PMAP-CutDBQ08209.

Expressioni

Gene expression databases

BgeeiENSG00000138814.
CleanExiHS_PPP3CA.
ExpressionAtlasiQ08209. baseline and differential.
GenevisibleiQ08209. HS.

Organism-specific databases

HPAiCAB018581.
HPA012778.

Interactioni

Subunit structurei

Interacts with CIB1; the interaction increases upon cardiomyocytes hypertrophy (By similarity). Interacts with CHP1 and CHP2 (By similarity). 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 CMYA5; this interaction represses calcineurin activity in muscle (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
C16orf74R4GN893EBI-352922,EBI-10225238
Cacng8Q8VHW52EBI-352922,EBI-9086576From a different organism.
GRB2P629933EBI-352922,EBI-401755
PPP3R1P630985EBI-352922,EBI-915984
USP14P545783EBI-352922,EBI-1048016

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • protein dimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi111522. 58 interactors.
DIPiDIP-6095N.
IntActiQ08209. 17 interactors.
MINTiMINT-1037516.
STRINGi9606.ENSP00000378323.

Chemistry databases

BindingDBiQ08209.

Structurei

Secondary structure

1521
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi11 – 13Combined sources3
Helixi31 – 34Combined sources4
Helixi43 – 51Combined sources9
Helixi58 – 73Combined sources16
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 – 169Combined sources8
Helixi172 – 183Combined sources12
Beta strandi188 – 191Combined sources4
Turni192 – 194Combined sources3
Beta strandi195 – 200Combined sources6
Beta strandi206 – 208Combined sources3
Helixi210 – 213Combined sources4
Beta strandi218 – 220Combined sources3
Beta strandi223 – 225Combined sources3
Helixi226 – 232Combined sources7
Turni237 – 240Combined sources4
Beta strandi247 – 250Combined sources4
Turni252 – 254Combined sources3
Beta strandi255 – 260Combined sources6
Helixi262 – 271Combined sources10
Beta strandi276 – 279Combined sources4
Beta strandi287 – 290Combined sources4
Turni295 – 297Combined sources3
Beta strandi298 – 306Combined sources9
Helixi311 – 313Combined sources3
Beta strandi319 – 325Combined sources7
Beta strandi328 – 334Combined sources7
Helixi344 – 346Combined sources3
Helixi349 – 369Combined sources21
Helixi396 – 409Combined sources14
Helixi470 – 477Combined sources8
Helixi478 – 481Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AUIX-ray2.10A1-521[»]
1M63X-ray2.80A/E1-372[»]
1MF8X-ray3.10A20-392[»]
2JOGNMR-A21-347[»]
2JZINMR-B391-414[»]
2P6BX-ray2.30A/C1-380[»]
2R28X-ray1.86C/D389-413[»]
2W73X-ray1.45K/L/M/O395-411[»]
3LL8X-ray2.00A/C14-370[»]
4F0ZX-ray1.70A1-370[»]
4Q5UX-ray1.95C391-414[»]
5C1VX-ray3.35A/B2-346[»]
DisProtiDP00092.
ProteinModelPortaliQ08209.
SMRiQ08209.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ08209.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 301CatalyticAdd BLAST300
Regioni247 – 253Calcineurin B binding-site 1Sequence analysis7
Regioni296 – 301Calcineurin B binding-site 2Sequence analysis6
Regioni392 – 414Calmodulin-bindingSequence analysisAdd BLAST23
Regioni465 – 487Inhibitory domainAdd BLAST23

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0375. Eukaryota.
COG0639. LUCA.
GeneTreeiENSGT00530000063087.
HOGENOMiHOG000172699.
HOVERGENiHBG002819.
InParanoidiQ08209.
KOiK04348.
OMAiELICEGD.
OrthoDBiEOG091G094R.
PhylomeDBiQ08209.
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 (5)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q08209-1) [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 SYPAVCEFLQ 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
KALTSETNGT DSNGSNSSNI Q
Length:521
Mass (Da):58,688
Last modified:February 1, 1996 - v1
Checksum:i16480D62DDBF1F40
GO
Isoform 2 (identifier: Q08209-2) [UniParc]FASTAAdd to basket

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

Show »
Length:511
Mass (Da):57,659
Checksum:iB1E98CC0D6034CCC
GO
Isoform 3 (identifier: Q08209-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     318-359: Missing.
     448-457: Missing.

Show »
Length:469
Mass (Da):52,672
Checksum:iA3365471746633B7
GO
Isoform 4 (identifier: Q08209-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     87-318: Missing.

Show »
Length:289
Mass (Da):31,736
Checksum:iB3AEE20F6A4F19B7
GO
Isoform 5 (identifier: Q08209-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     20-86: Missing.

Show »
Length:454
Mass (Da):51,245
Checksum:iE28DCB758984D380
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05446720 – 86Missing in isoform 5. 1 PublicationAdd BLAST67
Alternative sequenceiVSP_04775587 – 318Missing in isoform 4. 1 PublicationAdd BLAST232
Alternative sequenceiVSP_043378318 – 359Missing in isoform 3. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_018562448 – 457Missing in isoform 2 and isoform 3. 3 Publications10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L14778 mRNA. Translation: AAA02631.1.
EU192652 mRNA. Translation: ABW74484.1.
EU192653 mRNA. Translation: ABW74485.1.
AY904364 mRNA. Translation: AAY17314.1.
AK290532 mRNA. Translation: BAF83221.1.
AL353950 mRNA. Translation: CAB89253.1.
AB451338 mRNA. Translation: BAG70152.1.
AB451487 mRNA. Translation: BAG70301.1.
AC092671 Genomic DNA. No translation available.
AP001816 Genomic DNA. No translation available.
AP001870 Genomic DNA. No translation available.
AP001939 Genomic DNA. No translation available.
CH471057 Genomic DNA. Translation: EAX06125.1.
CH471057 Genomic DNA. Translation: EAX06124.1.
BC025714 mRNA. Translation: AAH25714.1.
CCDSiCCDS34037.1. [Q08209-1]
CCDS47113.1. [Q08209-3]
CCDS47114.1. [Q08209-2]
PIRiS35067.
RefSeqiNP_000935.1. NM_000944.4. [Q08209-1]
NP_001124163.1. NM_001130691.1. [Q08209-2]
NP_001124164.1. NM_001130692.1. [Q08209-3]
UniGeneiHs.435512.

Genome annotation databases

EnsembliENST00000323055; ENSP00000320580; ENSG00000138814. [Q08209-3]
ENST00000394853; ENSP00000378322; ENSG00000138814. [Q08209-2]
ENST00000394854; ENSP00000378323; ENSG00000138814. [Q08209-1]
ENST00000512215; ENSP00000422781; ENSG00000138814. [Q08209-4]
GeneIDi5530.
KEGGihsa:5530.
UCSCiuc003hvu.3. human. [Q08209-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Wikipedia

Calcineurin entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L14778 mRNA. Translation: AAA02631.1.
EU192652 mRNA. Translation: ABW74484.1.
EU192653 mRNA. Translation: ABW74485.1.
AY904364 mRNA. Translation: AAY17314.1.
AK290532 mRNA. Translation: BAF83221.1.
AL353950 mRNA. Translation: CAB89253.1.
AB451338 mRNA. Translation: BAG70152.1.
AB451487 mRNA. Translation: BAG70301.1.
AC092671 Genomic DNA. No translation available.
AP001816 Genomic DNA. No translation available.
AP001870 Genomic DNA. No translation available.
AP001939 Genomic DNA. No translation available.
CH471057 Genomic DNA. Translation: EAX06125.1.
CH471057 Genomic DNA. Translation: EAX06124.1.
BC025714 mRNA. Translation: AAH25714.1.
CCDSiCCDS34037.1. [Q08209-1]
CCDS47113.1. [Q08209-3]
CCDS47114.1. [Q08209-2]
PIRiS35067.
RefSeqiNP_000935.1. NM_000944.4. [Q08209-1]
NP_001124163.1. NM_001130691.1. [Q08209-2]
NP_001124164.1. NM_001130692.1. [Q08209-3]
UniGeneiHs.435512.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AUIX-ray2.10A1-521[»]
1M63X-ray2.80A/E1-372[»]
1MF8X-ray3.10A20-392[»]
2JOGNMR-A21-347[»]
2JZINMR-B391-414[»]
2P6BX-ray2.30A/C1-380[»]
2R28X-ray1.86C/D389-413[»]
2W73X-ray1.45K/L/M/O395-411[»]
3LL8X-ray2.00A/C14-370[»]
4F0ZX-ray1.70A1-370[»]
4Q5UX-ray1.95C391-414[»]
5C1VX-ray3.35A/B2-346[»]
DisProtiDP00092.
ProteinModelPortaliQ08209.
SMRiQ08209.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111522. 58 interactors.
DIPiDIP-6095N.
IntActiQ08209. 17 interactors.
MINTiMINT-1037516.
STRINGi9606.ENSP00000378323.

Chemistry databases

BindingDBiQ08209.
ChEMBLiCHEMBL4445.

PTM databases

DEPODiQ08209.
iPTMnetiQ08209.
PhosphoSitePlusiQ08209.
SwissPalmiQ08209.

Polymorphism and mutation databases

BioMutaiPPP3CA.
DMDMi1352673.

Proteomic databases

EPDiQ08209.
MaxQBiQ08209.
PaxDbiQ08209.
PeptideAtlasiQ08209.
PRIDEiQ08209.

Protocols and materials databases

DNASUi5530.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000323055; ENSP00000320580; ENSG00000138814. [Q08209-3]
ENST00000394853; ENSP00000378322; ENSG00000138814. [Q08209-2]
ENST00000394854; ENSP00000378323; ENSG00000138814. [Q08209-1]
ENST00000512215; ENSP00000422781; ENSG00000138814. [Q08209-4]
GeneIDi5530.
KEGGihsa:5530.
UCSCiuc003hvu.3. human. [Q08209-1]

Organism-specific databases

CTDi5530.
DisGeNETi5530.
GeneCardsiPPP3CA.
HGNCiHGNC:9314. PPP3CA.
HPAiCAB018581.
HPA012778.
MIMi114105. gene.
neXtProtiNX_Q08209.
OpenTargetsiENSG00000138814.
PharmGKBiPA33678.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0375. Eukaryota.
COG0639. LUCA.
GeneTreeiENSGT00530000063087.
HOGENOMiHOG000172699.
HOVERGENiHBG002819.
InParanoidiQ08209.
KOiK04348.
OMAiELICEGD.
OrthoDBiEOG091G094R.
PhylomeDBiQ08209.
TreeFamiTF105557.

Enzyme and pathway databases

BioCyciZFISH:HS06568-MONOMER.
ReactomeiR-HSA-180024. DARPP-32 events.
R-HSA-2871809. FCERI mediated Ca+2 mobilization.
R-HSA-4086398. Ca2+ pathway.
R-HSA-5607763. CLEC7A (Dectin-1) induces NFAT activation.
SIGNORiQ08209.

Miscellaneous databases

ChiTaRSiPPP3CA. human.
EvolutionaryTraceiQ08209.
GeneWikiiPPP3CA.
GenomeRNAii5530.
PMAP-CutDBQ08209.
PROiQ08209.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138814.
CleanExiHS_PPP3CA.
ExpressionAtlasiQ08209. baseline and differential.
GenevisibleiQ08209. HS.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiPP2BA_HUMAN
AccessioniPrimary (citable) accession number: Q08209
Secondary accession number(s): A1A441
, A8K3B7, A8W6Z7, A8W6Z8, B5BUA2, Q8TAW9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 30, 2016
This is version 180 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.