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Protein

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

Gene

PPP2CA

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

Functioni

PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'.By similarity3 Publications

Catalytic activityi

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

Cofactori

Mn2+1 PublicationNote: Binds 2 manganese ions per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi57Manganese 11 Publication1
Metal bindingi59Manganese 11 Publication1
Metal bindingi85Manganese 11 Publication1
Metal bindingi85Manganese 21 Publication1
Metal bindingi117Manganese 21 Publication1
Active sitei118Proton donorBy similarity1
Metal bindingi167Manganese 21 Publication1
Metal bindingi241Manganese 21 Publication1

GO - Molecular functioni

  • GABA receptor binding Source: Ensembl
  • metal ion binding Source: UniProtKB-KW
  • phosphoprotein phosphatase activity Source: ARUK-UCL
  • protein C-terminus binding Source: Ensembl
  • protein heterodimerization activity Source: UniProtKB
  • protein serine/threonine phosphatase activity Source: ARUK-UCL

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protein phosphatase
Biological processMeiosis
LigandManganese, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS03696-MONOMER
ReactomeiR-HSA-113501 Inhibition of replication initiation of damaged DNA by RB1/E2F1
R-HSA-1295596 Spry regulation of FGF signaling
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-163685 Integration of energy metabolism
R-HSA-163767 PP2A-mediated dephosphorylation of key metabolic factors
R-HSA-180024 DARPP-32 events
R-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-196299 Beta-catenin phosphorylation cascade
R-HSA-198753 ERK/MAPK targets
R-HSA-202670 ERKs are inactivated
R-HSA-2465910 MASTL Facilitates Mitotic Progression
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-2995383 Initiation of Nuclear Envelope Reformation
R-HSA-389513 CTLA4 inhibitory signaling
R-HSA-432142 Platelet sensitization by LDL
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5339716 Misspliced GSK3beta mutants stabilize beta-catenin
R-HSA-5358747 S33 mutants of beta-catenin aren't phosphorylated
R-HSA-5358749 S37 mutants of beta-catenin aren't phosphorylated
R-HSA-5358751 S45 mutants of beta-catenin aren't phosphorylated
R-HSA-5358752 T41 mutants of beta-catenin aren't phosphorylated
R-HSA-5467337 APC truncation mutants have impaired AXIN binding
R-HSA-5467340 AXIN missense mutants destabilize the destruction complex
R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-5673000 RAF activation
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6804757 Regulation of TP53 Degradation
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-68877 Mitotic Prometaphase
R-HSA-69231 Cyclin D associated events in G1
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-70171 Glycolysis
R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
SignaLinkiP67775
SIGNORiP67775

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (EC:3.1.3.16)
Short name:
PP2A-alpha
Alternative name(s):
Replication protein C
Short name:
RP-C
Gene namesi
Name:PPP2CA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113575.9
HGNCiHGNC:9299 PPP2CA
MIMi176915 gene
neXtProtiNX_P67775

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

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi309L → A: Loss of binding to PP2A B-alpha regulatory subunit. 1 Publication1

Organism-specific databases

DisGeNETi5515
OpenTargetsiENSG00000113575
PharmGKBiPA33663

Chemistry databases

ChEMBLiCHEMBL4703
DrugBankiDB00163 Vitamin E

Polymorphism and mutation databases

BioMutaiPPP2CA
DMDMi54038809

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000588391 – 309Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoformAdd BLAST309

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei307PhosphotyrosineBy similarity1
Modified residuei309Leucine methyl ester1 Publication1

Post-translational modificationi

Reversibly methyl esterified on Leu-309 by leucine carboxyl methyltransferase 1 (LCMT1) and protein phosphatase methylesterase 1 (PPME1). Carboxyl methylation influences the affinity of the catalytic subunit for the different regulatory subunits, thereby modulating the PP2A holoenzyme's substrate specificity, enzyme activity and cellular localization.1 Publication
Phosphorylation of either threonine (by autophosphorylation-activated protein kinase) or tyrosine results in inactivation of the phosphatase. Auto-dephosphorylation has been suggested as a mechanism for reactivation.
Polyubiquitinated, leading to its degradation by the proteasome.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP67775
MaxQBiP67775
PaxDbiP67775
PeptideAtlasiP67775
PRIDEiP67775
ProteomicsDBi57521

PTM databases

DEPODiP67775
iPTMnetiP67775
PhosphoSitePlusiP67775

Expressioni

Gene expression databases

BgeeiENSG00000113575 Expressed in 233 organ(s), highest expression level in adrenal tissue
CleanExiHS_PPP2CA
ExpressionAtlasiP67775 baseline and differential
GenevisibleiP67775 HS

Organism-specific databases

HPAiCAB003848
HPA043236

Interactioni

Subunit structurei

PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with NXN; the interaction is direct (By similarity). Interacts with KCTD20 (By similarity). Interacts with BTBD10 (By similarity). Interacts with TP53, SGO1 and SGO2. Interacts with AXIN1; the interaction dephosphorylates AXIN1. Interacts with PIM3; this interaction promotes dephosphorylation, ubiquitination and proteasomal degradation of PIM3. Interacts with RAF1. Interaction with IGBP1 protects unassembled PPP2CA from degradative ubiquitination. Interacts with GSK3B (via C2 domain). Interacts with MFHAS1; retains PPP2CA into the cytoplasm and excludes it from the nucleus (PubMed:28609714). Interacts with FAM122A (PubMed:27588481).By similarity15 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111507, 276 interactors
CORUMiP67775
DIPiDIP-29395N
IntActiP67775, 166 interactors
MINTiP67775
STRINGi9606.ENSP00000418447

Chemistry databases

BindingDBiP67775

Structurei

Secondary structure

1309
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP67775
SMRiP67775
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP67775

Family & Domainsi

Sequence similaritiesi

Belongs to the PPP phosphatase family. PP-1 subfamily.Curated

Phylogenomic databases

eggNOGiKOG0371 Eukaryota
COG0639 LUCA
GeneTreeiENSGT00550000074618
HOGENOMiHOG000172696
HOVERGENiHBG000216
InParanoidiP67775
KOiK04382
OMAiNKIFCPH
OrthoDBiEOG091G0B6S
PhylomeDBiP67775
TreeFamiTF105559

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.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P67775-1) [UniParc]FASTAAdd to basket
Also known as: PP2Acalpha1

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
MDEKVFTKEL DQWIEQLNEC KQLSESQVKS LCEKAKEILT KESNVQEVRC
60 70 80 90 100
PVTVCGDVHG QFHDLMELFR IGGKSPDTNY LFMGDYVDRG YYSVETVTLL
110 120 130 140 150
VALKVRYRER ITILRGNHES RQITQVYGFY DECLRKYGNA NVWKYFTDLF
160 170 180 190 200
DYLPLTALVD GQIFCLHGGL SPSIDTLDHI RALDRLQEVP HEGPMCDLLW
210 220 230 240 250
SDPDDRGGWG ISPRGAGYTF GQDISETFNH ANGLTLVSRA HQLVMEGYNW
260 270 280 290 300
CHDRNVVTIF SAPNYCYRCG NQAAIMELDD TLKYSFLQFD PAPRRGEPHV

TRRTPDYFL
Length:309
Mass (Da):35,594
Last modified:October 11, 2004 - v1
Checksum:iC602291F78F34555
GO
Isoform 2 (identifier: P67775-2) [UniParc]FASTAAdd to basket
Also known as: PP2Acalpha2

The sequence of this isoform differs from the canonical sequence as follows:
     193-246: Missing.

Note: Catalytically inactive, shows enhanced binding to IGBP1, and does not interact with the scaffolding subunit PPP2R1A.
Show »
Length:255
Mass (Da):29,735
Checksum:iB50450F64CB286AB
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7ESG8E7ESG8_HUMAN
Serine/threonine-protein phosphatas...
PPP2CA
145Annotation score:
E5RHP4E5RHP4_HUMAN
Serine/threonine-protein phosphatas...
PPP2CA
126Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05173552V → A. Corresponds to variant dbSNP:rs11552681Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044320193 – 246Missing in isoform 2. CuratedAdd BLAST54

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X12646 mRNA Translation: CAA31176.1
J03804 mRNA Translation: AAB38019.1
M60483 Genomic DNA Translation: AAA36466.1
BC000400 mRNA Translation: AAH00400.1
BC002657 mRNA Translation: AAH02657.1
BC019275 mRNA Translation: AAH19275.1
BC031696 mRNA Translation: AAH31696.1
CCDSiCCDS4173.1 [P67775-1]
PIRiS01986 PAHU2A
RefSeqiNP_002706.1, NM_002715.2 [P67775-1]
UniGeneiHs.105818

Genome annotation databases

EnsembliENST00000481195; ENSP00000418447; ENSG00000113575 [P67775-1]
GeneIDi5515
KEGGihsa:5515
UCSCiuc003kze.4 human [P67775-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X12646 mRNA Translation: CAA31176.1
J03804 mRNA Translation: AAB38019.1
M60483 Genomic DNA Translation: AAA36466.1
BC000400 mRNA Translation: AAH00400.1
BC002657 mRNA Translation: AAH02657.1
BC019275 mRNA Translation: AAH19275.1
BC031696 mRNA Translation: AAH31696.1
CCDSiCCDS4173.1 [P67775-1]
PIRiS01986 PAHU2A
RefSeqiNP_002706.1, NM_002715.2 [P67775-1]
UniGeneiHs.105818

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2IAEX-ray3.50C/F1-309[»]
2IE3X-ray2.80C1-309[»]
2IE4X-ray2.60C1-309[»]
2NPPX-ray3.30C/F1-309[»]
2NYLX-ray3.80C/F2-294[»]
2NYMX-ray3.60C/F2-294[»]
3C5WX-ray2.80C1-309[»]
3DW8X-ray2.85C/F1-309[»]
3FGAX-ray2.70C1-309[»]
3K7VX-ray2.85C1-309[»]
3K7WX-ray2.96C1-309[»]
3P71X-ray2.70C1-309[»]
4I5LX-ray2.43C/F1-309[»]
4I5NX-ray2.80C/F1-309[»]
4IYPX-ray2.80C6-153[»]
4LACX-ray2.82C1-309[»]
5W0WX-ray3.80C/F/I/L1-309[»]
ProteinModelPortaliP67775
SMRiP67775
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111507, 276 interactors
CORUMiP67775
DIPiDIP-29395N
IntActiP67775, 166 interactors
MINTiP67775
STRINGi9606.ENSP00000418447

Chemistry databases

BindingDBiP67775
ChEMBLiCHEMBL4703
DrugBankiDB00163 Vitamin E

PTM databases

DEPODiP67775
iPTMnetiP67775
PhosphoSitePlusiP67775

Polymorphism and mutation databases

BioMutaiPPP2CA
DMDMi54038809

Proteomic databases

EPDiP67775
MaxQBiP67775
PaxDbiP67775
PeptideAtlasiP67775
PRIDEiP67775
ProteomicsDBi57521

Protocols and materials databases

DNASUi5515
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000481195; ENSP00000418447; ENSG00000113575 [P67775-1]
GeneIDi5515
KEGGihsa:5515
UCSCiuc003kze.4 human [P67775-1]

Organism-specific databases

CTDi5515
DisGeNETi5515
EuPathDBiHostDB:ENSG00000113575.9
GeneCardsiPPP2CA
HGNCiHGNC:9299 PPP2CA
HPAiCAB003848
HPA043236
MIMi176915 gene
neXtProtiNX_P67775
OpenTargetsiENSG00000113575
PharmGKBiPA33663
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0371 Eukaryota
COG0639 LUCA
GeneTreeiENSGT00550000074618
HOGENOMiHOG000172696
HOVERGENiHBG000216
InParanoidiP67775
KOiK04382
OMAiNKIFCPH
OrthoDBiEOG091G0B6S
PhylomeDBiP67775
TreeFamiTF105559

Enzyme and pathway databases

BioCyciMetaCyc:HS03696-MONOMER
ReactomeiR-HSA-113501 Inhibition of replication initiation of damaged DNA by RB1/E2F1
R-HSA-1295596 Spry regulation of FGF signaling
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-163685 Integration of energy metabolism
R-HSA-163767 PP2A-mediated dephosphorylation of key metabolic factors
R-HSA-180024 DARPP-32 events
R-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-196299 Beta-catenin phosphorylation cascade
R-HSA-198753 ERK/MAPK targets
R-HSA-202670 ERKs are inactivated
R-HSA-2465910 MASTL Facilitates Mitotic Progression
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-2995383 Initiation of Nuclear Envelope Reformation
R-HSA-389513 CTLA4 inhibitory signaling
R-HSA-432142 Platelet sensitization by LDL
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5339716 Misspliced GSK3beta mutants stabilize beta-catenin
R-HSA-5358747 S33 mutants of beta-catenin aren't phosphorylated
R-HSA-5358749 S37 mutants of beta-catenin aren't phosphorylated
R-HSA-5358751 S45 mutants of beta-catenin aren't phosphorylated
R-HSA-5358752 T41 mutants of beta-catenin aren't phosphorylated
R-HSA-5467337 APC truncation mutants have impaired AXIN binding
R-HSA-5467340 AXIN missense mutants destabilize the destruction complex
R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-5673000 RAF activation
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6804757 Regulation of TP53 Degradation
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-68877 Mitotic Prometaphase
R-HSA-69231 Cyclin D associated events in G1
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-70171 Glycolysis
R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
SignaLinkiP67775
SIGNORiP67775

Miscellaneous databases

ChiTaRSiPPP2CA human
EvolutionaryTraceiP67775
GeneWikiiPPP2CA
GenomeRNAii5515
PROiPR:P67775
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113575 Expressed in 233 organ(s), highest expression level in adrenal tissue
CleanExiHS_PPP2CA
ExpressionAtlasiP67775 baseline and differential
GenevisibleiP67775 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiPP2AA_HUMAN
AccessioniPrimary (citable) accession number: P67775
Secondary accession number(s): P05323, P13197
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: October 10, 2018
This is version 153 of the entry and version 1 of the sequence. See 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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