ID:PP2AA_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform; Short=PP2A-alpha; EC=3.1.3.16; AltName: Full=Replication protein C; Short=RP-C; FUNCTION: 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 SGOL2 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'. CATALYTIC ACTIVITY: A phosphoprotein + H(2)O = a protein + phosphate. COFACTOR: Binds 1 iron ion per subunit (By similarity). COFACTOR: Binds 1 manganese ion per subunit (By similarity). SUBUNIT: 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 TP53, SGOL1 and SGOL2. 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. INTERACTION: P78318:IGBP1; NbExp=9; IntAct=EBI-712311, EBI-1055954; P30153:PPP2R1A; NbExp=14; IntAct=EBI-712311, EBI-302388; P30154:PPP2R1B; NbExp=6; IntAct=EBI-712311, EBI-357094; O43815:STRN; NbExp=3; IntAct=EBI-712311, EBI-1046642; Q15645:TRIP13; NbExp=3; IntAct=EBI-712311, EBI-358993; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Chromosome, centromere. Cytoplasm, cytoskeleton, spindle pole. Note=In prometaphase cells, but not in anaphase cells, localizes at centromeres. During mitosis, also found at spindle poles. Centromeric localization requires the presence of SGOL2 (By similarity). PTM: Reversibly methyl esterified on Leu-309. Carboxyl methylation may play a role in holoenzyme assembly, enhancing the affinity of the PP2A core enzyme for some, but not all, regulatory subunits. It varies during the cell cycle. PTM: 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. SIMILARITY: Belongs to the PPP phosphatase family. PP-1 subfamily.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P67775
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004721 phosphoprotein phosphatase activity GO:0004722 protein serine/threonine phosphatase activity GO:0005515 protein binding GO:0008022 protein C-terminus binding GO:0016787 hydrolase activity GO:0046872 metal ion binding GO:0046982 protein heterodimerization activity GO:0050811 GABA receptor binding
Biological Process: GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay GO:0000188 inactivation of MAPK activity GO:0001932 regulation of protein phosphorylation GO:0006275 regulation of DNA replication GO:0006355 regulation of transcription, DNA-templated GO:0006470 protein dephosphorylation GO:0006672 ceramide metabolic process GO:0006915 apoptotic process GO:0007498 mesoderm development GO:0008380 RNA splicing GO:0010033 response to organic substance GO:0010288 response to lead ion GO:0010719 negative regulation of epithelial to mesenchymal transition GO:0019932 second-messenger-mediated signaling GO:0030111 regulation of Wnt signaling pathway GO:0030155 regulation of cell adhesion GO:0030308 negative regulation of cell growth GO:0035970 peptidyl-threonine dephosphorylation GO:0040008 regulation of growth GO:0042532 negative regulation of tyrosine phosphorylation of STAT protein GO:0045595 regulation of cell differentiation GO:0051321 meiotic cell cycle GO:0070262 peptidyl-serine dephosphorylation GO:0071902 positive regulation of protein serine/threonine kinase activity GO:1904526 regulation of microtubule binding GO:1904528 positive regulation of microtubule binding
AK294559 - Homo sapiens cDNA FLJ50492 complete cds, highly similar to Cyclin-dependent kinase-like 3 (EC 2.7.11.22). AK297586 - Homo sapiens cDNA FLJ50582 complete cds, highly similar to Cyclin-dependent kinase-like 3 (EC 2.7.11.22). JD238090 - Sequence 219114 from Patent EP1572962. JD491222 - Sequence 472246 from Patent EP1572962. JD283294 - Sequence 264318 from Patent EP1572962. JD497059 - Sequence 478083 from Patent EP1572962. JD497060 - Sequence 478084 from Patent EP1572962. JD452274 - Sequence 433298 from Patent EP1572962. JD249820 - Sequence 230844 from Patent EP1572962. JD148289 - Sequence 129313 from Patent EP1572962. AK097599 - Homo sapiens cDNA FLJ40280 fis, clone TESTI2027411, highly similar to Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (EC 3.1.3.16). BC002657 - Homo sapiens protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform, mRNA (cDNA clone MGC:4275 IMAGE:3607862), complete cds. X12646 - Human mRNA for protein phosphatase 2A (alpha-type). JD053210 - Sequence 34234 from Patent EP1572962. JD363432 - Sequence 344456 from Patent EP1572962. BC000400 - Homo sapiens protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform, mRNA (cDNA clone MGC:8533 IMAGE:2822635), complete cds. BC019275 - Homo sapiens protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform, mRNA (cDNA clone MGC:3670 IMAGE:2822635), complete cds. AK057424 - Homo sapiens cDNA FLJ32862 fis, clone TESTI2003598, highly similar to Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (EC 3.1.3.16). J03804 - Human phosphatase 2A mRNA, complete cds. BC031696 - Homo sapiens protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform, mRNA (cDNA clone MGC:34900 IMAGE:5001649), complete cds. JD139502 - Sequence 120526 from Patent EP1572962. AB451240 - Homo sapiens PPP2CA mRNA for serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform, complete cds, clone: FLJ08039AAAN. CR457417 - Homo sapiens full open reading frame cDNA clone RZPDo834A1014D for gene PPP2CA, protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform; complete cds, incl. stopcodon. KJ904530 - Synthetic construct Homo sapiens clone ccsbBroadEn_13924 PPP2CA-like gene, encodes complete protein. AB451365 - Homo sapiens PPP2CA mRNA for serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform, partial cds, clone: FLJ08039AAAF. AB385080 - Synthetic construct DNA, clone: pF1KB5302, Homo sapiens PPP2CA gene for serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform, complete cds, without stop codon, in Flexi system. JD019911 - Sequence 935 from Patent EP1572962. HZ481318 - JP 2015535430-A/1824: TERMINALLY MODIFIED RNA. HZ791249 - JP 2016504050-A/2994: SIGNAL-SENSOR POLYNUCLEOTIDES FOR THE ALTERATION OF CELLULAR PHENOTYPES. JC513981 - Sequence 4234 from Patent WO2014113089. LQ071569 - Sequence 1893 from Patent EP2964234. JD246124 - Sequence 227148 from Patent EP1572962. MA645070 - JP 2017113010-A/2994: SIGNAL-SENSOR POLYNUCLEOTIDES FOR THE ALTERATION OF CELLULAR PHENOTYPES. MA732954 - JP 2017140048-A/1824: TERMINALLY MODIFIED RNA. MA802123 - JP 2018183181-A/2994: SIGNAL-SENSOR POLYNUCLEOTIDES FOR THE ALTERATION OF CELLULAR PHENOTYPES.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_aktPathway - AKT Signaling Pathway h_ck1Pathway - Regulation of ck1/cdk5 by type 1 glutamate receptors h_akap95Pathway - AKAP95 role in mitosis and chromosome dynamics h_mTORPathway - mTOR Signaling Pathway h_telPathway - Telomeres, Telomerase, Cellular Aging, and Immortality h_wntPathway - WNT Signaling Pathway h_chrebpPathway - ChREBP regulation by carbohydrates and cAMP h_ctcfPathway - CTCF: First Multivalent Nuclear Factor h_erkPathway - Erk1/Erk2 Mapk Signaling pathway h_gsk3Pathway - Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages h_p35alzheimersPathway - Deregulation of CDK5 in Alzheimers Disease h_akapCentrosomePathway - Protein Kinase A at the Centrosome h_igf1mtorpathway - Skeletal muscle hypertrophy is regulated via AKT/mTOR pathway h_keratinocytePathway - Keratinocyte Differentiation
Reactome (by CSHL, EBI, and GO)
Protein P67775 (Reactome details) participates in the following event(s):
R-HSA-2995388 PP2A dephosphorylates BANF1 R-HSA-1295622 SPRY2 binds CBL R-HSA-163769 Activation of PP2A by Xylulose-5-phosphate R-HSA-195251 Assembly of the destruction complex R-HSA-389532 PP2A binds CTLA4 homodimer R-HSA-432143 PECAM-1 binds PP2A R-HSA-8857925 Inhibition of PP2A activity by phosphorylation of the catalytic subunit at tyrosine Y307 R-HSA-201685 Beta-catenin is released from the destruction complex R-HSA-388833 Phosphorylation of CTLA-4 R-HSA-6811454 MAPKs phosphorylate PP2A R-HSA-6811472 IER3 recruits MAPKs to PP2A-B56-beta,gamma R-HSA-8856945 PP2A methylation by LCMT1 R-HSA-8856951 PP2A demethylation by PPME1 R-HSA-2430552 p-S62-ARPP19/p-S67-ENSA binds PP2A-PPP2R2D R-HSA-6792871 CCNG1 recruits PP2A-PPP2R5C to MDM2 R-HSA-6792863 PP2A-PP2R5C dephosphorylates MDM2 R-HSA-934559 SPRY2 is phosphorylated by phosphorylated MNK1 R-HSA-1295609 SRC phosphorylates SPRY2 on Y55 and Y227 R-HSA-1295599 SPRY2 translocates to the plasma membrane R-HSA-1295613 SPRY2 binds GRB2 R-HSA-1549564 PPTN11 dephosphorylates SPRY2 R-HSA-1295632 PPA2A dephosphorylates SPRY2 R-HSA-163689 Dephosphorylation of pChREBP (Ser 196) by PP2A R-HSA-163750 Dephosphorylation of phosphoPFKFB1 by PP2A complex R-HSA-201790 DARPP-32 is dephosphorylated on Thr75 by PP2A R-HSA-5229343 AXIN is phosphorylated in the destruction complex R-HSA-195280 Dissociation of beta-catenin from Axin and association of beta catenin with phospho-(20 aa) APC in the detruction complex R-HSA-195275 Phosphorylation of APC component of the destruction complex R-HSA-2130279 Association of beta-catenin with the RBX1:SCF(beta-TrCP1) ubiquitin ligase complex R-HSA-141409 Mad1 binds kinetochore R-HSA-375302 Kinetochore capture of astral microtubules R-HSA-5666129 CDC42:GTP recruits DIAPH2-2 to kinetochores R-HSA-5666169 Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2 R-HSA-388809 CTLA-4 binds B7-1/B7-2 R-HSA-195304 Association of beta-catenin with the destruction complex R-HSA-390329 Dephosphorylation of AKT by PP2A R-HSA-5672957 PP2A dephosphorylates KSR1 R-HSA-5672961 PP2A dephosphorylates inactive RAFs R-HSA-5675431 PP2A dephosphorylates RAF1 R-HSA-6811504 AKT1 dephosphorylation by PP2A-B56-beta,gamma R-HSA-163688 Dephosphorylation of pChREBP (Thr 666) by PP2A R-HSA-164056 Dephosphorylation of pChREBP (Ser 568) by PP2A R-HSA-199959 ERKs are inactivated by protein phosphatase 2A R-HSA-113503 PP2A mediated localization of RB1 protein in chromatin R-HSA-1363274 Dephosphorylation of p107 (RBL1) by PP2A R-HSA-1363276 Dephosphorylation of p130 (RBL2) by PP2A R-HSA-4088141 PP2A-PPP2R2A dephosphorylates FOXM1 R-HSA-2130286 Multi-ubiquitination of phospho-beta-catenin by RBX1:SCF(beta-TrCP1) R-HSA-141431 MAD2 associates with the Mad1 kinetochore complex R-HSA-141439 Release of activated MAD2 from kinetochores R-HSA-2467811 Separation of sister chromatids R-HSA-2467809 ESPL1 (Separase) cleaves centromeric cohesin R-HSA-5666160 AURKB phosphorylates DIAPH2-2 at kinetochores R-HSA-195287 Phosphorylation of phospho-(Ser45 ) at Thr 41 by GSK-3 R-HSA-195318 Phosphorylation of beta-catenin at Ser45 by CK1 alpha R-HSA-195300 Phosphorylation of phospho-(Ser45,Thr41,Ser37) at Ser33 by GSK-3 R-HSA-195283 Phosphorylation of phospho- (Ser45, Thr41) beta-catenin at Ser37 by GSK-3 R-HSA-141422 MAD2 converted to an inhibitory state via interaction with Mad1 R-HSA-1638821 PP2A-B56 dephosphorylates centromeric cohesin R-HSA-1638803 Phosphorylation of cohesin by PLK1 at centromeres R-HSA-2468287 CDK1 phosphorylates CDCA5 (Sororin) at centromeres R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) R-HSA-927802 Nonsense-Mediated Decay (NMD) R-HSA-2995383 Initiation of Nuclear Envelope Reformation R-HSA-1295596 Spry regulation of FGF signaling R-HSA-163685 Energy Metabolism R-HSA-195253 Degradation of beta-catenin by the destruction complex R-HSA-389513 CTLA4 inhibitory signaling R-HSA-432142 Platelet sensitization by LDL 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-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition R-HSA-2465910 MASTL Facilitates Mitotic Progression R-HSA-6804757 Regulation of TP53 Degradation R-HSA-8953854 Metabolism of RNA R-HSA-2995410 Nuclear Envelope Reassembly R-HSA-5654726 Negative regulation of FGFR1 signaling R-HSA-5654727 Negative regulation of FGFR2 signaling R-HSA-5654732 Negative regulation of FGFR3 signaling R-HSA-5654733 Negative regulation of FGFR4 signaling R-HSA-1430728 Metabolism R-HSA-163767 PP2A-mediated dephosphorylation of key metabolic factors R-HSA-70171 Glycolysis R-HSA-180024 DARPP-32 events R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal R-HSA-68877 Mitotic Prometaphase R-HSA-5663220 RHO GTPases Activate Formins R-HSA-195721 Signaling by WNT R-HSA-388841 Costimulation by the CD28 family R-HSA-418346 Platelet homeostasis R-HSA-4839744 truncated APC mutants destabilize the destruction complex R-HSA-4839735 AXIN mutants destabilize the destruction complex, activating WNT signaling R-HSA-4839748 AMER1 mutants destabilize the destruction complex R-HSA-199418 Negative regulation of the PI3K/AKT network R-HSA-201681 TCF dependent signaling in response to WNT R-HSA-5673000 RAF activation R-HSA-5675221 Negative regulation of MAPK pathway R-HSA-198753 ERK/MAPK targets R-HSA-202670 ERKs are inactivated R-HSA-113501 Inhibition of replication initiation of damaged DNA by RB1/E2F1 R-HSA-69275 G2/M Transition R-HSA-69231 Cyclin D associated events in G1 R-HSA-68875 Mitotic Prophase R-HSA-6806003 Regulation of TP53 Expression and Degradation R-HSA-68882 Mitotic Anaphase R-HSA-5654736 Signaling by FGFR1 R-HSA-5654738 Signaling by FGFR2 R-HSA-5654741 Signaling by FGFR3 R-HSA-5654743 Signaling by FGFR4 R-HSA-70326 Glucose metabolism R-HSA-111885 Opioid Signalling R-HSA-5358751 S45 mutants of beta-catenin aren't phosphorylated R-HSA-5358752 T41 mutants of beta-catenin aren't phosphorylated R-HSA-5358749 S37 mutants of beta-catenin aren't phosphorylated R-HSA-5358747 S33 mutants of beta-catenin aren't phosphorylated R-HSA-2500257 Resolution of Sister Chromatid Cohesion R-HSA-2467813 Separation of Sister Chromatids R-HSA-141424 Amplification of signal from the kinetochores R-HSA-68886 M Phase R-HSA-195258 RHO GTPase Effectors R-HSA-196299 Beta-catenin phosphorylation cascade R-HSA-5339716 Misspliced GSK3beta mutants stabilize beta-catenin R-HSA-162582 Signal Transduction R-HSA-1280218 Adaptive Immune System R-HSA-109582 Hemostasis R-HSA-4791275 Signaling by WNT in cancer R-HSA-1257604 PIP3 activates AKT signaling R-HSA-5673001 RAF/MAP kinase cascade R-HSA-198725 Nuclear Events (kinase and transcription factor activation) R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinases R-HSA-113510 E2F mediated regulation of DNA replication R-HSA-453274 Mitotic G2-G2/M phases R-HSA-69236 G1 Phase R-HSA-5633007 Regulation of TP53 Activity R-HSA-2555396 Mitotic Metaphase and Anaphase R-HSA-190236 Signaling by FGFR R-HSA-71387 Metabolism of carbohydrates R-HSA-418594 G alpha (i) signalling events R-HSA-4839743 phosphorylation site mutants of CTNNB1 are not targeted to the proteasome by the destruction complex R-HSA-69618 Mitotic Spindle Checkpoint R-HSA-69278 Cell Cycle (Mitotic) R-HSA-194315 Signaling by Rho GTPases R-HSA-168256 Immune System R-HSA-5663202 Diseases of signal transduction R-HSA-9006925 Intracellular signaling by second messengers R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-187037 Signaling by NTRK1 (TRKA) R-HSA-450294 MAP kinase activation R-HSA-69206 G1/S Transition R-HSA-453279 Mitotic G1-G1/S phases R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-388396 GPCR downstream signalling R-HSA-69620 Cell Cycle Checkpoints R-HSA-1640170 Cell Cycle R-HSA-1643685 Disease R-HSA-5683057 MAPK family signaling cascades R-HSA-166520 Signaling by NTRKs R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade R-HSA-448424 Interleukin-17 signaling R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-975871 MyD88 cascade initiated on plasma membrane R-HSA-212436 Generic Transcription Pathway R-HSA-372790 Signaling by GPCR R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade R-HSA-168898 Toll-Like Receptors Cascades R-HSA-449147 Signaling by Interleukins R-HSA-166166 MyD88-independent TLR4 cascade R-HSA-975155 MyD88 dependent cascade initiated on endosome R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade R-HSA-73857 RNA Polymerase II Transcription R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade R-HSA-168249 Innate Immune System R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-74160 Gene expression (Transcription)
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
