PP2AA_BOVIN
ID PP2AA_BOVIN Reviewed; 309 AA.
AC P67774; A6QLI7; P05323; P13197;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform;
DE Short=PP2A-alpha;
DE EC=3.1.3.16 {ECO:0000250|UniProtKB:P67775};
GN Name=PPP2CA;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Aortic smooth muscle;
RA Tang P.M., de Paoli-Roach A.A.;
RL Submitted (MAR-1990) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3037526; DOI=10.1073/pnas.84.14.4880;
RA Green D.D., Yang S.-I., Mumby M.C.;
RT "Molecular cloning and sequence analysis of the catalytic subunit of bovine
RT type 2A protein phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:4880-4884(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Chen S., Boynton A.;
RL Submitted (MAR-1993) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal muscle;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PROTEIN SEQUENCE OF 42-48 AND 284-308, AND METHYLATION AT LEU-309.
RC TISSUE=Brain;
RX PubMed=8396127; DOI=10.1016/s0021-9258(19)36497-x;
RA Lee J., Stock J.;
RT "Protein phosphatase 2A catalytic subunit is methyl-esterified at its
RT carboxyl terminus by a novel methyltransferase.";
RL J. Biol. Chem. 268:19192-19195(1993).
RN [6]
RP PHOSPHORYLATION AT TYR-307.
RX PubMed=7681598; DOI=10.1073/pnas.90.6.2500;
RA Guo H., Damuni Z.;
RT "Autophosphorylation-activated protein kinase phosphorylates and
RT inactivates protein phosphatase 2A.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:2500-2504(1993).
CC -!- FUNCTION: PP2A is the major phosphatase for microtubule-associated
CC proteins (MAPs). PP2A can modulate the activity of phosphorylase B
CC kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase
CC (By similarity). Cooperates with SGO2 to protect centromeric cohesin
CC from separase-mediated cleavage in oocytes specifically during meiosis
CC I (By similarity). Can dephosphorylate p53/TP53. Activates RAF1 by
CC dephosphorylating it at 'Ser-259'. Mediates dephosphorylation of WEE1,
CC preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein
CC levels, and promoting the G2/M checkpoint. Mediates dephosphorylation
CC of MYC; promoting its ubiquitin-mediated proteolysis: interaction with
CC AMBRA1 enhances interaction between PPP2CA and MYC (By similarity).
CC Mediates dephosphorylation of FOXO3; promoting its stabilization:
CC interaction with AMBRA1 enhances interaction between PPP2CA and FOXO3
CC (By similarity). {ECO:0000250|UniProtKB:P63330,
CC ECO:0000250|UniProtKB:P67775}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:83421; EC=3.1.3.16;
CC Evidence={ECO:0000250|UniProtKB:P67775};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:61977; EC=3.1.3.16;
CC Evidence={ECO:0000250|UniProtKB:P67775};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P67775};
CC Note=Binds 2 manganese ions per subunit.
CC {ECO:0000250|UniProtKB:P67775};
CC -!- SUBUNIT: PP2A consists of a common heterodimeric core enzyme, composed
CC of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa
CC constant regulatory subunit (PR65 or subunit A), that associates with a
CC variety of regulatory subunits. Proteins that associate with the core
CC dimer include three families of regulatory subunits B (the
CC R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48
CC kDa variable regulatory subunit, viral proteins, and cell signaling
CC molecules (By similarity). Interacts with NXN; the interaction is
CC direct (By similarity). Interacts with KCTD20 (By similarity).
CC Interacts with BTBD10 (By similarity). Interacts with SGO1 and SGO2.
CC Interacts with TP53. Interacts with AXIN1; the interaction
CC dephosphorylates AXIN1. Interacts with PIM3; this interaction promotes
CC dephosphorylation, ubiquitination and proteasomal degradation of PIM3.
CC Interacts with RAF1. Interaction with IGBP1 protects unassembled PPP2CA
CC from degradative ubiquitination. Interacts with GSK3B (via C2 domain).
CC Interacts with MFHAS1; retains PPP2CA into the cytoplasm and excludes
CC it from the nucleus. Interacts with PABIR1/FAM122A. Interacts with
CC ADCY8; interaction is phosphatase activity-dependent; antagonizes
CC interaction between ADCY8 and calmodulin. Interacts with CRTC3 (when
CC phosphorylated at 'Ser-391'). Interacts with SPRY2; the interaction is
CC inhibited by TESK1 interaction with SPRY2, possibly by vesicular
CC sequestration of SPRY2. Interacts with TRAF3IP3. Interacts with AMBRA1
CC (via PxP motifs); enhancing interaction between PPP2CA and MYC or FOXO3
CC (By similarity). Forms a complex with AMBRA1 and BECN1; AMBRA1 and
CC BECN1 components of the complex regulate MYC stability via different
CC pathways (By similarity). {ECO:0000250|UniProtKB:P63330,
CC ECO:0000250|UniProtKB:P67775}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P67775}. Nucleus
CC {ECO:0000250|UniProtKB:P67775}. Chromosome, centromere
CC {ECO:0000250|UniProtKB:P67775}. Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000250|UniProtKB:P67775}. Note=In prometaphase cells, but not in
CC anaphase cells, localizes at centromeres. During mitosis, also found at
CC spindle poles (By similarity). Centromeric localization requires the
CC presence of SGO2 (By similarity). {ECO:0000250|UniProtKB:P63330,
CC ECO:0000250|UniProtKB:P67775}.
CC -!- PTM: Reversibly methyl esterified on Leu-309 by leucine carboxyl
CC methyltransferase 1 (LCMT1) and protein phosphatase methylesterase 1
CC (PPME1). Carboxyl methylation influences the affinity of the catalytic
CC subunit for the different regulatory subunits, thereby modulating the
CC PP2A holoenzyme's substrate specificity, enzyme activity and cellular
CC localization. {ECO:0000269|PubMed:8396127}.
CC -!- PTM: Phosphorylation of either threonine (by autophosphorylation-
CC activated protein kinase) or tyrosine results in inactivation of the
CC phosphatase. Auto-dephosphorylation has been suggested as a mechanism
CC for reactivation. {ECO:0000269|PubMed:7681598}.
CC -!- PTM: The N-terminus is blocked. {ECO:0000269|PubMed:3037526}.
CC -!- PTM: Polyubiquitinated, leading to its degradation by the proteasome.
CC {ECO:0000250|UniProtKB:P67775}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-1 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA30695.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X52554; CAA36789.1; -; mRNA.
DR EMBL; M16968; AAA30695.1; ALT_FRAME; mRNA.
DR EMBL; X72858; CAA51381.1; -; mRNA.
DR EMBL; BC147979; AAI47980.1; -; mRNA.
DR PIR; A28029; A28029.
DR PIR; S10371; S10371.
DR RefSeq; NP_851374.1; NM_181031.2.
DR AlphaFoldDB; P67774; -.
DR SMR; P67774; -.
DR BioGRID; 159582; 3.
DR IntAct; P67774; 4.
DR MINT; P67774; -.
DR STRING; 9913.ENSBTAP00000000596; -.
DR BindingDB; P67774; -.
DR ChEMBL; CHEMBL3862; -.
DR iPTMnet; P67774; -.
DR PaxDb; P67774; -.
DR PeptideAtlas; P67774; -.
DR PRIDE; P67774; -.
DR Ensembl; ENSBTAT00000000596; ENSBTAP00000000596; ENSBTAG00000000469.
DR GeneID; 282320; -.
DR KEGG; bta:282320; -.
DR CTD; 5515; -.
DR VEuPathDB; HostDB:ENSBTAG00000000469; -.
DR VGNC; VGNC:33251; PPP2CA.
DR eggNOG; KOG0371; Eukaryota.
DR GeneTree; ENSGT00550000074618; -.
DR HOGENOM; CLU_004962_0_5_1; -.
DR InParanoid; P67774; -.
DR OMA; SWSHQES; -.
DR OrthoDB; 808922at2759; -.
DR TreeFam; TF105559; -.
DR Reactome; R-BTA-1295596; Spry regulation of FGF signaling.
DR Reactome; R-BTA-195253; Degradation of beta-catenin by the destruction complex.
DR Reactome; R-BTA-196299; Beta-catenin phosphorylation cascade.
DR Reactome; R-BTA-198753; ERK/MAPK targets.
DR Reactome; R-BTA-202670; ERKs are inactivated.
DR Reactome; R-BTA-389513; CTLA4 inhibitory signaling.
DR Reactome; R-BTA-432142; Platelet sensitization by LDL.
DR Reactome; R-BTA-5673000; RAF activation.
DR Reactome; R-BTA-5675221; Negative regulation of MAPK pathway.
DR PRO; PR:P67774; -.
DR Proteomes; UP000009136; Chromosome 7.
DR Bgee; ENSBTAG00000000469; Expressed in occipital lobe and 101 other tissues.
DR GO; GO:0000775; C:chromosome, centromeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0000159; C:protein phosphatase type 2A complex; IEA:Ensembl.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0050811; F:GABA receptor binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISS:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:Ensembl.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0007498; P:mesoderm development; IEA:Ensembl.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IEA:Ensembl.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; IEA:Ensembl.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IEA:Ensembl.
DR GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR Pfam; PF00149; Metallophos; 1.
DR PRINTS; PR00114; STPHPHTASE.
DR SMART; SM00156; PP2Ac; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1.
PE 1: Evidence at protein level;
KW Centromere; Chromosome; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Hydrolase; Manganese; Meiosis; Metal-binding; Methylation; Nucleus;
KW Phosphoprotein; Protein phosphatase; Reference proteome; Ubl conjugation.
FT CHAIN 1..309
FT /note="Serine/threonine-protein phosphatase 2A catalytic
FT subunit alpha isoform"
FT /id="PRO_0000058838"
FT ACT_SITE 118
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P36873"
FT BINDING 57
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P67775"
FT BINDING 59
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P67775"
FT BINDING 85
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P67775"
FT BINDING 85
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P67775"
FT BINDING 117
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P67775"
FT BINDING 167
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P67775"
FT BINDING 241
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P67775"
FT MOD_RES 307
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:7681598"
FT MOD_RES 309
FT /note="Leucine methyl ester"
FT /evidence="ECO:0000269|PubMed:8396127"
SQ SEQUENCE 309 AA; 35594 MW; C602291F78F34555 CRC64;
MDEKVFTKEL DQWIEQLNEC KQLSESQVKS LCEKAKEILT KESNVQEVRC PVTVCGDVHG
QFHDLMELFR IGGKSPDTNY LFMGDYVDRG YYSVETVTLL VALKVRYRER ITILRGNHES
RQITQVYGFY DECLRKYGNA NVWKYFTDLF DYLPLTALVD GQIFCLHGGL SPSIDTLDHI
RALDRLQEVP HEGPMCDLLW SDPDDRGGWG ISPRGAGYTF GQDISETFNH ANGLTLVSRA
HQLVMEGYNW CHDRNVVTIF SAPNYCYRCG NQAAIMELDD TLKYSFLQFD PAPRRGEPHV
TRRTPDYFL
