P63331 · PP2AA_RAT
- ProteinSerine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
- GenePpp2ca
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids309 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalytic subunit of protein phosphatase 2A (PP2A), a serine/threonine phosphatase involved in the regulation of a wide variety of enzymes, signal transduction pathways, and cellular events. 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 (By similarity).
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'. Mediates dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint. Mediates dephosphorylation of MYC; promoting its ubiquitin-mediated proteolysis: interaction with AMBRA1 enhances interaction between PPP2CA and MYC. Mediates dephosphorylation of FOXO3; promoting its stabilization: interaction with AMBRA1 enhances interaction between PPP2CA and FOXO3 (By similarity).
Catalyzes dephosphorylation of the pyrin domain of NLRP3, promoting assembly of the NLRP3 inflammasome (By similarity).
Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (By similarity).
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'. Mediates dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint. Mediates dephosphorylation of MYC; promoting its ubiquitin-mediated proteolysis: interaction with AMBRA1 enhances interaction between PPP2CA and MYC. Mediates dephosphorylation of FOXO3; promoting its stabilization: interaction with AMBRA1 enhances interaction between PPP2CA and FOXO3 (By similarity).
Catalyzes dephosphorylation of the pyrin domain of NLRP3, promoting assembly of the NLRP3 inflammasome (By similarity).
Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (By similarity).
Catalytic activity
- H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate
Cofactor
Note: Binds 2 manganese ions per subunit.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 57 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 59 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 85 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 85 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 117 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Active site | 118 | Proton donor | ||||
Sequence: H | ||||||
Binding site | 167 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 241 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
- EC number
- Short namesPP2A-alpha
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP63331
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: In prometaphase cells, but not in anaphase cells, localizes at centromeres. During mitosis, also found at spindle poles (By similarity).
Centromeric localization requires the presence of SGO2 (By similarity).
Centromeric localization requires the presence of SGO2 (By similarity).
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000058843 | 1-309 | Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform | |||
Sequence: MDEKLFTKELDQWIEQLNECKQLSESQVKSLCEKAKEILTKESNVQEVRCPVTVCGDVHGQFHDLMELFRIGGKSPDTNYLFMGDYVDRGYYSVETVTLLVALKVRYRERITILRGNHESRQITQVYGFYDECLRKYGNANVWKYFTDLFDYLPLTALVDGQIFCLHGGLSPSIDTLDHIRALDRLQEVPHEGPMCDLLWSDPDDRGGWGISPRGAGYTFGQDISETFNHANGLTLVSRAHQLVMEGYNWCHDRNVVTIFSAPNYCYRCGNQAAIMELDDTLKYSFLQFDPAPRRGEPHVTRRTPDYFL | ||||||
Modified residue | 307 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 309 | Leucine methyl ester | ||||
Sequence: L |
Post-translational modification
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 (By similarity).
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 (By similarity).
Polyubiquitinated, leading to its degradation by the proteasome.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
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 the PP2A A subunit PPP2R1A (By similarity).
Interacts (via C-terminus) with PTPA (By similarity).
Interacts with NXN; the interaction is direct (By similarity).
Interacts with KCTD20 (By similarity).
Interacts with BTBD10 (By similarity).
Interacts with SGO1 and SGO2. Interacts with TP53. 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. Interacts with PABIR1/FAM122A. Interacts with ADCY8; interaction is phosphatase activity-dependent; antagonizes interaction between ADCY8 and calmodulin. Interacts with CRTC3 (when phosphorylated at 'Ser-391'). Interacts with SPRY2; the interaction is inhibited by TESK1 interaction with SPRY2, possibly by vesicular sequestration of SPRY2. Interacts with TRAF3IP3. Interacts with AMBRA1 (via PxP motifs); enhancing interaction between PPP2CA and MYC or FOXO3. Forms a complex with AMBRA1 and BECN1; AMBRA1 and BECN1 components of the complex regulate MYC stability via different pathways (By similarity).
Part of the core of STRIPAK complexes composed of PP2A catalytic and scaffolding subunits, the striatins (PP2A regulatory subunits), the striatin-associated proteins MOB4, STRIP1 and STRIP2, PDCD10 and members of the STE20 kinases, such as STK24 and STK26 (By similarity).
Interacts (via C-terminus) with PTPA (By similarity).
Interacts with NXN; the interaction is direct (By similarity).
Interacts with KCTD20 (By similarity).
Interacts with BTBD10 (By similarity).
Interacts with SGO1 and SGO2. Interacts with TP53. 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. Interacts with PABIR1/FAM122A. Interacts with ADCY8; interaction is phosphatase activity-dependent; antagonizes interaction between ADCY8 and calmodulin. Interacts with CRTC3 (when phosphorylated at 'Ser-391'). Interacts with SPRY2; the interaction is inhibited by TESK1 interaction with SPRY2, possibly by vesicular sequestration of SPRY2. Interacts with TRAF3IP3. Interacts with AMBRA1 (via PxP motifs); enhancing interaction between PPP2CA and MYC or FOXO3. Forms a complex with AMBRA1 and BECN1; AMBRA1 and BECN1 components of the complex regulate MYC stability via different pathways (By similarity).
Part of the core of STRIPAK complexes composed of PP2A catalytic and scaffolding subunits, the striatins (PP2A regulatory subunits), the striatin-associated proteins MOB4, STRIP1 and STRIP2, PDCD10 and members of the STE20 kinases, such as STK24 and STK26 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | P63331 | ANP32A P39687 | 2 | EBI-7050205, EBI-359234 | |
BINARY | P63331 | Dpysl2 P47942 | 2 | EBI-7050205, EBI-917570 | |
XENO | P63331 | TIPRL O75663 | 3 | EBI-7050205, EBI-1054735 |
Protein-protein interaction databases
Structure
Sequence
- Sequence statusComplete
- Length309
- Mass (Da)35,608
- Last updated2004-10-11 v1
- Checksum8DC11276E6DF9E33
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X16043 EMBL· GenBank· DDBJ | CAA34166.1 EMBL· GenBank· DDBJ | mRNA | ||
X14159 EMBL· GenBank· DDBJ | CAB42983.1 EMBL· GenBank· DDBJ | mRNA | ||
M33114 EMBL· GenBank· DDBJ | AAA41904.1 EMBL· GenBank· DDBJ | mRNA | ||
BC070914 EMBL· GenBank· DDBJ | AAH70914.1 EMBL· GenBank· DDBJ | mRNA | ||
BC072531 EMBL· GenBank· DDBJ | AAH72531.1 EMBL· GenBank· DDBJ | mRNA |