Overview
| Uniprot ID | P67775 |
|---|
| Protein Name | Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform |
|---|
| Gene Name | PPP2CA |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 21 |
IEQLNECKQLSESQV |
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 (PubMed:10801873, PubMed:12473674, PubMed:17245430, PubMed:22613722, PubMed:33243860, PubMed:34004147, PubMed:9920888). PP2A is the major phosphatase for microtubule-associated proteins (MAPs) (PubMed:22613722). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase (PubMed:22613722). Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate various proteins, such as SV40 large T antigen, AXIN1, p53/TP53, PIM3, WEE1 (PubMed:10801873, PubMed:12473674, PubMed:17245430, PubMed:9920888). Activates RAF1 by dephosphorylating it at 'Ser-259' (PubMed:10801873). Mediates dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint (PubMed:33108758). Mediates dephosphorylation of MYC; promoting its ubiquitin-mediated proteolysis: interaction with AMBRA1 enhances interaction between PPP2CA and MYC (PubMed:25438055). Mediates dephosphorylation of FOXO3; promoting its stabilization: interaction with AMBRA1 enhances interaction between PPP2CA and FOXO3 (PubMed:30513302). Catalyzes dephosphorylation of the pyrin domain of NLRP3, promoting assembly of the NLRP3 inflammasome (By similarity). Together with RACK1 adapter, mediates dephosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and AKT-mTOR signaling pathway (By similarity). Dephosphorylation of AKT1 is essential for regulatory T-cells (Treg) homeostasis and stability (By similarity). Catalyzes dephosphorylation of PIM3, promoting PIM3 ubiquitination and proteasomal degradation (PubMed:12473674). Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes (PubMed:33633399). STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling (PubMed:33633399). Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:33633399). Key mediator of a quality checkpoint during transcription elongation as part of the Integrator-PP2A (INTAC) complex (PubMed:33243860, PubMed:34004147, PubMed:37080207). The INTAC complex drives premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: within the INTAC complex, PPP2CA catalyzes dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, thereby preventing transcriptional elongation (PubMed:33243860, PubMed:34004147, PubMed:37080207)
Protein Sequence
10
MDEKVFTKEL
20
DQWIEQLNEC
30
KQLSESQVKS
40
LCEKAKEILT
50
KESNVQEVRC
60
PVTVCGDVHG
70
QFHDLMELFR
80
IGGKSPDTNY
90
LFMGDYVDRG
100
YYSVETVTLL
110
VALKVRYRER
120
ITILRGNHES
130
RQITQVYGFY
140
DECLRKYGNA
150
NVWKYFTDLF
160
DYLPLTALVD
170
GQIFCLHGGL
180
SPSIDTLDHI
190
RALDRLQEVP
200
HEGPMCDLLW
210
SDPDDRGGWG
220
ISPRGAGYTF
230
GQDISETFNH
240
ANGLTLVSRA
250
HQLVMEGYNW
260
CHDRNVVTIF
270
SAPNYCYRCG
280
NQAAIMELDD
290
TLKYSFLQFD
300
PAPRRGEPHV
TRRTPDYFL
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0000785 |
chromatin |
| Cellular Component |
GO:0000775 |
chromosome, centromeric region |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0070062 |
extracellular exosome |
| Cellular Component |
GO:0090443 |
FAR/SIN/STRIPAK complex |
| Cellular Component |
GO:0160232 |
INTAC complex |
| Cellular Component |
GO:0016020 |
membrane |
| Cellular Component |
GO:0045121 |
membrane raft |
| Cellular Component |
GO:0015630 |
microtubule cytoskeleton |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Cellular Component |
GO:0000159 |
protein phosphatase type 2A complex |
| Cellular Component |
GO:0000922 |
spindle pole |
| Cellular Component |
GO:0045202 |
synapse |
| Molecular Function |
GO:0050811 |
GABA receptor binding |
| Molecular Function |
GO:0046872 |
metal ion binding |
| Molecular Function |
GO:0004721 |
phosphoprotein phosphatase activity |
| Molecular Function |
GO:0046982 |
protein heterodimerization activity |
| Molecular Function |
GO:0004722 |
protein serine/threonine phosphatase activity |
| Molecular Function |
GO:0004725 |
protein tyrosine phosphatase activity |
| Molecular Function |
GO:0180006 |
RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity |
| Molecular Function |
GO:0180007 |
RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity |
| Molecular Function |
GO:0180008 |
RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity |
| Molecular Function |
GO:0048156 |
tau protein binding |
| Biological Process |
GO:0035556 |
intracellular signal transduction |
| Biological Process |
GO:0051321 |
meiotic cell cycle |
| Biological Process |
GO:0000278 |
mitotic cell cycle |
| Biological Process |
GO:0090090 |
negative regulation of canonical Wnt signaling pathway |
| Biological Process |
GO:0010719 |
negative regulation of epithelial to mesenchymal transition |
| Biological Process |
GO:1904539 |
negative regulation of glycolytic process through fructose-6-phosphate |
| Biological Process |
GO:0035331 |
negative regulation of hippo signaling |
| Biological Process |
GO:0051898 |
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| Biological Process |
GO:1900227 |
positive regulation of NLRP3 inflammasome complex assembly |
| Biological Process |
GO:0006470 |
protein dephosphorylation |
| Biological Process |
GO:0045595 |
regulation of cell differentiation |
| Biological Process |
GO:2000045 |
regulation of G1/S transition of mitotic cell cycle |
| Biological Process |
GO:0040008 |
regulation of growth |
| Biological Process |
GO:0035330 |
regulation of hippo signaling |
| Biological Process |
GO:0031113 |
regulation of microtubule polymerization |
| Biological Process |
GO:0034243 |
regulation of transcription elongation by RNA polymerase II |
| Biological Process |
GO:0010288 |
response to lead ion |
| Biological Process |
GO:0160240 |
RNA polymerase II transcription initiation surveillance |
| Biological Process |
GO:0016180 |
snRNA processing |
| Biological Process |
GO:0043029 |
T cell homeostasis |
| Biological Process |
GO:0097706 |
vascular endothelial cell response to oscillatory fluid shear stress |
Reference
PMID: N/A