PPP2CA
entrez
5515
canonical
uniprot
P67775
canonical
ensembl
ENSG00000113575
resolver
ensp
ENSP00000418447
resolver
ensp
ENSP00000430869
resolver
ensp
ENSP00000515257
resolver
enst
ENST00000522385
resolver
enst
ENST00000703311
resolver
genesymbol
PPP2CA
resolver
hgnc
HGNC:9299
resolver
uniprot
A0ACM8QG87
resolver
uniprot
B3KQ51
resolver
uniprot
B3KUN1
resolver
uniprot
E5RHP4
resolver
uniprot
P05323
resolver
uniprot
P13197
resolver
uniprot_entry
A0ACM8QG87_HUMAN
resolver
uniprot_entry
B3KQ51_HUMAN
resolver
uniprot_entry
B3KUN1_HUMAN
resolver
uniprot_entry
PP2AA_HUMAN
resolver
uniprot_sec
E5RHP4
resolver
uniprot_sec
P05323
resolver
uniprot_sec
P13197
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by the interaction between PPP2R2A and ARPP19; this inhibition is enhanced when ARPP19 is phosphorylated (PubMed:38123684). Inhibited by the interaction between PPP2R2A and PABIR1/FAM122A (PubMed:38123684). {ECO:0000269|PubMed:38123684}.
uniprot
proteins
amino_acid_sequence
MDEKVFTKELDQWIEQLNECKQLSESQVKSLCEKAKEILTKESNVQEVRCPVTVCGDVHGQFHDLMELFRIGGKSPDTNYLFMGDYVDRGYYSVETVTLLVALKVRYRERITILRGNHESRQITQVYGFYDECLRKYGNANVWKYFTDLFDYLPLTALVDGQIFCLHGGLSPSIDTLDHIRALDRLQEVPHEGPMCDLLWSDPDDRGGWGISPRGAGYTFGQDISETFNHANGLTLVSRAHQLVMEGYNWCHDRNVVTIFSAPNYCYRCGNQAAIMELDDTLKYSFLQFDPAPRRGEPHVTRRTPDYFL
uniprot
proteins
disease_involvement
DISEASE: Houge-Janssens syndrome 3 (HJS3) [MIM:618354]: An autosomal dominant neurodevelopmental disorder characterized by global developmental delay with onset in infancy and additional variable features including hypotonia, epilepsy, brain abnormalities such as ventriculomegaly and a small corpus callosum, and autism spectrum disorder. {ECO:0000269|PubMed:30595372}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.3.16
uniprot
proteins
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 (PubMed:10801873, PubMed:12473674, PubMed:17245430, PubMed:22613722, PubMed:33243860, PubMed:34004147, PubMed:9920888, PubMed:41986709). 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). {ECO:0000250|UniProtKB:P63330, ECO:0000269|PubMed:10801873, ECO:0000269|PubMed:12473674, ECO:0000269|PubMed:17245430, ECO:0000269|PubMed:22613722, ECO:0000269|PubMed:25438055, ECO:0000269|PubMed:30513302, ECO:0000269|PubMed:33108758, ECO:0000269|PubMed:33243860, ECO:0000269|PubMed:33633399, ECO:0000269|PubMed:34004147, ECO:0000269|PubMed:37080207, ECO:0000269|PubMed:41986709, ECO:0000269|PubMed:9920888}.
uniprot
proteins
mass_dalton
35594
uniprot
proteins
mutagenesis
MUTAGEN 85; /note="D->N: Loss of phosphatase activity."; /evidence="ECO:0000269|PubMed:30595372"; MUTAGEN 309; /note="L->A: Loss of binding to PP2AB-alpha regulatory subunit."; /evidence="ECO:0000269|PubMed:10191253
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:8206937}.; 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. {ECO:0000250|UniProtKB:P67774}.; PTM: Polyubiquitinated, leading to its degradation by the proteasome. {ECO:0000269|PubMed:27588481}.; PTM: Ubiquitinated by the SCF(FBXO42) complex; leading to proteasomal degradation. {ECO:0000269|PubMed:41986709}.
uniprot
proteins
protein_family
PP-1 subfamily
uniprot
proteins
protein_family
PPP phosphatase family
uniprot
proteins
pubmed
10191253
uniprot
proteins
pubmed
10801873
uniprot
proteins
pubmed
12473674
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16258073
uniprot
proteins
pubmed
16541025
uniprot
proteins
pubmed
16580887
uniprot
proteins
pubmed
17055435
uniprot
proteins
pubmed
17245430
uniprot
proteins
pubmed
17485487
uniprot
proteins
pubmed
17974561
uniprot
proteins
pubmed
18394995
uniprot
proteins
pubmed
1846293
uniprot
proteins
pubmed
1848668
uniprot
proteins
pubmed
19818709
uniprot
proteins
pubmed
20080667
uniprot
proteins
pubmed
20092282
uniprot
proteins
pubmed
22167190
uniprot
proteins
pubmed
22613722
uniprot
proteins
pubmed
25003389
uniprot
proteins
pubmed
25438055
uniprot
proteins
pubmed
2555176
uniprot
proteins
pubmed
25803737
uniprot
proteins
pubmed
25925585
uniprot
proteins
pubmed
27588481
uniprot
proteins
pubmed
2837763
uniprot
proteins
pubmed
2849764
uniprot
proteins
pubmed
28609714
uniprot
proteins
pubmed
30115741
uniprot
proteins
pubmed
30513302
uniprot
proteins
pubmed
30595372
uniprot
proteins
pubmed
30611118
uniprot
proteins
pubmed
33108758
uniprot
proteins
pubmed
33243860
uniprot
proteins
pubmed
33633399
uniprot
proteins
pubmed
34004147
uniprot
proteins
pubmed
34762484
uniprot
proteins
pubmed
36869814
uniprot
proteins
pubmed
37080207
uniprot
proteins
pubmed
37761890
uniprot
proteins
pubmed
38123684
uniprot
proteins
pubmed
38570683
uniprot
proteins
pubmed
39032490
uniprot
proteins
pubmed
41986709
uniprot
proteins
pubmed
8206937
uniprot
proteins
pubmed
9647778
uniprot
proteins
pubmed
9920888
uniprot
proteins
sequence_length
309
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16541025, ECO:0000269|PubMed:39032490}. Nucleus {ECO:0000269|PubMed:16541025, ECO:0000269|PubMed:33243860, ECO:0000269|PubMed:34004147, ECO:0000269|PubMed:39032490}. Chromosome {ECO:0000269|PubMed:33243860, ECO:0000269|PubMed:34004147}. Chromosome, centromere {ECO:0000269|PubMed:16541025}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:16541025}. Note=In prometaphase cells, but not in anaphase cells, localizes at centromeres (PubMed:16541025). During mitosis, also found at spindle poles (PubMed:16541025). Centromeric localization requires the presence of SGO2 (By similarity). Recruited to chromatin and transcription pause-release checkpoint via its association with the Integrator complex (PubMed:33243860, PubMed:34004147). {ECO:0000250|UniProtKB:P63330, ECO:0000269|PubMed:16541025, ECO:0000269|PubMed:33243860, ECO:0000269|PubMed:34004147}.
uniprot
proteins