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Details on Person UniProt:P30153 PPP2R1A

Class:Id	ReferenceGeneProduct:49125
_chainChangeLog	initiator methionine:1 added on Sat February 7 2015;chain:2-589 added on Sat February 7 2015;initiator methionine:1 for 49125 removed on Fri Nov 03 2023;initiator methionine: for 49125 added on Fri Nov 03 2023;initiator methionine: for 49125 removed on Fri Aug 15 2025;initiator methionine:1 for 49125 added on Fri Aug 15 2025
_displayName	UniProt:P30153 PPP2R1A
_timestamp	2025-08-15 21:27:56
chain	initiator methionine:1 chain:2-589
checksum	5174EBE94D537836
comment	FUNCTION The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit (PubMed:15525651, PubMed:16580887, PubMed:33243860, PubMed:33633399, PubMed:34004147, PubMed:8694763). Upon interaction with GNA12 promotes dephosphorylation of microtubule associated protein TAU/MAPT (PubMed:15525651). Required for proper chromosome segregation and for centromeric localization of SGO1 in mitosis (PubMed:16580887). 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). Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes (PubMed:18782753, 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:18782753, 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:18782753, PubMed:33633399). Key mediator of a quality checkpoint during transcription elongation as part of the Integrator-PP2A (INTAC) complex (PubMed:33243860, PubMed:34004147). The INTAC complex drives premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: within the INTAC complex, acts as a scaffolding subunit for PPP2CA, which 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). Regulates the recruitment of the SKA complex to kinetochores (PubMed:28982702).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 (PubMed:38123684). 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 (PubMed:38123684). Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD (By similarity). Interacts with the PP2A C catalytic subunit PPP2CA (PubMed:37761890, PubMed:38123684). Interacts with the PP2A B subunit PPP2R2A (PubMed:38123684). Interacts with the PP2A B subunit PPP2R5D (PubMed:37761890). Interacts with FOXO1; the interaction dephosphorylates FOXO1 on AKT-mediated phosphorylation sites (By similarity). Interacts with IPO9 (PubMed:12670497). Interacts with TP53 and SGO1 (PubMed:16580887, PubMed:17245430). Interacts with PLA2G16; this interaction might decrease PP2A activity (PubMed:17374643). Interacts with CTTNBP2NL (PubMed:18782753). Interacts with GNA12; the interaction promotes protein phosphatase 2A activation causing dephosphorylation of MAPT (PubMed:15525651). Interacts with CIP2A; this interaction stabilizes CIP2A (PubMed:28174209). Interacts with PABIR1/FAM122A (PubMed:27588481). Interacts with ADCY8; antagonizes interaction between ADCY8 and calmodulin (By similarity). Interacts with CRTC3 (when phosphorylated at 'Ser-391') (PubMed:30611118). Interacts with SPRY2 (PubMed:17974561). 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 (PubMed:18782753). Component of the Integrator-PP2A (INTAC) complex, composed of the Integrator core complex and protein phosphatase 2A subunits PPP2CA and PPP2R1A (PubMed:34004147, PubMed:33243860, PubMed:34762484, PubMed:36869814, PubMed:38570683).SUBUNIT (Microbial infection) Interacts with JC virus small t antigen; this interaction inhibits PPP2R1A activity.INTERACTION Centromeric localization requires the presence of BUB1 (PubMed:16580887). Recruited to chromatin and transcription pause-release checkpoint via its association with the Integrator complex (PubMed:34004147, PubMed:33243860).DOMAIN Each HEAT repeat appears to consist of two alpha helices joined by a hydrophilic region, the intrarepeat loop. The repeat units may be arranged laterally to form a rod-like structure.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the phosphatase 2A regulatory subunit A family.
description	recommendedName: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform shortName evidence="28"PP2Aa alternativeName: Medium tumor antigen-associated 61 kDa protein alternativeName: PP2A subunit A isoform PR65-alpha alternativeName: PP2A subunit A isoform R1-alpha
geneName	PPP2R1A
identifier	P30153
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Cell membrane Cell projection Centromere Chromosome Chromosome partition Cytoplasm Direct protein sequencing Disease variant Host-virus interaction Intellectual disability Membrane Nucleus Proteomics identification Reference proteome Repeat
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
name	PPP2R1A
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8958478] ENSEMBL:ENSG00000105568 PPP2R1A [Homo sapiens]
secondaryIdentifier	2AAA_HUMAN Q13773 Q6ICQ3 Q96DH3
sequenceLength	589
species	[Species:48887] Homo sapiens
(referenceEntity)	[EntityWithAccessionedSequence:165968] PPP2R1A [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:165982] PPP2R1A [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2466048] PPP2R1A [chromosome, centromeric region] [Homo sapiens] [EntityWithAccessionedSequence:8958544] PPP2R1A [extracellular region] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P30153 PPP2R1A (49125)