{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P30153","secondaryAccessions":["Q13773","Q6ICQ3","Q96DH3"],"uniProtkbId":"2AAA_HUMAN","entryAudit":{"firstPublicDate":"1993-04-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2007-04-03","entryVersion":240,"sequenceVersion":4},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"38123684"}],"value":"PP2Aa"}]},"alternativeNames":[{"fullName":{"value":"Medium tumor antigen-associated 61 kDa protein"}},{"fullName":{"value":"PP2A subunit A isoform PR65-alpha"}},{"fullName":{"value":"PP2A subunit A isoform R1-alpha"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:9302"}],"value":"PPP2R1A"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q76MZ3"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15525651"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16580887"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18782753"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28982702"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33243860"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33633399"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34004147"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8694763"}],"value":"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)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q32PI5"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q76MZ3"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12670497"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15525651"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16580887"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17245430"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17374643"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17974561"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18394995"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18782753"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27588481"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28167675"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28174209"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30611118"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33243860"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34004147"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34762484"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36869814"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37761890"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38123684"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38570683"}],"value":"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). Interacts with ARPP19 (PubMed:28167675)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18353419"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20485545"}],"value":"(Microbial infection) Interacts with JC virus small t antigen; this interaction inhibits PPP2R1A activity"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P31749","geneName":"AKT1","intActId":"EBI-296087"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q9C0C7","geneName":"AMBRA1","intActId":"EBI-2512975"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q14155","geneName":"ARHGEF7","intActId":"EBI-717515"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q96GD4","geneName":"AURKB","intActId":"EBI-624291"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q9Y2V2","geneName":"CARHSP1","intActId":"EBI-718719"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P51959","geneName":"CCNG1","intActId":"EBI-3905829"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q8TCG1","geneName":"CIP2A","intActId":"EBI-1379376"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q9Y534","geneName":"CSDC2","intActId":"EBI-1763657"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q4G163","geneName":"FBXO43","intActId":"EBI-12053217"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q9NYA3","geneName":"GOLGA6A","intActId":"EBI-11163335"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q08AF8","geneName":"GOLGA8G","intActId":"EBI-10181260"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P53816","geneName":"PLAAT3","intActId":"EBI-746318"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P67775","geneName":"PPP2CA","intActId":"EBI-712311"},"numberOfExperiments":59,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P67775-1","geneName":"PPP2CA","intActId":"EBI-16765970"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P30154","geneName":"PPP2R1B","intActId":"EBI-357094"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P63151","geneName":"PPP2R2A","intActId":"EBI-1048931"},"numberOfExperiments":31,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q00005","geneName":"PPP2R2B","intActId":"EBI-1052159"},"numberOfExperiments":13,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q15172","geneName":"PPP2R5A","intActId":"EBI-641666"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q15173","geneName":"PPP2R5B","intActId":"EBI-1369497"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q13362","geneName":"PPP2R5C","intActId":"EBI-1266156"},"numberOfExperiments":13,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q13362-1","geneName":"PPP2R5C","intActId":"EBI-1266170"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q13362-2","geneName":"PPP2R5C","intActId":"EBI-1266173"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q14738","geneName":"PPP2R5D","intActId":"EBI-396563"},"numberOfExperiments":15,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q16537","geneName":"PPP2R5E","intActId":"EBI-968374"},"numberOfExperiments":10,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P60510","geneName":"PPP4C","intActId":"EBI-1046072"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P53041","geneName":"PPP5C","intActId":"EBI-716663"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q15257-2","geneName":"PTPA","intActId":"EBI-12164121"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q04206","geneName":"RELA","intActId":"EBI-73886"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"O43815","geneName":"STRN","intActId":"EBI-1046642"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"O43815-2","geneName":"STRN","intActId":"EBI-1266294"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q13033-2","geneName":"STRN3","intActId":"EBI-1053876"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P04637","geneName":"TP53","intActId":"EBI-366083"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P03129","geneName":"E7","intActId":"EBI-866453"},"numberOfExperiments":3,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P04020","geneName":"E7","intActId":"EBI-7005254"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P97346","geneName":"Nxn","intActId":"EBI-309684"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"Q60996-3","geneName":"Ppp2r5c","intActId":"EBI-1369292"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P30153","intActId":"EBI-302388"},"interactantTwo":{"uniProtKBAccession":"P03081","intActId":"EBI-1266256"},"numberOfExperiments":5,"organismDiffer":true}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16580887"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33243860"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34004147"}],"value":"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)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q32PI5"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30611118"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33243860"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34004147"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33243860"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34004147"}],"value":"Chromosome","id":"SL-0468"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16580887"}],"value":"Chromosome, centromere","id":"SL-0047"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15525651"}],"value":"Lateral cell membrane","id":"SL-0153"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15525651"}],"value":"Cell projection, dendrite","id":"SL-0283"}}]},{"texts":[{"value":"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"}],"commentType":"DOMAIN"},{"commentType":"DISEASE","disease":{"diseaseId":"Houge-Janssens syndrome 2","diseaseAccession":"DI-04420","acronym":"HJS2","description":"An autosomal dominant disorder characterized by global developmental delay, hypotonia, variably impaired intellectual development, poor speech, and dysmorphic facial features. Some patients may develop seizures.","diseaseCrossReference":{"database":"MIM","id":"616362"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25533962"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26168268"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37761890"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the phosphatase 2A regulatory subunit A family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Initiator methionine","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":1,"modifier":"EXACT"}},"description":"Removed","evidences":[{"evidenceCode":"ECO:0007744","source":"PubMed","id":"19413330"},{"evidenceCode":"ECO:0007744","source":"PubMed","id":"22223895"},{"evidenceCode":"ECO:0007744","source":"PubMed","id":"22814378"},{"evidenceCode":"ECO:0007744","source":"PubMed","id":"25944712"}]},{"type":"Chain","location":{"start":{"value":2,"modifier":"EXACT"},"end":{"value":589,"modifier":"EXACT"}},"description":"Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform","featureId":"PRO_0000071400"},{"type":"Repeat","location":{"start":{"value":8,"modifier":"EXACT"},"end":{"value":46,"modifier":"EXACT"}},"description":"HEAT 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