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UniProtKB - P30153 (2AAA_HUMAN)

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Protein

Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform

Gene

PPP2R1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. 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).2 Publications

GO - Molecular functioni

  • protein antigen binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein phosphatase regulator activity Source: UniProtKB
  • protein serine/threonine phosphatase activity Source: Ensembl
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • apoptotic process Source: UniProtKB
  • ceramide metabolic process Source: UniProtKB
  • chromosome segregation Source: UniProtKB
  • ciliary basal body-plasma membrane docking Source: Reactome
  • female meiotic nuclear division Source: Ensembl
  • G2/M transition of mitotic cell cycle Source: Reactome
  • inactivation of MAPK activity Source: UniProtKB
  • meiotic sister chromatid cohesion, centromeric Source: Ensembl
  • meiotic spindle elongation Source: Ensembl
  • mitotic sister chromatid separation Source: Ensembl
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of tyrosine phosphorylation of STAT protein Source: UniProtKB
  • nuclear-transcribed mRNA catabolic process, nonsense-mediated decay Source: Reactome
  • peptidyl-serine dephosphorylation Source: Ensembl
  • positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  • protein-containing complex assembly Source: UniProtKB
  • protein dephosphorylation Source: UniProtKB
  • regulation of cell adhesion Source: UniProtKB
  • regulation of cell differentiation Source: UniProtKB
  • regulation of DNA replication Source: UniProtKB
  • regulation of G2/M transition of mitotic cell cycle Source: Reactome
  • regulation of growth Source: UniProtKB
  • regulation of meiotic cell cycle process involved in oocyte maturation Source: Ensembl
  • regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of Wnt signaling pathway Source: UniProtKB
  • response to organic substance Source: UniProtKB
  • RNA splicing Source: UniProtKB
  • second-messenger-mediated signaling Source: UniProtKB
View the complete GO annotation on QuickGO ...

Keywordsi

Biological processChromosome partition

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000105568-MONOMER
ReactomeiR-HSA-113501 Inhibition of replication initiation of damaged DNA by RB1/E2F1
R-HSA-1295596 Spry regulation of FGF signaling
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-163685 Integration of energy metabolism
R-HSA-163767 PP2A-mediated dephosphorylation of key metabolic factors
R-HSA-180024 DARPP-32 events
R-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-196299 Beta-catenin phosphorylation cascade
R-HSA-198753 ERK/MAPK targets
R-HSA-202670 ERKs are inactivated
R-HSA-2465910 MASTL Facilitates Mitotic Progression
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition
R-HSA-2995383 Initiation of Nuclear Envelope Reformation
R-HSA-380259 Loss of Nlp from mitotic centrosomes
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes
R-HSA-389513 CTLA4 inhibitory signaling
R-HSA-432142 Platelet sensitization by LDL
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5339716 Misspliced GSK3beta mutants stabilize beta-catenin
R-HSA-5358747 S33 mutants of beta-catenin aren't phosphorylated
R-HSA-5358749 S37 mutants of beta-catenin aren't phosphorylated
R-HSA-5358751 S45 mutants of beta-catenin aren't phosphorylated
R-HSA-5358752 T41 mutants of beta-catenin aren't phosphorylated
R-HSA-5467337 APC truncation mutants have impaired AXIN binding
R-HSA-5467340 AXIN missense mutants destabilize the destruction complex
R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex
R-HSA-5620912 Anchoring of the basal body to the plasma membrane
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-5673000 RAF activation
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6804757 Regulation of TP53 Degradation
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-68877 Mitotic Prometaphase
R-HSA-69231 Cyclin D associated events in G1
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-70171 Glycolysis
R-HSA-8854518 AURKA Activation by TPX2
R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
SignaLinkiP30153
SIGNORiP30153

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform
Alternative name(s):
Medium tumor antigen-associated 61 kDa protein
PP2A subunit A isoform PR65-alpha
PP2A subunit A isoform R1-alpha
Gene namesi
Name:PPP2R1A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105568.17
HGNCiHGNC:9302 PPP2R1A
MIMi605983 gene
neXtProtiNX_P30153

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Centromere, Chromosome, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Mental retardation, autosomal dominant 36 (MRD36)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
See also OMIM:616362
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073718132V → L in MRD36. 1 Publication1
Natural variantiVAR_074488179P → L in MRD36; reduces PPP2CA binding; reduces PPP2R5A binding; reduces PPP2R5C binding; does not affect PPP2R5D binding; reduces PPP2R2A binding; reduces PPP2R2B binding; does not affect PPP2R3A binding; decreases phosphatase activity of PPP2CA. 1 PublicationCorresponds to variant dbSNP:rs786205228EnsemblClinVar.1
Natural variantiVAR_074489182R → W in MRD36; reduces PPP2CA binding; reduces PPP2R5A binding; reduces PPP2R5C binding; does not affect PPP2R5D binding; reduces PPP2R2A binding; reduces PPP2R2B binding; reduces PPP2R3A binding; decreases phosphatase activity of PPP2CA. 1 PublicationCorresponds to variant dbSNP:rs786205227EnsemblClinVar.1
Natural variantiVAR_074490258R → H in MRD36; reduces PPP2CA binding; reduces PPP2R5A binding; reduces PPP2R5C binding; does not affect PPP2R5D binding; reduces PPP2R2A binding; reduces PPP2R2B binding; reduces PPP2R3A binding; does not affect phosphatase activity of PPP2CA. 1 PublicationCorresponds to variant dbSNP:rs863225094EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi5518
MalaCardsiPPP2R1A
MIMi616362 phenotype
OpenTargetsiENSG00000105568
PharmGKBiPA33666

Polymorphism and mutation databases

BioMutaiPPP2R1A
DMDMi143811355

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000714002 – 589Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoformAdd BLAST588

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei280N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP30153
MaxQBiP30153
PaxDbiP30153
PeptideAtlasiP30153
PRIDEiP30153

2D gel databases

OGPiP30153
REPRODUCTION-2DPAGEiIPI00554737

PTM databases

iPTMnetiP30153
PhosphoSitePlusiP30153
SwissPalmiP30153

Miscellaneous databases

PMAP-CutDBiP30153

Expressioni

Gene expression databases

BgeeiENSG00000105568
CleanExiHS_PPP2R1A
ExpressionAtlasiP30153 baseline and differential
GenevisibleiP30153 HS

Organism-specific databases

HPAiCAB018599

Interactioni

Subunit structurei

Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD (By similarity). Interacts with FOXO1; the interaction dephosphorylates FOXO1 on AKT-mediated phosphorylation sites (By similarity). 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 IPO9 (PubMed:12670497). Interacts with TP53 and SGO1 (PubMed:17245430, PubMed:16580887). 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 FAM122A (PubMed:27588481).By similarity9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein antigen binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi111510, 304 interactors
CORUMiP30153
DIPiDIP-29394N
IntActiP30153, 231 interactors
MINTiP30153
STRINGi9606.ENSP00000324804

Structurei

Secondary structure

1589
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni6 – 8Combined sources3
Helixi11 – 19Combined sources9
Helixi25 – 33Combined sources9
Helixi35 – 41Combined sources7
Helixi44 – 49Combined sources6
Helixi51 – 57Combined sources7
Helixi63 – 73Combined sources11
Helixi78 – 80Combined sources3
Helixi83 – 89Combined sources7
Helixi90 – 96Combined sources7
Beta strandi99 – 101Combined sources3
Helixi102 – 116Combined sources15
Helixi121 – 126Combined sources6
Helixi128 – 136Combined sources9
Beta strandi138 – 140Combined sources3
Helixi141 – 147Combined sources7
Helixi148 – 150Combined sources3
Helixi151 – 154Combined sources4
Turni155 – 157Combined sources3
Helixi160 – 174Combined sources15
Helixi179 – 194Combined sources16
Helixi198 – 203Combined sources6
Helixi205 – 213Combined sources9
Helixi218 – 221Combined sources4
Helixi224 – 234Combined sources11
Helixi237 – 239Combined sources3
Helixi240 – 243Combined sources4
Helixi245 – 252Combined sources8
Helixi257 – 265Combined sources9
Helixi267 – 274Combined sources8
Helixi276 – 281Combined sources6
Helixi283 – 291Combined sources9
Helixi296 – 311Combined sources16
Turni315 – 317Combined sources3
Helixi318 – 324Combined sources7
Helixi326 – 334Combined sources9
Helixi339 – 346Combined sources8
Helixi349 – 352Combined sources4
Helixi353 – 356Combined sources4
Helixi358 – 364Combined sources7
Helixi366 – 373Combined sources8
Helixi378 – 385Combined sources8
Helixi389 – 394Combined sources6
Helixi397 – 412Combined sources16
Helixi417 – 434Combined sources18
Helixi436 – 438Combined sources3
Helixi441 – 449Combined sources9
Helixi450 – 452Combined sources3
Helixi456 – 473Combined sources18
Helixi475 – 481Combined sources7
Helixi483 – 488Combined sources6
Turni489 – 491Combined sources3
Helixi495 – 520Combined sources26
Helixi522 – 527Combined sources6
Helixi528 – 530Combined sources3
Helixi534 – 547Combined sources14
Helixi548 – 550Combined sources3
Helixi553 – 567Combined sources15
Helixi573 – 585Combined sources13

3D structure databases

ProteinModelPortaliP30153
SMRiP30153
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30153

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati8 – 46HEAT 1Add BLAST39
Repeati47 – 84HEAT 2Add BLAST38
Repeati85 – 123HEAT 3Add BLAST39
Repeati124 – 161HEAT 4Add BLAST38
Repeati162 – 200HEAT 5Add BLAST39
Repeati201 – 239HEAT 6Add BLAST39
Repeati240 – 278HEAT 7Add BLAST39
Repeati279 – 321HEAT 8Add BLAST43
Repeati322 – 360HEAT 9Add BLAST39
Repeati361 – 399HEAT 10Add BLAST39
Repeati400 – 438HEAT 11Add BLAST39
Repeati439 – 477HEAT 12Add BLAST39
Repeati478 – 516HEAT 13Add BLAST39
Repeati517 – 555HEAT 14Add BLAST39
Repeati556 – 589HEAT 15Add BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni8 – 399PP2A subunit B bindingAdd BLAST392
Regioni47 – 321Polyoma small and medium T antigens BindingAdd BLAST275
Regioni85 – 239SV40 small T antigen bindingAdd BLAST155
Regioni400 – 589PP2A subunit C bindingAdd BLAST190

Domaini

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.

Sequence similaritiesi

Belongs to the phosphatase 2A regulatory subunit A family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0211 Eukaryota
ENOG410XQVI LUCA
GeneTreeiENSGT00730000110944
HOGENOMiHOG000078539
HOVERGENiHBG000011
InParanoidiP30153
KOiK03456
OMAiWAQNTVI
OrthoDBiEOG091G045V
PhylomeDBiP30153
TreeFamiTF105552

Family and domain databases

Gene3Di1.25.10.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR000357 HEAT
IPR021133 HEAT_type_2
IPR031090 PP2A_A_meta
PANTHERiPTHR10648:SF2 PTHR10648:SF2, 1 hit
PfamiView protein in Pfam
PF02985 HEAT, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit
PROSITEiView protein in PROSITE
PS50077 HEAT_REPEAT, 11 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P30153-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAADGDDSL YPIAVLIDEL RNEDVQLRLN SIKKLSTIAL ALGVERTRSE 
        60         70         80         90        100
LLPFLTDTIY DEDEVLLALA EQLGTFTTLV GGPEYVHCLL PPLESLATVE 
       110        120        130        140        150
ETVVRDKAVE SLRAISHEHS PSDLEAHFVP LVKRLAGGDW FTSRTSACGL 
       160        170        180        190        200
FSVCYPRVSS AVKAELRQYF RNLCSDDTPM VRRAAASKLG EFAKVLELDN 
       210        220        230        240        250
VKSEIIPMFS NLASDEQDSV RLLAVEACVN IAQLLPQEDL EALVMPTLRQ 
       260        270        280        290        300
AAEDKSWRVR YMVADKFTEL QKAVGPEITK TDLVPAFQNL MKDCEAEVRA 
       310        320        330        340        350
AASHKVKEFC ENLSADCREN VIMSQILPCI KELVSDANQH VKSALASVIM 
       360        370        380        390        400
GLSPILGKDN TIEHLLPLFL AQLKDECPEV RLNIISNLDC VNEVIGIRQL 
       410        420        430        440        450
SQSLLPAIVE LAEDAKWRVR LAIIEYMPLL AGQLGVEFFD EKLNSLCMAW 
       460        470        480        490        500
LVDHVYAIRE AATSNLKKLV EKFGKEWAHA TIIPKVLAMS GDPNYLHRMT 
       510        520        530        540        550
TLFCINVLSE VCGQDITTKH MLPTVLRMAG DPVANVRFNV AKSLQKIGPI 
       560        570        580 
LDNSTLQSEV KPILEKLTQD QDVDVKYFAQ EALTVLSLA
Length:589
Mass (Da):65,309
Last modified:April 3, 2007 - v4
Checksum:i5174EBE94D537836
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti130P → A in AAA35531 (PubMed:2554323).Curated1
Sequence conflicti258R → A in AAA36399 (PubMed:2159327).Curated1
Sequence conflicti272K → R AA sequence (PubMed:8694763).Curated1
Sequence conflicti551L → P in CAG29336 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073718132V → L in MRD36. 1 Publication1
Natural variantiVAR_074488179P → L in MRD36; reduces PPP2CA binding; reduces PPP2R5A binding; reduces PPP2R5C binding; does not affect PPP2R5D binding; reduces PPP2R2A binding; reduces PPP2R2B binding; does not affect PPP2R3A binding; decreases phosphatase activity of PPP2CA. 1 PublicationCorresponds to variant dbSNP:rs786205228EnsemblClinVar.1
Natural variantiVAR_074489182R → W in MRD36; reduces PPP2CA binding; reduces PPP2R5A binding; reduces PPP2R5C binding; does not affect PPP2R5D binding; reduces PPP2R2A binding; reduces PPP2R2B binding; reduces PPP2R3A binding; decreases phosphatase activity of PPP2CA. 1 PublicationCorresponds to variant dbSNP:rs786205227EnsemblClinVar.1
Natural variantiVAR_074490258R → H in MRD36; reduces PPP2CA binding; reduces PPP2R5A binding; reduces PPP2R5C binding; does not affect PPP2R5D binding; reduces PPP2R2A binding; reduces PPP2R2B binding; reduces PPP2R3A binding; does not affect phosphatase activity of PPP2CA. 1 PublicationCorresponds to variant dbSNP:rs863225094EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31786 mRNA Translation: AAA35531.1
J02902 mRNA Translation: AAA36399.1
CR450340 mRNA Translation: CAG29336.1
BC001537 mRNA Translation: AAH01537.1
CCDSiCCDS12849.1
PIRiA34541
RefSeqiNP_055040.2, NM_014225.5
UniGeneiHs.467192

Genome annotation databases

EnsembliENST00000322088; ENSP00000324804; ENSG00000105568
GeneIDi5518
KEGGihsa:5518
UCSCiuc002pyp.4 human

Similar proteinsi

Entry informationi

Entry namei2AAA_HUMAN
AccessioniPrimary (citable) accession number: P30153
Secondary accession number(s): Q13773, Q6ICQ3, Q96DH3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 3, 2007
Last modified: July 18, 2018
This is version 193 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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