PPP2R1A protein phosphatase 2 scaffold subunit Aalpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: PPP2R1Aprovided by HGNC
Official Full Name: protein phosphatase 2 scaffold subunit Aalphaprovided by HGNC
Primary source: HGNC:HGNC:9302
See related: Ensembl:ENSG00000105568 MIM:605983; AllianceGenome:HGNC:9302
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HJS2; MRD36; PP2AA; PR65A; PP2AAALPHA; PP2A-Aalpha
Summary: This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes an alpha isoform of the constant regulatory subunit A. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]
Expression: Ubiquitous expression in heart (RPKM 78.3), adrenal (RPKM 73.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.41

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (52190052..52229518)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (55277246..55316713)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (52693305..52732771)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Novel Variants of PPP2R1A in Catalytic Subunit Binding Domain and Genotype-Phenotype Analysis in Neurodevelopmentally Delayed Patients.
Title: Novel Variants of PPP2R1A in Catalytic Subunit Binding Domain and Genotype-Phenotype Analysis in Neurodevelopmentally Delayed Patients.
PPP2R1A neurodevelopmental disorder is associated with congenital heart defects.
Title: PPP2R1A neurodevelopmental disorder is associated with congenital heart defects.
Chk1 Inhibition Ameliorates Alzheimer's Disease Pathogenesis and Cognitive Dysfunction Through CIP2A/PP2A Signaling.
Title: Chk1 Inhibition Ameliorates Alzheimer's Disease Pathogenesis and Cognitive Dysfunction Through CIP2A/PP2A Signaling.
Targeting Ribonucleotide Reductase Induces Synthetic Lethality in PP2A-Deficient Uterine Serous Carcinoma.
Title: Targeting Ribonucleotide Reductase Induces Synthetic Lethality in PP2A-Deficient Uterine Serous Carcinoma.
The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction.
Title: The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction.
Phosphoproteome and drug-response effects mediated by the three protein phosphatase 2A inhibitor proteins CIP2A, SET, and PME-1.
Title: Phosphoproteome and drug-response effects mediated by the three protein phosphatase 2A inhibitor proteins CIP2A, SET, and PME-1.
R183W mutant of PPP2R1A, the gene encoding the PP2A Aalpha scaffolding subunit, failed to suppress tumor growth in vivo through activation of the MAPK pathway in RAS-mutant transformed cells. Cells expressing R183W were less sensitive to MEK inhibitors. Results demonstrate that the R183W mutation in PPP2R1A potentiates oncogenic signaling and reduces drug sensitivity of RAS-mutant cells to MEK inhibitors.
Title: Inactivation of PP2A by a recurrent mutation drives resistance to MEK inhibitors.
Association of the rs10406151 C variant with AD risk appears to involve brain PPP2R1A gene expression alterations.
Title: Association of PPP2R1A with Alzheimer's disease and specific cognitive domains.
In addition, 6 other cancer-associated genes (BRAF, NRAS, HRAS, ERK1, ERK2 and PTEN) were also analyzed. In total, four somatic mutations were identified in three out of 101 ovarian endometriotic lesions (4%, 4/101), including a KRAS p.G12V, a PPP2R1A p.S256F and two ARID1A nonsense mutations (p.Q403* and p.G1926*); while no mutations were identified in the remaining 7 genes (BRAF, NRAS, HRAS, ERK1, ERK2, PTEN and PIK3CA)
Title: The presence of KRAS, PPP2R1A and ARID1A mutations in 101 Chinese samples with ovarian endometriosis.
PP2A controls mitotic exit through EG5 dephosphorylation.
Title: Protein Phosphatase 2A (PP2A) Regulates EG5 to Control Mitotic Progression.

Submit: New GeneRIF Correction See all GeneRIFs (40)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Houge-Janssens syndrome 2 MedGen: C4225352 OMIM: 616362 GeneReviews: PPP2R1A-Related Neurodevelopmental Disorder	Compare labs

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2023-12-06) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2023-12-06) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat upregulates the total levels of PP2A protein and downregulates the inactive form of phosphorylated PP2A, which leads to inhibit hTERT activity directly or indirectly in CD4+ T cells	PubMed
	tat	An increase in the amount of PP2A core enzyme with a concomitant decrease in the amount of PP2A holoenzyme inhibits HIV-1 Tat-stimulated transcription from the HIV-1 LTR promoter, indicating a role for PP2A in the modulation of HIV-1 gene expression	PubMed
Vpr	vpr	ATR-induced phosphorylation of Chk1-Ser(345) requires PP2A only when Vpr activates ATR	PubMed
	vpr	Depletion of A-alpha and C-beta subunits of PP2A reduces Vpr-induced G2 arrest to the same extent as depletion of ATM and Rad3-related (ATR)	PubMed
	vpr	A-alpha and C-beta subunits of PP2A are required for the HIV-1 Vpr-induced cell cycle G2 arrest	PubMed
	vpr	Amino-acid peptide sequence (residues 77-92) of HIV-1 Vpr binds to PP2A1. The sequence from HIV-1 89.6 strain is a cell penetrating and death domain	PubMed
	vpr	HIV-1 Vpr was found to upregulate PP2A in fission yeast	PubMed
	vpr	HIV-1 Vpr forms a complex with HIV-1 nucleocapsid that directly activates PP2A	PubMed
Vpu	vpu	IFN-alpha and IFN-beta increases SCYL2 expression and the increase induces PP2A-mediated dephosphorylation of Vpu, suggesting that SCYL2 affects Vpu function through a phosphorylation-dependent mechanism	PubMed
nucleocapsid	gag	HIV-1 Vpr forms a complex with HIV-1 nucleocapsid that directly activates PP2A	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Ppp2r1a (e-PCR), detects polymorphism
- UniSTS:526874

PPP2R1A_2703 (e-PCR)
- UniSTS:462450

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein antigen binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase regulator activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine phosphatase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in T cell homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in chromosome segregation	IBA Inferred from Biological aspect of Ancestor more info
involved_in chromosome segregation	IDA Inferred from Direct Assay more info	PubMed
involved_in female meiotic nuclear division	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	NAS Non-traceable Author Statement more info	PubMed
involved_in meiotic sister chromatid cohesion, centromeric	IEA Inferred from Electronic Annotation more info
involved_in meiotic spindle elongation	IEA Inferred from Electronic Annotation more info
involved_in mitotic sister chromatid separation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	IEA Inferred from Electronic Annotation more info
involved_in protein dephosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein-containing complex assembly	TAS Traceable Author Statement more info	PubMed
involved_in regulation of cell differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of growth	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of meiotic cell cycle process involved in oocyte maturation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in chromosome, centromeric region	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info	PubMed
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in lateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in microtubule cytoskeleton	NAS Non-traceable Author Statement more info	PubMed
located_in mitochondrion	NAS Non-traceable Author Statement more info	PubMed
located_in neuron projection	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
part_of protein phosphatase type 2A complex	IBA Inferred from Biological aspect of Ancestor more info
part_of protein phosphatase type 2A complex	IDA Inferred from Direct Assay more info	PubMed
part_of protein phosphatase type 2A complex	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform

Names: medium tumor antigen-associated 61 KDA protein; protein phosphatase 2, regulatory subunit A, alpha; testicular secretory protein Li 1

NP_001350585.1

EC 3.1.3.16

NP_055040.2

EC 3.1.3.16

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_047068.2 RefSeqGene

Range

5002..44468

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001363656.2 → NP_001350585.1 serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform 2

Status: REVIEWED

Source sequence(s)

AC010320, AK090488, BC026733, CA426613

Consensus CDS

CCDS86798.1

UniProtKB/TrEMBL

B3KQV6

Related

ENSP00000470504.1, ENST00000462990.5

Conserved Domains (3) summary

sd00044
Location:66 → 90

HEAT; HEAT repeat [structural motif]

pfam13646
Location:309 → 404

HEAT_2; HEAT repeats

cl26104
Location:8 → 283

HEAT_2; HEAT repeats
NM_014225.6 → NP_055040.2 serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform 1

See identical proteins and their annotated locations for NP_055040.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the functional protein.

Source sequence(s)

AC010320, BC026733, CA426613

Consensus CDS

CCDS12849.1

UniProtKB/Swiss-Prot

P30153, Q13773, Q6ICQ3, Q96DH3

UniProtKB/TrEMBL

A8K7B7

Related

ENSP00000324804.6, ENST00000322088.11

Conserved Domains (3) summary

COG1413
Location:187 → 462

HEAT; HEAT repeat [General function prediction only]

sd00044
Location:245 → 269

HEAT; HEAT repeat [structural motif]

pfam02985
Location:166 → 196

HEAT; HEAT repeat

RNA

NR_033500.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC010320, AK293493, BC026733, CA426613