PPP2R4 protein phosphatase 2A activator, regulatory subunit 4 [Homo sapiens] - Gene

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Summary

Official Symbol: PPP2R4provided by HGNC
Official Full Name: protein phosphatase 2A activator, regulatory subunit 4provided by HGNC
Primary source: HGNC:9308
Locus tag: RP11-247A12.4
See related: Ensembl:ENSG00000119383; HPRD:02858; MIM:600756; Vega:OTTHUMG00000020774
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: PP2A; PR53; PTPA; MGC2184
Summary: Protein phosphatase 2A is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2A holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B' family. This gene encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 9q34

Sequence :: Chromosome: 9; NC_000009.11 (131873228..131911225)

See PPP2R4 in Epigenomics, MapViewer

Chromosome 9 - NC_000009.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Data reveal that the tumour suppressor PP2A may act via S369 to regulated NEDD9-mediated cell spreading.
Title: PP2A phosphatase suppresses function of the mesenchymal invasion regulator NEDD9.
Striatin orchestrates the regulation of Mst3 by PP2A.
Title: Protein phosphatase 2a (PP2A) binds within the oligomerization domain of striatin and regulates the phosphorylation and activation of the mammalian Ste20-Like kinase Mst3.
Compared with healthy individuals, the activity of PP2A in AML patients is obviously lower.
Title: [Influence of PP2A activator on proliferation of HL-60 cells and analysis of PP2A activity changes in patients with acute myeloid leukemia].
findings suggest that decreased B55alpha expression in AML is at least partially responsible for increased AKT signaling in AML and suggests that therapeutic targeting of PP2A could counteract this
Title: Low expression of PP2A regulatory subunit B55α is associated with T308 phosphorylation of AKT and shorter complete remission duration in acute myeloid leukemia patients.
when lung fibroblasts are attached to collagen matrix, the beta1 integrin/Src/PP2A-mediated 4EBP-1 regulatory pathway is activated
Title: Eukaryotic translation initiation factor 4E binding protein 1 (4EBP-1) function is suppressed by Src and protein phosphatase 2A (PP2A) on extracellular matrix.
Loss of PP2A is associated with acute myeloid leukemia.
Title: PP2A impaired activity is a common event in acute myeloid leukemia and its activation by forskolin has a potent anti-leukemic effect.
cyclin dependent kinase 5 interacts with p53 to phosphorylate it at Serine20 and Serine46 residues thereby promoting its recruitment on p21 and bax promoters
Title: Cdk5 phosphorylates non-genotoxically overexpressed p53 following inhibition of PP2A to induce cell cycle arrest/apoptosis and inhibits tumor progression.
A critical role of PP2A is uncovered in maintaining embryonic stem cell self-renewal capability, and a defined medium has been developed for their culture.
Title: Optimal suppression of protein phosphatase 2A activity is critical for maintenance of human embryonic stem cell self-renewal.
Sphingosine interaction with acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) regulates PP2A activity and cyclooxygenase (COX)-2 expression in human endothelial cells.
Title: Sphingosine interaction with acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) regulates PP2A activity and cyclooxygenase (COX)-2 expression in human endothelial cells.
Data show that distinct phosphatases dephosphorylate conserved AKT motifs within the FOXO family and that PP2A is entwined in a dynamic interplay with AKT and 14-3-3 to directly regulate FOXO3a subcellular localization and transcriptional activation.
Title: Protein phosphatase 2A reactivates FOXO3a through a dynamic interplay with 14-3-3 and AKT.

Submit: New GeneRIF Correction See all (39)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Protein phosphatase-2A (PP2A) and protein phosphatase-1 (PP1) regulate HIV-1 Tat-activated transcription through dephosphorylation of CDK9	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	HIV-1 Vpr was reported to mediate G2 arrest by forming a complex with PP2A through binding to the B55 regulatory subunit, thereby targeting the complex to the nucleus and enhancing cdc25 dephosphorylation, however the paper was subsequently retracted	PubMed
	vpr	HIV-1 Vpr cell death causing peptide (amino acid residues 71-96) can activate the expression of PP2A when applied extracellularly to CD4+ T cells as well as cause the activation of PP2A from brain, liver, and adipose tissues	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
nucleocapsid	gag	HIV-1 Vpr forms a complex with HIV-1 nucleocapsid that directly activates PP2A	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
Q15257	P51959	CCNG1	HPRD	PubMed
Q15257	Q16589	CCNG2	HPRD	PubMed
Q15257	P68400	CSNK2A1	HPRD	PubMed
Q15257	P12931	SRC	HPRD	PubMed
BioGRID:111516	BioGRID:106902	ARRB2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111516	BioGRID:107068	BCL2	BioGRID	PubMed	Biochemical Activity
BioGRID:111516	BioGRID:107340	CCNG1	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:111516	BioGRID:115827	CCT2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111516	BioGRID:113054	CCT3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111516	BioGRID:115826	CCT4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111516	BioGRID:116603	CCT5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111516	BioGRID:107346	CCT6A	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111516	BioGRID:115825	CCT7	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111516	BioGRID:115933	CCT8	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111516	BioGRID:107958	CYP17A1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111516	BioGRID:109268	H2AFX	BioGRID	PubMed	Biochemical Activity
BioGRID:111516	BioGRID:115106	HDAC4	BioGRID	PubMed	Reconstituted Complex
BioGRID:111516	BioGRID:32277	HTA1	BioGRID	PubMed	Biochemical Activity; Co-localization
BioGRID:111516	BioGRID:109920	JAK2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111516	BioGRID:110712	MYH9	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111516	BioGRID:118947	MYLPF	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111516	BioGRID:125044	MYOCD	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111516	BioGRID:111310	PIM1	BioGRID	PubMed	Biochemical Activity
BioGRID:111516	BioGRID:111507	PPP2CA	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:111516	BioGRID:111510	PPP2R1A	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111516	BioGRID:111515	PPP2R3A	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:111516	BioGRID:111523	PPP4C	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111516	BioGRID:111700	PTEN	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111516	BioGRID:111817	RAC1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111516	BioGRID:36031	RRD2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111516	BioGRID:112316	SET	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:111516	BioGRID:111269	SLC25A3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111516	BioGRID:118999	STRN3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111516	BioGRID:112810	TCP1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111516	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
ATP binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to ATPase activity	IDA Inferred from Direct Assay more info	PubMed
isomerase activity	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
peptidyl-prolyl cis-trans isomerase activity	IEA Inferred from Electronic Annotation more info
phosphatase activator activity	IEA Inferred from Electronic Annotation more info
protein heterodimerization activity	TAS Traceable Author Statement more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
protein phosphatase 2A binding	IDA Inferred from Direct Assay more info	PubMed
protein phosphatase type 2A regulator activity	IDA Inferred from Direct Assay more info	PubMed
protein phosphatase type 2A regulator activity	TAS Traceable Author Statement more info	PubMed
protein tyrosine phosphatase activator activity	IDA Inferred from Direct Assay more info	PubMed
receptor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
ATP catabolic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of phosphoprotein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of protein dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of phosphoprotein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of protein dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
protein folding	IEA Inferred from Electronic Annotation more info
regulation of phosphoprotein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
calcium channel complex	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
NOT nucleolus	IDA Inferred from Direct Assay more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
protein phosphatase type 2A complex	TAS Traceable Author Statement more info	PubMed
soluble fraction	TAS Traceable Author Statement more info	PubMed

General protein information

Preferred Names: serine/threonine-protein phosphatase 2A activator

Names: serine/threonine-protein phosphatase 2A activator; PP2A phosphatase activator; PP2A subunit B' isoform PR53; phosphotyrosyl phosphatase activator; protein phosphatase 2A, regulatory subunit B' (PR 53); serine/threonine-protein phosphatase 2A regulatory subunit B'

NP_001180326.1

EC 5.2.1.8

NP_066954.2

EC 5.2.1.8

NP_821067.1

EC 5.2.1.8

NP_821068.1

EC 5.2.1.8

NP_821070.1

EC 5.2.1.8

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NCBI Reference Sequences (RefSeq)

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_029370.1 RefSeqGene

Range

5001..42998

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001193397.1 → NP_001180326.1 serine/threonine-protein phosphatase 2A activator isoform e

Status: REVIEWED

Description

Transcript Variant: This variant (6) contains a different first exon, which results in the use of an in-frame downstream start codon, and lacks an alternate coding segment, compared to variant 1. The resulting protein (isoform e) is shorter when compared to isoform a.

Source sequence(s)

AL158151, CD630703, DA052599, X73478

UniProtKB/Swiss-Prot

Q15257

Related

ENSP00000403542, OTTHUMP00000196049, ENST00000417728, OTTHUMT00000315871

Conserved Domains (1) summary

cd04087
Location:12 – 277
Blast Score: 1052

PTPA; Phosphotyrosyl phosphatase activator (PTPA) is also known as protein phosphatase 2A (PP2A) phosphatase activator. PTPA is an essential, well conserved protein that stimulates the tyrosyl phosphatase activity of PP2A. It also reactivates the serine ...
NM_021131.4 → NP_066954.2 serine/threonine-protein phosphatase 2A activator isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and lacks an in-frame segment of the coding region, compared to variant 1. Variants 2 and 3 encode a shorter protein (isoform b), also known as isoform alpha, that is missing an internal segment compared to isoform a.

Source sequence(s)

AL158151, BC002545, DB009663, X73478

Consensus CDS

CCDS6920.1

UniProtKB/Swiss-Prot

Q15257

Related

ENSP00000351885, OTTHUMP00000022333, ENST00000358994, OTTHUMT00000054566

Conserved Domains (1) summary

cd04087
Location:47 – 312
Blast Score: 1055

PTPA; Phosphotyrosyl phosphatase activator (PTPA) is also known as protein phosphatase 2A (PP2A) phosphatase activator. PTPA is an essential, well conserved protein that stimulates the tyrosyl phosphatase activity of PP2A. It also reactivates the serine ...
NM_178000.2 → NP_821067.1 serine/threonine-protein phosphatase 2A activator isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks one of the coding exons compared to transcript variant 1. It maintains the reading frame and encodes a protein (isoform b), also known as isoform alpha, that is missing an internal segment of the protein compared to isoform a. Variants 2 and 3 encode the same isoform.

Source sequence(s)

AL158151, AU133279, BT020119, DC375389, X73478

Consensus CDS

CCDS6920.1

UniProtKB/Swiss-Prot

Q15257

Related

ENSP00000377036, OTTHUMP00000022334, ENST00000393370, OTTHUMT00000054567

Conserved Domains (1) summary

cd04087
Location:47 – 312
Blast Score: 1055

PTPA; Phosphotyrosyl phosphatase activator (PTPA) is also known as protein phosphatase 2A (PP2A) phosphatase activator. PTPA is an essential, well conserved protein that stimulates the tyrosyl phosphatase activity of PP2A. It also reactivates the serine ...
NM_178001.2 → NP_821068.1 serine/threonine-protein phosphatase 2A activator isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. It encodes the longest protein (isoform a), also known as isoform beta.

Source sequence(s)

AL158151, AU125192, DA737954, DC375389, X73478

UniProtKB/Swiss-Prot

Q15257

Related

ENSP00000337448, ENST00000337738

Conserved Domains (1) summary

cd04087
Location:47 – 347
Blast Score: 1017

PTPA; Phosphotyrosyl phosphatase activator (PTPA) is also known as protein phosphatase 2A (PP2A) phosphatase activator. PTPA is an essential, well conserved protein that stimulates the tyrosyl phosphatase activity of PP2A. It also reactivates the serine ...
NM_178003.2 → NP_821070.1 serine/threonine-protein phosphatase 2A activator isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an in-frame segment of the coding region, compared to variant 1. It encodes a shorter protein (isoform d), also known as isoform epsilon, that is missing an internal segment compared to isoform a.

Source sequence(s)

AL158151, BQ896712, DA387148, DC375389, X73478

UniProtKB/Swiss-Prot

Q15257

Related

ENSP00000347109, OTTHUMP00000194822, ENST00000355007, OTTHUMT00000313606

Conserved Domains (1) summary

cd04087
Location:47 – 270
Blast Score: 823

PTPA; Phosphotyrosyl phosphatase activator (PTPA) is also known as protein phosphatase 2A (PP2A) phosphatase activator. PTPA is an essential, well conserved protein that stimulates the tyrosyl phosphatase activity of PP2A. It also reactivates the serine ...

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000009.11 Reference GRCh37.p5 Primary Assembly

Range

131873228..131911225

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000141.1 Alternate HuRef

Range

101480193..101518132

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_178002.1: Suppressed sequence

Description

NM_178002.1: This RefSeq was permanently suppressed because currently there is insufficient support for this transcript variant and PMID:10880964 indicates that the encoded isoform may not be functional.

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF134185.1	AAF24143.1
genomic	AL158151.16	CAI12872.1
		CAI12873.1
		CAM14694.1
		CAM14695.1
		CAO03338.1
		CAO03339.1
		CAO03340.1
		CAO03341.1
		CAO03342.1
		CAO03343.1
		CAP58847.2
		CAX15251.1
		CAX15252.1
		CAX15253.1
		CAX15254.1
		CAX15255.1
genomic	CH471090.1	EAW87876.1
		EAW87877.1
		EAW87878.1
		EAW87879.1
		EAW87880.1
		EAW87881.1
		EAW87882.1
		EAW87883.1
		EAW87884.1
		EAW87885.1
genomic	X86428.1	CAA60163.1
		CAB77601.1
		CAB77602.1
		CAB77603.1
genomic	X86439.1 (112..1665)	None
mRNA	AK222788.1	BAD96508.1
mRNA	AK297202.1	BAG59687.1
mRNA	AK302043.1	BAG63436.1
mRNA	AK302897.1	BAG64070.1
mRNA	AK307424.1	None
mRNA	AK310328.1	None
mRNA	AK310543.1	None
mRNA	AU125192.1	None
mRNA	AU133279.1	None
mRNA	BC002545.2	AAH02545.1
mRNA	BC010497.1	None
mRNA	BC011605.2	AAH11605.1
mRNA	BC020581.1	None
mRNA	BE732116.1	None
mRNA	BG255640.1	None
mRNA	BQ896712.1	None
mRNA	BT020119.1	AAV38922.1
mRNA	CD630703.1	None
mRNA	CR749810.1	CAH18670.1
mRNA	DA052599.1	None
mRNA	DA387148.1	None
mRNA	DA737954.1	None
mRNA	DB009663.1	None
mRNA	DC375389.1	None
mRNA	X73478.1	CAA51873.1
other-genetic	DQ892154.2	ABM83080.1
other-genetic	DQ894879.2	ABM85805.1
other-genetic	DQ895349.2	ABM86275.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
Q15257.3	GenPept	UniProtKB/Swiss-Prot:Q15257
Q5T948	GenPept	UniProtKB/TrEMBL:Q5T948
Q5T949	GenPept	UniProtKB/TrEMBL:Q5T949
Q68CR8	GenPept	UniProtKB/TrEMBL:Q68CR8