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    PPP2R5E protein phosphatase 2 regulatory subunit B'epsilon [ Homo sapiens (human) ]

    Gene ID: 5529, updated on 28-Oct-2024

    Summary

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    Official Symbol
    PPP2R5Eprovided by HGNC
    Official Full Name
    protein phosphatase 2 regulatory subunit B'epsilonprovided by HGNC
    Primary source
    HGNC:HGNC:9313
    See related
    Ensembl:ENSG00000154001 MIM:601647; AllianceGenome:HGNC:9313
    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
    B56E; B56epsilon
    Summary
    The protein encoded by this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A 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 B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes an epsilon isoform of the regulatory subunit B56 subfamily. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]
    Expression
    Ubiquitous expression in thyroid (RPKM 11.5), colon (RPKM 9.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PPP2R5E in Genome Data Viewer
    Location:
    14q23.2
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (63371364..63543377, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (57578735..57750775, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (63838082..64010095, complement)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene ras homolog family member J Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:63764973-63765474 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:63765475-63765974 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:63799179-63799678 Neighboring gene glycoprotein hormone subunit beta 5 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_34994 Neighboring gene Sharpr-MPRA regulatory region 14795 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8504 Neighboring gene U6 spliceosomal RNA Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8505 Neighboring gene uncharacterized LOC124900352 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:63950021-63950522 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:63950523-63951022 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8506 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8507 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8508 Neighboring gene loricrin-like Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5827 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5828 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:64010147-64011138 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8510 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:64030470-64031292 Neighboring gene ribosomal protein L31 pseudogene 5 Neighboring gene glycine C-acetyltransferase pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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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    Related articles in PubMed

    1. Deregulation of the miR-19b/PPP2R5E Signaling Axis Shows High Functional Impact in Colorectal Cancer Cells. Santos A, et al. Int J Mol Sci, 2023 Apr 24. PMID 37175484, Free PMC Article
    2. Protein phosphatase 2A regulatory subunits and cancer. Eichhorn PJ, et al. Biochim Biophys Acta, 2009 Jan. PMID 18588945
    3. From promiscuity to precision: protein phosphatases get a makeover. Virshup DM, et al. Mol Cell, 2009 Mar 13. PMID 19285938
    4. Downregulation of PPP2R5E is a common event in acute myeloid leukemia that affects the oncogenic potential of leukemic cells. Cristóbal I, et al. Haematologica, 2013 Sep. PMID 23812941, Free PMC Article
    5. Downregulation of protein phosphatase 2A by apolipoprotein E: Implications for Alzheimer's disease. Theendakara V, et al. Mol Cell Neurosci, 2017 Sep. PMID 28720530

    See all (97) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Deregulation of the miR-19b/PPP2R5E Signaling Axis Shows High Functional Impact in Colorectal Cancer Cells.
      Title: Deregulation of the miR-19b/PPP2R5E Signaling Axis Shows High Functional Impact in Colorectal Cancer Cells.
    2. Functional and Structural Insights into a Vif/PPP2R5 Complex Elucidated Using Patient HIV-1 Isolates and Computational Modeling.
      Title: Functional and Structural Insights into a Vif/PPP2R5 Complex Elucidated Using Patient HIV-1 Isolates and Computational Modeling.
    3. EFNA5, BAHD1 and PPP2R5E were particularly good candidates for novel disease loci
      Title: Mapping of breakpoints in balanced chromosomal translocations by shallow whole-genome sequencing points to EFNA5, BAHD1 and PPP2R5E as novel candidates for genes causing human Mendelian disorders.
    4. results suggest that the PPP2R5E phosphatase may contribute to microtubule organization by stabilizing MTCL1.
      Title: A regulatory subunit of protein phosphatase 2A, PPP2R5E, regulates the abundance of microtubule crosslinking factor 1.
    5. PP2A holoenzyme containing B56 is responsible for the dephosphorylation of gamma-H2AX and regulation of DNA repair of double strand breaks induced by camptothecin.
      Title: PP2A-B56ϵ complex is involved in dephosphorylation of γ-H2AX in the repair process of CPT-induced DNA double-strand breaks.
    6. KIF4A and PP2A-B56G and -B56E create a spatially restricted negative feedback loop counteracting Aurora B in anaphase.
      Title: KIF4A and PP2A-B56 form a spatially restricted feedback loop opposing Aurora B at the anaphase central spindle.
    7. the significance of miR-23a and PPP2R5E in the proliferation and apoptosis of gastric cancer cells
      Title: Downregulation of PPP2R5E expression by miR-23a suppresses apoptosis to facilitate the growth of gastric cancer cells.
    8. The two functional variants in PPP2R1A and PPP2R5E and their combinations are associated with lung cancer risk in the Chinese.
      Title: Functional genetic polymorphisms in PP2A subunit genes confer increased risks of lung cancer in southern and eastern Chinese.
    9. Downregulation of PPP2R5E affects the oncogenic potential of leukemic cells.
      Title: Downregulation of PPP2R5E is a common event in acute myeloid leukemia that affects the oncogenic potential of leukemic cells.
    10. identified the phosphorylation of hSgo2 by Aurora B at the N-terminal coiled-coil region and the middle region, and showed that these phosphorylations separately promote binding of hSgo2 to PP2A and MCAK
      Title: Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres.
    Submit: New GeneRIF Correction See all GeneRIFs (12)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Association between single nucleotide polymorphism-genotype and outcome of patients with chronic lymphocytic leukemia in a randomized chemotherapy trial.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of protein phosphatase 2, regulatory subunit B', epsilon isoform (PPP2R5E) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

    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 Protein phosphatase-2A (PP2A) and protein phosphatase-1 (PP1) regulate HIV-1 Tat-activated transcription through dephosphorylation of CDK9 PubMed
    tat HIV-1 Tat associates with the promoters of both PPP2R1B and PPP2R5E to increase PPP2R1B and PPP2R5E RNA and protein levels as well as PP2A activity in Jurkat 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 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 HIV-1 Vpu is identified to have a physical interaction with protein phosphatase 2, regulatory subunit B', epsilon isoform (PPP2R5E) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    nucleocapsid gag HIV-1 Vpr forms a complex with HIV-1 nucleocapsid that directly activates PP2A PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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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

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein phosphatase activator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein phosphatase regulator activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in protein dephosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm TAS
    Traceable Author Statement
    more info
    		 PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of protein phosphatase type 2A complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform
    Names
    PP2A, B subunit, B' epsilon
    PP2A, B subunit, B56 epsilon
    PP2A, B subunit, PR61 epsilon
    PP2A, B subunit, R5 epsilon
    protein phosphatase 2 regulatory subunit B', epsilon
    serine/threonine protein phosphatase 2A, 56 kDa regulatory subunit, epsilon

    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.

    mRNA and Protein(s)

    1. NM_001282179.3 → NP_001269108.1  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform a

      See identical proteins and their annotated locations for NP_001269108.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice junction in the 5' UTR compared to variant 1. Variants 1 and 2 both encode the same isoform (a).
      Source sequence(s)
      AA782601, AB209811, AL118555, AL136038, AW134792, CB989123, CK820060, L76703
      Consensus CDS
      CCDS9758.1
      UniProtKB/Swiss-Prot
      A4FU37, B7ZAW5, B7ZKK8, B7ZKK9, J3KQN6, Q16537, Q52LW4
      UniProtKB/TrEMBL
      B5BTZ7, Q562F2
      Conserved Domains (2) summary
      pfam01603
      Location:55 → 435
      B56; Protein phosphatase 2A regulatory B subunit (B56 family)
      cl27532
      Location:2 → 67
      B56; Protein phosphatase 2A regulatory B subunit (B56 family)

    2. NM_001282180.3 → NP_001269109.1  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform b

      See identical proteins and their annotated locations for NP_001269109.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate in-frame splice junction at an end of a 3' exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.
      Source sequence(s)
      AA782601, AK299520, AL118555, AL132992, AL136038, AW134792, CB989123, CK820060, L76703
      Consensus CDS
      CCDS61468.1
      UniProtKB/TrEMBL
      B7Z5X1
      Related
      ENSP00000452396.1, ENST00000555899.1
      Conserved Domains (2) summary
      pfam01603
      Location:55 → 430
      B56; Protein phosphatase 2A regulatory B subunit (B56 family)
      cl27532
      Location:2 → 67
      B56; Protein phosphatase 2A regulatory B subunit (B56 family)

    3. NM_001282181.3 → NP_001269110.1  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform c

      See identical proteins and their annotated locations for NP_001269110.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains a distinct 5' UTR and lacks an in-frame portion of the 5' coding region, compared to variant 1. The resulting isoform (c) has a shorter N-terminus compared to isoform a. Variants 4 and 5 both encode the same isoform (c).
      Source sequence(s)
      AA782601, AK301796, AL118555, AW134792, BC093766, CK820060, L76703
      Consensus CDS
      CCDS61467.1
      UniProtKB/TrEMBL
      B7Z7C0
      Related
      ENSP00000404632.2, ENST00000422769.6
      Conserved Domains (1) summary
      pfam01603
      Location:2 → 359
      B56; Protein phosphatase 2A regulatory B subunit (B56 family)

    4. NM_001282182.3 → NP_001269111.1  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform c

      See identical proteins and their annotated locations for NP_001269111.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) contains a distinct 5' UTR and lacks an in-frame portion of the 5' coding region, compared to variant 1. The resulting isoform (c) has a shorter N-terminus compared to isoform a. Variants 4 and 5 both encode the same isoform (c).
      Source sequence(s)
      AA782601, AK301796, AK316430, AL118555, AW134792, BC093766, CK820060, L76703
      Consensus CDS
      CCDS61467.1
      UniProtKB/TrEMBL
      B7Z7C0
      Conserved Domains (1) summary
      pfam01603
      Location:2 → 359
      B56; Protein phosphatase 2A regulatory B subunit (B56 family)

    5. NM_001354926.2 → NP_001341855.1  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform d

      Status: REVIEWED

      Source sequence(s)
      AL132992, AL136038, BC056156
      Related
      ENST00000556878.1
      Conserved Domains (1) summary
      cl27532
      Location:55 → 120
      B56; Protein phosphatase 2A regulatory B subunit (B56 family)

    6. NM_006246.5 → NP_006237.1  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform a

      See identical proteins and their annotated locations for NP_006237.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a). Variants 1 and 2 both encode the same isoform (a).
      Source sequence(s)
      AA782601, AL118555, AL136038, AW134792, BC093766, CB989123, CK820060, L76703
      Consensus CDS
      CCDS9758.1
      UniProtKB/Swiss-Prot
      A4FU37, B7ZAW5, B7ZKK8, B7ZKK9, J3KQN6, Q16537, Q52LW4
      UniProtKB/TrEMBL
      B5BTZ7, Q562F2
      Related
      ENSP00000337641.3, ENST00000337537.8
      Conserved Domains (2) summary
      pfam01603
      Location:55 → 435
      B56; Protein phosphatase 2A regulatory B subunit (B56 family)
      cl27532
      Location:2 → 67
      B56; Protein phosphatase 2A regulatory B subunit (B56 family)

    RNA

    1. NR_104104.3 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) lacks an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AA782601, AL118555, AL136038, AW134792, BC013154, CB989123, CK820060, L76703

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      63371364..63543377 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047431543.1 → XP_047287499.1  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X2

    2. XM_024449647.2 → XP_024305415.1  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1

      UniProtKB/Swiss-Prot
      A4FU37, B7ZAW5, B7ZKK8, B7ZKK9, J3KQN6, Q16537, Q52LW4
      UniProtKB/TrEMBL
      B5BTZ7, Q562F2
      Conserved Domains (2) summary
      pfam01603
      Location:55 → 435
      B56; Protein phosphatase 2A regulatory B subunit (B56 family)
      cl27532
      Location:2 → 67
      B56; Protein phosphatase 2A regulatory B subunit (B56 family)

    3. XM_047431544.1 → XP_047287500.1  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      57578735..57750775 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054376319.1 → XP_054232294.1  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X2

    2. XM_054376318.1 → XP_054232293.1  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1

      UniProtKB/Swiss-Prot
      A4FU37, B7ZAW5, B7ZKK8, B7ZKK9, J3KQN6, Q16537, Q52LW4
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q16537.1 GenPept UniProtKB/Swiss-Prot:Q16537

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