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    PPP4R1 protein phosphatase 4 regulatory subunit 1 [ Homo sapiens (human) ]

    Gene ID: 9989, updated on 2-Nov-2024

    Summary

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    Official Symbol
    PPP4R1provided by HGNC
    Official Full Name
    protein phosphatase 4 regulatory subunit 1provided by HGNC
    Primary source
    HGNC:HGNC:9320
    See related
    Ensembl:ENSG00000154845 MIM:604908; AllianceGenome:HGNC:9320
    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
    MEG1; PP4R1; PP4(Rmeg)
    Summary
    This gene encodes one of several alternate regulatory subunits of serine/threonine protein phosphatase 4 (PP4). The protein features multiple HEAT repeats. This protein forms a complex with PP4RC. This complex may have a distinct role from other PP4 complexes, including regulation of HDAC3 (Zhang et al., PMID: 15805470). There is also a transcribed pseudogene on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]
    Expression
    Ubiquitous expression in esophagus (RPKM 39.0), testis (RPKM 25.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PPP4R1 in Genome Data Viewer
    Location:
    18p11.22
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (9546794..9617199, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (9710190..9781391, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (9546792..9614557, complement)

    Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene ralA binding protein 1 Neighboring gene iroquois homeobox 4 pseudogene 1 Neighboring gene RNA, U2 small nuclear 27, pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr18:9570108-9570290 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr18:9574228-9574738 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr18:9574739-9575249 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13076 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9284 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9285 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9286 Neighboring gene PPP4R1 antisense RNA 1 Neighboring gene RNA, U6 small nuclear 903, pseudogene Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr18:9643443-9644016 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:9644964-9645470 Neighboring gene long intergenic non-protein coding RNA 2856

    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. PP4R1 interacts with HMGA2 to promote non-small-cell lung cancer migration and metastasis via activating MAPK/ERK-induced epithelial-mesenchymal transition. Wang B, et al. Mol Carcinog, 2020 May. PMID 32077156
    2. The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen. Abdul-Sada H, et al. Oncotarget, 2017 Apr 11. PMID 28445980, Free PMC Article
    3. A PP4 holoenzyme balances physiological and oncogenic nuclear factor-kappa B signaling in T lymphocytes. Brechmann M, et al. Immunity, 2012 Oct 19. PMID 23084358
    4. Cloning and characterization of a novel subunit of protein serine/threonine phosphatase 4 from mesangial cells. Wada T, et al. J Am Soc Nephrol, 2001 Dec. PMID 11729228
    5. Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4. Zhang X, et al. Genes Dev, 2005 Apr 1. PMID 15805470, Free PMC Article

    See all (52) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. AMBRA1 promotes intestinal inflammation by antagonizing PP4R1/PP4c mediated IKK dephosphorylation in an autophagy-independent manner.
      Title: AMBRA1 promotes intestinal inflammation by antagonizing PP4R1/PP4c mediated IKK dephosphorylation in an autophagy-independent manner.
    2. PP4R1 promotes glycolysis and gallbladder cancer progression through facilitating ERK1/2 mediated PKM2 nuclear translocation.
      Title: PP4R1 promotes glycolysis and gallbladder cancer progression through facilitating ERK1/2 mediated PKM2 nuclear translocation.
    3. PP4R1 accelerates the malignant progression of NSCLC via up-regulating HSPA6 expression and HSPA6-mediated ER stress.
      Title: PP4R1 accelerates the malignant progression of NSCLC via up-regulating HSPA6 expression and HSPA6-mediated ER stress.
    4. PP4R1 interacts with HMGA2 to promote non-small-cell lung cancer migration and metastasis via activating MAPK/ERK-induced epithelial-mesenchymal transition.
      Title: PP4R1 interacts with HMGA2 to promote non-small-cell lung cancer migration and metastasis via activating MAPK/ERK-induced epithelial-mesenchymal transition.
    5. Data identify PP4R1 as a novel target for virus subversion of the host anti-viral response.
      Title: The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen.
    6. PP4R1 could mediate the dephosphorylation of TRAF2 Ser11.
      Title: The PP4R1 subunit of protein phosphatase PP4 targets TRAF2 and TRAF6 to mediate inhibition of NF-κB activation.
    7. PP4R1 expression was triggered upon activation and proliferation of primary human T lymphocytes and deficiency for PP4R1 caused sustained and increased IKK activity, T cell hyperactivation, and aberrant NF-kappaB signaling in NF-kappaB-addicted T cell lymphomas
      Title: A PP4 holoenzyme balances physiological and oncogenic nuclear factor-kappa B signaling in T lymphocytes.
    8. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    Submit: New GeneRIF Correction

    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

    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

    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
    contributes_to phosphoprotein phosphatase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein phosphatase regulator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein phosphatase regulator activity NAS
    Non-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 protein phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in signal transduction NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of protein phosphatase 4 complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    serine/threonine-protein phosphatase 4 regulatory subunit 1
    Names
    serine/threonine phosphatase 4

    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_001042388.3 → NP_001035847.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform a

      See identical proteins and their annotated locations for NP_001035847.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longer protein (isoform a).
      Source sequence(s)
      AF100744, AK027064, BC060829, DR006046
      Consensus CDS
      CCDS42412.1
      UniProtKB/Swiss-Prot
      Q8TF05, Q99774, Q9UNQ7
      UniProtKB/TrEMBL
      A8K923, B2RCG9
      Related
      ENSP00000383402.3, ENST00000400556.8
      Conserved Domains (2) summary
      pfam15017
      Location:449 → 473
      AF1Q; Drug resistance and apoptosis regulator
      sd00044
      Location:133 → 157
      HEAT; HEAT repeat [structural motif]

    2. NM_001382562.1 → NP_001369491.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform c

      Status: REVIEWED

      Source sequence(s)
      AP000902, AP001381
      UniProtKB/TrEMBL
      A8K923, B2RCG9
      Conserved Domains (2) summary
      sd00044
      Location:44 → 68
      HEAT; HEAT repeat [structural motif]
      pfam15017
      Location:364 → 382
      WRNPLPNID; Putative WW-binding domain and destruction box

    3. NM_005134.4 → NP_005125.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform b

      See identical proteins and their annotated locations for NP_005125.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site compared to variant 1.This results in a shorter protein (isoform b), compared to isoform a.
      Source sequence(s)
      AF100744, BC060829
      Consensus CDS
      CCDS42413.1
      UniProtKB/TrEMBL
      A8K923, B2RCG9
      Related
      ENSP00000383401.3, ENST00000400555.7
      Conserved Domains (2) summary
      pfam15017
      Location:432 → 456
      AF1Q; Drug resistance and apoptosis regulator
      sd00044
      Location:116 → 140
      HEAT; HEAT repeat [structural motif]

    RNA

    1. NR_052003.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has multiple differences 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)
      AI621152, AK293869, AK295533, AP001381, DR006046

    2. NR_168403.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AP000902, AP001381

    3. NR_168404.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AP000902, AP001381

    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_000018.10 Reference GRCh38.p14 Primary Assembly

      Range
      9546794..9617199 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047437976.1 → XP_047293932.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X8

    2. XM_047437973.1 → XP_047293929.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X4

    3. XM_011525776.2 → XP_011524078.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X2

      UniProtKB/TrEMBL
      A8K923, B2RCG9
      Conserved Domains (2) summary
      pfam15017
      Location:484 → 508
      AF1Q; Drug resistance and apoptosis regulator
      sd00044
      Location:168 → 192
      HEAT; HEAT repeat [structural motif]

    4. XM_011525779.4 → XP_011524081.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X6

      UniProtKB/TrEMBL
      A8K923, B2RCG9
      Conserved Domains (1) summary
      sd00044
      Location:605 → 633
      HEAT; HEAT repeat [structural motif]

    5. XM_017026105.3 → XP_016881594.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X3

      UniProtKB/TrEMBL
      A8K923, B2RCG9

    6. XM_011525775.4 → XP_011524077.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X1

      UniProtKB/TrEMBL
      A8K923, B2RCG9
      Conserved Domains (2) summary
      pfam15017
      Location:501 → 525
      AF1Q; Drug resistance and apoptosis regulator
      sd00044
      Location:185 → 209
      HEAT; HEAT repeat [structural motif]

    7. XM_047437979.1 → XP_047293935.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X11

    8. XM_047437975.1 → XP_047293931.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X7

    9. XM_047437978.1 → XP_047293934.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X10

      Conserved Domains (2) summary
      sd00044
      Location:553 → 581
      HEAT; HEAT repeat [structural motif]
      pfam15017
      Location:342 → 360
      WRNPLPNID; Putative WW-binding domain and destruction box

    10. XM_047437974.1 → XP_047293930.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X5

    11. XM_047437977.1 → XP_047293933.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X9

    12. XM_047437980.1 → XP_047293936.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X12

    RNA

    1. XR_007066261.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060942.1 Alternate T2T-CHM13v2.0

      Range
      9710190..9781391 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054319424.1 → XP_054175399.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X8

    2. XM_054319420.1 → XP_054175395.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X4

    3. XM_054319418.1 → XP_054175393.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X2

    4. XM_054319422.1 → XP_054175397.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X6

    5. XM_054319419.1 → XP_054175394.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X3

    6. XM_054319417.1 → XP_054175392.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X1

    7. XM_054319427.1 → XP_054175402.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X11

    8. XM_054319423.1 → XP_054175398.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X7

    9. XM_054319426.1 → XP_054175401.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X10

    10. XM_054319421.1 → XP_054175396.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X5

    11. XM_054319425.1 → XP_054175400.1  serine/threonine-protein phosphatase 4 regulatory subunit 1 isoform X9

    RNA

    1. XR_008485037.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8TF05.1 GenPept UniProtKB/Swiss-Prot:Q8TF05

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