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    PPP6C protein phosphatase 6 catalytic subunit [ Homo sapiens (human) ]

    Gene ID: 5537, updated on 5-Mar-2024

    Summary

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    Official Symbol
    PPP6Cprovided by HGNC
    Official Full Name
    protein phosphatase 6 catalytic subunitprovided by HGNC
    Primary source
    HGNC:HGNC:9323
    See related
    Ensembl:ENSG00000119414 MIM:612725; AllianceGenome:HGNC:9323
    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
    PP6; PP6C
    Summary
    This gene encodes the catalytic subunit of protein phosphatase, a component of a signaling pathway regulating cell cycle progression. Splice variants encoding different protein isoforms exist. The pseudogene of this gene is located on chromosome X. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in thyroid (RPKM 20.0), fat (RPKM 18.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    9q33.3
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (125146573..125189803, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (137344915..137388140, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (127908852..127952082, complement)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene suppressor of cancer cell invasion Neighboring gene NANOG hESC enhancer GRCh37_chr9:127737373-127737931 Neighboring gene frataxin pseudogene 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:127806191-127806703 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:127806704-127807217 Neighboring gene uncharacterized LOC124902355 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20274 Neighboring gene phosphoribosyl pyrophosphate synthetase 1 pseudogene 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:127951404-127952190 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:127952191-127952977 Neighboring gene NADH:ubiquinone oxidoreductase subunit B3 pseudogene 2 Neighboring gene uncharacterized LOC105376271 Neighboring gene ribosomal protein SA pseudogene 76

    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
    • 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. PP6 negatively modulates LUBAC-mediated M1-ubiquitination of RIPK1 and c-FLIP(L) to promote TNFα-mediated cell death. Wu G, et al. Cell Death Dis, 2022 Sep 7. PMID 36071040, Free PMC Article
    2. Protein phosphatase 6 promotes neurite outgrowth by promoting mTORC2 activity in N2a cells. Kitamura N, et al. J Biochem, 2021 Sep 22. PMID 34314486
    3. PPP6C negatively regulates oncogenic ERK signaling through dephosphorylation of MEK. Cho E, et al. Cell Rep, 2021 Mar 30. PMID 33789117, Free PMC Article
    4. Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells. Rusin SF, et al. Sci Signal, 2015 Oct 13. PMID 26462736, Free PMC Article
    5. Adaptation of HepG2 cells to a steady-state reduction in the content of protein phosphatase 6 (PP6) catalytic subunit. Boylan JM, et al. Exp Cell Res, 2015 Jul 15. PMID 25999147, Free PMC Article

    See all (136) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. PP6 negatively modulates LUBAC-mediated M1-ubiquitination of RIPK1 and c-FLIPL to promote TNFalpha-mediated cell death.
      Title: PP6 negatively modulates LUBAC-mediated M1-ubiquitination of RIPK1 and c-FLIP(L) to promote TNFα-mediated cell death.
    2. PPP6C negatively regulates oncogenic ERK signaling through dephosphorylation of MEK.
      Title: PPP6C negatively regulates oncogenic ERK signaling through dephosphorylation of MEK.
    3. MiR-20a-5p functions as a potent tumor suppressor by targeting PPP6C in acute myeloid leukemia.
      Title: MiR-20a-5p functions as a potent tumor suppressor by targeting PPP6C in acute myeloid leukemia.
    4. Protein phosphatase 6 promotes neurite outgrowth by promoting mTORC2 activity in N2a cells.
      Title: Protein phosphatase 6 promotes neurite outgrowth by promoting mTORC2 activity in N2a cells.
    5. PPP6C Negatively Regulates STING-Dependent Innate Immune Responses.
      Title: PPP6C Negatively Regulates STING-Dependent Innate Immune Responses.
    6. Dephosphorylation of cGAS by PPP6C impairs its substrate binding activity and innate antiviral response.
      Title: Dephosphorylation of cGAS by PPP6C impairs its substrate binding activity and innate antiviral response.
    7. Data suggest that this Plk1-PP6 interaction generates a feedback loop that coordinates and reinforces the activities of Plk1 and Aurora A during mitotic entry and is terminated by the degradation of Plk1 during mitotic exit. Thus, a mechanism for the previously puzzling observation of the Plk1-dependent regulation of Aurora A has been identified.
      Title: Global assessment of its network dynamics reveals that the kinase Plk1 inhibits the phosphatase PP6 to promote Aurora A activity.
    8. PP6 rapidly interacts with ASK3 in an osmolality-dependent manner, and it inactivates ASK3 to induce RVI and, thereby, cell survival under hyperosmotic stress.
      Title: A PP6-ASK3 Module Coordinates the Bidirectional Cell Volume Regulation under Osmotic Stress.
    9. findings define the WHIP-TRIM14-PPP6C mitochondrial signalosome required for RIG-I-mediated innate antiviral immunity.
      Title: Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated Antiviral Signaling.
    10. Knockdown of Alpha4 preferentially impacts the expression of PP4c and PP6c compared to expression levels of PP2Ac.
      Title: The three Type 2A protein phosphatases, PP2Ac, PP4c and PP6c, are differentially regulated by Alpha4.
    Submit: New GeneRIF Correction See all GeneRIFs (30)

    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

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Rev rev HIV-1 Rev interacting protein, protein phosphatase 6, catalytic subunit (PPP6C), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells 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

    Clone Names

    • FLJ92648, MGC12249

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables myosin phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein serine/threonine phosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein serine/threonine phosphatase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine/threonine phosphatase activity TAS
    Traceable Author Statement
    more info
    		  
    Process Evidence Code Pubs
    involved_in COPII vesicle coating TAS
    Traceable Author Statement
    more info
    		  
    involved_in G1/S transition of mitotic cell cycle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in innate immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of cGAS/STING signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within protein dephosphorylation IDA
    Inferred from Direct Assay
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    serine/threonine-protein phosphatase 6 catalytic subunit
    Names
    serine/threonine protein phosphatase catalytic subunit
    NP_001116827.1
    NP_001116841.1
    NP_002712.1
    XP_011517149.1
    XP_047279522.1
    XP_047279523.1
    XP_047279524.1
    XP_054219214.1
    XP_054219215.1
    XP_054219216.1
    XP_054219217.1

    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_001123355.2 → NP_001116827.1  serine/threonine-protein phosphatase 6 catalytic subunit isoform a

      See identical proteins and their annotated locations for NP_001116827.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) is the longest transcript; it encodes the longest isoform (a).
      Source sequence(s)
      AA251321, AL445930, BC006990, CB250498, DB037210, DC334216
      Consensus CDS
      CCDS48018.1
      UniProtKB/Swiss-Prot
      O00743
      Related
      ENSP00000392147.1, ENST00000451402.5
      Conserved Domains (1) summary
      cd07415
      Location:5 → 326
      MPP_PP2A_PP4_PP6; PP2A, PP4, and PP6 phosphoprotein phosphatases, metallophosphatase domain

    2. NM_001123369.2 → NP_001116841.1  serine/threonine-protein phosphatase 6 catalytic subunit isoform c

      See identical proteins and their annotated locations for NP_001116841.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks one coding exon compared to variant 1 and encodes isoform c, which is shorter than isoform a.
      Source sequence(s)
      AA251321, AL445930, BC006990, CB250498, DC369815
      Consensus CDS
      CCDS48019.1
      UniProtKB/Swiss-Prot
      O00743
      Related
      ENSP00000411744.1, ENST00000415905.5
      Conserved Domains (1) summary
      cd07415
      Location:5 → 267
      MPP_PP2A_PP4_PP6; PP2A, PP4, and PP6 phosphoprotein phosphatases, metallophosphatase domain

    3. NM_002721.5 → NP_002712.1  serine/threonine-protein phosphatase 6 catalytic subunit isoform b

      See identical proteins and their annotated locations for NP_002712.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site and lacks an exon in the coding region, compared to variant 1; it encodes a shorter isoform (b).
      Source sequence(s)
      AA251321, AL445930, BC006990, CB250498, DB037210
      Consensus CDS
      CCDS6861.1
      UniProtKB/Swiss-Prot
      B2R5V6, B7Z2W9, B7Z5K9, O00743, Q5U0A2, Q9UIC9
      UniProtKB/TrEMBL
      A0A024R861
      Related
      ENSP00000362648.4, ENST00000373547.9
      Conserved Domains (1) summary
      cd07415
      Location:5 → 289
      MPP_PP2A_PP4_PP6; PP2A, PP4, and PP6 phosphoprotein phosphatases, metallophosphatase domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      125146573..125189803 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047423566.1 → XP_047279522.1  serine/threonine-protein phosphatase 6 catalytic subunit isoform X1

    2. XM_047423568.1 → XP_047279524.1  serine/threonine-protein phosphatase 6 catalytic subunit isoform X3

    3. XM_011518847.4 → XP_011517149.1  serine/threonine-protein phosphatase 6 catalytic subunit isoform X2

      Conserved Domains (2) summary
      PTZ00239
      Location:15 → 293
      PTZ00239; serine/threonine protein phosphatase 2A; Provisional
      cd07415
      Location:13 → 277
      MPP_PP2A_PP4_PP6; PP2A, PP4, and PP6 phosphoprotein phosphatases, metallophosphatase domain

    4. XM_047423567.1 → XP_047279523.1  serine/threonine-protein phosphatase 6 catalytic subunit isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      137344915..137388140 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054363239.1 → XP_054219214.1  serine/threonine-protein phosphatase 6 catalytic subunit isoform X1

    2. XM_054363242.1 → XP_054219217.1  serine/threonine-protein phosphatase 6 catalytic subunit isoform X3

    3. XM_054363240.1 → XP_054219215.1  serine/threonine-protein phosphatase 6 catalytic subunit isoform X2

    4. XM_054363241.1 → XP_054219216.1  serine/threonine-protein phosphatase 6 catalytic subunit isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O00743.1 GenPept UniProtKB/Swiss-Prot:O00743

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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