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    PPME1 protein phosphatase methylesterase 1 [ Homo sapiens (human) ]

    Gene ID: 51400, updated on 2-Nov-2024

    Summary

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    Official Symbol
    PPME1provided by HGNC
    Official Full Name
    protein phosphatase methylesterase 1provided by HGNC
    Primary source
    HGNC:HGNC:30178
    See related
    Ensembl:ENSG00000214517 MIM:611117; AllianceGenome:HGNC:30178
    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
    PME-1; ABDH19
    Summary
    This gene encodes a protein phosphatase methylesterase localized to the nucleus. The encoded protein acts on the protein phosphatase-2A catalytic subunit and supports the ERK pathway through dephosphorylation of regulatory proteins. It plays a role in malignant glioma progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]
    Expression
    Ubiquitous expression in testis (RPKM 18.8), brain (RPKM 17.5) and 25 other tissues See more
    Orthologs
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    Genomic context

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    See PPME1 in Genome Data Viewer
    Location:
    11q13.4
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (74171289..74254703)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (74100633..74184047)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (73882334..73965748)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene MED14-independent group 3 enhancer GRCh37_chr11:73715060-73716259 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:73719425-73719605 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:73719739-73720378 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5249 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:73747696-73748895 Neighboring gene uncoupling protein 3 Neighboring gene C2 domain containing 3 centriole elongation regulator Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5250 Neighboring gene NANOG hESC enhancer GRCh37_chr11:73808354-73808901 Neighboring gene Sharpr-MPRA regulatory region 9619 Neighboring gene H3K27ac hESC enhancers GRCh37_chr11:73881282-73882205 and GRCh37_chr11:73882206-73883128 Neighboring gene uncharacterized LOC105369383 Neighboring gene RNA, 5S ribosomal pseudogene 343 Neighboring gene Sharpr-MPRA regulatory region 15540 Neighboring gene small nucleolar RNA SNORA7 Neighboring gene prolyl 4-hydroxylase subunit alpha 3 Neighboring gene P4HA3 antisense RNA 1 Neighboring gene uncharacterized LOC112268078 Neighboring gene phosphoglucomutase 2 like 1 Neighboring gene heterogeneous nuclear ribonucleoprotein A1 pseudogene 40

    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. Hydrogen peroxide redistributes the localization of protein phosphatase methylesterase 1. Tang S, et al. Life Sci, 2018 Nov 15. PMID 30340029
    2. Genetic amplification of PPME1 in gastric and lung cancer and its potential as a novel therapeutic target. Li J, et al. Cancer Biol Ther, 2014 Jan. PMID 24253382, Free PMC Article
    3. Inhibition of protein methylesterase 1 decreased cancerous phenotypes in endometrial adenocarcinoma cell lines and xenograft tumor models. Pusey M, et al. Tumour Biol, 2016 Sep. PMID 27048286
    4. Academic cross-fertilization by public screening yields a remarkable class of protein phosphatase methylesterase-1 inhibitors. Bachovchin DA, et al. Proc Natl Acad Sci U S A, 2011 Apr 26. PMID 21398589, Free PMC Article
    5. A LCMT1-PME-1 methylation equilibrium controls mitotic spindle size. Xia X, et al. Cell Cycle, 2015. PMID 25839665, Free PMC Article

    See all (72) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The luciferase-based in vivo protein-protein interaction assay revealed that CHK1 promotes PP2A and PME-1 interaction.
      Title: The luciferase-based in vivo protein-protein interaction assay revealed that CHK1 promotes PP2A and PME-1 interaction.
    2. PP2A methylesterase PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers.
      Title: PP2A methylesterase PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers.
    3. DNAH17-AS1 promotes pancreatic carcinoma by increasing PPME1 expression via inhibition of miR-432-5p.
      Title: DNAH17-AS1 promotes pancreatic carcinoma by increasing PPME1 expression via inhibition of miR-432-5p.
    4. 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.
    5. Glycogen synthase kinase-3beta suppresses the expression of protein phosphatase methylesterase-1 through beta-catenin.
      Title: Glycogen synthase kinase-3β suppresses the expression of protein phosphatase methylesterase-1 through β-catenin.
    6. USP36 regulates PME-1 as a DUB and participates in the ERK and Akt signaling pathways
      Title: PME-1 is regulated by USP36 in ERK and Akt signaling pathways.
    7. Authors found that PME-1 is exported from the nucleus to the cytoplasm upon H2O2 treatment and redistributes dem-p-PP2Ac in subcellular compartments. These findings offer new insight into the regulation of PME-1 localization and PP2A demethylation under oxidative stress.
      Title: Hydrogen peroxide redistributes the localization of protein phosphatase methylesterase 1.
    8. We demonstrate that NNMT outcompetes leucine carboxyl methyl transferase 1 (LCMT1) for methyl transfer from principal methyl donor SAM in biological systems. Inhibiting NNMT increased the availability of methyl groups for LCMT1 to methylate PP2A, resulting in the inhibition of oncogenic serine/threonine kinases (STK).
      Title: NNMT Silencing Activates Tumor Suppressor PP2A, Inactivates Oncogenic STKs, and Inhibits Tumor Forming Ability.
    9. Studies indicate that protein phosphatase methylesterase-1 (PME-1) negatively regulates protein phosphatase 2A (PP2A) activity by highly complex mechanisms.
      Title: Regulation of protein phosphatase 2A (PP2A) tumor suppressor function by PME-1.
    10. Data suggest that discovery of more potent protein phosphatase methylesterase-1 (PME-1) inhibitors may be beneficial for the treatment of endometrial cancer.
      Title: Inhibition of protein methylesterase 1 decreased cancerous phenotypes in endometrial adenocarcinoma cell lines and xenograft tumor models.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    Phenotypes

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    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

    Clone Names

    • FLJ22226

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cadherin binding HDA PubMed 
    enables lncRNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein C-terminal methylesterase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein C-terminal methylesterase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein C-terminal methylesterase activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein phosphatase 2A binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein phosphatase binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein phosphatase inhibitor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein phosphatase regulator activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in G2/M transition of mitotic cell cycle TAS
    Traceable Author Statement
    more info
    		  
    involved_in protein demethylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    protein phosphatase methylesterase 1
    Names
    testicular secretory protein Li 39
    NP_001258522.1
    NP_057231.1
    XP_016873402.1
    XP_047283072.1
    XP_054225084.1
    XP_054225085.1

    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_001271593.2 → NP_001258522.1  protein phosphatase methylesterase 1 isoform b

      See identical proteins and their annotated locations for NP_001258522.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site compared to variant 1. It encodes a longer protein (isoform b) compared to isoform a.
      Source sequence(s)
      AK225647, BC050705, DA824678
      Consensus CDS
      CCDS60891.1
      UniProtKB/Swiss-Prot
      Q9Y570
      Related
      ENSP00000381461.4, ENST00000398427.6
      Conserved Domains (1) summary
      COG0596
      Location:66 → 384
      MhpC; Pimeloyl-ACP methyl ester carboxylesterase [Coenzyme transport and metabolism, General function prediction only]

    2. NM_016147.3 → NP_057231.1  protein phosphatase methylesterase 1 isoform a

      See identical proteins and their annotated locations for NP_057231.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the shorter transcript and encodes the shorter isoform (a).
      Source sequence(s)
      AF157028, AK022725
      Consensus CDS
      CCDS44678.1
      UniProtKB/Swiss-Prot
      B3KMU6, B5MEE7, J3QT22, Q8WYG8, Q9NVT5, Q9UI18, Q9Y570
      UniProtKB/TrEMBL
      A0A140VK39
      Related
      ENSP00000329867.8, ENST00000328257.13
      Conserved Domains (1) summary
      COG0596
      Location:66 → 370
      MhpC; Pimeloyl-ACP methyl ester carboxylesterase [Coenzyme transport and metabolism, General function prediction only]

    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_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      74171289..74254703
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047427116.1 → XP_047283072.1  protein phosphatase methylesterase 1 isoform X1

    2. XM_017017913.3 → XP_016873402.1  protein phosphatase methylesterase 1 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      74100633..74184047
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054369109.1 → XP_054225084.1  protein phosphatase methylesterase 1 isoform X1

    2. XM_054369110.1 → XP_054225085.1  protein phosphatase methylesterase 1 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y570.3 GenPept UniProtKB/Swiss-Prot:Q9Y570

    Gene LinkOut

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