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

Gene ID: 51400, updated on 5-Mar-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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Location:
11q13.4
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (74171289..74254703)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (74100633..74184047)
105.20220307 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
  • 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. PP2A methylesterase PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers. Aakula A, et al. Mol Oncol, 2023 Jun. PMID 36461911, Free PMC Article
  2. Hydrogen peroxide redistributes the localization of protein phosphatase methylesterase 1. Tang S, et al. Life Sci, 2018 Nov 15. PMID 30340029
  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. 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
  5. PME-1 is regulated by USP36 in ERK and Akt signaling pathways. Kim SY, et al. FEBS Lett, 2018 May. PMID 29577269

See all (63) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. LCMT1-PME-1 methylation equilibrium is critical for regulating mitotic spindle size and thereby proper cell division
    Title: A LCMT1-PME-1 methylation equilibrium controls mitotic spindle size.
Submit: New GeneRIF Correction See all GeneRIFs (17)

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

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 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 methylesterase activity IBA
Inferred from Biological aspect of Ancestor
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 IBA
Inferred from Biological aspect of Ancestor
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_2023_10

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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