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    PPM1E protein phosphatase, Mg2+/Mn2+ dependent 1E [ Homo sapiens (human) ]

    Gene ID: 22843, updated on 14-Nov-2024

    Summary

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    Official Symbol
    PPM1Eprovided by HGNC
    Official Full Name
    protein phosphatase, Mg2+/Mn2+ dependent 1Eprovided by HGNC
    Primary source
    HGNC:HGNC:19322
    See related
    Ensembl:ENSG00000175175 MIM:619308; AllianceGenome:HGNC:19322
    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
    POPX1; PP2CH; caMKN; CAMKPN; CaMKP-N
    Summary
    This gene encodes a member of the PPM family of serine/threonine-protein phosphatases. The encoded protein is localized to the nucleus and dephosphorylates and inactivates multiple substrates including serine/threonine-protein kinase PAK 1, 5'-AMP-activated protein kinase (AMPK) and the multifunctional calcium/calmodulin-dependent protein kinases. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]
    Expression
    Biased expression in brain (RPKM 6.5), testis (RPKM 3.8) and 3 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PPM1E in Genome Data Viewer
    Location:
    17q22
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (58755854..58985179)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (59623935..59853253)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (56833215..57062540)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene testis expressed 14, intercellular bridge forming factor Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12490 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12491 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:56777426-56777594 Neighboring gene MPRA-validated peak2919 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12492 Neighboring gene IGBP1 family member C Neighboring gene RNA, variant U1 small nuclear 34 Neighboring gene uncharacterized LOC105371843 Neighboring gene RAD51 paralog C Neighboring gene ReSE screen-validated silencer GRCh37_chr17:56833223-56833371 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8775 Neighboring gene RNA, U6 small nuclear 518, pseudogene Neighboring gene ribosomal protein S12 pseudogene 30 Neighboring gene MPRA-validated peak2922 silencer Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr17:57078614-57079813 Neighboring gene tripartite motif containing 37 Neighboring gene RNA, 7SL, cytoplasmic 716, pseudogene Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:57183329-57183988 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:57183989-57184648 Neighboring gene uncharacterized LOC124904039 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12499 Neighboring gene spindle and kinetochore associated complex subunit 2

    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. Reduced Expression Level of Protein Phosphatase PPM1E Serves to Maintain Insulin Secretion in Type 2 Diabetes. Gheibi S, et al. Diabetes, 2023 Apr 1. PMID 36662636
    2. Identification and characterization of nuclear localization signals of CaMKP-N. Takeuchi M, et al. J Biochem, 2004 Aug. PMID 15496589
    3. AMPKα phosphatase Ppm1E upregulation in human gastric cancer is required for cell proliferation. Chen MB, et al. Oncotarget, 2017 May 9. PMID 28423719, Free PMC Article
    4. Identification and characterization of CaMKP-N, nuclear calmodulin-dependent protein kinase phosphatase. Takeuchi M, et al. J Biochem, 2001 Dec. PMID 11726284
    5. microRNA-135b expression silences Ppm1e to provoke AMPK activation and inhibit osteoblastoma cell proliferation. Li ZW, et al. Oncotarget, 2017 Apr 18. PMID 28460435, Free PMC Article

    See all (31) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Reduced Expression Level of Protein Phosphatase PPM1E Serves to Maintain Insulin Secretion in Type 2 Diabetes.
      Title: Reduced Expression Level of Protein Phosphatase PPM1E Serves to Maintain Insulin Secretion in Type 2 Diabetes.
    2. Ppm1E upregulation in human gastric cancer is important for cell proliferation, possible via regulating AMPK-mTOR signaling.
      Title: AMPKα phosphatase Ppm1E upregulation in human gastric cancer is required for cell proliferation.
    3. miR-135b-5p expression downregulates Ppm1e to activate AMPK signaling, which inhibits LPS-induced TNFalpha production via suppressing ROS production and NFkappaB activation.
      Title: miR-135b-5p inhibits LPS-induced TNFα production via silencing AMPK phosphatase Ppm1e.
    4. our results suggest that miR-135b-induced Ppm1e silence induces AMPK activation to inhibit osteoblastoma cell proliferation.
      Title: microRNA-135b expression silences Ppm1e to provoke AMPK activation and inhibit osteoblastoma cell proliferation.
    5. Data show that miR-135b selectively targets the AMPK phosphatase Ppm1e.
      Title: miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone.
    6. The Ppm1E contributes to dephosphorylation of AMP-activated protein kinase.
      Title: Ppm1E is an in cellulo AMP-activated protein kinase phosphatase.
    7. The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family. (POPX1; POPX2)
      Title: The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family.
    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

    EBI GWAS Catalog

    Description
    Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham Study.
    EBI GWAS Catalog
    Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia.
    EBI GWAS Catalog
    Meta-analysis identifies four new loci associated with testicular germ cell tumor.
    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)

    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

    • KIAA1072, DKFZp781F1422

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables MAP kinase serine/threonine phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables RNA polymerase II CTD heptapeptide repeat T4 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables RNA polymerase II CTD heptapeptide repeat Y1 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calmodulin-dependent protein phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AXS140 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cellular response to lipopolysaccharide IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to xenobiotic stimulus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of protein kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in peptidyl-threonine dephosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of stress fiber assembly IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of stress fiber assembly IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    protein phosphatase 1E
    Names
    ca(2+)/calmodulin-dependent protein kinase phosphatase N
    caMKP-nucleus
    nuclear calmodulin-dependent protein kinase phosphatase
    partner of PIX 1
    partner of PIX-alpha
    partner of PIXA
    protein phosphatase 1E (PP2C domain containing)
    NP_055721.3
    XP_024306425.1
    XP_047291586.1
    XP_054171466.1
    XP_054171467.1

    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_014906.5 → NP_055721.3  protein phosphatase 1E

      See identical proteins and their annotated locations for NP_055721.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and is protein-coding.
      Source sequence(s)
      AC025521, AC100832, AK289966
      Consensus CDS
      CCDS11613.1
      UniProtKB/Swiss-Prot
      A7E2X1, Q68DW1, Q7LAF3, Q8WY54, Q9UPT0
      Related
      ENSP00000312411.2, ENST00000308249.4
      Conserved Domains (1) summary
      cd00143
      Location:230 → 488
      PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...

    RNA

    1. NR_048561.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an 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)
      AC100832, AK289966, BC143845

    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_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      58755854..58985179
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047435630.1 → XP_047291586.1  protein phosphatase 1E isoform X2

    2. XM_024450657.2 → XP_024306425.1  protein phosphatase 1E isoform X1

      Conserved Domains (1) summary
      cd00143
      Location:1 → 249
      PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      59623935..59853253
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054315492.1 → XP_054171467.1  protein phosphatase 1E isoform X2

    2. XM_054315491.1 → XP_054171466.1  protein phosphatase 1E isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8WY54.3 GenPept UniProtKB/Swiss-Prot:Q8WY54

    Gene LinkOut

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

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