The protein encoded by this gene is a magnesium or manganese-requiring phosphatase that is involved in several signaling pathways. The encoded protein downregulates apoptosis signal-regulating kinase 1, a protein that initiates a signaling cascade that leads to apoptosis when cells are subjected to cytotoxic stresses. This protein also is an endoplasmic reticulum transmembrane ... See more...

Aliases for PPM1L Gene

Aliases for PPM1L Gene

  • Protein Phosphatase, Mg2+/Mn2+ Dependent 1L 2 3 5
  • PP2CE 2 3 4
  • Protein Phosphatase 2C Epsilon Isoform 2 3
  • Protein Phosphatase 2C Isoform Epsilon 3 4
  • Protein Phosphatase 1L 3 4
  • PP2C-Epsilon 3 4
  • EC 3.1.3.16 4 51
  • Protein Phosphatase, Mg2+/Mn2+ Dependent, 1L 2
  • Protein Phosphatase 1 (Formerly 2C)-Like 2
  • Protein Phosphatase 1-Like 4
  • PP2C Epsilon 3
  • PP2Cepsilon 2
  • PPM1-LIKE 3
  • EC 3.1.3 51
  • PPM1L 5

External Ids for PPM1L Gene

Previous GeneCards Identifiers for PPM1L Gene

  • GC03P161880
  • GC03P162042
  • GC03P160473
  • GC03P157872

Summaries for PPM1L Gene

Entrez Gene Summary for PPM1L Gene

  • The protein encoded by this gene is a magnesium or manganese-requiring phosphatase that is involved in several signaling pathways. The encoded protein downregulates apoptosis signal-regulating kinase 1, a protein that initiates a signaling cascade that leads to apoptosis when cells are subjected to cytotoxic stresses. This protein also is an endoplasmic reticulum transmembrane protein that helps regulate ceramide transport from the endoplasmic reticulum to the Golgi apparatus. Finally, this gene may be involved in adiposity since it is upregulated in adipose tissues. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

GeneCards Summary for PPM1L Gene

PPM1L (Protein Phosphatase, Mg2+/Mn2+ Dependent 1L) is a Protein Coding gene. Diseases associated with PPM1L include Inflammatory Bowel Disease 7 and Inflammatory Bowel Disease 4. Among its related pathways are Sphingolipid metabolism and Metabolism. Gene Ontology (GO) annotations related to this gene include protein serine/threonine phosphatase activity. An important paralog of this gene is PPM1K.

UniProtKB/Swiss-Prot Summary for PPM1L Gene

  • Acts as a suppressor of the SAPK signaling pathways by associating with and dephosphorylating MAP3K7/TAK1 and MAP3K5, and by attenuating the association between MAP3K7/TAK1 and MAP2K4 or MAP2K6.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PPM1L Gene

Genomics for PPM1L Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PPM1L Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03J160754 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 600.7 +1.1 1069 5.2 ZNF629 PRDM10 REST ZNF692 JUND PRDM1 ZNF143 ZNF776 ZIC2 ZSCAN4 ENSG00000260572 PPM1L SMC4 SPTSSB piR-38580-210 NMD3
GH03J160842 Promoter 0.3 EPDnew 600.2 +86.6 86598 0.1 PPM1L piR-38580-210 piR-45035-134 NMD3
GH03J160935 Enhancer 0.8 ENCODE 11.4 +180.0 180036 0.2 CEBPG GATAD2A REST ZHX2 SP1 CEBPA CEBPB CTBP1 RNF2 FOXA2 piR-45035-134 PPM1L ARL14 NMD3 piR-38580-210
GH03J160836 Enhancer 0.6 Ensembl ENCODE 10.6 +82.2 82169 3.8 RUNX3 ATF2 MYC MAX PPM1L SPTSSB PSMC1P7 piR-38580-210 piR-45035-134 NMD3
GH03J160929 Enhancer 0.5 Ensembl 11.2 +174.2 174169 0.6 ZNF341 CTCF ZNF444 ZNF189 NFIB RAD21 MAFK NFIA PPM1L B3GALNT1 NMD3 piR-45035-134 piR-38580-210
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PPM1L on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PPM1L

Top Transcription factor binding sites by QIAGEN in the PPM1L gene promoter:
  • aMEF-2
  • AP-1
  • ATF-2
  • c-Fos
  • c-Jun
  • CREB
  • MEF-2
  • MEF-2A

Genomic Locations for PPM1L Gene

Genomic Locations for PPM1L Gene
chr3:160,755,532-161,078,907
(GRCh38/hg38)
Size:
323,376 bases
Orientation:
Plus strand
chr3:160,473,390-160,796,695
(GRCh37/hg19)
Size:
323,306 bases
Orientation:
Plus strand

Genomic View for PPM1L Gene

Genes around PPM1L on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PPM1L Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PPM1L Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PPM1L Gene

Proteins for PPM1L Gene

  • Protein details for PPM1L Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q5SGD2-PPM1L_HUMAN
    Recommended name:
    Protein phosphatase 1L
    Protein Accession:
    Q5SGD2
    Secondary Accessions:
    • Q2M3J2
    • Q96NM7

    Protein attributes for PPM1L Gene

    Size:
    360 amino acids
    Molecular mass:
    41053 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Cofactor:
    Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
    Quaternary structure:
    • Interacts with MAP3K7/TAK1 (By similarity). Interacts with MAP3K5.

    Alternative splice isoforms for PPM1L Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PPM1L Gene

Selected DME Specific Peptides for PPM1L Gene

Q5SGD2:
  • LASDGLW
  • WRVQGILA
  • ANVGDSR

Post-translational modifications for PPM1L Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PPM1L Gene

Domains & Families for PPM1L Gene

Gene Families for PPM1L Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for PPM1L Gene

Suggested Antigen Peptide Sequences for PPM1L Gene

GenScript: Design optimal peptide antigens:
  • Protein phosphatase 2C isoform epsilon (PPM1L_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q5SGD2

UniProtKB/Swiss-Prot:

PPM1L_HUMAN :
  • Belongs to the PP2C family.
Family:
  • Belongs to the PP2C family.
genes like me logo Genes that share domains with PPM1L: view

Function for PPM1L Gene

Molecular function for PPM1L Gene

UniProtKB/Swiss-Prot Function:
Acts as a suppressor of the SAPK signaling pathways by associating with and dephosphorylating MAP3K7/TAK1 and MAP3K5, and by attenuating the association between MAP3K7/TAK1 and MAP2K4 or MAP2K6.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, ChEBI:CHEBI:83421; EC=3.1.3.16;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, ChEBI:CHEBI:61977; EC=3.1.3.16;.

Enzyme Numbers (IUBMB) for PPM1L Gene

Phenotypes From GWAS Catalog for PPM1L Gene

Gene Ontology (GO) - Molecular Function for PPM1L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0004721 phosphoprotein phosphatase activity IEA --
GO:0004722 protein serine/threonine phosphatase activity TAS --
GO:0004724 magnesium-dependent protein serine/threonine phosphatase activity IBA 21873635
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with PPM1L: view
genes like me logo Genes that share phenotypes with PPM1L: view

Animal Models for PPM1L Gene

MGI Knock Outs for PPM1L:

Animal Model Products

CRISPR Products

miRNA for PPM1L Gene

miRTarBase miRNAs that target PPM1L

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PPM1L

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PPM1L Gene

Localization for PPM1L Gene

Subcellular locations from UniProtKB/Swiss-Prot for PPM1L Gene

Membrane. Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PPM1L gene
Compartment Confidence
extracellular 4
endoplasmic reticulum 4
nucleus 3
cytosol 3
mitochondrion 2
golgi apparatus 2
plasma membrane 1
cytoskeleton 1
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PPM1L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005789 endoplasmic reticulum membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0070062 extracellular exosome HDA 19199708
genes like me logo Genes that share ontologies with PPM1L: view

Pathways & Interactions for PPM1L Gene

genes like me logo Genes that share pathways with PPM1L: view

Pathways by source for PPM1L Gene

1 BioSystems pathway for PPM1L Gene
2 GeneGo (Thomson Reuters) pathways for PPM1L Gene
  • Apoptosis and survival BAD phosphorylation
  • Regulation of CFTR activity (norm and CF)
1 R&D Systems pathway for PPM1L Gene
1 Qiagen pathway for PPM1L Gene
  • AMPK Enzyme Complex Pathway

SIGNOR curated interactions for PPM1L Gene

Inactivates:

Gene Ontology (GO) - Biological Process for PPM1L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IEA --
GO:0006470 protein dephosphorylation IEA --
GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway IEA --
GO:0030148 sphingolipid biosynthetic process TAS --
genes like me logo Genes that share ontologies with PPM1L: view

Drugs & Compounds for PPM1L Gene

(4) Drugs for PPM1L Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Magnesium Approved, Experimental, Investigational Pharma 0
Phosphoric acid Approved Pharma 0
Water Approved Pharma 0
Manganese Approved Nutra 56
genes like me logo Genes that share compounds with PPM1L: view

Transcripts for PPM1L Gene

mRNA/cDNA for PPM1L Gene

3 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PPM1L

Alternative Splicing Database (ASD) splice patterns (SP) for PPM1L Gene

No ASD Table

Relevant External Links for PPM1L Gene

GeneLoc Exon Structure for
PPM1L

Expression for PPM1L Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PPM1L Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PPM1L Gene

This gene is overexpressed in Muscle - Skeletal (x4.2).

Protein differential expression in normal tissues from HIPED for PPM1L Gene

This gene is overexpressed in Peripheral blood mononuclear cells (18.9), Frontal cortex (13.7), Liver (8.2), and Islet of Langerhans (7.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PPM1L Gene



Protein tissue co-expression partners for PPM1L Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PPM1L

SOURCE GeneReport for Unigene cluster for PPM1L Gene:

Hs.389027

mRNA Expression by UniProt/SwissProt for PPM1L Gene:

Q5SGD2-PPM1L_HUMAN
Tissue specificity: Ubiquitous. Highly expressed in heart, placenta, lung, liver, kidney and pancreas.

Evidence on tissue expression from TISSUES for PPM1L Gene

  • Nervous system(4.4)
genes like me logo Genes that share expression patterns with PPM1L: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for PPM1L Gene

Orthologs for PPM1L Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for PPM1L Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PPM1L 30 31
  • 99.54 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia PPM1L 31
  • 98 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia PPM1L 30 31
  • 95.19 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia PPM1L 30 31
  • 94.07 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Ppm1l 30 17 31
  • 91.2 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Ppm1l 30
  • 91.02 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia PPM1L 31
  • 83 (a)
OneToOne
Chicken
(Gallus gallus)
Aves PPM1L 30 31
  • 84.72 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia PPM1L 31
  • 97 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia ppm1l 30
  • 82.87 (n)
Str.16930 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.26315 30
Zebrafish
(Danio rerio)
Actinopterygii ppm1la 30 31
  • 77.75 (n)
OneToMany
ppm1lb 31
  • 70 (a)
OneToMany
Dr.7261 30
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.6639 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008536 30
  • 55.08 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta CG7115 30 31
  • 52.34 (n)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PTC1 31
  • 31 (a)
OneToMany
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AT5G24940 30
  • 50.28 (n)
Rice
(Oryza sativa)
Liliopsida Os06g0698300 30
  • 50.14 (n)
Species where no ortholog for PPM1L was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for PPM1L Gene

ENSEMBL:
Gene Tree for PPM1L (if available)
TreeFam:
Gene Tree for PPM1L (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PPM1L: view image

Paralogs for PPM1L Gene

genes like me logo Genes that share paralogs with PPM1L: view

Variants for PPM1L Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PPM1L Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
rs13326359 - p.Ala262Ser

Additional dbSNP identifiers (rs#s) for PPM1L Gene

Structural Variations from Database of Genomic Variants (DGV) for PPM1L Gene

Variant ID Type Subtype PubMed ID
dgv8662n54 CNV loss 21841781
esv1469152 CNV deletion 17803354
esv1495071 CNV insertion 17803354
esv2121069 CNV deletion 18987734
esv24553 CNV loss 19812545
esv2476287 CNV deletion 19546169
esv2519831 CNV deletion 19546169
esv2647987 CNV deletion 19546169
esv2657324 CNV deletion 23128226
esv2665188 CNV deletion 23128226
esv2672481 CNV deletion 23128226
esv2674643 CNV deletion 23128226
esv2726116 CNV deletion 23290073
esv2726118 CNV deletion 23290073
esv32963 CNV gain 17666407
esv3305379 CNV mobile element insertion 20981092
esv3430004 CNV insertion 20981092
esv3441804 CNV duplication 20981092
esv3562806 CNV deletion 23714750
esv3562807 CNV deletion 23714750
esv3562809 CNV deletion 23714750
esv3569081 CNV loss 25503493
esv3569082 CNV loss 25503493
esv3598389 CNV loss 21293372
esv3598390 CNV loss 21293372
esv3598395 CNV loss 21293372
esv3598396 CNV loss 21293372
esv3598397 CNV loss 21293372
esv3598398 CNV loss 21293372
esv994945 CNV deletion 20482838
nsv1007004 CNV loss 25217958
nsv1073691 CNV deletion 25765185
nsv1114444 CNV deletion 24896259
nsv477622 CNV novel sequence insertion 20440878
nsv507133 OTHER sequence alteration 20534489
nsv517658 CNV loss 19592680
nsv518915 CNV loss 19592680
nsv519474 CNV loss 19592680
nsv592128 CNV loss 21841781
nsv592129 CNV loss 21841781
nsv592135 CNV loss 21841781
nsv967245 CNV deletion 23825009
nsv979895 CNV duplication 23825009

Variation tolerance for PPM1L Gene

Residual Variation Intolerance Score: 32.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.30; 25.95% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PPM1L Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PPM1L

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PPM1L Gene

Disorders for PPM1L Gene

MalaCards: The human disease database

(6) MalaCards diseases for PPM1L Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search PPM1L in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PPM1L

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with PPM1L: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PPM1L Gene

Publications for PPM1L Gene

  1. Molecular cloning and characterization of a novel human protein phosphatase 2C cDNA (PP2C epsilon*). (PMID: 15560375) Jin F … Mao Y (Molecular biology reports 2004) 3 4 23
  2. Regulation of the interleukin-1-induced signaling pathways by a novel member of the protein phosphatase 2C family (PP2Cepsilon). (PMID: 12556533) Li MG … Tamura S (The Journal of biological chemistry 2003) 2 3 23
  3. Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis. (PMID: 22446961) Lee YC … Wu JY (Nature genetics 2012) 3 41
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41
  5. Protein phosphatase 2Cepsilon is an endoplasmic reticulum integral membrane protein that dephosphorylates the ceramide transport protein CERT to enhance its association with organelle membranes. (PMID: 18165232) Saito S … Kobayashi T (The Journal of biological chemistry 2008) 3 23

Products for PPM1L Gene

Sources for PPM1L Gene