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PPM1L protein phosphatase, Mg2+/Mn2+ dependent 1L [ Homo sapiens (human) ]

Gene ID: 151742, updated on 11-Apr-2024

Summary

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Official Symbol
PPM1Lprovided by HGNC
Official Full Name
protein phosphatase, Mg2+/Mn2+ dependent 1Lprovided by HGNC
Primary source
HGNC:HGNC:16381
See related
Ensembl:ENSG00000163590 MIM:611931; AllianceGenome:HGNC:16381
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
PP2CE; PPM1-LIKE; PP2C-epsilon
Summary
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]
Expression
Ubiquitous expression in brain (RPKM 9.7), thyroid (RPKM 6.9) and 24 other tissues See more
Orthologs
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Genomic context

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Location:
3q25.33-q26.1
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (160756231..161078902)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (163530851..163853639)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (160474019..160796690)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene small nucleolar RNA SNORA72 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20762 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20763 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14858 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14859 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14860 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14861 Neighboring gene PPM1L divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20764 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20765 Neighboring gene Sharpr-MPRA regulatory region 1323 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14862 Neighboring gene MPRA-validated peak4889 silencer Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:160701588-160702158 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20766 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20767 Neighboring gene uncharacterized LOC124909453 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14863 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14864 Neighboring gene beta-1,3-N-acetylgalactosaminyltransferase 1 (Globoside blood group) Neighboring gene uncharacterized LOC124906300 Neighboring gene uncharacterized LOC105374186

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. Adiposity Alters Genes Important in Inflammation and Cell Cycle Division in Human Cumulus Granulosa Cell. Merhi Z, et al. Reprod Sci, 2015 Oct. PMID 25676576, Free PMC Article
  2. Dynamically regulated miRNA-mRNA networks revealed by exercise. Tonevitsky AG, et al. BMC Physiol, 2013 Jun 7. PMID 24219008, Free PMC Article
  3. Genome-wide scan identifies a copy number variable region at 3q26 that regulates PPM1L in APC mutation-negative familial colorectal cancer patients. Thean LF, et al. Genes Chromosomes Cancer, 2010 Feb. PMID 19847890
  4. Molecular cloning and characterization of a novel human protein phosphatase 2C cDNA (PP2C epsilon*). Jin F, et al. Mol Biol Rep, 2004 Sep. PMID 15560375
  5. PPM1l encodes an inositol requiring-protein 1 (IRE1) specific phosphatase that regulates the functional outcome of the ER stress response. Lu G, et al. Mol Metab, 2013. PMID 24327956, Free PMC Article

See all (22) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. identified ACBD3 as an interacting partner of PPM1L, and showed that this association, which recruits PPM1L to ER-Golgi membrane contact sites, is mediated by a GOLD (Golgi dynamics) domain in ACBD3
    Title: Acyl-CoA binding domain containing 3 (ACBD3) recruits the protein phosphatase PPM1L to ER-Golgi membrane contact sites.
  2. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
  3. Genetic variation at chromosome 3 harbors an element that regulates expression of an upstream candidate tumor suppressor, PPM1L, thus providing a novel mechanism for colorectal tumorigenesis.
    Title: Genome-wide scan identifies a copy number variable region at 3q26 that regulates PPM1L in APC mutation-negative familial colorectal cancer patients.
  4. CERT is a physiological substrate of PP2Cepsilon and that dephosphorylation of CERT by PP2Cepsilon may play an important role in the regulation of ceramide trafficking from the ER to the Golgi apparatus.
    Title: Protein phosphatase 2Cepsilon is an endoplasmic reticulum integral membrane protein that dephosphorylates the ceramide transport protein CERT to enhance its association with organelle membranes.
  5. cloning and characterization of a novel human protein phosphatase 2C cDNA (PP2C epsilon*)
    Title: Molecular cloning and characterization of a novel human protein phosphatase 2C cDNA (PP2C epsilon*).
  6. These results suggest that PP2Cepsilon maintains ASK1 in an inactive state by dephosphorylation in quiescent cells, supporting the possibility that PP2Cepsilon and PP5 play different roles in H2O2-induced regulation of ASK1 activity.
    Title: Regulation of apoptosis signal-regulating kinase 1 by protein phosphatase 2Cepsilon.
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
Genome-wide analysis of methotrexate pharmacogenomics in rheumatoid arthritis shows multiple novel risk variants and leads for TYMS regulation.
EBI GWAS Catalog
Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis.
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)

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

  • MGC132545, MGC132547

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 serine/threonine phosphatase activity TAS
Traceable Author Statement
more info
  
Process Evidence Code Pubs
involved_in MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in cell surface receptor protein serine/threonine kinase signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in protein dephosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in sphingolipid biosynthetic process TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 

General protein information

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Preferred Names
protein phosphatase 1L
Names
PP2C epsilon
NP_001304840.1
NP_001304841.1
NP_640338.2
XP_011510742.1
XP_054201313.1

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_001317911.2 → NP_001304840.1  protein phosphatase 1L isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate first exon in place of that of variant 1. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AC021649, AC117413, AK055115, AW274846, BC104885
    Consensus CDS
    CCDS82868.1
    UniProtKB/Swiss-Prot
    Q5SGD2
    Related
    ENSP00000295839.9, ENST00000295839.9
    Conserved Domains (1) summary
    cd00143
    Location:8 → 224
    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 ...

  2. NM_001317912.2 → NP_001304841.1  protein phosphatase 1L isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses two alternate exons in place of the first exon compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1.
    Source sequence(s)
    AC021649, AC117413, AK055115, AW274846
    Consensus CDS
    CCDS82869.1
    UniProtKB/Swiss-Prot
    Q5SGD2
    Related
    ENSP00000420746.1, ENST00000464260.5
    Conserved Domains (1) summary
    cd00143
    Location:12 → 172
    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 ...

  3. NM_139245.4 → NP_640338.2  protein phosphatase 1L isoform 1

    See identical proteins and their annotated locations for NP_640338.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AC021649, AW274846, AY337264
    Consensus CDS
    CCDS33886.1
    UniProtKB/Swiss-Prot
    Q2M3J2, Q5SGD2, Q96NM7
    Related
    ENSP00000417659.1, ENST00000498165.6
    Conserved Domains (1) summary
    cd00143
    Location:93 → 351
    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_134243.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses two alternate exons in place of the first exon and contains an alternate 3' exon compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
    Source sequence(s)
    AC021649, AW274846, BC090872

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_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    160756231..161078902
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011512440.4 → XP_011510742.1  protein phosphatase 1L isoform X1

    Conserved Domains (1) summary
    cl00120
    Location:93 → 192
    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_060927.1 Alternate T2T-CHM13v2.0

    Range
    163530851..163853639
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054345338.1 → XP_054201313.1  protein phosphatase 1L isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q5SGD2.1 GenPept UniProtKB/Swiss-Prot:Q5SGD2

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