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

Summary

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: mouse all
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Genomic context

Location:: 3q25.33-q26.1

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (160756231..161078902)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (163530851..163853639)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (160474019..160796690)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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*).
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.

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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 EBI GWAS CatalogPubMed
Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-142611 (e-PCR)
- UniSTS:171548

SHGC-81842 (e-PCR)
- UniSTS:103973

D3S3059 (e-PCR)
- UniSTS:4151

SHGC-111719 (e-PCR)
- UniSTS:168507

NoName (e-PCR)
- UniSTS:489023

D3S1543 (e-PCR)
- UniSTS:33364

SHGC-104992 (e-PCR)
- UniSTS:169045

SHGC-149038 (e-PCR)
- UniSTS:176757

G59303 (e-PCR)
- UniSTS:136618

SHGC-77498 (e-PCR)
- UniSTS:67764

D3S3579 (e-PCR), detects polymorphism
- UniSTS:62391

SHGC-78794 (e-PCR)
- UniSTS:95683

SHGC-78467 (e-PCR)
- UniSTS:183786

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 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 chromatin remodeling	IEA Inferred from Electronic Annotation more info
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
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 more info	PubMed

General protein information

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Preferred Names: protein phosphatase 1L

Names: PP2C epsilon

NP_001304840.1

EC 3.1.3.16

NP_001304841.1

EC 3.1.3.16

NP_640338.2

EC 3.1.3.16

XP_011510742.1

EC 3.1.3.16

XP_054201313.1

EC 3.1.3.16

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)

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 ...
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 ...
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

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_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

160756231..161078902

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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 ...