PLPP3 phospholipid phosphatase 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PLPP3provided by HGNC
Official Full Name: phospholipid phosphatase 3provided by HGNC
Primary source: HGNC:HGNC:9229
See related: Ensembl:ENSG00000162407 MIM:607125; AllianceGenome:HGNC:9229
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: LPP3; VCIP; Dri42; PAP2B; PPAP2B
Summary: The protein encoded by this gene is a member of the phosphatidic acid phosphatase (PAP) family. PAPs convert phosphatidic acid to diacylglycerol, and function in de novo synthesis of glycerolipids as well as in receptor-activated signal transduction mediated by phospholipase D. This protein is a membrane glycoprotein localized at the cell plasma membrane. It has been shown to actively hydrolyze extracellular lysophosphatidic acid and short-chain phosphatidic acid. The expression of this gene is found to be enhanced by epidermal growth factor in Hela cells. [provided by RefSeq, Mar 2010]
Expression: Broad expression in thyroid (RPKM 205.6), placenta (RPKM 102.2) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p32.2

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (56494761..56579563, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (56373591..56458441, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (56960433..57045236, complement)

Chromosome 1 - NC_000001.11 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: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Lipid phosphate phosphatase 3 maintains NO-mediated flow-mediated dilatation in human adipose resistance arterioles.
Title: Lipid phosphate phosphatase 3 maintains NO-mediated flow-mediated dilatation in human adipose resistance arterioles.
Autotaxin-LPA-LPP3 Axis in Energy Metabolism and Metabolic Disease.
Title: Autotaxin-LPA-LPP3 Axis in Energy Metabolism and Metabolic Disease.
Roles for lysophosphatidic acid signaling in vascular development and disease.
Title: Roles for lysophosphatidic acid signaling in vascular development and disease.
Findings indicate that up-regulation of PLPP3 during inflammation and atherosclerosis results from canonical activation of the NF-kappaB signaling cascade to increase PLPP3 expression through nuclear import and binding of RelA and RelB transcription factors to the PLPP3 promoter and suggest a mechanism by which the LPP3 substrate, LPA, can regulate PLPP3 expression.
Title: Regulation of PLPP3 gene expression by NF-κB family transcription factors.
DNA methylation of a MIR-based enhancer downregulates the expression of PLPP3 and promotes the mineralization of the aortic valve in calcific aortic valve disease.
Title: DNA methylation of a PLPP3 MIR transposon-based enhancer promotes an osteogenic programme in calcific aortic valve disease.
ENPP2 was in silico discovered to be genetically altered in some patients with lung cancer, whereas increased autotaxin (ATX) staining and activity were detected in patients and mouse models, accompanied by a downregulation of PLPP3 expression. Most importantly, genetic deletion of Enpp2 or Lpar1 in mice resulted in disease attenuation, thus confirming a pro-carcinogenic role of ATX/LPA in the lung.
Title: The Autotaxin-Lysophosphatidic Acid Axis Promotes Lung Carcinogenesis.
LPP3 is the key enzyme in the breakdown of LPA by melanoma cells.
Title: LPP3 mediates self-generation of chemotactic LPA gradients by melanoma cells.
LPP3 is a negative regulator of inflammatory cytokines, leucocyte adhesion, cell survival, and migration in HAECs, suggesting a protective role of LPP3 against endothelial dysfunction.
Title: Role of lipid phosphate phosphatase 3 in human aortic endothelial cell function.
Data show gender-related differences in the association between phosphatidic acid phosphatase type 2B (PPAP2B) gene single nucleotide polymorphisms (SNPs) and coronary heart disease (CHD) susceptibility in the Chinese Han population.
Title: Association between PPAP2B gene polymorphisms and coronary heart disease susceptibility in Chinese Han males and females.
Mechanosensitive PPAP2B plays a critical role in promoting anti-inflammatory phenotype and maintaining vascular integrity of endothelial monolayer under atheroprotective flow.
Title: Mechanosensitive PPAP2B Regulates Endothelial Responses to Atherorelevant Hemodynamic Forces.

Submit: New GeneRIF Correction See all GeneRIFs (20)

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
A genome-wide association study in europeans and South asians identifies 5 new Loci for coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants. 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

G54098 (e-PCR)
- UniSTS:109335

SHGC-74887 (e-PCR)
- UniSTS:81951

SHGC-74867 (e-PCR)
- UniSTS:20777

D1S2091 (e-PCR)
- UniSTS:55900

G13351 (e-PCR)
- UniSTS:633

RH91798 (e-PCR)
- UniSTS:90247

SHGC-56634 (e-PCR)
- UniSTS:54416

D1S1566 (e-PCR)
- UniSTS:61594

A002U15 (e-PCR)
- UniSTS:60829

PPAP2B (e-PCR)
- UniSTS:503204

D1S2089 (e-PCR)
- UniSTS:33190

RH93360 (e-PCR)
- UniSTS:88795

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ceramide-1-phosphate phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables integrin binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidate phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables phosphatidate phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sphingosine-1-phosphate phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables sphingosine-1-phosphate phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables sphingosine-1-phosphate phosphatase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in Bergmann glial cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in blood vessel development	IEA Inferred from Electronic Annotation more info
involved_in cell-cell adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell adhesion mediated by integrin	IDA Inferred from Direct Assay more info	PubMed
involved_in ceramide metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in gastrulation with mouth forming second	IEA Inferred from Electronic Annotation more info
involved_in homotypic cell-cell adhesion	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of integrin-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in phospholipid dephosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in phospholipid dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in phospholipid metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in phospholipid metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in phospholipid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell-cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of peptidyl-tyrosine phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in protein stabilization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in regulation of sphingolipid mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in sphingolipid catabolic process	TAS Traceable Author Statement more info
involved_in sphingosine metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in wound healing	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi membrane	IEA Inferred from Electronic Annotation more info
located_in adherens junction	TAS Traceable Author Statement more info	PubMed
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum exit site	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum-Golgi intermediate compartment membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane raft	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in trans-Golgi network	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: phospholipid phosphatase 3

Names: PAP2 beta; lipid phosphate phosphohydrolase 3; phosphatidate phosphohydrolase type 2b; phosphatidic acid phosphatase type 2B; type-2 phosphatidic acid phosphatase-beta; vascular endothelial growth factor and type I collagen inducible

NP_003704.3

EC 3.1.3.4

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_003713.5 → NP_003704.3 phospholipid phosphatase 3

See identical proteins and their annotated locations for NP_003704.3

Status: REVIEWED

Source sequence(s)

AC099562, AF043329, BQ027458, DA580891

Consensus CDS

CCDS604.1

UniProtKB/Swiss-Prot

B2R651, D3DQ52, O14495, Q5U0F7, Q96GW0, Q99782

Related

ENSP00000360296.3, ENST00000371250.4

Conserved Domains (1) summary

cd03384
Location:125 → 271

PAP2_wunen; PAP2, wunen subfamily. Most likely a family of membrane associated phosphatidic acid phosphatases. Wunen is a drosophila protein expressed in the central nervous system, which provides repellent activity towards primordial germ cells (PGCs), controls the ...

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_000001.11 Reference GRCh38.p14 Primary Assembly

Range

56494761..56579563 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

56373591..56458441 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_177414.1: Suppressed sequence

Description

NM_177414.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript, which aligns to the reference assembly with non-consensus splice sites for the intron in the 5' UTR.