PLPP3 (phospholipid phosphatase 3)

Gene

• Entrez ID: 8613
• Gene name: Phospholipid phosphatase 3
• Gene symbol: PLPP3
• Synonyms: Dri42, LPP3, PAP2B, PPAP2B, VCIP
• Chromosome: 1
• Chromosome location: 1p32.2
• 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]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017904	hsa-miR-335-5p	Microarray	18185580
MIRT022602	hsa-miR-124-3p	Microarray	18668037
MIRT025737	hsa-miR-7-5p	Microarray	19073608
MIRT027643	hsa-miR-98-5p	Microarray	19088304
MIRT542762	hsa-miR-4446-5p	PAR-CLIP	21572407
MIRT542763	hsa-miR-5006-3p	PAR-CLIP	21572407
MIRT542764	hsa-miR-4755-5p	PAR-CLIP	21572407
MIRT542765	hsa-miR-620	PAR-CLIP	21572407
MIRT542766	hsa-miR-1270	PAR-CLIP	21572407
MIRT542767	hsa-miR-4531	PAR-CLIP	21572407
MIRT542768	hsa-miR-6883-3p	PAR-CLIP	21572407
MIRT542769	hsa-miR-5192	PAR-CLIP	21572407
MIRT542770	hsa-miR-5186	PAR-CLIP	21572407
MIRT542771	hsa-miR-3120-5p	PAR-CLIP	21572407
MIRT542772	hsa-miR-4502	PAR-CLIP	21572407
MIRT542773	hsa-miR-3162-3p	PAR-CLIP	21572407
MIRT542774	hsa-miR-181b-5p	PAR-CLIP	21572407
MIRT542775	hsa-miR-181d-5p	PAR-CLIP	21572407
MIRT542776	hsa-miR-181c-5p	PAR-CLIP	21572407
MIRT542777	hsa-miR-181a-5p	PAR-CLIP	21572407
MIRT542778	hsa-miR-4262	PAR-CLIP	21572407
MIRT542779	hsa-miR-185-5p	PAR-CLIP	21572407
MIRT542780	hsa-miR-4306	PAR-CLIP	21572407
MIRT542781	hsa-miR-4644	PAR-CLIP	21572407
MIRT555428	hsa-miR-451b	PAR-CLIP	21572407
MIRT555429	hsa-miR-2278	PAR-CLIP	21572407
MIRT555430	hsa-miR-4511	PAR-CLIP	21572407
MIRT555431	hsa-miR-15a-5p	PAR-CLIP	21572407
MIRT555432	hsa-miR-424-5p	PAR-CLIP	21572407
MIRT555433	hsa-miR-15b-5p	PAR-CLIP	21572407
MIRT555434	hsa-miR-16-5p	PAR-CLIP	21572407
MIRT555435	hsa-miR-497-5p	PAR-CLIP	21572407
MIRT555436	hsa-miR-6838-5p	PAR-CLIP	21572407
MIRT555437	hsa-miR-195-5p	PAR-CLIP	21572407
MIRT622632	hsa-miR-6833-3p	HITS-CLIP	23824327
MIRT622633	hsa-miR-4768-5p	HITS-CLIP	23824327
MIRT622634	hsa-miR-6873-3p	HITS-CLIP	23824327
MIRT622635	hsa-miR-6817-3p	HITS-CLIP	23824327
MIRT622636	hsa-miR-7110-3p	HITS-CLIP	23824327
MIRT622637	hsa-miR-6845-3p	HITS-CLIP	23824327
MIRT622638	hsa-miR-138-2-3p	HITS-CLIP	23824327
MIRT627834	hsa-miR-6809-3p	HITS-CLIP	23824327
MIRT632563	hsa-miR-6827-3p	HITS-CLIP	23824327
MIRT632564	hsa-miR-340-3p	HITS-CLIP	23824327
MIRT678349	hsa-miR-4279	HITS-CLIP	23824327
MIRT678350	hsa-miR-365b-5p	HITS-CLIP	23824327
MIRT678351	hsa-miR-365a-5p	HITS-CLIP	23824327
MIRT678352	hsa-miR-8052	HITS-CLIP	23824327
MIRT678353	hsa-miR-3199	HITS-CLIP	23824327
MIRT678354	hsa-miR-6789-3p	HITS-CLIP	23824327
MIRT678355	hsa-miR-6778-3p	HITS-CLIP	23824327
MIRT678356	hsa-miR-1976	HITS-CLIP	23824327
MIRT678357	hsa-miR-3653-5p	HITS-CLIP	23824327
MIRT678358	hsa-miR-150-5p	HITS-CLIP	23824327
MIRT678359	hsa-miR-6747-3p	HITS-CLIP	23824327
MIRT678360	hsa-miR-6727-3p	HITS-CLIP	23824327
MIRT678361	hsa-miR-4722-3p	HITS-CLIP	23824327
MIRT678362	hsa-miR-6814-5p	HITS-CLIP	23824327
MIRT678363	hsa-miR-5697	HITS-CLIP	23824327
MIRT678364	hsa-miR-1295b-3p	HITS-CLIP	23824327
MIRT678365	hsa-miR-625-3p	HITS-CLIP	23824327
MIRT678366	hsa-miR-562	HITS-CLIP	23824327
MIRT700681	hsa-miR-4532	HITS-CLIP	23313552
MIRT700682	hsa-miR-1247-3p	HITS-CLIP	23313552
MIRT700683	hsa-miR-6887-3p	HITS-CLIP	23313552
MIRT700684	hsa-miR-122-3p	HITS-CLIP	23313552
MIRT732747	hsa-miR-184	Immunoblot, Luciferase reporter assay, qRT-PCR	27825105

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	IEA
GO:0001933	Process	Negative regulation of protein phosphorylation	IDA	20123964
GO:0005178	Function	Integrin binding	IDA	12660161
GO:0005515	Function	Protein binding	IPI	20123964
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005794	Component	Golgi apparatus	IDA	23591818
GO:0005802	Component	Trans-Golgi network	IDA	23591818
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0005912	Component	Adherens junction	TAS	20123964
GO:0006644	Process	Phospholipid metabolic process	IBA	21873635
GO:0006644	Process	Phospholipid metabolic process	IDA	9305923, 9705349
GO:0006644	Process	Phospholipid metabolic process	IEA
GO:0006670	Process	Sphingosine metabolic process	IDA	9305923, 9705349
GO:0006672	Process	Ceramide metabolic process	IDA	9305923, 9705349
GO:0006890	Process	Retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	IMP	23591818
GO:0007165	Process	Signal transduction	IBA	21873635
GO:0007229	Process	Integrin-mediated signaling pathway	IDA	12660161
GO:0008195	Function	Phosphatidate phosphatase activity	IBA	21873635
GO:0008195	Function	Phosphatidate phosphatase activity	IDA	9305923, 9705349
GO:0016020	Component	Membrane	IDA	9305923
GO:0016021	Component	Integral component of membrane	IDA	9705349
GO:0016323	Component	Basolateral plasma membrane	IDA	14527693
GO:0030111	Process	Regulation of Wnt signaling pathway	IEA
GO:0030148	Process	Sphingolipid biosynthetic process	TAS
GO:0033116	Component	Endoplasmic reticulum-Golgi intermediate compartment membrane	IDA	23591818
GO:0033631	Process	Cell-cell adhesion mediated by integrin	IDA	12660161
GO:0034109	Process	Homotypic cell-cell adhesion	IDA	20123964
GO:0042392	Function	Sphingosine-1-phosphate phosphatase activity	IBA	21873635
GO:0042392	Function	Sphingosine-1-phosphate phosphatase activity	IDA	9305923, 9705349
GO:0042577	Function	Lipid phosphatase activity	IBA	21873635
GO:0044328	Process	Canonical Wnt signaling pathway involved in positive regulation of endothelial cell migration	IMP	20123964
GO:0044329	Process	Canonical Wnt signaling pathway involved in positive regulation of cell-cell adhesion	IMP	20123964
GO:0044330	Process	Canonical Wnt signaling pathway involved in positive regulation of wound healing	IMP	20123964
GO:0045121	Component	Membrane raft	IDA	17005594
GO:0046839	Process	Phospholipid dephosphorylation	IBA	21873635
GO:0046839	Process	Phospholipid dephosphorylation	IDA	9305923, 9705349
GO:0050821	Process	Protein stabilization	IDA	20123964
GO:0051091	Process	Positive regulation of DNA-binding transcription factor activity	IDA	20123964
GO:0060070	Process	Canonical Wnt signaling pathway	IBA	21873635
GO:0070971	Component	Endoplasmic reticulum exit site	IDA	23591818
GO:0106235	Function	Ceramide-1-phosphate phosphatase activity	IDA	9705349

Other IDs

• MIM: 607125
• HGNC: 9229
• e!Ensembl: ENSG00000162407

Protein

• UniProt ID: O14495
• Protein name: Phospholipid phosphatase 3 (EC 3.1.3.-) (EC 3.1.3.4) (Lipid phosphate phosphohydrolase 3) (PAP2-beta) (Phosphatidate phosphohydrolase type 2b) (Phosphatidic acid phosphatase 2b) (PAP-2b) (PAP2b) (Vascular endothelial growth factor and type I collagen-inducible protein) (VCIP)
• Protein function: Magnesium-independent phospholipid phosphatase of the plasma membrane that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, diacylglycerol pyrophosphate/DGPP, sphingosine 1-phosphate/S1P and ceramide 1-phosphate/C1P (PubMed:9705349, PubMed:9607309, PubMed:27694435). Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential physiological compound (PubMed:9607309). Has both an extracellular and an intracellular phosphatase activity, allowing the hydrolysis and the cellular uptake of these bioactive lipid mediators from the milieu, regulating signal transduction in different cellular processes (PubMed:9607309, PubMed:23591818, PubMed:27694435). Through the dephosphorylation of extracellular sphingosine-1-phosphate and the regulation of its extra- and intracellular availability, plays a role in vascular homeostasis, regulating endothelial cell migration, adhesion, survival, proliferation and the production of pro-inflammatory cytokines (PubMed:27694435). By maintaining the appropriate levels of this lipid in the cerebellum, also ensure its proper development and function (By similarity). Through its intracellular lipid phosphatase activity may act in early compartments of the secretory pathway, regulating the formation of Golgi to endoplasmic reticulum retrograde transport carriers (PubMed:23591818). ; Independently of this phosphatase activity may also function in the Wnt signaling pathway and the stabilization of beta-catenin/CTNNB1, thereby regulating cell proliferation, migration and differentiation in angiogenesis or yet in tumor growth (PubMed:20123964, PubMed:21569306). Also plays a role in integrin-mediated cell-cell adhesion in angiogenesis (PubMed:12660161, PubMed:16099422).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01569	PAP2	129 → 279	PAP2 superfamily	Family

• Sequence:

  MQNYKYDKAIVPESKNGGSPALNNNPRRSGSKRVLLICLDLFCLFMAGLPFLIIETSTIK
  PYHRGFYCNDESIKYPLKTGETINDAVLCAVGIVIAILAIITGEFYRIYYLKKSRSTIQN
  PYVAALYKQVGCFLFGCAISQSFTDIAKVSIGRLRPHFLSVCNPDFSQINCSEGYIQNYR
  CRGDDSKVQEARKSFFSGHASFSMYTMLYLVLYLQARFTWRGARLLRPLLQFTLIMMAFY
  TGLSRVSDHKHHPSDVLAGFAQGALVACCIVFFVSDLFKTKTTLSLPAPAIRKEILSPVD
  IIDRNNHHNMM

• Sequence length: 311

Pathways

KEGG:

Glycerolipid metabolism
Glycerophospholipid metabolism
Ether lipid metabolism
Sphingolipid metabolism
Metabolic pathways
Phospholipase D signaling pathway
Fc gamma R-mediated phagocytosis
Fat digestion and absorption
Choline metabolism in cancer

Reactome:

Sphingolipid de novo biosynthesis

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Coronary artery disease	CORONARY ARTERY DISEASE, AUTOSOMAL DOMINANT, 1, Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	23202125, 24262325, 30104761, 29212778, 21378990, 26343387, 28714975
Coronary heart disease	Coronary heart disease	rs-1	21846871, 21378990, 21378988, 24262325
Myocardial infarction	Myocardial Infarction	rs12316150, rs41303970, rs909253, rs7291467, rs2234693	26343387

Unknown
Disease name	Disease term	dbSNP ID	References
Cardiovascular diseases	Cardiovascular Diseases		30595370
Coronary arteriosclerosis	Coronary Arteriosclerosis		21378990
Stroke	Cerebrovascular accident		24262325