UniProtKB - O14495 (PLPP3_HUMAN)
Phospholipid phosphatase 3
PLPP3
Functioni
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).
By similarity4 PublicationsIndependently 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).
4 PublicationsCatalytic activityi
- EC:3.1.3.42 PublicationsThis reaction proceeds in the forward1 Publication direction.
- 1,2-dihexadecanoyl-sn-glycero-3-phosphate + H2O = 1,2-dihexadecanoyl-sn-glycerol + phosphate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1,2-di-(9Z-octadecenoyl)-sn-glycerol + phosphate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- (9Z)-octadecenoyl-sn-glycero-3-phosphate + H2O = (9Z-octadecenoyl)-glycerol + phosphate2 PublicationsThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- H2O + N-(9Z-octadecenoyl)-ethanolamine phosphate = N-(9Z-octadecenoyl) ethanolamine + phosphate1 PublicationThis reaction proceeds in the forward1 Publication direction.
Activity regulationi
Kineticsi
- KM=100 µM for 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate1 Publication
- KM=110 µM for (9Z)-octadecenoyl-sn-glycero-3-phosphate1 Publication
- KM=56 µM for N-oleoyl ethanolamine phosphatidic acid1 Publication
- Vmax=0.27 nmol/min/mg enzyme with 1,2-dihexadecanoyl-sn-glycero-3-phosphate as substrate1 Publication
- Vmax=0.46 nmol/min/mg enzyme with (9Z)-octadecenoyl-sn-glycero-3-phosphate as substrate1 Publication
- Vmax=0.36 nmol/min/mg enzyme with N-(octanoyl)-sphing-4-enine-1-phosphate as substrate1 Publication
- Vmax=0.24 nmol/min/mg enzyme with sphing-4-enine 1-phosphate as substrate1 Publication
- Vmax=13 nmol/min/mg enzyme with 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate as substrate1 Publication
- Vmax=15 nmol/min/mg enzyme with (9Z)-octadecenoyl-sn-glycero-3-phosphate as substrate1 Publication
- Vmax=29 nmol/min/mg enzyme with N-(9Z-octadecenoyl)-ethanolamine phosphate as substrate1 Publication
: phospholipid metabolism Pathwayi
This protein is involved in the pathway phospholipid metabolism, which is part of Lipid metabolism.3 PublicationsView all proteins of this organism that are known to be involved in the pathway phospholipid metabolism and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 199 | Proton donorsBy similarity | 1 | |
Active sitei | 251 | NucleophileBy similarity | 1 | |
Sitei | 255 | Stabilizes the active site histidine for nucleophilic attackBy similarity | 1 |
GO - Molecular functioni
- ceramide-1-phosphate phosphatase activity Source: UniProtKB
- integrin binding Source: UniProtKB
- lipid phosphatase activity Source: GO_Central
- phosphatidate phosphatase activity Source: UniProtKB
- sphingosine-1-phosphate phosphatase activity Source: UniProtKB
GO - Biological processi
- canonical Wnt signaling pathway Source: GO_Central
- canonical Wnt signaling pathway involved in positive regulation of cell-cell adhesion Source: BHF-UCL
- canonical Wnt signaling pathway involved in positive regulation of endothelial cell migration Source: BHF-UCL
- canonical Wnt signaling pathway involved in positive regulation of wound healing Source: BHF-UCL
- cell-cell adhesion mediated by integrin Source: UniProtKB
- ceramide metabolic process Source: UniProtKB
- homotypic cell-cell adhesion Source: BHF-UCL
- integrin-mediated signaling pathway Source: UniProtKB
- negative regulation of protein phosphorylation Source: BHF-UCL
- phospholipid dephosphorylation Source: UniProtKB
- phospholipid metabolic process Source: UniProtKB
- positive regulation of DNA-binding transcription factor activity Source: BHF-UCL
- protein stabilization Source: BHF-UCL
- regulation of Wnt signaling pathway Source: InterPro
- retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum Source: UniProtKB
- signal transduction Source: GO_Central
- sphingolipid biosynthetic process Source: Reactome
- sphingosine metabolic process Source: UniProtKB
Keywordsi
Molecular function | Hydrolase |
Biological process | Lipid metabolism |
Enzyme and pathway databases
BRENDAi | 3.1.3.4, 2681 |
PathwayCommonsi | O14495 |
Reactomei | R-HSA-1660661, Sphingolipid de novo biosynthesis |
SignaLinki | O14495 |
UniPathwayi | UPA00085 |
Chemistry databases
SwissLipidsi | SLP:000001642 |
Names & Taxonomyi
Protein namesi | Recommended name: Phospholipid phosphatase 3Curated (EC:3.1.3.-1 Publication, EC:3.1.3.42 Publications)Alternative name(s): Lipid phosphate phosphohydrolase 3 PAP2-beta Phosphatidate phosphohydrolase type 2b Phosphatidic acid phosphatase 2b Short name: PAP-2b Short name: PAP2b Vascular endothelial growth factor and type I collagen-inducible protein1 Publication Short name: VCIP1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:9229, PLPP3 |
MIMi | 607125, gene |
neXtProti | NX_O14495 |
VEuPathDBi | HostDB:ENSG00000162407 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein By similarity
Golgi apparatus
- Golgi apparatus membrane 1 Publication; Multi-pass membrane protein By similarity
- trans-Golgi network membrane 1 Publication; Multi-pass membrane protein By similarity
Plasma membrane
- Cell membrane 3 Publications; Multi-pass membrane protein By similarity
- Basolateral cell membrane 1 Publication; Multi-pass membrane protein By similarity
Other locations
- Endoplasmic reticulum-Golgi intermediate compartment membrane 1 Publication; Multi-pass membrane protein By similarity
- Membrane raft 1 Publication; Multi-pass membrane protein By similarity
Note: Cycles between the endoplasmic reticulum and the Golgi.1 Publication
Endoplasmic reticulum
- endoplasmic reticulum exit site Source: UniProtKB
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Golgi apparatus
- Golgi apparatus Source: UniProtKB
- Golgi membrane Source: UniProtKB-SubCell
- trans-Golgi network Source: UniProtKB
Plasma Membrane
- basolateral plasma membrane Source: UniProtKB
- integral component of plasma membrane Source: GO_Central
- plasma membrane Source: Reactome
Other locations
- adherens junction Source: BHF-UCL
- endoplasmic reticulum-Golgi intermediate compartment membrane Source: UniProtKB
- integral component of membrane Source: UniProtKB
- membrane Source: UniProtKB
- membrane raft Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 33 | Cytoplasmic1 PublicationAdd BLAST | 33 | |
Transmembranei | 34 – 54 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 55 – 85 | Extracellular1 PublicationAdd BLAST | 31 | |
Transmembranei | 86 – 106 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 107 – 122 | Cytoplasmic1 PublicationAdd BLAST | 16 | |
Transmembranei | 123 – 143 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 144 – 193 | Extracellular1 PublicationAdd BLAST | 50 | |
Transmembranei | 194 – 214 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 215 – 225 | Cytoplasmic1 PublicationAdd BLAST | 11 | |
Transmembranei | 226 – 243 | HelicalSequence analysisAdd BLAST | 18 | |
Topological domaini | 244 – 257 | Extracellular1 PublicationAdd BLAST | 14 | |
Transmembranei | 258 – 278 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 279 – 311 | Cytoplasmic1 PublicationAdd BLAST | 33 |
Keywords - Cellular componenti
Cell membrane, Endoplasmic reticulum, Golgi apparatus, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 106 | Y → A: No effect on basolateral localization in polarized cells. 1 Publication | 1 | |
Mutagenesisi | 109 | Y → A: Loss of basolateral localization in polarized cells. 1 Publication | 1 | |
Mutagenesisi | 110 | Y → A: Loss of basolateral localization in polarized cells. 1 Publication | 1 | |
Mutagenesisi | 184 | D → E: Loss of binding to integrin. Loss of function in integrin-mediated cell-cell interaction. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 8613 |
OpenTargetsi | ENSG00000162407 |
PharmGKBi | PA33553 |
Miscellaneous databases
Pharosi | O14495, Tbio |
Genetic variation databases
BioMutai | PLPP3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000220912 | 1 – 311 | Phospholipid phosphatase 3Add BLAST | 311 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 19 | PhosphoserineCombined sources | 1 | |
Glycosylationi | 170 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
EPDi | O14495 |
jPOSTi | O14495 |
MassIVEi | O14495 |
MaxQBi | O14495 |
PaxDbi | O14495 |
PeptideAtlasi | O14495 |
PRIDEi | O14495 |
ProteomicsDBi | 48039 |
PTM databases
DEPODi | PLPP3 |
GlyGeni | O14495, 1 site |
iPTMneti | O14495 |
PhosphoSitePlusi | O14495 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000162407, Expressed in metanephric glomerulus and 248 other tissues |
Genevisiblei | O14495, HS |
Organism-specific databases
HPAi | ENSG00000162407, Low tissue specificity |
Interactioni
Subunit structurei
Forms functional homodimers and homooligomers that are not required for substrate recognition and catalytic activity (PubMed:14725715). Can also form heterooligomers with other PLPP2 and PLPP3 (PubMed:18215144).
Interacts with CTNND1; negatively regulates the PLPP3-mediated stabilization of beta-catenin/CTNNB1 (PubMed:20123964).
3 PublicationsBinary interactionsi
O14495
With | #Exp. | IntAct |
---|---|---|
CTNND1 [O60716] | 9 | EBI-766232,EBI-701927 |
GO - Molecular functioni
- integrin binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 114171, 27 interactors |
CORUMi | O14495 |
IntActi | O14495, 5 interactors |
MINTi | O14495 |
STRINGi | 9606.ENSP00000360296 |
Miscellaneous databases
RNActi | O14495, protein |
Structurei
3D structure databases
AlphaFoldDBi | O14495 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 148 – 156 | Phosphatase sequence motif IBy similarity | 9 | |
Regioni | 196 – 199 | Phosphatase sequence motif IIBy similarity | 4 | |
Regioni | 244 – 255 | Phosphatase sequence motif IIIBy similarityAdd BLAST | 12 | |
Regioni | 275 – 311 | Mediates interaction with CTNND11 PublicationAdd BLAST | 37 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 109 – 110 | Dityrosine basolateral targeting motif1 Publication | 2 | |
Motifi | 182 – 184 | Integrin-binding motif2 Publications | 3 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3030, Eukaryota |
GeneTreei | ENSGT00940000156450 |
HOGENOMi | CLU_021458_3_0_1 |
InParanoidi | O14495 |
OMAi | KYPANSG |
OrthoDBi | 1621899at2759 |
PhylomeDBi | O14495 |
TreeFami | TF316040 |
Family and domain databases
InterProi | View protein in InterPro IPR028675, LPP3 IPR036938, P_Acid_Pase_2/haloperoxi_sf IPR000326, P_Acid_Pase_2/haloperoxidase IPR043216, PA_PP_rel |
PANTHERi | PTHR10165, PTHR10165, 1 hit PTHR10165:SF79, PTHR10165:SF79, 1 hit |
Pfami | View protein in Pfam PF01569, PAP2, 1 hit |
SMARTi | View protein in SMART SM00014, acidPPc, 1 hit |
SUPFAMi | SSF48317, SSF48317, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MQNYKYDKAI VPESKNGGSP ALNNNPRRSG SKRVLLICLD LFCLFMAGLP
60 70 80 90 100
FLIIETSTIK PYHRGFYCND ESIKYPLKTG ETINDAVLCA VGIVIAILAI
110 120 130 140 150
ITGEFYRIYY LKKSRSTIQN PYVAALYKQV GCFLFGCAIS QSFTDIAKVS
160 170 180 190 200
IGRLRPHFLS VCNPDFSQIN CSEGYIQNYR CRGDDSKVQE ARKSFFSGHA
210 220 230 240 250
SFSMYTMLYL VLYLQARFTW RGARLLRPLL QFTLIMMAFY TGLSRVSDHK
260 270 280 290 300
HHPSDVLAGF AQGALVACCI VFFVSDLFKT KTTLSLPAPA IRKEILSPVD
310
IIDRNNHHNM M
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 32 | K → M in AAV38396 (Ref. 7) Curated | 1 | |
Sequence conflicti | 282 | T → M in AAH09196 (PubMed:15489334).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB000889 mRNA Translation: BAA22594.1 AF017786 mRNA Translation: AAC63433.1 AF480883 mRNA Translation: AAO84481.1 AF043329 mRNA Translation: AAD02271.1 U79294 mRNA Translation: AAB50222.1 Frameshift. AK312439 mRNA Translation: BAG35348.1 BT019589 mRNA Translation: AAV38396.1 CH471059 Genomic DNA Translation: EAX06651.1 CH471059 Genomic DNA Translation: EAX06652.1 CH471059 Genomic DNA Translation: EAX06653.1 BC009196 mRNA Translation: AAH09196.1 |
CCDSi | CCDS604.1 |
RefSeqi | NP_003704.3, NM_003713.4 |
Genome annotation databases
Ensembli | ENST00000371250.4; ENSP00000360296.3; ENSG00000162407.9 |
GeneIDi | 8613 |
KEGGi | hsa:8613 |
MANE-Selecti | ENST00000371250.4; ENSP00000360296.3; NM_003713.5; NP_003704.3 |
UCSCi | uc001cyj.3, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB000889 mRNA Translation: BAA22594.1 AF017786 mRNA Translation: AAC63433.1 AF480883 mRNA Translation: AAO84481.1 AF043329 mRNA Translation: AAD02271.1 U79294 mRNA Translation: AAB50222.1 Frameshift. AK312439 mRNA Translation: BAG35348.1 BT019589 mRNA Translation: AAV38396.1 CH471059 Genomic DNA Translation: EAX06651.1 CH471059 Genomic DNA Translation: EAX06652.1 CH471059 Genomic DNA Translation: EAX06653.1 BC009196 mRNA Translation: AAH09196.1 |
CCDSi | CCDS604.1 |
RefSeqi | NP_003704.3, NM_003713.4 |
3D structure databases
AlphaFoldDBi | O14495 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 114171, 27 interactors |
CORUMi | O14495 |
IntActi | O14495, 5 interactors |
MINTi | O14495 |
STRINGi | 9606.ENSP00000360296 |
Chemistry databases
SwissLipidsi | SLP:000001642 |
PTM databases
DEPODi | PLPP3 |
GlyGeni | O14495, 1 site |
iPTMneti | O14495 |
PhosphoSitePlusi | O14495 |
Genetic variation databases
BioMutai | PLPP3 |
Proteomic databases
EPDi | O14495 |
jPOSTi | O14495 |
MassIVEi | O14495 |
MaxQBi | O14495 |
PaxDbi | O14495 |
PeptideAtlasi | O14495 |
PRIDEi | O14495 |
ProteomicsDBi | 48039 |
Protocols and materials databases
Antibodypediai | 33239, 134 antibodies from 25 providers |
DNASUi | 8613 |
Genome annotation databases
Ensembli | ENST00000371250.4; ENSP00000360296.3; ENSG00000162407.9 |
GeneIDi | 8613 |
KEGGi | hsa:8613 |
MANE-Selecti | ENST00000371250.4; ENSP00000360296.3; NM_003713.5; NP_003704.3 |
UCSCi | uc001cyj.3, human |
Organism-specific databases
CTDi | 8613 |
DisGeNETi | 8613 |
GeneCardsi | PLPP3 |
HGNCi | HGNC:9229, PLPP3 |
HPAi | ENSG00000162407, Low tissue specificity |
MIMi | 607125, gene |
neXtProti | NX_O14495 |
OpenTargetsi | ENSG00000162407 |
PharmGKBi | PA33553 |
VEuPathDBi | HostDB:ENSG00000162407 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3030, Eukaryota |
GeneTreei | ENSGT00940000156450 |
HOGENOMi | CLU_021458_3_0_1 |
InParanoidi | O14495 |
OMAi | KYPANSG |
OrthoDBi | 1621899at2759 |
PhylomeDBi | O14495 |
TreeFami | TF316040 |
Enzyme and pathway databases
UniPathwayi | UPA00085 |
BRENDAi | 3.1.3.4, 2681 |
PathwayCommonsi | O14495 |
Reactomei | R-HSA-1660661, Sphingolipid de novo biosynthesis |
SignaLinki | O14495 |
Miscellaneous databases
BioGRID-ORCSi | 8613, 6 hits in 1071 CRISPR screens |
ChiTaRSi | PLPP3, human |
GeneWikii | PPAP2B |
GenomeRNAii | 8613 |
Pharosi | O14495, Tbio |
PROi | PR:O14495 |
RNActi | O14495, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000162407, Expressed in metanephric glomerulus and 248 other tissues |
Genevisiblei | O14495, HS |
Family and domain databases
InterProi | View protein in InterPro IPR028675, LPP3 IPR036938, P_Acid_Pase_2/haloperoxi_sf IPR000326, P_Acid_Pase_2/haloperoxidase IPR043216, PA_PP_rel |
PANTHERi | PTHR10165, PTHR10165, 1 hit PTHR10165:SF79, PTHR10165:SF79, 1 hit |
Pfami | View protein in Pfam PF01569, PAP2, 1 hit |
SMARTi | View protein in SMART SM00014, acidPPc, 1 hit |
SUPFAMi | SSF48317, SSF48317, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PLPP3_HUMAN | |
Accessioni | O14495Primary (citable) accession number: O14495 Secondary accession number(s): B2R651 Q99782 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 15, 2004 |
Last sequence update: | January 1, 1998 | |
Last modified: | May 25, 2022 | |
This is version 180 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families