UniProtKB - O14494 (PLPP1_HUMAN)
Protein
Phospholipid phosphatase 1
Gene
PLPP1
Organism
Homo sapiens (Human)
Status
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:9305923, PubMed:9705349, PubMed:9607309, PubMed:10962286, PubMed:17379599). Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential physiological compound (PubMed:9607309). Through its extracellular phosphatase activity allows both the hydrolysis and the cellular uptake of these bioactive lipid mediators from the milieu, regulating signal transduction in different cellular processes (PubMed:10962286, PubMed:12909631, PubMed:15461590, PubMed:17379599). It is for instance essential for the extracellular hydrolysis of S1P and subsequent conversion into intracellular S1P (PubMed:17379599). Involved in the regulation of inflammation, platelets activation, cell proliferation and migration among other processes (PubMed:12909631, PubMed:15461590). May also have an intracellular activity to regulate phospholipid-mediated signaling pathways (By similarity).By similarity7 Publications
Caution
Some reports could not detect a significant activity with sphingosine 1-phosphate as substrate.1 Publication
Catalytic activityi
- EC:3.1.3.44 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 + phosphate2 PublicationsThis 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 + phosphate3 PublicationsThis reaction proceeds in the forward1 Publication direction.
- EC:3.1.3.106By similarityThis reaction proceeds in the forwardBy similarity direction.
- 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z-octadecenoyl)-sn-glycerol + phosphateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- a 1,2-diacyl-sn-glycerol 3-diphosphate + H2O = a 1,2-diacyl-sn-glycero-3-phosphate + H+ + phosphateBy similarityEC:3.1.3.81By similarityThis reaction proceeds in the forwardBy similarity 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.
- 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + phosphateBy similarityThis reaction proceeds in the forwardBy similarity direction.
Activity regulationi
Magnesium-independent phospholipid phosphatase (PubMed:9305923). Insensitive to N-ethylmaleimide (PubMed:9305923). Inhibited by sphingosine, zinc ions and modestly by propanolol (PubMed:9305923, PubMed:9705349). Inhibited by vanadate (PubMed:10962286).3 Publications
Kineticsi
- KM=98 µM for 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate1 Publication
- KM=170 µM for (9Z)-octadecenoyl-sn-glycero-3-phosphate1 Publication
- KM=116 µM for N-(9Z-octadecenoyl)-ethanolamine phosphate1 Publication
- Vmax=0.54 nmol/min/mg enzyme with 1,2-dihexadecanoyl-sn-glycero-3-phosphate as substrate1 Publication
- Vmax=0.50 nmol/min/mg enzyme with (9Z)-octadecenoyl-sn-glycero-3-phosphate as substrate1 Publication
- Vmax=0.30 nmol/min/mg enzyme with N-(octanoyl)-sphing-4-enine-1-phosphate as substrate1 Publication
- Vmax=0.32 nmol/min/mg enzyme with sphing-4-enine 1-phosphate as substrate1 Publication
- Vmax=41 nmol/min/mg enzyme with 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate as substrate1 Publication
- Vmax=33 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.4 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 | 171 | Proton donorsBy similarity | 1 | |
Active sitei | 223 | NucleophileBy similarity | 1 | |
Sitei | 227 | Stabilizes the active site histidine for nucleophilic attackBy similarity | 1 |
GO - Molecular functioni
- ceramide-1-phosphate phosphatase activity Source: UniProtKB
- diacylglycerol diphosphate phosphatase activity Source: UniProtKB
- lipid phosphatase activity Source: UniProtKB
- phosphatidate phosphatase activity Source: UniProtKB
- sphingosine-1-phosphate phosphatase activity Source: UniProtKB
GO - Biological processi
- androgen receptor signaling pathway Source: UniProtKB
- ceramide metabolic process Source: UniProtKB
- intracellular steroid hormone receptor signaling pathway Source: UniProtKB
- negative regulation of cell population proliferation Source: UniProtKB
- phospholipid dephosphorylation Source: UniProtKB
- phospholipid metabolic process Source: UniProtKB
- protein kinase C-activating G protein-coupled receptor signaling pathway Source: UniProtKB
- regulation of lipid metabolic process Source: UniProtKB
- signal transduction Source: UniProtKB
- sphingolipid biosynthetic process Source: Reactome
- sphingosine metabolic process Source: UniProtKB
Keywordsi
Molecular function | Hydrolase |
Biological process | Lipid metabolism |
Enzyme and pathway databases
PathwayCommonsi | O14494 |
Reactomei | R-HSA-1660661, Sphingolipid de novo biosynthesis |
UniPathwayi | UPA00085 |
Chemistry databases
SwissLipidsi | SLP:000000160 |
Names & Taxonomyi
Protein namesi | Recommended name: Phospholipid phosphatase 1Curated (EC:3.1.3.-5 Publications, EC:3.1.3.106By similarity, EC:3.1.3.44 Publications, EC:3.1.3.81By similarity)Alternative name(s): Lipid phosphate phosphohydrolase 1 PAP2-alpha Phosphatidate phosphohydrolase type 2a Phosphatidic acid phosphatase 2a Short name: PAP-2a Short name: PAP2a |
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:9228, PLPP1 |
MIMi | 607124, gene |
neXtProti | NX_O14494 |
VEuPathDBi | HostDB:ENSG00000067113.16 |
Subcellular locationi
Plasma membrane
- Cell membrane 2 Publications; Multi-pass membrane protein Sequence analysis
- Apical cell membrane 1 Publication; Multi-pass membrane protein Sequence analysis
Other locations
- Membrane raft 1 Publication; Multi-pass membrane protein Sequence analysis
- caveola By similarity; Multi-pass membrane protein Sequence analysis
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Plasma Membrane
- apical plasma membrane Source: UniProtKB
- caveola Source: UniProtKB
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: Reactome
Other locations
- membrane Source: UniProtKB
- membrane raft Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 6 | CytoplasmicBy similarity | 6 | |
Transmembranei | 7 – 27 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 28 – 53 | ExtracellularBy similarityAdd BLAST | 26 | |
Transmembranei | 54 – 74 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 75 – 94 | CytoplasmicBy similarityAdd BLAST | 20 | |
Transmembranei | 95 – 115 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 116 – 164 | ExtracellularBy similarityAdd BLAST | 49 | |
Transmembranei | 165 – 185 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 186 – 199 | CytoplasmicBy similarityAdd BLAST | 14 | |
Transmembranei | 200 – 220 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 221 – 229 | ExtracellularBy similarity | 9 | |
Transmembranei | 230 – 250 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 251 – 284 | CytoplasmicBy similarityAdd BLAST | 34 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 217 | R → K: Decreased lipid phosphatase activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 8611 |
OpenTargetsi | ENSG00000067113 |
PharmGKBi | PA33552 |
Miscellaneous databases
Pharosi | O14494, Tbio |
Genetic variation databases
BioMutai | PLPP1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000220905 | 1 – 284 | Phospholipid phosphatase 1Add BLAST | 284 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 142 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
N-glycosylated (PubMed:9305923, PubMed:10962286). N-linked sugars are of the complex type. N-glycosylation is not required for the phosphatase activity (By similarity).By similarity2 Publications
Keywords - PTMi
GlycoproteinProteomic databases
EPDi | O14494 |
jPOSTi | O14494 |
MassIVEi | O14494 |
MaxQBi | O14494 |
PeptideAtlasi | O14494 |
PRIDEi | O14494 |
ProteomicsDBi | 33687 48037 [O14494-1] 48038 [O14494-2] |
PTM databases
DEPODi | PLPP1 |
GlyGeni | O14494, 1 site |
iPTMneti | O14494 |
PhosphoSitePlusi | O14494 |
SwissPalmi | O14494 |
Expressioni
Tissue specificityi
Widely expressed with highest expression found in prostate (PubMed:9305923). Found to be down-regulated in colon adenocarcinomas (PubMed:9570154).2 Publications
Predominant in kidney, lung, placenta and liver.1 Publication
Predominant in heart and pancreas.1 Publication
Inductioni
By androgens.1 Publication
Gene expression databases
Bgeei | ENSG00000067113, Expressed in prostate gland and 243 other tissues |
ExpressionAtlasi | O14494, baseline and differential |
Genevisiblei | O14494, HS |
Organism-specific databases
HPAi | ENSG00000067113, Low tissue specificity |
Interactioni
Subunit structurei
Forms functional homodimers and homooligomers that are not required for substrate recognition and catalytic activity (By similarity). Can also form heterooligomers with PLPP2 and PLPP3 (By similarity).
By similarityBinary interactionsi
Hide detailsO14494
Protein-protein interaction databases
BioGRIDi | 114169, 13 interactors |
IntActi | O14494, 13 interactors |
MINTi | O14494 |
Miscellaneous databases
RNActi | O14494, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 120 – 128 | Phosphatase sequence motif IBy similarity | 9 | |
Regioni | 168 – 171 | Phosphatase sequence motif IIBy similarity | 4 | |
Regioni | 216 – 227 | Phosphatase sequence motif IIIBy similarityAdd BLAST | 12 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 5 – 7 | PDZ-binding; involved in localization to the apical cell membrane1 Publication | 3 |
Sequence similaritiesi
Belongs to the PA-phosphatase related phosphoesterase family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
GeneTreei | ENSGT00940000156730 |
HOGENOMi | CLU_021458_3_1_1 |
InParanoidi | O14494 |
OMAi | QRGFFCT |
PhylomeDBi | O14494 |
TreeFami | TF316040 |
Family and domain databases
InterProi | View protein in InterPro IPR028670, LPP1 IPR036938, P_Acid_Pase_2/haloperoxi_sf IPR000326, P_Acid_Pase_2/haloperoxidase IPR043216, PLPP |
PANTHERi | PTHR10165, PTHR10165, 1 hit PTHR10165:SF26, PTHR10165:SF26, 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 |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketNote: Additional isoforms seem to exist.
This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: O14494-1) [UniParc]FASTAAdd to basket
Also known as: Alpha-1, hLPP1, PAP2-a1
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MFDKTRLPYV ALDVLCVLLA GLPFAILTSR HTPFQRGVFC NDESIKYPYK
60 70 80 90 100
EDTIPYALLG GIIIPFSIIV IILGETLSVY CNLLHSNSFI RNNYIATIYK
110 120 130 140 150
AIGTFLFGAA ASQSLTDIAK YSIGRLRPHF LDVCDPDWSK INCSDGYIEY
160 170 180 190 200
YICRGNAERV KEGRLSFYSG HSSFSMYCML FVALYLQARM KGDWARLLRP
210 220 230 240 250
TLQFGLVAVS IYVGLSRVSD YKHHWSDVLT GLIQGALVAI LVAVYVSDFF
260 270 280
KERTSFKERK EEDSHTTLHE TPTTGNHYPS NHQP
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketD6REC3 | D6REC3_HUMAN | Phospholipid phosphatase 1 | PLPP1 | 110 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Sequence conflicti | 27 | L → FTSRHI in AAC32041 (PubMed:9705349).Curated | 1 | ||
Sequence conflicti | 91 | R → S in AAC16033 (PubMed:9570154).Curated | 1 | ||
Isoform 2 (identifier: O14494-2) | |||||
Sequence conflicti | 55 | V → A in AAC16033 (PubMed:9570154).Curated | 1 | ||
Sequence conflicti | 56 | T → A in AAC16033 (PubMed:9570154).Curated | 1 | ||
Sequence conflicti | 69 | I → V in AAC16033 (PubMed:9570154).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_009651 | 21 – 70 | GLPFA…FSIIV → SMPMAVLKLGQIYPFQRGFF CKDNSINYPYHDSTVTSTVL ILVGVGLPISS in isoform 2. 1 PublicationAdd BLAST | 50 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB000888 mRNA Translation: BAA22593.1 AF014402 mRNA Translation: AAC16032.1 AF014403 mRNA Translation: AAC16033.1 Y14436 mRNA Translation: CAC14588.1 AF017116 mRNA Translation: AAC32041.1 AC010480 Genomic DNA No translation available. AC025777 Genomic DNA No translation available. CH471123 Genomic DNA Translation: EAW54920.1 CH471123 Genomic DNA Translation: EAW54922.1 BC039847 mRNA Translation: AAH39847.1 BC117133 mRNA Translation: AAI17134.1 BC143281 mRNA Translation: AAI43282.1 |
CCDSi | CCDS34159.1 [O14494-1] CCDS34160.1 [O14494-2] |
RefSeqi | NP_003702.2, NM_003711.3 [O14494-1] NP_795714.1, NM_176895.2 [O14494-2] |
Genome annotation databases
Ensembli | ENST00000264775; ENSP00000264775; ENSG00000067113 [O14494-2] ENST00000307259; ENSP00000302229; ENSG00000067113 [O14494-1] |
GeneIDi | 8611 |
KEGGi | hsa:8611 |
UCSCi | uc003jpz.5, human [O14494-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB000888 mRNA Translation: BAA22593.1 AF014402 mRNA Translation: AAC16032.1 AF014403 mRNA Translation: AAC16033.1 Y14436 mRNA Translation: CAC14588.1 AF017116 mRNA Translation: AAC32041.1 AC010480 Genomic DNA No translation available. AC025777 Genomic DNA No translation available. CH471123 Genomic DNA Translation: EAW54920.1 CH471123 Genomic DNA Translation: EAW54922.1 BC039847 mRNA Translation: AAH39847.1 BC117133 mRNA Translation: AAI17134.1 BC143281 mRNA Translation: AAI43282.1 |
CCDSi | CCDS34159.1 [O14494-1] CCDS34160.1 [O14494-2] |
RefSeqi | NP_003702.2, NM_003711.3 [O14494-1] NP_795714.1, NM_176895.2 [O14494-2] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 114169, 13 interactors |
IntActi | O14494, 13 interactors |
MINTi | O14494 |
Chemistry databases
SwissLipidsi | SLP:000000160 |
PTM databases
DEPODi | PLPP1 |
GlyGeni | O14494, 1 site |
iPTMneti | O14494 |
PhosphoSitePlusi | O14494 |
SwissPalmi | O14494 |
Genetic variation databases
BioMutai | PLPP1 |
Proteomic databases
EPDi | O14494 |
jPOSTi | O14494 |
MassIVEi | O14494 |
MaxQBi | O14494 |
PeptideAtlasi | O14494 |
PRIDEi | O14494 |
ProteomicsDBi | 33687 48037 [O14494-1] 48038 [O14494-2] |
Protocols and materials databases
Antibodypediai | 11159, 179 antibodies |
DNASUi | 8611 |
Genome annotation databases
Ensembli | ENST00000264775; ENSP00000264775; ENSG00000067113 [O14494-2] ENST00000307259; ENSP00000302229; ENSG00000067113 [O14494-1] |
GeneIDi | 8611 |
KEGGi | hsa:8611 |
UCSCi | uc003jpz.5, human [O14494-1] |
Organism-specific databases
CTDi | 8611 |
DisGeNETi | 8611 |
GeneCardsi | PLPP1 |
HGNCi | HGNC:9228, PLPP1 |
HPAi | ENSG00000067113, Low tissue specificity |
MIMi | 607124, gene |
neXtProti | NX_O14494 |
OpenTargetsi | ENSG00000067113 |
PharmGKBi | PA33552 |
VEuPathDBi | HostDB:ENSG00000067113.16 |
GenAtlasi | Search... |
Phylogenomic databases
GeneTreei | ENSGT00940000156730 |
HOGENOMi | CLU_021458_3_1_1 |
InParanoidi | O14494 |
OMAi | QRGFFCT |
PhylomeDBi | O14494 |
TreeFami | TF316040 |
Enzyme and pathway databases
UniPathwayi | UPA00085 |
PathwayCommonsi | O14494 |
Reactomei | R-HSA-1660661, Sphingolipid de novo biosynthesis |
Miscellaneous databases
BioGRID-ORCSi | 8611, 16 hits in 992 CRISPR screens |
ChiTaRSi | PLPP1, human |
GeneWikii | PPAP2A |
GenomeRNAii | 8611 |
Pharosi | O14494, Tbio |
PROi | PR:O14494 |
RNActi | O14494, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000067113, Expressed in prostate gland and 243 other tissues |
ExpressionAtlasi | O14494, baseline and differential |
Genevisiblei | O14494, HS |
Family and domain databases
InterProi | View protein in InterPro IPR028670, LPP1 IPR036938, P_Acid_Pase_2/haloperoxi_sf IPR000326, P_Acid_Pase_2/haloperoxidase IPR043216, PLPP |
PANTHERi | PTHR10165, PTHR10165, 1 hit PTHR10165:SF26, PTHR10165:SF26, 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PLPP1_HUMAN | |
Accessioni | O14494Primary (citable) accession number: O14494 Secondary accession number(s): B7ZKN8 Q17RZ4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 15, 2004 |
Last sequence update: | January 1, 1998 | |
Last modified: | April 7, 2021 | |
This is version 176 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 5
Human chromosome 5: 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