PLPP3_RAT
ID PLPP3_RAT Reviewed; 312 AA.
AC P97544;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 25-MAY-2022, entry version 123.
DE RecName: Full=Phospholipid phosphatase 3 {ECO:0000305};
DE EC=3.1.3.- {ECO:0000250|UniProtKB:O14495};
DE EC=3.1.3.4 {ECO:0000250|UniProtKB:O14495};
DE AltName: Full=Differentially expressed in rat intestine 42;
DE Short=Dri42;
DE AltName: Full=Lipid phosphate phosphohydrolase 3;
DE AltName: Full=PAP2-beta;
DE AltName: Full=Phosphatidate phosphohydrolase type 2b;
DE AltName: Full=Phosphatidic acid phosphatase 2b;
DE Short=PAP-2b;
DE Short=PAP2b;
GN Name=Plpp3 {ECO:0000312|RGD:620454}; Synonyms=Lpp3, Ppap2b;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TOPOLOGY, AND
RP GLYCOSYLATION.
RC STRAIN=Wistar; TISSUE=Small intestine;
RX PubMed=8939937; DOI=10.1074/jbc.271.47.29928;
RA Barila D., Plateroti M., Nobili F., Muda A.O., Xie Y., Morimoto T.,
RA Perozzi G.;
RT "The Dri 42 gene, whose expression is upregulated during epithelial
RT differentiation, encodes a novel ER resident transmembrane protein.";
RL J. Biol. Chem. 271:29928-29936(1996).
RN [2]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=8055940; DOI=10.1111/j.1432-1033.1994.tb19043.x;
RA Barila D., Murgia C., Nobili F., Gaetani S., Perozzi G.;
RT "Subtractive hybridization cloning of novel genes differentially expressed
RT during intestinal development.";
RL Eur. J. Biochem. 223:701-709(1994).
RN [3]
RP TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=11704545; DOI=10.1152/ajplung.2001.281.6.l1484;
RA Nanjundan M., Possmayer F.;
RT "Molecular cloning and expression of pulmonary lipid phosphate
RT phosphohydrolases.";
RL Am. J. Physiol. 281:L1484-L1493(2001).
CC -!- FUNCTION: Magnesium-independent phospholipid phosphatase of the plasma
CC membrane that catalyzes the dephosphorylation of a variety of
CC glycerolipid and sphingolipid phosphate esters including
CC phosphatidate/PA, lysophosphatidate/LPA, diacylglycerol
CC pyrophosphate/DGPP, sphingosine 1-phosphate/S1P and ceramide 1-
CC phosphate/C1P. Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-
CC octadecenoyl)-ethanolamine phosphate, a potential physiological
CC compound. Has both an extracellular and an intracellular phosphatase
CC activity, allowing the hydrolysis and the cellular uptake of these
CC bioactive lipid mediators from the milieu, regulating signal
CC transduction in different cellular processes. Through the
CC dephosphorylation of extracellular sphingosine-1-phosphate and the
CC regulation of its extra- and intracellular availability, plays a role
CC in vascular homeostasis, regulating endothelial cell migration,
CC adhesion, survival, proliferation and the production of pro-
CC inflammatory cytokines (By similarity). By maintaining the appropriate
CC levels of this lipid in the cerebellum, also ensure its proper
CC development and function (By similarity). Through its intracellular
CC lipid phosphatase activity may act in early compartments of the
CC secretory pathway, regulating the formation of Golgi to endoplasmic
CC reticulum retrograde transport carriers (By similarity).
CC {ECO:0000250|UniProtKB:O14495, ECO:0000250|UniProtKB:Q99JY8}.
CC -!- FUNCTION: Independently of this phosphatase activity may also function
CC in the Wnt signaling pathway and the stabilization of beta-
CC catenin/CTNNB1, thereby regulating cell proliferation, migration and
CC differentiation in angiogenesis or yet in tumor growth. Also plays a
CC role in integrin-mediated cell-cell adhesion in angiogenesis.
CC {ECO:0000250|UniProtKB:Q99JY8}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphate + H2O = a 1,2-diacyl-sn-
CC glycerol + phosphate; Xref=Rhea:RHEA:27429, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:43474, ChEBI:CHEBI:58608; EC=3.1.3.4;
CC Evidence={ECO:0000250|UniProtKB:O14495};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27430;
CC Evidence={ECO:0000250|UniProtKB:O14495};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphate + H2O = 1,2-
CC dihexadecanoyl-sn-glycerol + phosphate; Xref=Rhea:RHEA:43236,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:72859,
CC ChEBI:CHEBI:82929; Evidence={ECO:0000250|UniProtKB:O14495};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43237;
CC Evidence={ECO:0000250|UniProtKB:O14495};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1,2-
CC di-(9Z-octadecenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43244,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:52333,
CC ChEBI:CHEBI:74546; Evidence={ECO:0000250|UniProtKB:O14495};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43245;
CC Evidence={ECO:0000250|UniProtKB:O14495};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + monoacyl-sn-glycero-3-phosphate = a monoacylglycerol +
CC phosphate; Xref=Rhea:RHEA:46736, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17408, ChEBI:CHEBI:43474, ChEBI:CHEBI:77589;
CC Evidence={ECO:0000250|UniProtKB:O14495};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46737;
CC Evidence={ECO:0000250|UniProtKB:O14495};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-sn-glycero-3-phosphate + H2O = (9Z-
CC octadecenoyl)-glycerol + phosphate; Xref=Rhea:RHEA:50884,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:75937,
CC ChEBI:CHEBI:84973; Evidence={ECO:0000250|UniProtKB:O14495};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50885;
CC Evidence={ECO:0000250|UniProtKB:O14495};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + sphing-4-enine 1-phosphate = phosphate + sphing-4-enine;
CC Xref=Rhea:RHEA:27518, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:60119;
CC Evidence={ECO:0000250|UniProtKB:O14495};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27519;
CC Evidence={ECO:0000250|UniProtKB:O14495};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphing-4-enine 1-phosphate + H2O = an N-acylsphing-4-
CC enine + phosphate; Xref=Rhea:RHEA:33743, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:52639, ChEBI:CHEBI:57674;
CC Evidence={ECO:0000250|UniProtKB:O14495};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33744;
CC Evidence={ECO:0000250|UniProtKB:O14495};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(octanoyl)-sphing-4-enine-1-phosphate = N-
CC octanoylsphing-4-enine + phosphate; Xref=Rhea:RHEA:62040,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:45815,
CC ChEBI:CHEBI:85376; Evidence={ECO:0000250|UniProtKB:O14495};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62041;
CC Evidence={ECO:0000250|UniProtKB:O14495};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl)-ethanolamine phosphate = N-(9Z-
CC octadecenoyl) ethanolamine + phosphate; Xref=Rhea:RHEA:62160,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:71466,
CC ChEBI:CHEBI:145465; Evidence={ECO:0000250|UniProtKB:O14495};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62161;
CC Evidence={ECO:0000250|UniProtKB:O14495};
CC -!- ACTIVITY REGULATION: Magnesium-independent phospholipid phosphatase.
CC Insensitive to N-ethylmaleimide. Inhibited by sphingosine, zinc ions
CC and modestly by propanolol. {ECO:0000250|UniProtKB:O14495}.
CC -!- PATHWAY: Lipid metabolism; phospholipid metabolism.
CC {ECO:0000250|UniProtKB:O14495}.
CC -!- SUBUNIT: Forms functional homodimers and homooligomers that are not
CC required for substrate recognition and catalytic activity. Can also
CC form heterooligomers with other PLPP2 and PLPP3. Interacts with CTNND1;
CC negatively regulates the PLPP3-mediated stabilization of beta-
CC catenin/CTNNB1. {ECO:0000250|UniProtKB:O14495}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O14495};
CC Multi-pass membrane protein {ECO:0000269|PubMed:8939937}. Basolateral
CC cell membrane {ECO:0000250|UniProtKB:O14495}; Multi-pass membrane
CC protein {ECO:0000269|PubMed:8939937}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:8939937}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:8939937}. Endoplasmic reticulum-Golgi intermediate
CC compartment membrane {ECO:0000250|UniProtKB:O14495}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:8939937}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:O14495}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:8939937}. Golgi apparatus, trans-Golgi network
CC membrane {ECO:0000250|UniProtKB:O14495}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:8939937}. Membrane raft
CC {ECO:0000250|UniProtKB:O14495}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:8939937}. Note=Cycles between the endoplasmic
CC reticulum and the Golgi. {ECO:0000250|UniProtKB:O14495}.
CC -!- TISSUE SPECIFICITY: Detected in epithelial cells of intestinal mucosa,
CC lung, liver and brain. {ECO:0000269|PubMed:11704545,
CC ECO:0000269|PubMed:8055940}.
CC -!- DEVELOPMENTAL STAGE: Expression is increased during epithelial
CC differentiation in intestinal mucosa as well as in kidney, liver and
CC lung. {ECO:0000269|PubMed:8055940}.
CC -!- DOMAIN: The integrin-binding motif mediates the binding to integrin
CC alpha-5/beta-1 (ITGA5:ITGB1) and integrin alpha-V/beta-3 (ITGAV:ITGB3)
CC and is required for the function in integrin-mediated cell-cell
CC adhesion. {ECO:0000250|UniProtKB:O14495}.
CC -!- DOMAIN: The dityrosine basolateral targeting motif mediates
CC localization to the basolateral membrane in polarized cells.
CC {ECO:0000250|UniProtKB:O14495}.
CC -!- PTM: N-glycosylated (PubMed:8939937). Contains high-mannose
CC oligosaccharides (By similarity). {ECO:0000250|UniProtKB:O14495,
CC ECO:0000269|PubMed:8939937}.
CC -!- SIMILARITY: Belongs to the PA-phosphatase related phosphoesterase
CC family. {ECO:0000305}.
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DR EMBL; Y07783; CAA69106.1; -; mRNA.
DR AlphaFoldDB; P97544; -.
DR STRING; 10116.ENSRNOP00000011237; -.
DR GlyGen; P97544; 1 site.
DR PhosphoSitePlus; P97544; -.
DR PaxDb; P97544; -.
DR PRIDE; P97544; -.
DR UCSC; RGD:620454; rat.
DR RGD; 620454; Plpp3.
DR eggNOG; KOG3030; Eukaryota.
DR InParanoid; P97544; -.
DR PhylomeDB; P97544; -.
DR Reactome; R-RNO-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00085; -.
DR PRO; PR:P97544; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0070971; C:endoplasmic reticulum exit site; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:RGD.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0106235; F:ceramide-1-phosphate phosphatase activity; ISS:UniProtKB.
DR GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR GO; GO:0042577; F:lipid phosphatase activity; ISO:RGD.
DR GO; GO:0008195; F:phosphatidate phosphatase activity; ISS:UniProtKB.
DR GO; GO:0042392; F:sphingosine-1-phosphate phosphatase activity; ISS:UniProtKB.
DR GO; GO:0060020; P:Bergmann glial cell differentiation; ISO:RGD.
DR GO; GO:0001568; P:blood vessel development; ISO:RGD.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0044329; P:canonical Wnt signaling pathway involved in positive regulation of cell-cell adhesion; ISO:RGD.
DR GO; GO:0044328; P:canonical Wnt signaling pathway involved in positive regulation of endothelial cell migration; ISO:RGD.
DR GO; GO:0044330; P:canonical Wnt signaling pathway involved in positive regulation of wound healing; ISO:RGD.
DR GO; GO:0007155; P:cell adhesion; ISO:RGD.
DR GO; GO:0098609; P:cell-cell adhesion; ISO:RGD.
DR GO; GO:0033631; P:cell-cell adhesion mediated by integrin; ISS:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; ISS:UniProtKB.
DR GO; GO:0001702; P:gastrulation with mouth forming second; ISO:RGD.
DR GO; GO:0034109; P:homotypic cell-cell adhesion; ISO:RGD.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0046839; P:phospholipid dephosphorylation; ISS:UniProtKB.
DR GO; GO:0006644; P:phospholipid metabolic process; ISS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:1902068; P:regulation of sphingolipid mediated signaling pathway; ISO:RGD.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; ISO:RGD.
DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0006670; P:sphingosine metabolic process; ISS:UniProtKB.
DR InterPro; IPR028675; LPP3.
DR InterPro; IPR036938; P_Acid_Pase_2/haloperoxi_sf.
DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
DR InterPro; IPR043216; PA_PP_rel.
DR PANTHER; PTHR10165; PTHR10165; 1.
DR PANTHER; PTHR10165:SF79; PTHR10165:SF79; 1.
DR Pfam; PF01569; PAP2; 1.
DR SMART; SM00014; acidPPc; 1.
DR SUPFAM; SSF48317; SSF48317; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Endoplasmic reticulum; Glycoprotein; Golgi apparatus;
KW Hydrolase; Lipid metabolism; Membrane; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..312
FT /note="Phospholipid phosphatase 3"
FT /id="PRO_0000220914"
FT TOPO_DOM 1..33
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:8939937"
FT TRANSMEM 34..54
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 55..85
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:8939937"
FT TRANSMEM 86..106
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 107..123
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:8939937"
FT TRANSMEM 124..144
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 145..194
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:8939937"
FT TRANSMEM 195..215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 216..226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:8939937"
FT TRANSMEM 227..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 245..258
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:8939937"
FT TRANSMEM 259..279
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 280..312
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:8939937"
FT REGION 149..157
FT /note="Phosphatase sequence motif I"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 197..200
FT /note="Phosphatase sequence motif II"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 245..256
FT /note="Phosphatase sequence motif III"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 276..312
FT /note="Mediates interaction with CTNND1"
FT /evidence="ECO:0000250|UniProtKB:O14495"
FT MOTIF 109..110
FT /note="Dityrosine basolateral targeting motif"
FT /evidence="ECO:0000250|UniProtKB:O14495"
FT MOTIF 183..185
FT /note="Integrin-binding motif"
FT /evidence="ECO:0000250|UniProtKB:O14495"
FT ACT_SITE 200
FT /note="Proton donors"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT ACT_SITE 252
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT SITE 256
FT /note="Stabilizes the active site histidine for
FT nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14495"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 312 AA; 35318 MW; 9B447FD321DB0419 CRC64;
MQSYKYDKAI VPESKNGGSP ALNNNPRKGG SKRVLLICLD LFCLFMAALP FLIIETSTIK
PYRRGFYCND ESIKYPLKVS ETINDAVLCA VGIVIAILRI ITGEFYRIYY LKEKSRSTIQ
NPYVAALYKQ VGCFLFGCAI SQSFTDIAKV SIGRLRPHFL SVCDPDFSQI NCSEGYIQNY
RCRGEDSKVQ EARKSFFSGH ASFSMFTMLY LVLYLQARFT WRGARLLRPL LQFTLLMMAF
YTGLSRVSDY KHHPSDVLAG FAQGALVACC IVFFVSDLFK TKTTLSLPAP AIRREILSPV
DIMDRSNHHN MV
