PLPP1_RAT
ID PLPP1_RAT Reviewed; 282 AA.
AC O08564; Q8K594;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Phospholipid phosphatase 1 {ECO:0000305};
DE EC=3.1.3.- {ECO:0000269|PubMed:10359651, ECO:0000269|PubMed:8663293};
DE EC=3.1.3.106 {ECO:0000250|UniProtKB:Q61469};
DE EC=3.1.3.4 {ECO:0000269|PubMed:10359651, ECO:0000269|PubMed:8663293};
DE EC=3.1.3.81 {ECO:0000269|PubMed:10359651};
DE AltName: Full=Lipid phosphate phosphohydrolase 1;
DE AltName: Full=PAP2-alpha;
DE AltName: Full=Phosphatidate phosphohydrolase type 2a;
DE AltName: Full=Phosphatidic acid phosphatase 2a;
DE Short=PAP-2a;
DE Short=PAP2a;
GN Name=Plpp1 {ECO:0000312|RGD:621832}; Synonyms=Lpp1, Ppap2a;
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] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP SUBSTRATE SPECIFICITY, ACTIVITY REGULATION, AND PATHWAY.
RC TISSUE=Liver;
RX PubMed=10359651; DOI=10.1042/bj3400677;
RA Jasinska R., Zhang Q.-X., Pilquil C., Singh I., Xu J., Dewald J.,
RA Dillon D.A., Berthiaume L.G., Carman G.M., Waggoner D.W., Brindley D.N.;
RT "Lipid phosphate phosphohydrolase-1 degrades exogenous glycerolipid and
RT sphingolipid phosphate esters.";
RL Biochem. J. 340:677-686(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=Sprague-Dawley; TISSUE=Lung;
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).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND SUBCELLULAR LOCATION.
RX PubMed=8663293; DOI=10.1074/jbc.271.28.16506;
RA Waggoner D.W., Gomez-Munoz A., Dewald J., Brindley D.N.;
RT "Phosphatidate phosphohydrolase catalyzes the hydrolysis of ceramide 1-
RT phosphate, lysophosphatidate, and sphingosine 1-phosphate.";
RL J. Biol. Chem. 271:16506-16509(1996).
RN [4]
RP FUNCTION.
RX PubMed=17057224; DOI=10.1074/jbc.m601670200;
RA Pilquil C., Dewald J., Cherney A., Gorshkova I., Tigyi G., English D.,
RA Natarajan V., Brindley D.N.;
RT "Lipid phosphate phosphatase-1 regulates lysophosphatidate-induced
RT fibroblast migration by controlling phospholipase D2-dependent
RT phosphatidate generation.";
RL J. Biol. Chem. 281:38418-38429(2006).
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 (PubMed:10359651, PubMed:8663293). Also acts on N-oleoyl
CC ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a
CC potential physiological compound (By similarity). Through its
CC extracellular phosphatase activity allows both the hydrolysis and the
CC cellular uptake of these bioactive lipid mediators from the milieu,
CC regulating signal transduction in different cellular processes
CC (PubMed:10359651). It is for instance essential for the extracellular
CC hydrolysis of S1P and subsequent conversion into intracellular S1P (By
CC similarity). Involved in the regulation of inflammation, platelets
CC activation, cell proliferation and migration among other processes (By
CC similarity). May also have an intracellular activity to regulate
CC phospholipid-mediated signaling pathways (PubMed:17057224).
CC {ECO:0000250|UniProtKB:O14494, ECO:0000269|PubMed:10359651,
CC ECO:0000269|PubMed:17057224, ECO:0000269|PubMed:8663293}.
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:0000269|PubMed:10359651, ECO:0000269|PubMed:8663293};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27430;
CC Evidence={ECO:0000305|PubMed:10359651};
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:O14494};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43237;
CC Evidence={ECO:0000250|UniProtKB:O14494};
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:0000269|PubMed:8663293};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43245;
CC Evidence={ECO:0000305|PubMed:8663293};
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:0000269|PubMed:10359651, ECO:0000269|PubMed:8663293};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46737;
CC Evidence={ECO:0000269|PubMed:10359651};
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:0000269|PubMed:8663293};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50885;
CC Evidence={ECO:0000305|PubMed:8663293};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-sn-glycero-3-phosphate + H2O = a 1-acyl-sn-glycerol +
CC phosphate; Xref=Rhea:RHEA:33155, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57970, ChEBI:CHEBI:64683;
CC EC=3.1.3.106; Evidence={ECO:0000269|PubMed:8663293};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33156;
CC Evidence={ECO:0000305|PubMed:8663293};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z-
CC octadecenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:39835,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:74544,
CC ChEBI:CHEBI:75757; Evidence={ECO:0000250|UniProtKB:Q61469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39836;
CC Evidence={ECO:0000250|UniProtKB:Q61469};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycerol 3-diphosphate + H2O = a 1,2-diacyl-
CC sn-glycero-3-phosphate + H(+) + phosphate; Xref=Rhea:RHEA:27449,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58608, ChEBI:CHEBI:59996; EC=3.1.3.81;
CC Evidence={ECO:0000269|PubMed:10359651};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27450;
CC Evidence={ECO:0000305|PubMed:10359651};
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:0000269|PubMed:10359651, ECO:0000269|PubMed:8663293};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27519;
CC Evidence={ECO:0000305|PubMed:10359651};
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:0000269|PubMed:10359651, ECO:0000269|PubMed:8663293};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33744;
CC Evidence={ECO:0000305|PubMed:10359651};
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:O14494};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62041;
CC Evidence={ECO:0000250|UniProtKB:O14494};
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:O14494};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62161;
CC Evidence={ECO:0000250|UniProtKB:O14494};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC H2O = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + phosphate;
CC Xref=Rhea:RHEA:41255, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:64839, ChEBI:CHEBI:75466;
CC Evidence={ECO:0000269|PubMed:10359651};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41256;
CC Evidence={ECO:0000305|PubMed:10359651};
CC -!- ACTIVITY REGULATION: Magnesium-independent phospholipid phosphatase
CC (PubMed:10359651, PubMed:8663293). Insensitive to N-ethylmaleimide
CC (PubMed:10359651). {ECO:0000269|PubMed:10359651,
CC ECO:0000269|PubMed:8663293}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.5 uM for 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate (at pH
CC 6.5 and 37 degrees Celsius) {ECO:0000269|PubMed:8663293};
CC KM=0.4 uM for (9Z)-octadecenoyl-sn-glycero-3-phosphate (at pH 6.5 and
CC 37 degrees Celsius) {ECO:0000269|PubMed:8663293};
CC KM=1.9 uM for N-acylsphing-4-enine 1-phosphate (at pH 6.5 and 37
CC degrees Celsius) {ECO:0000269|PubMed:8663293};
CC KM=4.0 uM for sphing-4-enine 1-phosphate (at pH 6.5 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:8663293};
CC Vmax=0.55 umol/min/mg enzyme with 1,2-di-(9Z-octadecenoyl)-sn-
CC glycero-3-phosphate as substrate {ECO:0000269|PubMed:8663293};
CC Vmax=0.19 umol/min/mg enzyme with (9Z)-octadecenoyl-sn-glycero-3-
CC phosphate as substrate {ECO:0000269|PubMed:8663293};
CC Vmax=0.26 umol/min/mg enzyme with N-acylsphing-4-enine 1-phosphate as
CC substrate {ECO:0000269|PubMed:8663293};
CC Vmax=0.15 umol/min/mg enzyme with sphing-4-enine 1-phosphate as
CC substrate {ECO:0000269|PubMed:8663293};
CC -!- PATHWAY: Lipid metabolism; phospholipid metabolism.
CC {ECO:0000269|PubMed:10359651, ECO:0000269|PubMed:8663293}.
CC -!- SUBUNIT: Forms functional homodimers and homooligomers that are not
CC required for substrate recognition and catalytic activity (By
CC similarity). Can also form heterooligomers with PLPP2 and PLPP3 (By
CC similarity). {ECO:0000250|UniProtKB:O88956,
CC ECO:0000250|UniProtKB:Q61469}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8663293};
CC Multi-pass membrane protein {ECO:0000255}. Apical cell membrane
CC {ECO:0000250|UniProtKB:O14494}; Multi-pass membrane protein
CC {ECO:0000255}. Membrane raft {ECO:0000250|UniProtKB:O14494}; Multi-pass
CC membrane protein {ECO:0000255}. Membrane, caveola
CC {ECO:0000250|UniProtKB:Q61469}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=O08564-1; Sequence=Displayed;
CC Name=2; Synonyms=LPP1a;
CC IsoId=O08564-2; Sequence=VSP_009653;
CC -!- PTM: N-glycosylated. N-linked sugars are of the complex type. N-
CC glycosylation is not required for the phosphatase activity.
CC {ECO:0000250|UniProtKB:Q61469}.
CC -!- SIMILARITY: Belongs to the PA-phosphatase related phosphoesterase
CC family. {ECO:0000305}.
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DR EMBL; U90556; AAB50246.1; -; mRNA.
DR EMBL; AF503609; AAM28631.1; -; mRNA.
DR AlphaFoldDB; O08564; -.
DR SwissLipids; SLP:000000610; -.
DR GlyGen; O08564; 1 site.
DR iPTMnet; O08564; -.
DR PhosphoSitePlus; O08564; -.
DR PaxDb; O08564; -.
DR PRIDE; O08564; -.
DR RGD; 621832; Plpp1.
DR eggNOG; KOG3030; Eukaryota.
DR InParanoid; O08564; -.
DR PhylomeDB; O08564; -.
DR Reactome; R-RNO-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00085; -.
DR PRO; PR:O08564; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0106235; F:ceramide-1-phosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0000810; F:diacylglycerol diphosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0042577; F:lipid phosphatase activity; ISO:RGD.
DR GO; GO:0008195; F:phosphatidate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0042392; F:sphingosine-1-phosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; IDA:UniProtKB.
DR GO; GO:0046839; P:phospholipid dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006644; P:phospholipid metabolic process; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; ISS:UniProtKB.
DR GO; GO:0006670; P:sphingosine metabolic process; IDA:UniProtKB.
DR InterPro; IPR028670; LPP1.
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:SF26; PTHR10165:SF26; 1.
DR Pfam; PF01569; PAP2; 1.
DR SMART; SM00014; acidPPc; 1.
DR SUPFAM; SSF48317; SSF48317; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Glycoprotein; Hydrolase;
KW Lipid metabolism; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..282
FT /note="Phospholipid phosphatase 1"
FT /id="PRO_0000220908"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q61469"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..53
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q61469"
FT TRANSMEM 54..74
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 75..88
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q61469"
FT TRANSMEM 89..109
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 110..164
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q61469"
FT TRANSMEM 165..185
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 186..194
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q61469"
FT TRANSMEM 195..215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 216..229
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q61469"
FT TRANSMEM 230..250
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 251..282
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q61469"
FT REGION 120..128
FT /note="Phosphatase sequence motif I"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 168..171
FT /note="Phosphatase sequence motif II"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 216..227
FT /note="Phosphatase sequence motif III"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 257..282
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 5..7
FT /note="PDZ-binding; involved in localization to the apical
FT cell membrane"
FT /evidence="ECO:0000250|UniProtKB:O14494"
FT ACT_SITE 171
FT /note="Proton donors"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT ACT_SITE 223
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT SITE 227
FT /note="Stabilizes the active site histidine for
FT nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 21..70
FT /note="GLPFIILTSRHTPFQRGVFCTDESIKYPYREDTIPYALLGGIVIPFCIIV
FT -> SMPMAVVNLGQIYPFQRGFFCSDNSVKYPYHDSTVTTSVLVLVGLGIPIFS (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:11704545"
FT /id="VSP_009653"
SQ SEQUENCE 282 AA; 31996 MW; A4ED3DEB33FD7943 CRC64;
MFDKPRLPYV VLDVICVLLA GLPFIILTSR HTPFQRGVFC TDESIKYPYR EDTIPYALLG
GIVIPFCIIV MITGETLSVY FNVLHSNSFV SNHYIATIYK AVGAFLFGAS ASQSLTDIAK
YSIGRLRPHF LAVCNPDWSK INCSDGYIEN FVCQGNEQKV REGRLSFYSG HSSFSMYCML
FVALYLQARM KGDWARLLRP MLQFGLVALS IYVGLSRVSD YKHHWSDVLI GLIQGAVVAI
LVVLYVTDFF KTTESNKERK EDSHTTLHET TNRQSYARNH EP
