ID PLPP1_CAVPO Reviewed; 285 AA.
AC O88956; O88957;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 22-FEB-2023, entry version 104.
DE RecName: Full=Phospholipid phosphatase 1 {ECO:0000305};
DE EC=3.1.3.- {ECO:0000250|UniProtKB:O14494};
DE EC=3.1.3.106 {ECO:0000250|UniProtKB:Q61469};
DE EC=3.1.3.4 {ECO:0000269|PubMed:18215144};
DE EC=3.6.1.75 {ECO:0000250|UniProtKB:Q61469};
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:0000250|UniProtKB:O14494}; Synonyms=LPP1, PAP2A, PPAP2A;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Airway smooth muscle;
RX PubMed=10405762; DOI=10.1016/s0898-6568(99)00028-5;
RA Tate R.J., Tolan D., Pyne S.;
RT "Molecular cloning of magnesium-independent type 2 phosphatidic acid
RT phosphatases from airway smooth muscle.";
RL Cell. Signal. 11:515-522(1999).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBUNIT, AND MUTAGENESIS OF ARG-127
RP AND HIS-223.
RX PubMed=18215144; DOI=10.1042/bj20071607;
RA Long J.S., Pyne N.J., Pyne S.;
RT "Lipid phosphate phosphatases form homo- and hetero-oligomers: catalytic
RT competency, subcellular distribution and function.";
RL Biochem. J. 411:371-377(2008).
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:18215144). Also acts on N-oleoyl ethanolamine
CC phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential
CC physiological compound (By similarity). Through its extracellular
CC phosphatase activity allows both the hydrolysis and the cellular uptake
CC of these bioactive lipid mediators from the milieu, regulating signal
CC transduction in different cellular processes (By similarity). It is for
CC instance essential for the extracellular hydrolysis of S1P and
CC subsequent conversion into intracellular S1P (By similarity). Involved
CC in the regulation of inflammation, platelets activation, cell
CC proliferation and migration among other processes (By similarity). May
CC also have an intracellular activity to regulate phospholipid-mediated
CC signaling pathways (By similarity). {ECO:0000250|UniProtKB:O08564,
CC ECO:0000250|UniProtKB:O14494, ECO:0000269|PubMed:18215144}.
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:18215144};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27430;
CC Evidence={ECO:0000305|PubMed:18215144};
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:0000250|UniProtKB:O14494};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43245;
CC Evidence={ECO:0000250|UniProtKB:O14494};
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:O14494};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46737;
CC Evidence={ECO:0000250|UniProtKB:O14494};
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:O14494};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50885;
CC Evidence={ECO:0000250|UniProtKB:O14494};
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:0000250|UniProtKB:Q61469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33156;
CC Evidence={ECO:0000250|UniProtKB:Q61469};
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=3.6.1.75;
CC Evidence={ECO:0000250|UniProtKB:Q61469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27450;
CC Evidence={ECO:0000250|UniProtKB:Q61469};
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:O14494};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27519;
CC Evidence={ECO:0000250|UniProtKB:O14494};
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:O14494};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33744;
CC Evidence={ECO:0000250|UniProtKB:O14494};
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:0000250|UniProtKB:O08564};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41256;
CC Evidence={ECO:0000250|UniProtKB:O08564};
CC -!- ACTIVITY REGULATION: Magnesium-independent phospholipid phosphatase.
CC Insensitive to N-ethylmaleimide. {ECO:0000250|UniProtKB:O14494}.
CC -!- PATHWAY: Lipid metabolism; phospholipid metabolism.
CC {ECO:0000269|PubMed:18215144}.
CC -!- SUBUNIT: Forms functional homodimers and homooligomers that are not
CC required for substrate recognition and catalytic activity
CC (PubMed:18215144). Can also form heterooligomers with PLPP2 and PLPP3
CC (PubMed:18215144). {ECO:0000269|PubMed:18215144}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O14494};
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 Name=1; Synonyms=PAP2a1;
CC IsoId=O88956-1; Sequence=Displayed;
CC Name=2; Synonyms=PAP2a2;
CC IsoId=O88956-2; Sequence=VSP_009650;
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; AF088283; AAC63333.1; -; mRNA.
DR EMBL; AF088284; AAC63334.1; -; mRNA.
DR RefSeq; NP_001166474.1; NM_001173003.1.
DR AlphaFoldDB; O88956; -.
DR STRING; 10141.ENSCPOP00000008809; -.
DR GlyCosmos; O88956; 1 site, No reported glycans.
DR GeneID; 100135603; -.
DR KEGG; cpoc:100135603; -.
DR CTD; 8611; -.
DR eggNOG; KOG3030; Eukaryota.
DR InParanoid; O88956; -.
DR OrthoDB; 25293at2759; -.
DR UniPathway; UPA00085; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005901; C:caveola; ISS: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; ISS:UniProtKB.
DR GO; GO:0106235; F:ceramide-1-phosphate phosphatase activity; ISS:UniProtKB.
DR GO; GO:0000810; F:diacylglycerol diphosphate phosphatase activity; ISS:UniProtKB.
DR GO; GO:0008195; F:phosphatidate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0042392; F:sphingosine-1-phosphate phosphatase activity; ISS:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; ISS: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; ISS:UniProtKB.
DR CDD; cd03384; PAP2_wunen; 1.
DR Gene3D; 1.20.144.10; Phosphatidic acid phosphatase type 2/haloperoxidase; 1.
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; LIPID PHOSPHATE PHOSPHATASE; 1.
DR PANTHER; PTHR10165:SF26; PHOSPHOLIPID PHOSPHATASE 1; 1.
DR Pfam; PF01569; PAP2; 1.
DR SMART; SM00014; acidPPc; 1.
DR SUPFAM; SSF48317; Acid phosphatase/Vanadium-dependent haloperoxidase; 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..285
FT /note="Phospholipid phosphatase 1"
FT /id="PRO_0000220904"
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..94
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q61469"
FT TRANSMEM 95..115
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 116..165
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q61469"
FT TRANSMEM 166..186
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 187..199
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q61469"
FT TRANSMEM 200..220
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 221..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..285
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 260..285
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 COMPBIAS 270..285
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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="GLPFAILTSRHTPFQRGIFCNDESIKYPYKEDTIPYALLGGIMIPFSIVV
FT -> SMPMAVLNLGQIYPFQRGFFCNDNSIQYPYHDSTVASTILTIVGLGLPISS (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:10405762"
FT /id="VSP_009650"
FT MUTAGEN 127
FT /note="R->K: Loss of lipid phosphatase activity."
FT /evidence="ECO:0000269|PubMed:18215144"
FT MUTAGEN 223
FT /note="H->L: Decreased lipid phosphatase activity."
FT /evidence="ECO:0000269|PubMed:18215144"
FT CONFLICT 5
FT /note="A -> T (in Ref. 1; AAC63334)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="I -> V (in Ref. 1; AAC63334)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 285 AA; 32133 MW; E6F48E188DED6CF5 CRC64;
MFDKARLPYV ALDVLCVVLA GLPFAILTSR HTPFQRGIFC NDESIKYPYK EDTIPYALLG
GIMIPFSIVV MIIGETLSVY CNLLHSNSFI RNNYIATIYK SIGTFLFGAA ASQSLTDIAK
YSIGRLRPHF LSVCDPDWSK VNCSDGYIEY YVCRGNAEKV KEGRLSFYSG HSSFSMYCMV
FVALYLQARM KGDWARLLRP TLQFGLVAAS IYVGLSRISD YKHHWSDVLT GLIQGAIVAI
LVAVYVSDFF KARNSPFQER KEEDSHTTLH ETPTAGNHYR SNHQP
//
