PLPP1_HUMAN
ID PLPP1_HUMAN Reviewed; 284 AA.
AC O14494; B7ZKN8; G3XA95; O60457; O60463; Q17RZ4;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Phospholipid phosphatase 1 {ECO:0000305};
DE EC=3.1.3.- {ECO:0000269|PubMed:10962286, ECO:0000269|PubMed:17379599, ECO:0000269|PubMed:9305923, ECO:0000269|PubMed:9607309, ECO:0000269|PubMed:9705349};
DE EC=3.1.3.106 {ECO:0000250|UniProtKB:Q61469};
DE EC=3.1.3.4 {ECO:0000269|PubMed:10962286, ECO:0000269|PubMed:9305923, ECO:0000269|PubMed:9607309, ECO:0000269|PubMed:9705349};
DE EC=3.1.3.81 {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:0000312|HGNC:HGNC:9228}; Synonyms=LPP1, PPAP2A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP SUBSTRATE SPECIFICITY, ACTIVITY REGULATION, PATHWAY, SUBCELLULAR LOCATION,
RP GLYCOSYLATION, TISSUE SPECIFICITY, AND CAUTION.
RX PubMed=9305923; DOI=10.1074/jbc.272.39.24572;
RA Kai M., Wada I., Imai S., Sakane F., Kanoh H.;
RT "Cloning and characterization of two human isozymes of Mg2+-independent
RT phosphatidic acid phosphatase.";
RL J. Biol. Chem. 272:24572-24578(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=9570154; DOI=10.1089/dna.1998.17.377;
RA Leung D.W., Tompkins C.K., White T.;
RT "Molecular cloning of two alternatively spliced forms of human phosphatidic
RT acid phosphatase cDNAs that are differentially expressed in normal and
RT tumor cells.";
RL DNA Cell Biol. 17:377-385(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INDUCTION.
RC TISSUE=Prostate;
RX PubMed=9468526; DOI=10.1074/jbc.273.8.4660;
RA Ulrix W.E.J., Swinnen J., Heyns W., Verhoeven G.;
RT "Identification of the phosphatidic acid phosphatase type 2a isozyme as an
RT androgen-regulated gene in the human prostatic Adenocarcinoma cell line
RT LNCaP.";
RL J. Biol. Chem. 273:4660-4665(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, ACTIVITY REGULATION,
RP PATHWAY, AND SUBCELLULAR LOCATION.
RX PubMed=9705349; DOI=10.1074/jbc.273.34.22059;
RA Roberts R., Sciorra V.A., Morris A.J.;
RT "Human type 2 phosphatidic acid phosphohydrolases. Substrate specificity of
RT the type 2a, 2b, and 2c enzymes and cell surface activity of the 2a
RT isoform.";
RL J. Biol. Chem. 273:22059-22067(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, AND PATHWAY.
RX PubMed=9607309; DOI=10.1016/s0014-5793(98)00421-9;
RA Hooks S.B., Ragan S.P., Lynch K.R.;
RT "Identification of a novel human phosphatidic acid phosphatase type 2
RT isoform.";
RL FEBS Lett. 427:188-192(1998).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, SUBCELLULAR
RP LOCATION, AND GLYCOSYLATION.
RX PubMed=10962286; DOI=10.1016/s1388-1981(00)00081-0;
RA Roberts R.Z., Morris A.J.;
RT "Role of phosphatidic acid phosphatase 2a in uptake of extracellular lipid
RT phosphate mediators.";
RL Biochim. Biophys. Acta 1487:33-49(2000).
RN [10]
RP SUBCELLULAR LOCATION, AND MOTIF.
RX PubMed=14527693; DOI=10.1016/s0014-5793(03)00931-1;
RA Jia Y.J., Kai M., Wada I., Sakane F., Kanoh H.;
RT "Differential localization of lipid phosphate phosphatases 1 and 3 to cell
RT surface subdomains in polarized MDCK cells.";
RL FEBS Lett. 552:240-246(2003).
RN [11]
RP FUNCTION.
RX PubMed=12909631; DOI=10.1074/jbc.m306709200;
RA Smyth S.S., Sciorra V.A., Sigal Y.J., Pamulkar Z., Wang Z., Xu Y.,
RA Prestwich G.D., Morris A.J.;
RT "Lipid phosphate phosphatases regulate lysophosphatidic acid production and
RT signaling in platelets: studies using chemical inhibitors of lipid
RT phosphate phosphatase activity.";
RL J. Biol. Chem. 278:43214-43223(2003).
RN [12]
RP FUNCTION, AND MUTAGENESIS OF ARG-217.
RX PubMed=15461590; DOI=10.1042/bj20041160;
RA Zhao Y., Usatyuk P.V., Cummings R., Saatian B., He D., Watkins T.,
RA Morris A., Spannhake E.W., Brindley D.N., Natarajan V.;
RT "Lipid phosphate phosphatase-1 regulates lysophosphatidic acid-induced
RT calcium release, NF-kappaB activation and interleukin-8 secretion in human
RT bronchial epithelial cells.";
RL Biochem. J. 385:493-502(2005).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=17005594; DOI=10.1093/jb/mvj195;
RA Kai M., Sakane F., Jia Y.J., Imai S., Yasuda S., Kanoh H.;
RT "Lipid phosphate phosphatases 1 and 3 are localized in distinct lipid
RT rafts.";
RL J. Biochem. 140:677-686(2006).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=17379599; DOI=10.1074/jbc.m701279200;
RA Zhao Y., Kalari S.K., Usatyuk P.V., Gorshkova I., He D., Watkins T.,
RA Brindley D.N., Sun C., Bittman R., Garcia J.G., Berdyshev E.V.,
RA Natarajan V.;
RT "Intracellular generation of sphingosine 1-phosphate in human lung
RT endothelial cells: role of lipid phosphate phosphatase-1 and sphingosine
RT kinase 1.";
RL J. Biol. Chem. 282:14165-14177(2007).
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:9305923, PubMed:9705349, PubMed:9607309,
CC PubMed:10962286, PubMed:17379599). Also acts on N-oleoyl ethanolamine
CC phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential
CC physiological compound (PubMed:9607309). 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 (PubMed:10962286,
CC PubMed:12909631, PubMed:15461590, PubMed:17379599). It is for instance
CC essential for the extracellular hydrolysis of S1P and subsequent
CC conversion into intracellular S1P (PubMed:17379599). Involved in the
CC regulation of inflammation, platelets activation, cell proliferation
CC and migration among other processes (PubMed:12909631, PubMed:15461590).
CC May also have an intracellular activity to regulate phospholipid-
CC mediated signaling pathways (By similarity).
CC {ECO:0000250|UniProtKB:O08564, ECO:0000269|PubMed:10962286,
CC ECO:0000269|PubMed:12909631, ECO:0000269|PubMed:15461590,
CC ECO:0000269|PubMed:17379599, ECO:0000269|PubMed:9305923,
CC ECO:0000269|PubMed:9607309, ECO:0000269|PubMed:9705349}.
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:10962286, ECO:0000269|PubMed:9305923,
CC ECO:0000269|PubMed:9607309, ECO:0000269|PubMed:9705349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27430;
CC Evidence={ECO:0000305|PubMed:9305923};
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:0000269|PubMed:9705349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43237;
CC Evidence={ECO:0000305|PubMed:9705349};
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:9305923,
CC ECO:0000269|PubMed:9607309};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43245;
CC Evidence={ECO:0000305|PubMed:9305923};
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:10962286, ECO:0000269|PubMed:9305923,
CC ECO:0000269|PubMed:9607309, ECO:0000269|PubMed:9705349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46737;
CC Evidence={ECO:0000305|PubMed:9305923};
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:9305923,
CC ECO:0000269|PubMed:9607309, ECO:0000269|PubMed:9705349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50885;
CC Evidence={ECO:0000305|PubMed:9305923};
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=3.1.3.81;
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:0000269|PubMed:17379599, ECO:0000269|PubMed:9705349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27519;
CC Evidence={ECO:0000305|PubMed:9705349};
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:9305923, ECO:0000269|PubMed:9705349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33744;
CC Evidence={ECO:0000305|PubMed:9305923};
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:0000269|PubMed:9705349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62041;
CC Evidence={ECO:0000305|PubMed:9705349};
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:0000269|PubMed:9607309};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62161;
CC Evidence={ECO:0000305|PubMed:9607309};
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 (PubMed:9305923). Insensitive to N-ethylmaleimide (PubMed:9305923).
CC Inhibited by sphingosine, zinc ions and modestly by propanolol
CC (PubMed:9305923, PubMed:9705349). Inhibited by vanadate
CC (PubMed:10962286). {ECO:0000269|PubMed:10962286,
CC ECO:0000269|PubMed:9305923, ECO:0000269|PubMed:9705349}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=98 uM for 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate
CC {ECO:0000269|PubMed:9607309};
CC KM=170 uM for (9Z)-octadecenoyl-sn-glycero-3-phosphate
CC {ECO:0000269|PubMed:9607309};
CC KM=116 uM for N-(9Z-octadecenoyl)-ethanolamine phosphate
CC {ECO:0000269|PubMed:9607309};
CC Vmax=0.54 nmol/min/mg enzyme with 1,2-dihexadecanoyl-sn-glycero-3-
CC phosphate as substrate {ECO:0000269|PubMed:9705349};
CC Vmax=0.50 nmol/min/mg enzyme with (9Z)-octadecenoyl-sn-glycero-3-
CC phosphate as substrate {ECO:0000269|PubMed:9705349};
CC Vmax=0.30 nmol/min/mg enzyme with N-(octanoyl)-sphing-4-enine-1-
CC phosphate as substrate {ECO:0000269|PubMed:9705349};
CC Vmax=0.32 nmol/min/mg enzyme with sphing-4-enine 1-phosphate as
CC substrate {ECO:0000269|PubMed:9705349};
CC Vmax=41 nmol/min/mg enzyme with 1,2-di-(9Z-octadecenoyl)-sn-glycero-
CC 3-phosphate as substrate {ECO:0000269|PubMed:9607309};
CC Vmax=33 nmol/min/mg enzyme with (9Z)-octadecenoyl-sn-glycero-3-
CC phosphate as substrate {ECO:0000269|PubMed:9607309};
CC Vmax=29 nmol/min/mg enzyme with N-(9Z-octadecenoyl)-ethanolamine
CC phosphate as substrate {ECO:0000269|PubMed:9607309};
CC -!- PATHWAY: Lipid metabolism; phospholipid metabolism.
CC {ECO:0000269|PubMed:10962286, ECO:0000269|PubMed:9305923,
CC ECO:0000269|PubMed:9607309, ECO:0000269|PubMed:9705349}.
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 -!- INTERACTION:
CC O14494; P05067: APP; NbExp=3; IntAct=EBI-2865290, EBI-77613;
CC O14494; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-2865290, EBI-1383687;
CC O14494; P29466-3: CASP1; NbExp=3; IntAct=EBI-2865290, EBI-12248206;
CC O14494; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-2865290, EBI-9087876;
CC O14494; O15529: GPR42; NbExp=3; IntAct=EBI-2865290, EBI-18076404;
CC O14494; P17612: PRKACA; NbExp=3; IntAct=EBI-2865290, EBI-476586;
CC O14494; P49768-2: PSEN1; NbExp=3; IntAct=EBI-2865290, EBI-11047108;
CC O14494; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-2865290, EBI-17280858;
CC O14494; Q15583: TGIF1; NbExp=3; IntAct=EBI-2865290, EBI-714215;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10962286,
CC ECO:0000269|PubMed:9705349}; Multi-pass membrane protein {ECO:0000255}.
CC Apical cell membrane {ECO:0000269|PubMed:14527693}; Multi-pass membrane
CC protein {ECO:0000255}. Membrane raft {ECO:0000269|PubMed:17005594};
CC Multi-pass 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; Synonyms=Alpha-1, hLPP1, PAP2-a1;
CC IsoId=O14494-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha-2, hLPP1-a, PAP2-a2;
CC IsoId=O14494-2; Sequence=VSP_009651;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest expression found in
CC prostate (PubMed:9305923). Found to be down-regulated in colon
CC adenocarcinomas (PubMed:9570154). {ECO:0000269|PubMed:9305923,
CC ECO:0000269|PubMed:9570154}.
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Predominant in kidney, lung, placenta
CC and liver. {ECO:0000269|PubMed:9570154}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Predominant in heart and pancreas.
CC {ECO:0000269|PubMed:9570154}.
CC -!- INDUCTION: By androgens. {ECO:0000269|PubMed:9468526}.
CC -!- PTM: N-glycosylated (PubMed:9305923, PubMed:10962286). N-linked sugars
CC are of the complex type. N-glycosylation is not required for the
CC phosphatase activity (By similarity). {ECO:0000250|UniProtKB:Q61469,
CC ECO:0000269|PubMed:10962286, ECO:0000269|PubMed:9305923}.
CC -!- SIMILARITY: Belongs to the PA-phosphatase related phosphoesterase
CC family. {ECO:0000305}.
CC -!- CAUTION: Some reports could not detect a significant activity with
CC sphingosine 1-phosphate as substrate. {ECO:0000269|PubMed:9305923}.
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DR EMBL; AB000888; BAA22593.1; -; mRNA.
DR EMBL; AF014402; AAC16032.1; -; mRNA.
DR EMBL; AF014403; AAC16033.1; -; mRNA.
DR EMBL; Y14436; CAC14588.1; -; mRNA.
DR EMBL; AF017116; AAC32041.1; -; mRNA.
DR EMBL; AC010480; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025777; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471123; EAW54920.1; -; Genomic_DNA.
DR EMBL; CH471123; EAW54922.1; -; Genomic_DNA.
DR EMBL; BC039847; AAH39847.1; -; mRNA.
DR EMBL; BC117133; AAI17134.1; -; mRNA.
DR EMBL; BC143281; AAI43282.1; -; mRNA.
DR CCDS; CCDS34159.1; -. [O14494-1]
DR CCDS; CCDS34160.1; -. [O14494-2]
DR RefSeq; NP_003702.2; NM_003711.3. [O14494-1]
DR RefSeq; NP_795714.1; NM_176895.2. [O14494-2]
DR AlphaFoldDB; O14494; -.
DR BioGRID; 114169; 33.
DR IntAct; O14494; 13.
DR MINT; O14494; -.
DR SwissLipids; SLP:000000160; -.
DR DEPOD; PLPP1; -.
DR GlyGen; O14494; 1 site.
DR iPTMnet; O14494; -.
DR PhosphoSitePlus; O14494; -.
DR SwissPalm; O14494; -.
DR BioMuta; PLPP1; -.
DR EPD; O14494; -.
DR jPOST; O14494; -.
DR MassIVE; O14494; -.
DR MaxQB; O14494; -.
DR PeptideAtlas; O14494; -.
DR PRIDE; O14494; -.
DR ProteomicsDB; 33687; -.
DR ProteomicsDB; 48037; -. [O14494-1]
DR ProteomicsDB; 48038; -. [O14494-2]
DR Antibodypedia; 11159; 182 antibodies from 27 providers.
DR DNASU; 8611; -.
DR Ensembl; ENST00000264775.9; ENSP00000264775.5; ENSG00000067113.17. [O14494-2]
DR Ensembl; ENST00000307259.9; ENSP00000302229.8; ENSG00000067113.17. [O14494-1]
DR GeneID; 8611; -.
DR KEGG; hsa:8611; -.
DR MANE-Select; ENST00000307259.9; ENSP00000302229.8; NM_003711.4; NP_003702.2.
DR UCSC; uc003jpz.5; human. [O14494-1]
DR CTD; 8611; -.
DR DisGeNET; 8611; -.
DR GeneCards; PLPP1; -.
DR HGNC; HGNC:9228; PLPP1.
DR HPA; ENSG00000067113; Low tissue specificity.
DR MIM; 607124; gene.
DR neXtProt; NX_O14494; -.
DR OpenTargets; ENSG00000067113; -.
DR PharmGKB; PA33552; -.
DR VEuPathDB; HostDB:ENSG00000067113; -.
DR GeneTree; ENSGT00940000156730; -.
DR HOGENOM; CLU_021458_3_1_1; -.
DR InParanoid; O14494; -.
DR OMA; YTMIYLA; -.
DR PhylomeDB; O14494; -.
DR TreeFam; TF316040; -.
DR PathwayCommons; O14494; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR SignaLink; O14494; -.
DR UniPathway; UPA00085; -.
DR BioGRID-ORCS; 8611; 19 hits in 1069 CRISPR screens.
DR ChiTaRS; PLPP1; human.
DR GeneWiki; PPAP2A; -.
DR GenomeRNAi; 8611; -.
DR Pharos; O14494; Tbio.
DR PRO; PR:O14494; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O14494; protein.
DR Bgee; ENSG00000067113; Expressed in decidua and 200 other tissues.
DR ExpressionAtlas; O14494; baseline and differential.
DR Genevisible; O14494; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0106235; F:ceramide-1-phosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0000810; F:diacylglycerol diphosphate phosphatase activity; ISS:UniProtKB.
DR GO; GO:0042577; F:lipid phosphatase activity; IDA:UniProtKB.
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:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; IDA:UniProtKB.
DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; TAS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; NAS:UniProtKB.
DR GO; GO:0046839; P:phospholipid dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006644; P:phospholipid metabolic process; IDA:UniProtKB.
DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; TAS:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; NAS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
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..284
FT /note="Phospholipid phosphatase 1"
FT /id="PRO_0000220905"
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..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..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..284
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..284
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:0000269|PubMed:14527693"
FT COMPBIAS 269..284
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="GLPFAILTSRHTPFQRGVFCNDESIKYPYKEDTIPYALLGGIIIPFSIIV
FT -> SMPMAVLKLGQIYPFQRGFFCKDNSINYPYHDSTVTSTVLILVGVGLPISS (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:9570154"
FT /id="VSP_009651"
FT MUTAGEN 217
FT /note="R->K: Decreased lipid phosphatase activity."
FT /evidence="ECO:0000269|PubMed:15461590"
FT CONFLICT 27
FT /note="L -> FTSRHI (in Ref. 4; AAC32041)"
FT /evidence="ECO:0000305"
FT CONFLICT 91
FT /note="R -> S (in Ref. 2; AAC16033)"
FT /evidence="ECO:0000305"
FT CONFLICT O14494-2:55
FT /note="V -> A (in Ref. 2; AAC16033)"
FT /evidence="ECO:0000305"
FT CONFLICT O14494-2:56
FT /note="T -> A (in Ref. 2; AAC16033)"
FT /evidence="ECO:0000305"
FT CONFLICT O14494-2:69
FT /note="I -> V (in Ref. 2; AAC16033)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 284 AA; 32156 MW; FC2F00617EE07EB3 CRC64;
MFDKTRLPYV ALDVLCVLLA GLPFAILTSR HTPFQRGVFC NDESIKYPYK EDTIPYALLG
GIIIPFSIIV IILGETLSVY CNLLHSNSFI RNNYIATIYK AIGTFLFGAA ASQSLTDIAK
YSIGRLRPHF LDVCDPDWSK INCSDGYIEY YICRGNAERV KEGRLSFYSG HSSFSMYCML
FVALYLQARM KGDWARLLRP TLQFGLVAVS IYVGLSRVSD YKHHWSDVLT GLIQGALVAI
LVAVYVSDFF KERTSFKERK EEDSHTTLHE TPTTGNHYPS NHQP
