PLPP3_HUMAN
ID PLPP3_HUMAN Reviewed; 311 AA.
AC O14495; B2R651; D3DQ52; Q5U0F7; Q96GW0; Q99782;
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 3 {ECO:0000305};
DE EC=3.1.3.- {ECO:0000269|PubMed:27694435};
DE EC=3.1.3.4 {ECO:0000269|PubMed:9607309, ECO:0000269|PubMed:9705349};
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;
DE AltName: Full=Vascular endothelial growth factor and type I collagen-inducible protein {ECO:0000303|PubMed:12660161};
DE Short=VCIP {ECO:0000303|PubMed:12660161};
GN Name=PLPP3 {ECO:0000312|HGNC:HGNC:9229}; Synonyms=LPP3, PPAP2B;
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], INDUCTION, AND TISSUE SPECIFICITY.
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], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, ACTIVITY REGULATION,
RP PATHWAY, SUBCELLULAR LOCATION, GLYCOSYLATION, AND MUTAGENESIS OF ASP-184.
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY,
RP TISSUE SPECIFICITY, AND MOTIF.
RX PubMed=12660161; DOI=10.1093/emboj/cdg165;
RA Humtsoe J.O., Feng S., Thakker G.D., Yang J., Hong J., Wary K.K.;
RT "Regulation of cell-cell interactions by phosphatidic acid phosphatase
RT 2b/VCIP.";
RL EMBO J. 22:1539-1554(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Leung D.W., Tompkins C.K.;
RT "Molecular cloning of and expression of an isoform of human phosphatidic
RT acid phosphatase cDNA.";
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=9110174; DOI=10.1101/gr.7.4.353;
RA Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W.,
RA Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.;
RT "Large-scale concatenation cDNA sequencing.";
RL Genome Res. 7:353-358(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [10]
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 [11]
RP SUBCELLULAR LOCATION, DOMAIN, 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 [12]
RP SUBUNIT.
RX PubMed=14725715; DOI=10.1186/1471-2091-5-2;
RA Burnett C., Makridou P., Hewlett L., Howard K.;
RT "Lipid phosphate phosphatases dimerise, but this interaction is not
RT required for in vivo activity.";
RL BMC Biochem. 5:2-2(2004).
RN [13]
RP FUNCTION, AND MOTIF.
RX PubMed=16099422; DOI=10.1016/j.bbrc.2005.07.157;
RA Humtsoe J.O., Bowling R.A. Jr., Feng S., Wary K.K.;
RT "Murine lipid phosphate phosphohydrolase-3 acts as a cell-associated
RT integrin ligand.";
RL Biochem. Biophys. Res. Commun. 335:906-919(2005).
RN [14]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-106; TYR-109 AND TYR-110.
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 [15]
RP SUBUNIT.
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).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP FUNCTION, INTERACTION WITH CTNND1, SUBCELLULAR LOCATION, AND REGION.
RX PubMed=20123964; DOI=10.1128/mcb.00038-09;
RA Humtsoe J.O., Liu M., Malik A.B., Wary K.K.;
RT "Lipid phosphate phosphatase 3 stabilization of beta-catenin induces
RT endothelial cell migration and formation of branching point structures.";
RL Mol. Cell. Biol. 30:1593-1606(2010).
RN [19]
RP FUNCTION.
RX PubMed=21569306; DOI=10.1186/1476-4598-10-51;
RA Chatterjee I., Humtsoe J.O., Kohler E.E., Sorio C., Wary K.K.;
RT "Lipid phosphate phosphatase-3 regulates tumor growth via beta-catenin and
RT CYCLIN-D1 signaling.";
RL Mol. Cancer 10:51-51(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23591818; DOI=10.1242/jcs.117705;
RA Gutierrez-Martinez E., Fernandez-Ulibarri I., Lazaro-Dieguez F.,
RA Johannes L., Pyne S., Sarri E., Egea G.;
RT "Lipid phosphate phosphatase 3 participates in transport carrier formation
RT and protein trafficking in the early secretory pathway.";
RL J. Cell Sci. 126:2641-2655(2013).
RN [22]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=27694435; DOI=10.1093/cvr/cvw217;
RA Touat-Hamici Z., Weidmann H., Blum Y., Proust C., Durand H., Iannacci F.,
RA Codoni V., Gaignard P., Therond P., Civelek M., Karabina S.A., Lusis A.J.,
RA Cambien F., Ninio E.;
RT "Role of lipid phosphate phosphatase 3 in human aortic endothelial cell
RT function.";
RL Cardiovasc. Res. 112:702-713(2016).
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:9705349, PubMed:9607309, PubMed:27694435). Also
CC acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-
CC ethanolamine phosphate, a potential physiological compound
CC (PubMed:9607309). Has both an extracellular and an intracellular
CC phosphatase activity, allowing the hydrolysis and the cellular uptake
CC of these bioactive lipid mediators from the milieu, regulating signal
CC transduction in different cellular processes (PubMed:9607309,
CC PubMed:23591818, PubMed:27694435). Through the dephosphorylation of
CC extracellular sphingosine-1-phosphate and the regulation of its
CC extra- and intracellular availability, plays a role in vascular
CC homeostasis, regulating endothelial cell migration, adhesion, survival,
CC proliferation and the production of pro-inflammatory cytokines
CC (PubMed:27694435). By maintaining the appropriate levels of this lipid
CC in the cerebellum, also ensure its proper development and function (By
CC similarity). Through its intracellular lipid phosphatase activity may
CC act in early compartments of the secretory pathway, regulating the
CC formation of Golgi to endoplasmic reticulum retrograde transport
CC carriers (PubMed:23591818). {ECO:0000250|UniProtKB:Q99JY8,
CC ECO:0000269|PubMed:23591818, ECO:0000269|PubMed:27694435,
CC ECO:0000269|PubMed:9607309, ECO:0000269|PubMed:9705349}.
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
CC (PubMed:20123964, PubMed:21569306). Also plays a role in integrin-
CC mediated cell-cell adhesion in angiogenesis (PubMed:12660161,
CC PubMed:16099422). {ECO:0000269|PubMed:12660161,
CC ECO:0000269|PubMed:16099422, ECO:0000269|PubMed:20123964,
CC ECO:0000269|PubMed:21569306}.
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:9607309, ECO:0000269|PubMed:9705349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27430;
CC Evidence={ECO:0000305|PubMed:9705349};
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:9607309};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43245;
CC Evidence={ECO:0000305|PubMed:9607309};
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:9607309, ECO:0000269|PubMed:9705349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46737;
CC Evidence={ECO:0000305|PubMed:9705349};
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:9607309,
CC ECO:0000269|PubMed:9705349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50885;
CC Evidence={ECO:0000305|PubMed:9705349};
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:27694435, ECO:0000269|PubMed:9705349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27519;
CC Evidence={ECO:0000269|PubMed:27694435};
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:9705349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33744;
CC Evidence={ECO:0000305|PubMed:9705349};
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 -!- ACTIVITY REGULATION: Magnesium-independent phospholipid phosphatase
CC (PubMed:9705349). Insensitive to N-ethylmaleimide (PubMed:9705349).
CC Inhibited by sphingosine, zinc ions and modestly by propanolol
CC (PubMed:9705349). {ECO:0000269|PubMed:9705349}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=100 uM for 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate
CC {ECO:0000269|PubMed:9607309};
CC KM=110 uM for (9Z)-octadecenoyl-sn-glycero-3-phosphate
CC {ECO:0000269|PubMed:9607309};
CC KM=56 uM for N-oleoyl ethanolamine phosphatidic acid
CC {ECO:0000269|PubMed:9607309};
CC Vmax=0.27 nmol/min/mg enzyme with 1,2-dihexadecanoyl-sn-glycero-3-
CC phosphate as substrate {ECO:0000269|PubMed:9705349};
CC Vmax=0.46 nmol/min/mg enzyme with (9Z)-octadecenoyl-sn-glycero-3-
CC phosphate as substrate {ECO:0000269|PubMed:9705349};
CC Vmax=0.36 nmol/min/mg enzyme with N-(octanoyl)-sphing-4-enine-1-
CC phosphate as substrate {ECO:0000269|PubMed:9705349};
CC Vmax=0.24 nmol/min/mg enzyme with sphing-4-enine 1-phosphate as
CC substrate {ECO:0000269|PubMed:9705349};
CC Vmax=13 nmol/min/mg enzyme with 1,2-di-(9Z-octadecenoyl)-sn-glycero-
CC 3-phosphate as substrate {ECO:0000269|PubMed:9607309};
CC Vmax=15 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:27694435, ECO:0000269|PubMed:9607309,
CC ECO:0000269|PubMed:9705349}.
CC -!- SUBUNIT: Forms functional homodimers and homooligomers that are not
CC required for substrate recognition and catalytic activity
CC (PubMed:14725715). Can also form heterooligomers with other PLPP2 and
CC PLPP3 (PubMed:18215144). Interacts with CTNND1; negatively regulates
CC the PLPP3-mediated stabilization of beta-catenin/CTNNB1
CC (PubMed:20123964). {ECO:0000269|PubMed:14725715,
CC ECO:0000269|PubMed:18215144, ECO:0000269|PubMed:20123964}.
CC -!- INTERACTION:
CC O14495; O60716: CTNND1; NbExp=9; IntAct=EBI-766232, EBI-701927;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12660161,
CC ECO:0000269|PubMed:20123964, ECO:0000269|PubMed:9705349}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P97544}. Basolateral cell
CC membrane {ECO:0000269|PubMed:14527693}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P97544}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:23591818}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P97544}. Endoplasmic reticulum-Golgi
CC intermediate compartment membrane {ECO:0000269|PubMed:23591818}; Multi-
CC pass membrane protein {ECO:0000250|UniProtKB:P97544}. Golgi apparatus
CC membrane {ECO:0000269|PubMed:23591818}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P97544}. Golgi apparatus, trans-Golgi network
CC membrane {ECO:0000269|PubMed:23591818}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P97544}. Membrane raft
CC {ECO:0000269|PubMed:17005594}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P97544}. Note=Cycles between the endoplasmic
CC reticulum and the Golgi. {ECO:0000269|PubMed:23591818}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed (PubMed:9305923,
CC PubMed:12660161). Highly expressed in heart and placenta
CC (PubMed:9305923). {ECO:0000269|PubMed:12660161,
CC ECO:0000269|PubMed:9305923}.
CC -!- INDUCTION: By EGF, VEGF, FGF2 and phorbol myristate acetate (PMA).
CC {ECO:0000269|PubMed:9305923}.
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:0000269|PubMed:12660161, ECO:0000269|PubMed:16099422}.
CC -!- DOMAIN: The dityrosine basolateral targeting motif mediates
CC localization to the basolateral membrane in polarized cells.
CC {ECO:0000269|PubMed:14527693}.
CC -!- PTM: N-glycosylated (PubMed:9705349). Contains high-mannose
CC oligosaccharides (PubMed:9705349). {ECO:0000269|PubMed:9705349}.
CC -!- SIMILARITY: Belongs to the PA-phosphatase related phosphoesterase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB50222.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB000889; BAA22594.1; -; mRNA.
DR EMBL; AF017786; AAC63433.1; -; mRNA.
DR EMBL; AF480883; AAO84481.1; -; mRNA.
DR EMBL; AF043329; AAD02271.1; -; mRNA.
DR EMBL; U79294; AAB50222.1; ALT_FRAME; mRNA.
DR EMBL; AK312439; BAG35348.1; -; mRNA.
DR EMBL; BT019589; AAV38396.1; -; mRNA.
DR EMBL; CH471059; EAX06651.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06652.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06653.1; -; Genomic_DNA.
DR EMBL; BC009196; AAH09196.1; -; mRNA.
DR CCDS; CCDS604.1; -.
DR RefSeq; NP_003704.3; NM_003713.4.
DR AlphaFoldDB; O14495; -.
DR BioGRID; 114171; 27.
DR CORUM; O14495; -.
DR IntAct; O14495; 5.
DR MINT; O14495; -.
DR STRING; 9606.ENSP00000360296; -.
DR SwissLipids; SLP:000001642; -.
DR DEPOD; PLPP3; -.
DR GlyGen; O14495; 1 site.
DR iPTMnet; O14495; -.
DR PhosphoSitePlus; O14495; -.
DR BioMuta; PLPP3; -.
DR EPD; O14495; -.
DR jPOST; O14495; -.
DR MassIVE; O14495; -.
DR MaxQB; O14495; -.
DR PaxDb; O14495; -.
DR PeptideAtlas; O14495; -.
DR PRIDE; O14495; -.
DR ProteomicsDB; 48039; -.
DR Antibodypedia; 33239; 137 antibodies from 26 providers.
DR DNASU; 8613; -.
DR Ensembl; ENST00000371250.4; ENSP00000360296.3; ENSG00000162407.9.
DR GeneID; 8613; -.
DR KEGG; hsa:8613; -.
DR MANE-Select; ENST00000371250.4; ENSP00000360296.3; NM_003713.5; NP_003704.3.
DR UCSC; uc001cyj.3; human.
DR CTD; 8613; -.
DR DisGeNET; 8613; -.
DR GeneCards; PLPP3; -.
DR HGNC; HGNC:9229; PLPP3.
DR HPA; ENSG00000162407; Low tissue specificity.
DR MIM; 607125; gene.
DR neXtProt; NX_O14495; -.
DR OpenTargets; ENSG00000162407; -.
DR PharmGKB; PA33553; -.
DR VEuPathDB; HostDB:ENSG00000162407; -.
DR eggNOG; KOG3030; Eukaryota.
DR GeneTree; ENSGT00940000156450; -.
DR HOGENOM; CLU_021458_3_0_1; -.
DR InParanoid; O14495; -.
DR OMA; KYPANSG; -.
DR OrthoDB; 1621899at2759; -.
DR PhylomeDB; O14495; -.
DR TreeFam; TF316040; -.
DR BRENDA; 3.1.3.4; 2681.
DR PathwayCommons; O14495; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR SignaLink; O14495; -.
DR UniPathway; UPA00085; -.
DR BioGRID-ORCS; 8613; 6 hits in 1071 CRISPR screens.
DR ChiTaRS; PLPP3; human.
DR GeneWiki; PPAP2B; -.
DR GenomeRNAi; 8613; -.
DR Pharos; O14495; Tbio.
DR PRO; PR:O14495; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O14495; protein.
DR Bgee; ENSG00000162407; Expressed in decidua and 204 other tissues.
DR Genevisible; O14495; HS.
DR GO; GO:0005912; C:adherens junction; TAS:BHF-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0070971; C:endoplasmic reticulum exit site; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0106235; F:ceramide-1-phosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB.
DR GO; GO:0042577; F:lipid phosphatase activity; IBA:GO_Central.
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:0060020; P:Bergmann glial cell differentiation; IEA:Ensembl.
DR GO; GO:0001568; P:blood vessel development; IEA:Ensembl.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0033631; P:cell-cell adhesion mediated by integrin; IDA:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; IDA:UniProtKB.
DR GO; GO:0001702; P:gastrulation with mouth forming second; IEA:Ensembl.
DR GO; GO:0034109; P:homotypic cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0046839; P:phospholipid dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006644; P:phospholipid metabolic process; IDA:UniProtKB.
DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; IMP:BHF-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0050821; P:protein stabilization; IDA:BHF-UCL.
DR GO; GO:1902068; P:regulation of sphingolipid mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
DR GO; GO:0006670; P:sphingosine metabolic process; IDA:UniProtKB.
DR GO; GO:0042060; P:wound healing; IMP:BHF-UCL.
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..311
FT /note="Phospholipid phosphatase 3"
FT /id="PRO_0000220912"
FT TOPO_DOM 1..33
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:12660161"
FT TRANSMEM 34..54
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 55..85
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:12660161"
FT TRANSMEM 86..106
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 107..122
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:12660161"
FT TRANSMEM 123..143
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 144..193
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:12660161"
FT TRANSMEM 194..214
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 215..225
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:12660161"
FT TRANSMEM 226..243
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 244..257
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:12660161"
FT TRANSMEM 258..278
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 279..311
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:12660161"
FT REGION 148..156
FT /note="Phosphatase sequence motif I"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 196..199
FT /note="Phosphatase sequence motif II"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 244..255
FT /note="Phosphatase sequence motif III"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 275..311
FT /note="Mediates interaction with CTNND1"
FT /evidence="ECO:0000269|PubMed:20123964"
FT MOTIF 109..110
FT /note="Dityrosine basolateral targeting motif"
FT /evidence="ECO:0000269|PubMed:14527693"
FT MOTIF 182..184
FT /note="Integrin-binding motif"
FT /evidence="ECO:0000269|PubMed:12660161,
FT ECO:0000269|PubMed:16099422"
FT ACT_SITE 199
FT /note="Proton donors"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT ACT_SITE 251
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT SITE 255
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:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:21406692"
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 106
FT /note="Y->A: No effect on basolateral localization in
FT polarized cells."
FT /evidence="ECO:0000269|PubMed:17005594"
FT MUTAGEN 109
FT /note="Y->A: Loss of basolateral localization in polarized
FT cells."
FT /evidence="ECO:0000269|PubMed:17005594"
FT MUTAGEN 110
FT /note="Y->A: Loss of basolateral localization in polarized
FT cells."
FT /evidence="ECO:0000269|PubMed:17005594"
FT MUTAGEN 184
FT /note="D->E: Loss of binding to integrin. Loss of function
FT in integrin-mediated cell-cell interaction."
FT /evidence="ECO:0000269|PubMed:9705349"
FT CONFLICT 32
FT /note="K -> M (in Ref. 7; AAV38396)"
FT /evidence="ECO:0000305"
FT CONFLICT 282
FT /note="T -> M (in Ref. 9; AAH09196)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 311 AA; 35116 MW; CB3F60189044DA31 CRC64;
MQNYKYDKAI VPESKNGGSP ALNNNPRRSG SKRVLLICLD LFCLFMAGLP FLIIETSTIK
PYHRGFYCND ESIKYPLKTG ETINDAVLCA VGIVIAILAI ITGEFYRIYY LKKSRSTIQN
PYVAALYKQV GCFLFGCAIS QSFTDIAKVS IGRLRPHFLS VCNPDFSQIN CSEGYIQNYR
CRGDDSKVQE ARKSFFSGHA SFSMYTMLYL VLYLQARFTW RGARLLRPLL QFTLIMMAFY
TGLSRVSDHK HHPSDVLAGF AQGALVACCI VFFVSDLFKT KTTLSLPAPA IRKEILSPVD
IIDRNNHHNM M
