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 27-MAR-2024, entry version 190. 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 CC 1,2-dihexadecanoyl-sn-glycero-3-phosphate as substrate CC {ECO:0000269|PubMed:9705349}; CC Vmax=0.46 nmol/min/mg enzyme with CC (9Z)-octadecenoyl-sn-glycero-3-phosphate as substrate CC {ECO:0000269|PubMed:9705349}; CC Vmax=0.36 nmol/min/mg enzyme with CC N-(octanoyl)-sphing-4-enine-1-phosphate as substrate CC {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 CC 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate as substrate CC {ECO:0000269|PubMed:9607309}; CC Vmax=15 nmol/min/mg enzyme with CC (9Z)-octadecenoyl-sn-glycero-3-phosphate as substrate CC {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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 6. DR MINT; O14495; -. DR STRING; 9606.ENSP00000360296; -. DR SwissLipids; SLP:000001642; -. DR DEPOD; PLPP3; -. DR GlyCosmos; O14495; 1 site, No reported glycans. DR GlyGen; O14495; 1 site. DR iPTMnet; O14495; -. DR PhosphoSitePlus; O14495; -. DR SwissPalm; O14495; -. DR BioMuta; PLPP3; -. DR EPD; O14495; -. DR jPOST; O14495; -. DR MassIVE; O14495; -. DR MaxQB; O14495; -. DR PaxDb; 9606-ENSP00000360296; -. DR PeptideAtlas; O14495; -. DR ProteomicsDB; 48039; -. DR Pumba; O14495; -. DR Antibodypedia; 33239; 159 antibodies from 27 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 AGR; HGNC:9229; -. 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; YRIHYLH; -. DR OrthoDB; 25293at2759; -. DR PhylomeDB; O14495; -. DR TreeFam; TF316040; -. DR BRENDA; 3.1.3.4; 2681. DR PathwayCommons; O14495; -. DR Reactome; R-HSA-428157; Sphingolipid metabolism. DR SignaLink; O14495; -. DR UniPathway; UPA00085; -. DR BioGRID-ORCS; 8613; 7 hits in 1156 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 206 other cell types or tissues. 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: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: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: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:0006665; P:sphingolipid metabolic process; TAS:Reactome. DR GO; GO:0006670; P:sphingosine metabolic process; IDA:UniProtKB. DR GO; GO:0042060; P:wound healing; IMP:BHF-UCL. 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:SF79; PHOSPHOLIPID PHOSPHATASE 3; 1. DR Pfam; PF01569; PAP2; 1. DR SMART; SM00014; acidPPc; 1. DR SUPFAM; SSF48317; Acid phosphatase/Vanadium-dependent haloperoxidase; 1. DR Genevisible; O14495; HS. 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 //