PLPP6_HUMAN
ID PLPP6_HUMAN Reviewed; 295 AA.
AC Q8IY26; B3KY05; Q5JVJ6; Q8NCK9;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 3.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Polyisoprenoid diphosphate/phosphate phosphohydrolase PLPP6 {ECO:0000305|PubMed:20110354};
DE EC=3.1.3.- {ECO:0000269|PubMed:18930839, ECO:0000269|PubMed:20110354};
DE EC=3.6.1.- {ECO:0000269|PubMed:16464866, ECO:0000269|PubMed:19220020, ECO:0000269|PubMed:20110354};
DE EC=3.6.1.68 {ECO:0000269|PubMed:20110354};
DE AltName: Full=Lipid phosphatase-related protein-B {ECO:0000303|PubMed:18930839};
DE Short=LPRP-B {ECO:0000303|PubMed:18930839};
DE AltName: Full=PA-PSP {ECO:0000303|PubMed:18930839};
DE AltName: Full=Phosphatidic acid phosphatase type 2 domain-containing protein 2 {ECO:0000303|PubMed:16464866, ECO:0000312|HGNC:HGNC:23682};
DE Short=PPAP2 domain-containing protein 2 {ECO:0000303|PubMed:16464866};
DE AltName: Full=Phospholipid phosphatase 6 {ECO:0000312|HGNC:HGNC:23682};
DE AltName: Full=Presqualene diphosphate phosphatase {ECO:0000303|PubMed:16464866};
DE AltName: Full=Type 1 polyisoprenoid diphosphate phosphatase {ECO:0000303|PubMed:20110354};
GN Name=PLPP6 {ECO:0000312|HGNC:HGNC:23682};
GN Synonyms=PDP1 {ECO:0000303|PubMed:20110354},
GN PPAPDC2 {ECO:0000303|PubMed:16464866, ECO:0000312|HGNC:HGNC:23682};
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 [LARGE SCALE MRNA].
RC TISSUE=Mammary gland, and Thymus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TRP-140.
RC TISSUE=Testis;
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 [4]
RP PROTEIN SEQUENCE OF 76-91, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, TOPOLOGY, AND TISSUE SPECIFICITY.
RX PubMed=16464866; DOI=10.1074/jbc.m512970200;
RA Fukunaga K., Arita M., Takahashi M., Morris A.J., Pfeffer M., Levy B.D.;
RT "Identification and functional characterization of a presqualene
RT diphosphate phosphatase.";
RL J. Biol. Chem. 281:9490-9497(2006).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=18930839; DOI=10.1016/j.bbalip.2008.09.001;
RA Theofilopoulos S., Lykidis A., Leondaritis G., Mangoura D.;
RT "Novel function of the human presqualene diphosphate phosphatase as a type
RT II phosphatidate phosphatase in phosphatidylcholine and triacylglyceride
RT biosynthesis pathways.";
RL Biochim. Biophys. Acta 1781:731-742(2008).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND PHOSPHORYLATION.
RX PubMed=19220020; DOI=10.1021/bi8020636;
RA Carlo T., Petasis N.A., Levy B.D.;
RT "Activation of polyisoprenyl diphosphate phosphatase 1 remodels cellular
RT presqualene diphosphate.";
RL Biochemistry 48:2997-3004(2009).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, SUBCELLULAR LOCATION,
RP TOPOLOGY, ACTIVE SITE, REGION, AND MUTAGENESIS OF LYS-184; SER-212 AND
RP HIS-256.
RX PubMed=20110354; DOI=10.1074/jbc.m109.083931;
RA Miriyala S., Subramanian T., Panchatcharam M., Ren H., McDermott M.I.,
RA Sunkara M., Drennan T., Smyth S.S., Spielmann H.P., Morris A.J.;
RT "Functional characterization of the atypical integral membrane lipid
RT phosphatase PDP1/PPAPDC2 identifies a pathway for interconversion of
RT isoprenols and isoprenoid phosphates in mammalian cells.";
RL J. Biol. Chem. 285:13918-13929(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=23568778; DOI=10.1096/fj.12-223982;
RA Carlo T., Kalwa H., Levy B.D.;
RT "15-Epi-lipoxin A4 inhibits human neutrophil superoxide anion generation by
RT regulating polyisoprenyl diphosphate phosphatase 1.";
RL FASEB J. 27:2733-2741(2013).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26 AND SER-36, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Magnesium-independent polyisoprenoid diphosphatase that
CC catalyzes the sequential dephosphorylation of presqualene, farnesyl,
CC geranyl and geranylgeranyl diphosphates (PubMed:16464866,
CC PubMed:19220020, PubMed:20110354). Functions in the innate immune
CC response through the dephosphorylation of presqualene diphosphate which
CC acts as a potent inhibitor of the signaling pathways contributing to
CC polymorphonuclear neutrophils activation (PubMed:16464866,
CC PubMed:23568778). May regulate the biosynthesis of cholesterol and
CC related sterols by dephosphorylating presqualene and farnesyl
CC diphosphate, two key intermediates in this biosynthetic pathway
CC (PubMed:20110354). May also play a role in protein prenylation by
CC acting on farnesyl diphosphate and its derivative geranylgeranyl
CC diphosphate, two precursors for the addition of isoprenoid anchors to
CC membrane proteins (PubMed:20110354). Has a lower activity towards
CC phosphatidic acid (PA), but through phosphatidic acid dephosphorylation
CC may participate in the biosynthesis of phospholipids and
CC triacylglycerols (PubMed:18930839). May also act on ceramide-1-P,
CC lysophosphatidic acid (LPA) and sphing-4-enine 1-phosphate/sphingosine-
CC 1-phosphate (PubMed:18930839, PubMed:20110354).
CC {ECO:0000269|PubMed:16464866, ECO:0000269|PubMed:18930839,
CC ECO:0000269|PubMed:19220020, ECO:0000269|PubMed:20110354,
CC ECO:0000269|PubMed:23568778}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + presqualene diphosphate = H(+) + phosphate + presqualene
CC monophosphate; Xref=Rhea:RHEA:67968, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57310,
CC ChEBI:CHEBI:176803; Evidence={ECO:0000269|PubMed:16464866,
CC ECO:0000269|PubMed:19220020, ECO:0000269|PubMed:20110354};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67969;
CC Evidence={ECO:0000269|PubMed:19220020};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + presqualene monophosphate = phosphate + presqualene
CC alcohol; Xref=Rhea:RHEA:68024, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:176803, ChEBI:CHEBI:176962;
CC Evidence={ECO:0000305|PubMed:20110354};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68025;
CC Evidence={ECO:0000305|PubMed:20110354};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + H2O = (2E,6E)-farnesyl
CC phosphate + H(+) + phosphate; Xref=Rhea:RHEA:48128,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:88226, ChEBI:CHEBI:175763;
CC Evidence={ECO:0000269|PubMed:19220020, ECO:0000269|PubMed:20110354};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48129;
CC Evidence={ECO:0000305|PubMed:20110354};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl phosphate + H2O = (2E,6E)-farnesol +
CC phosphate; Xref=Rhea:RHEA:48132, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:16619, ChEBI:CHEBI:43474, ChEBI:CHEBI:88226;
CC Evidence={ECO:0000305|PubMed:20110354};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48133;
CC Evidence={ECO:0000305|PubMed:20110354};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E,10E)-geranylgeranyl diphosphate + H2O = (2E,6E,10E)-
CC geranylgeranyl phosphate + H(+) + phosphate; Xref=Rhea:RHEA:68008,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58756, ChEBI:CHEBI:144936;
CC Evidence={ECO:0000269|PubMed:20110354};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68009;
CC Evidence={ECO:0000305|PubMed:20110354};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E,10E)-geranylgeranyl phosphate + H2O = (2E,6E,10E)-
CC geranylgeraniol + phosphate; Xref=Rhea:RHEA:68016, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:46762, ChEBI:CHEBI:144936;
CC Evidence={ECO:0000305|PubMed:20110354};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68017;
CC Evidence={ECO:0000305|PubMed:20110354};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-geranyl diphosphate + H2O = (2E)-geranyl phosphate + H(+)
CC + phosphate; Xref=Rhea:RHEA:47944, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:58057,
CC ChEBI:CHEBI:88107; EC=3.6.1.68;
CC Evidence={ECO:0000269|PubMed:20110354};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47945;
CC Evidence={ECO:0000305|PubMed:20110354};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-geranyl phosphate + H2O = (2E)-geraniol + phosphate;
CC Xref=Rhea:RHEA:68020, ChEBI:CHEBI:15377, ChEBI:CHEBI:17447,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:88107;
CC Evidence={ECO:0000305|PubMed:20110354};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68021;
CC Evidence={ECO:0000305|PubMed:20110354};
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:18930839,
CC ECO:0000269|PubMed:20110354};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43237;
CC Evidence={ECO:0000305|PubMed:18930839};
CC -!- ACTIVITY REGULATION: Inhibited by propranolol (PubMed:18930839). Not
CC inhibited by N-ethylmaleimide or bromoenolactome (PubMed:18930839).
CC {ECO:0000269|PubMed:18930839}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=44.8 nmol/min/mg enzyme with 1,2-dihexadecanoyl-sn-glycero-3-
CC phosphate as substrate {ECO:0000269|PubMed:18930839};
CC pH dependence:
CC Optimum pH is 7-8. {ECO:0000269|PubMed:16464866};
CC -!- INTERACTION:
CC Q8IY26; Q86WK6: AMIGO1; NbExp=3; IntAct=EBI-11721828, EBI-19125216;
CC Q8IY26; Q13520: AQP6; NbExp=3; IntAct=EBI-11721828, EBI-13059134;
CC Q8IY26; O94778: AQP8; NbExp=3; IntAct=EBI-11721828, EBI-19124986;
CC Q8IY26; Q7KYR7-4: BTN2A1; NbExp=3; IntAct=EBI-11721828, EBI-17841208;
CC Q8IY26; Q6UXG8-3: BTNL9; NbExp=3; IntAct=EBI-11721828, EBI-17953245;
CC Q8IY26; P11912: CD79A; NbExp=3; IntAct=EBI-11721828, EBI-7797864;
CC Q8IY26; Q9H5X1: CIAO2A; NbExp=3; IntAct=EBI-11721828, EBI-752069;
CC Q8IY26; Q96FX9: CLDN15; NbExp=3; IntAct=EBI-11721828, EBI-12867518;
CC Q8IY26; O95484: CLDN9; NbExp=3; IntAct=EBI-11721828, EBI-18341636;
CC Q8IY26; Q9H2X3: CLEC4M; NbExp=3; IntAct=EBI-11721828, EBI-1391211;
CC Q8IY26; A0A024R644: CLN5; NbExp=3; IntAct=EBI-11721828, EBI-12838990;
CC Q8IY26; P21964: COMT; NbExp=3; IntAct=EBI-11721828, EBI-372265;
CC Q8IY26; Q96BA8: CREB3L1; NbExp=5; IntAct=EBI-11721828, EBI-6942903;
CC Q8IY26; Q15125: EBP; NbExp=3; IntAct=EBI-11721828, EBI-3915253;
CC Q8IY26; Q8TBP5: FAM174A; NbExp=3; IntAct=EBI-11721828, EBI-18636064;
CC Q8IY26; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-11721828, EBI-18304435;
CC Q8IY26; Q96KR6: FAM210B; NbExp=3; IntAct=EBI-11721828, EBI-18938272;
CC Q8IY26; Q96LL3: FIMP; NbExp=3; IntAct=EBI-11721828, EBI-12887376;
CC Q8IY26; Q9Y680: FKBP7; NbExp=3; IntAct=EBI-11721828, EBI-3918971;
CC Q8IY26; Q8TBE3: FNDC9; NbExp=3; IntAct=EBI-11721828, EBI-12142257;
CC Q8IY26; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-11721828, EBI-12175685;
CC Q8IY26; O95377: GJB5; NbExp=3; IntAct=EBI-11721828, EBI-3909454;
CC Q8IY26; Q9NS71: GKN1; NbExp=3; IntAct=EBI-11721828, EBI-3933251;
CC Q8IY26; Q5T7V8: GORAB; NbExp=3; IntAct=EBI-11721828, EBI-3917143;
CC Q8IY26; Q8TED1: GPX8; NbExp=3; IntAct=EBI-11721828, EBI-11721746;
CC Q8IY26; Q13651: IL10RA; NbExp=3; IntAct=EBI-11721828, EBI-1031656;
CC Q8IY26; Q14627: IL13RA2; NbExp=3; IntAct=EBI-11721828, EBI-4320063;
CC Q8IY26; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-11721828, EBI-749265;
CC Q8IY26; Q6UX15-2: LAYN; NbExp=3; IntAct=EBI-11721828, EBI-19944128;
CC Q8IY26; Q5T700: LDLRAD1; NbExp=3; IntAct=EBI-11721828, EBI-10173166;
CC Q8IY26; Q8N4V1: MMGT1; NbExp=3; IntAct=EBI-11721828, EBI-6163737;
CC Q8IY26; Q96HJ5: MS4A3; NbExp=3; IntAct=EBI-11721828, EBI-12806656;
CC Q8IY26; P15941-11: MUC1; NbExp=3; IntAct=EBI-11721828, EBI-17263240;
CC Q8IY26; Q68D85: NCR3LG1; NbExp=3; IntAct=EBI-11721828, EBI-14061804;
CC Q8IY26; P16234-2: PDGFRA; NbExp=3; IntAct=EBI-11721828, EBI-13380852;
CC Q8IY26; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-11721828, EBI-716063;
CC Q8IY26; Q96KR7: PHACTR3; NbExp=3; IntAct=EBI-11721828, EBI-717068;
CC Q8IY26; P16471: PRLR; NbExp=3; IntAct=EBI-11721828, EBI-476182;
CC Q8IY26; P15151: PVR; NbExp=3; IntAct=EBI-11721828, EBI-3919694;
CC Q8IY26; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-11721828, EBI-10192441;
CC Q8IY26; Q96K19-5: RNF170; NbExp=3; IntAct=EBI-11721828, EBI-12055631;
CC Q8IY26; Q99942: RNF5; NbExp=3; IntAct=EBI-11721828, EBI-348482;
CC Q8IY26; Q9BY50: SEC11C; NbExp=3; IntAct=EBI-11721828, EBI-2855401;
CC Q8IY26; Q3SXP7: SHISAL1; NbExp=3; IntAct=EBI-11721828, EBI-18037857;
CC Q8IY26; Q96PQ1: SIGLEC12; NbExp=3; IntAct=EBI-11721828, EBI-17640454;
CC Q8IY26; Q8TBB6: SLC7A14; NbExp=3; IntAct=EBI-11721828, EBI-5235586;
CC Q8IY26; Q0VAQ4: SMAGP; NbExp=3; IntAct=EBI-11721828, EBI-10226799;
CC Q8IY26; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-11721828, EBI-17280858;
CC Q8IY26; Q16623: STX1A; NbExp=3; IntAct=EBI-11721828, EBI-712466;
CC Q8IY26; Q8N205-2: SYNE4; NbExp=3; IntAct=EBI-11721828, EBI-12099160;
CC Q8IY26; Q8TBG9: SYNPR; NbExp=3; IntAct=EBI-11721828, EBI-10273251;
CC Q8IY26; Q9BVX2: TMEM106C; NbExp=3; IntAct=EBI-11721828, EBI-2821497;
CC Q8IY26; Q9UBN6: TNFRSF10D; NbExp=3; IntAct=EBI-11721828, EBI-1044859;
CC Q8IY26; Q9H7M9: VSIR; NbExp=3; IntAct=EBI-11721828, EBI-744988;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:16464866, ECO:0000269|PubMed:18930839,
CC ECO:0000269|PubMed:20110354}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:20110354}. Nucleus envelope
CC {ECO:0000269|PubMed:18930839}. Nucleus inner membrane
CC {ECO:0000305|PubMed:20110354}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in most organs, in
CC particular gastrointestinal organs, spleen, placenta, kidney, thymus
CC and brain. {ECO:0000269|PubMed:16464866}.
CC -!- PTM: Phosphorylation by PKC activates the phosphatase activity towards
CC presqualene diphosphate. {ECO:0000269|PubMed:19220020,
CC ECO:0000269|PubMed:23568778}.
CC -!- SIMILARITY: Belongs to the PA-phosphatase related phosphoesterase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AK074672; 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; AK074672; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK128369; BAG54667.1; -; mRNA.
DR EMBL; AL136231; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC038108; AAH38108.2; -; mRNA.
DR CCDS; CCDS34981.1; -.
DR RefSeq; NP_982278.3; NM_203453.3.
DR AlphaFoldDB; Q8IY26; -.
DR SMR; Q8IY26; -.
DR BioGRID; 135624; 71.
DR IntAct; Q8IY26; 64.
DR MINT; Q8IY26; -.
DR STRING; 9606.ENSP00000371307; -.
DR DEPOD; PLPP6; -.
DR iPTMnet; Q8IY26; -.
DR PhosphoSitePlus; Q8IY26; -.
DR BioMuta; PLPP6; -.
DR DMDM; 108860900; -.
DR EPD; Q8IY26; -.
DR jPOST; Q8IY26; -.
DR MassIVE; Q8IY26; -.
DR MaxQB; Q8IY26; -.
DR PaxDb; Q8IY26; -.
DR PeptideAtlas; Q8IY26; -.
DR PRIDE; Q8IY26; -.
DR ProteomicsDB; 71092; -.
DR Antibodypedia; 3112; 134 antibodies from 27 providers.
DR DNASU; 403313; -.
DR Ensembl; ENST00000381883.5; ENSP00000371307.2; ENSG00000205808.7.
DR GeneID; 403313; -.
DR KEGG; hsa:403313; -.
DR MANE-Select; ENST00000381883.5; ENSP00000371307.2; NM_203453.5; NP_982278.3.
DR UCSC; uc003zin.5; human.
DR CTD; 403313; -.
DR DisGeNET; 403313; -.
DR GeneCards; PLPP6; -.
DR HGNC; HGNC:23682; PLPP6.
DR HPA; ENSG00000205808; Low tissue specificity.
DR MIM; 611666; gene.
DR neXtProt; NX_Q8IY26; -.
DR OpenTargets; ENSG00000205808; -.
DR PharmGKB; PA142671155; -.
DR VEuPathDB; HostDB:ENSG00000205808; -.
DR eggNOG; KOG4268; Eukaryota.
DR GeneTree; ENSGT00940000160907; -.
DR HOGENOM; CLU_072573_4_0_1; -.
DR InParanoid; Q8IY26; -.
DR OMA; GVCAGEN; -.
DR OrthoDB; 1356295at2759; -.
DR PhylomeDB; Q8IY26; -.
DR TreeFam; TF323272; -.
DR PathwayCommons; Q8IY26; -.
DR Reactome; R-HSA-191273; Cholesterol biosynthesis.
DR SignaLink; Q8IY26; -.
DR BioGRID-ORCS; 403313; 8 hits in 1067 CRISPR screens.
DR ChiTaRS; PLPP6; human.
DR GenomeRNAi; 403313; -.
DR Pharos; Q8IY26; Tbio.
DR PRO; PR:Q8IY26; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q8IY26; protein.
DR Bgee; ENSG00000205808; Expressed in secondary oocyte and 156 other tissues.
DR Genevisible; Q8IY26; HS.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005637; C:nuclear inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0016787; F:hydrolase activity; TAS:Reactome.
DR GO; GO:0106405; F:isoprenoid diphosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0042577; F:lipid phosphatase activity; IDA:UniProtKB.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0052642; F:lysophosphatidic acid 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:0006695; P:cholesterol biosynthetic process; TAS:Reactome.
DR GO; GO:0045339; P:farnesyl diphosphate catabolic process; IDA:UniProtKB.
DR GO; GO:0033383; P:geranyl diphosphate metabolic process; IDA:UniProtKB.
DR GO; GO:1902247; P:geranylgeranyl diphosphate catabolic process; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006720; P:isoprenoid metabolic process; IDA:UniProtKB.
DR GO; GO:0046839; P:phospholipid dephosphorylation; IDA:UniProtKB.
DR GO; GO:1902565; P:positive regulation of neutrophil activation; IMP:UniProtKB.
DR GO; GO:0018342; P:protein prenylation; IMP:UniProtKB.
DR InterPro; IPR036938; P_Acid_Pase_2/haloperoxi_sf.
DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
DR Pfam; PF01569; PAP2; 1.
DR SMART; SM00014; acidPPc; 1.
DR SUPFAM; SSF48317; SSF48317; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Endoplasmic reticulum; Hydrolase; Immunity;
KW Innate immunity; Lipid metabolism; Lyase; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..295
FT /note="Polyisoprenoid diphosphate/phosphate
FT phosphohydrolase PLPP6"
FT /id="PRO_0000239396"
FT TOPO_DOM 1..132
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:20110354"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 154..164
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:20110354"
FT TRANSMEM 165..185
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 186..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:20110354"
FT TRANSMEM 229..249
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..260
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:20110354"
FT TRANSMEM 261..281
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 282..295
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:20110354"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 61..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 184..192
FT /note="Phosphatase sequence motif I"
FT /evidence="ECO:0000305|PubMed:20110354"
FT REGION 211..214
FT /note="Phosphatase sequence motif II"
FT /evidence="ECO:0000305|PubMed:20110354"
FT REGION 249..260
FT /note="Phosphatase sequence motif III"
FT /evidence="ECO:0000305|PubMed:20110354"
FT COMPBIAS 13..27
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 214
FT /note="Proton donors"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT ACT_SITE 256
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O34349,
FT ECO:0000305|PubMed:20110354"
FT SITE 260
FT /note="Stabilizes the active site histidine for
FT nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 36
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D4F2"
FT VARIANT 7
FT /note="S -> G (in dbSNP:rs34250374)"
FT /id="VAR_050616"
FT VARIANT 8
FT /note="M -> T (in dbSNP:rs35791393)"
FT /id="VAR_050617"
FT VARIANT 140
FT /note="S -> W (in dbSNP:rs17857157)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_026645"
FT MUTAGEN 184
FT /note="K->R: Loss of polyisoprenoid diphosphate phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:20110354"
FT MUTAGEN 212
FT /note="S->T: Loss of polyisoprenoid diphosphate phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:20110354"
FT MUTAGEN 256
FT /note="H->A: Loss of polyisoprenoid diphosphate phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:20110354"
SQ SEQUENCE 295 AA; 32194 MW; 92024580CE727AED CRC64;
MPSPRRSMEG RPLGVSASSS SSSPGSPAHG GGGGGSRFEF QSLLSSRATA VDPTCARLRA
SESPVHRRGS FPLAAAGPSQ SPAPPLPEED RMDLNPSFLG IALRSLLAID LWLSKKLGVC
AGESSSWGSV RPLMKLLEIS GHGIPWLLGT LYCLCRSDSW AGREVLMNLL FALLLDLLLV
ALIKGLVRRR RPAHNQMDMF VTLSVDKYSF PSGHATRAAL MSRFILNHLV LAIPLRVLVV
LWAFVLGLSR VMLGRHNVTD VAFGFFLGYM QYSIVDYCWL SPHNAPVLFL LWSQR
