PLPP6_MOUSE
ID PLPP6_MOUSE Reviewed; 292 AA.
AC Q9D4F2;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Polyisoprenoid diphosphate/phosphate phosphohydrolase PLPP6 {ECO:0000305};
DE EC=3.1.3.- {ECO:0000250|UniProtKB:Q8IY26};
DE EC=3.6.1.- {ECO:0000250|UniProtKB:Q8IY26};
DE EC=3.6.1.68 {ECO:0000250|UniProtKB:Q8IY26};
DE AltName: Full=Phospholipid phosphatase 6 {ECO:0000312|MGI:MGI:1921661};
GN Name=Plpp6 {ECO:0000312|MGI:MGI:1921661};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-67, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-67, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Magnesium-independent polyisoprenoid diphosphatase that
CC catalyzes the sequential dephosphorylation of presqualene, farnesyl,
CC geranyl and geranylgeranyl diphosphates. 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. May regulate the biosynthesis
CC of cholesterol and related sterols by dephosphorylating presqualene and
CC farnesyl diphosphate, two key intermediates in this biosynthetic
CC pathway. May also play a role in protein prenylation by acting on
CC farnesyl diphosphate and its derivative geranylgeranyl diphosphate, two
CC precursors for the addition of isoprenoid anchors to membrane proteins.
CC Has a lower activity towards phosphatidic acid (PA), but through
CC phosphatidic acid dephosphorylation may participate in the biosynthesis
CC of phospholipids and triacylglycerols. May also act on ceramide-1-P,
CC lysophosphatidic acid (LPA) and sphing-4-enine 1-phosphate/sphingosine-
CC 1-phosphate. {ECO:0000250|UniProtKB:Q8IY26}.
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:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67969;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
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:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68025;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
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:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48129;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
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:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48133;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
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:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68009;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
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:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68017;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
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:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47945;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
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:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68021;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphate + H2O = 1,2-
CC dihexadecanoyl-sn-glycerol + phosphate; Xref=Rhea:RHEA:43236,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:72859,
CC ChEBI:CHEBI:82929; Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43237;
CC Evidence={ECO:0000250|UniProtKB:Q8IY26};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8IY26}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8IY26}. Nucleus envelope
CC {ECO:0000250|UniProtKB:Q8IY26}. Nucleus inner membrane
CC {ECO:0000250|UniProtKB:Q8IY26}.
CC -!- PTM: Phosphorylation by PKC activates the phosphatase activity towards
CC presqualene diphosphate. {ECO:0000250|UniProtKB:Q8IY26}.
CC -!- SIMILARITY: Belongs to the PA-phosphatase related phosphoesterase
CC family. {ECO:0000305}.
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DR EMBL; AK016572; BAB30313.1; -; mRNA.
DR EMBL; BC052412; AAH52412.1; -; mRNA.
DR CCDS; CCDS29728.1; -.
DR RefSeq; NP_083198.1; NM_028922.3.
DR AlphaFoldDB; Q9D4F2; -.
DR SMR; Q9D4F2; -.
DR BioGRID; 216729; 1.
DR STRING; 10090.ENSMUSP00000047776; -.
DR iPTMnet; Q9D4F2; -.
DR PhosphoSitePlus; Q9D4F2; -.
DR SwissPalm; Q9D4F2; -.
DR EPD; Q9D4F2; -.
DR jPOST; Q9D4F2; -.
DR MaxQB; Q9D4F2; -.
DR PaxDb; Q9D4F2; -.
DR PeptideAtlas; Q9D4F2; -.
DR PRIDE; Q9D4F2; -.
DR ProteomicsDB; 288257; -.
DR Antibodypedia; 3112; 134 antibodies from 27 providers.
DR DNASU; 74411; -.
DR Ensembl; ENSMUST00000045674; ENSMUSP00000047776; ENSMUSG00000040105.
DR GeneID; 74411; -.
DR KEGG; mmu:74411; -.
DR UCSC; uc008hcr.2; mouse.
DR CTD; 403313; -.
DR MGI; MGI:1921661; Plpp6.
DR VEuPathDB; HostDB:ENSMUSG00000040105; -.
DR eggNOG; KOG4268; Eukaryota.
DR GeneTree; ENSGT00940000160907; -.
DR HOGENOM; CLU_072573_4_0_1; -.
DR InParanoid; Q9D4F2; -.
DR OMA; GVCAGEN; -.
DR OrthoDB; 1356295at2759; -.
DR PhylomeDB; Q9D4F2; -.
DR TreeFam; TF323272; -.
DR Reactome; R-MMU-191273; Cholesterol biosynthesis.
DR BioGRID-ORCS; 74411; 1 hit in 40 CRISPR screens.
DR ChiTaRS; Plpp6; mouse.
DR PRO; PR:Q9D4F2; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9D4F2; protein.
DR Bgee; ENSMUSG00000040105; Expressed in epithelium of small intestine and 217 other tissues.
DR Genevisible; Q9D4F2; MM.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS: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; ISS:UniProtKB.
DR GO; GO:0106405; F:isoprenoid diphosphate phosphatase activity; ISO:MGI.
DR GO; GO:0042577; F:lipid phosphatase activity; ISO:MGI.
DR GO; GO:0052642; F:lysophosphatidic acid phosphatase activity; ISS:UniProtKB.
DR GO; GO:0008195; F:phosphatidate phosphatase activity; ISO:MGI.
DR GO; GO:0042392; F:sphingosine-1-phosphate phosphatase activity; ISO:MGI.
DR GO; GO:0045339; P:farnesyl diphosphate catabolic process; ISS:UniProtKB.
DR GO; GO:0033383; P:geranyl diphosphate metabolic process; ISS:UniProtKB.
DR GO; GO:1902247; P:geranylgeranyl diphosphate catabolic process; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006720; P:isoprenoid metabolic process; ISS:UniProtKB.
DR GO; GO:0046839; P:phospholipid dephosphorylation; ISO:MGI.
DR GO; GO:1902565; P:positive regulation of neutrophil activation; ISS:UniProtKB.
DR GO; GO:0018342; P:protein prenylation; ISS: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 Endoplasmic reticulum; Hydrolase; Immunity; Innate immunity;
KW Lipid metabolism; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..292
FT /note="Polyisoprenoid diphosphate/phosphate
FT phosphohydrolase PLPP6"
FT /id="PRO_0000239397"
FT TOPO_DOM 1..131
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT TRANSMEM 132..152
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 153..161
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT TRANSMEM 162..182
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 183..225
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT TRANSMEM 226..246
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 247..257
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT TRANSMEM 258..278
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 279..292
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 66..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 181..189
FT /note="Phosphatase sequence motif I"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 208..211
FT /note="Phosphatase sequence motif II"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT REGION 246..257
FT /note="Phosphatase sequence motif III"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT ACT_SITE 211
FT /note="Proton donors"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT ACT_SITE 253
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT SITE 257
FT /note="Stabilizes the active site histidine for
FT nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:O34349"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IY26"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
SQ SEQUENCE 292 AA; 31744 MW; 8B28C6DCA0BE7F17 CRC64;
MPSPRRTIEG RPLGSSGGSS VPGSPAHGGG SGGGRFEFQS LLNCRAGADP ACARLRASDS
PVHRRGSFPL AASGPAQAAP APPPEDARMN LNPSFLGIAL RSLLAIDLWL SKKLGVCAGE
SSAWGSVRPL MKLLEISGHG IPWLLGTLYC LLRSDSWAGR EVLMNLLFAL LLDLLLVAVI
KGLVRRRRPA HNQKDMFFTL SVDRYSFPSG HATRAALVSR FILNHLVLAI PLRVLVVLWA
FVLGLSRVML GRHNVTDVAF GFFLGYMQYS IVDYCWLSPH NVPVLFVLWN QQ
